COVID doi: 10.3390/covid6050082

Authors: Adriano Luis Fonseca Miriã Cândida Oliveira Daniela Rosana Pedro Fonseca João Pedro R. Afonso Heren Nepomuceno Costa Paixão Jairo Belém Soares Ribeiro Júnior Larissa Rodrigues Alves Tiago Vieira Fernandes Daniel Grossi Marconi Rodrigo A. C. Andraus Carlos Hassel Mendes Silva Iransé Oliveira-Silva Orlando Aguirre Guedes Claudia S. Oliveira Natasha Yumi Matsunaga Spicacci Maria Clara Real Pedro Fonseca Wilson Rodrigues Freitas Júnior Paolo Capodaglio Luis Vicente F. Oliveira

Introduction: Coronavirus disease 2019 (COVID-19) can cause persistent cardiovascular alterations, including autonomic dysfunction. Heart rate (HR) recovery (HRR) after exercise is a simple marker of autonomic modulation associated with functional capacity and clinical prognosis. Evaluating HRR during the six-minute walk test (6MWT) may help identify residual functional limitations in diverse patients. Objective: To compare pulmonary function, maximal inspiratory pressure (MIP), functional capacity, dyspnea, fatigue, and functional status in post-COVID-19 patients. Methods: This cross-sectional study included 75 adults (mean age: 47.6 ± 13.1 years; 54.7% male) who recovered from COVID-19 divided into 2 groups based on HRR 1 min after the 6MWT: delayed (≤12 beats/min); and non-delayed (>12 beats/min). Pulmonary function, MIP, exercise capacity (via 6MWT), dyspnea, muscle fatigue, and functional status were assessed. Results: Based on HRR 1 min after 6MWT, 27 (36%) participants were classified with abnormal HRR and 48 (64%) with normal HRR. There were statistical differences between the groups regarding demographic or clinical characteristics, pulmonary function, MIP, muscle fatigue, or functional status (p > 0.05). The delayed HRR group exhibited a smaller reduction in HR in first minute of recovery (ΔHR = 6 vs. 23 beats/min), higher baseline HR (p = 0.010), and greater dyspnea (p = 0.020). Furthermore, this group exhibited worse functional performance in the 6MWT, with shorter distance walked (437.33 vs. 494.27 m; p = 0.019) and a lower percentage of predicted distance (74.66 ± 12.98% vs. 82.94 ± 15.71%; p = 0.023) compared with the non-delayed HRR group. Conclusion: Delayed HRR post-COVID-19 was associated with poorer functional performance and greater dyspnea, regardless of pulmonary function. The blunted reduction in HRR after exertion suggests impaired cardiovascular autonomic modulation, possibly related to attenuated vagal reactivation, which may contribute to exercise intolerance observed in this population.

COVID doi: 10.3390/covid6050081

Authors: Cindy M. M. de Jong Bas F. M. van Raaij Louisa (M. L.) Antoni Sesmu (M. S.) Arbous Miranda (J. J. M.) Geelhoed Michiel A. de Graaf Geert H. Groeneveld Chris (S. C. H.) Hinnen Veronica R. Janssen Moniek M. ter Kuile Anna H. E. Roukens Lauran (J. L.) Stöger Maarten S. Werkman Frederikus A. Klok Bob Siegerink on behalf of the COVID-19 LUMC Group on behalf of the COVID-19 LUMC Group

Since the introduction of the Post-COVID-19 Functional Status (PCFS) scale early in the COVID-19 pandemic, the scale has been incorporated in research and clinical guidelines to assess and monitor functional status. In this explorative study, we aimed to evaluate characteristics of the PCFS scale based on its use during a 12-month follow-up of COVID-19 survivors to increase understanding of the scale over a longer period of time. Adult COVID-19 patients who were evaluated by multidisciplinary measures at 6 weeks and 12 months post-discharge at the Leiden University Medical Center (The Netherlands) were included. The distribution of PCFS scale grades, as well as descriptive patterns between PCFS grades and patient-reported outcome measures (PROMs), pulmonary function and physical function were evaluated with descriptive analyses; no statistical tests were performed due to data availability. Of the 79 included patients, 62% had a change in PCFS grade between the 6-week and 12-month follow-ups, of whom 63% improved over time. At 12 months, abnormal PROMs regarding psychological symptoms (according to clinical cut-offs), relatively lower quality of life (EQ VAS) scores, and MRC dyspnea grades ≥ 2 were observed in patients scoring PCFS grade ≥ 2. With increasing PCFS grade, a decrease in pulmonary function and physical function outcomes was observed. Higher PCFS grades (worse functional status) seemed related to worse outcomes at 12-month follow-up. Future studies are needed to investigate whether changes in PCFS grade reflect clinically relevant changes in patients’ self-perceived functioning.

COVID doi: 10.3390/covid6050080

Authors: Maya Asami Takagi Hevatib Mehmood Asef Raiyan Hoque Neli Ragina

American Indian and Alaska Native (AI/AN) communities experienced disproportionate COVID-19 morbidity and mortality, particularly in rural areas with limited public health infrastructure. This study examined primary COVID-19 information sources among AI/AN adults in rural Michigan and evaluated how trust in these sources relates to health knowledge, attitudes, and vaccination behaviors. We conducted a prospective, randomized pre-post interventional study among 273 adults at a tribal health clinic in rural Isabella County, Michigan (2022–2024). Participants were assigned to receive a culturally tailored educational video or infographic, and surveys assessed COVID-19 knowledge, vaccine attitudes, information sources, and perceived reliability. Social media was the most frequently used information source but was rated as less reliable, whereas healthcare workers (HCWs) were considered the most trusted. Reliance on HCWs and personal relationships was associated with higher baseline vaccine knowledge and greater uptake of influenza vaccination. Both educational formats resulted in modest improvements in COVID-19 knowledge and vaccine attitudes. While no consistent differences were observed between formats overall, infographic-based education was associated with greater gains in select vaccine knowledge domains among participants who relied on trusted interpersonal or clinical information sources. These findings highlight a “usage-trust gap” in rural AI/AN health communication, where frequently used information channels are not necessarily the most trusted. Culturally tailored messaging delivered through trusted clinical and interpersonal networks may enhance the effectiveness of public health communication and support vaccine uptake in underserved communities.

COVID doi: 10.3390/covid6050079

Authors: Elisa Bósquez Diana C. Oviedo-Céspedes Gabrielle B. Britton Adam E. Tratner Sofía Rodríguez-Araña Ramón Mon

Many people experienced difficulties grieving the death of a loved one during the COVID-19 pandemic. The main objective of this research was to examine the psychological manifestations of grief for people who experienced the death of a loved one between March 2020 and March 2022 in Panama. A sample of 110 participants completed an online survey including sociodemographic questions and psychological questionnaires. A subsample of twenty-six participants was interviewed about their experience of loss leading up to death, at the time of death, and after death. Results indicated that 43.6% of participants suffered from complicated grief (CG). Participants who experienced CG had more post-traumatic stress symptoms, somatic symptomatology, anxiety/insomnia, social dysfunction, severe depression, use of avoidant coping mechanisms, and more anxiety about the pandemic than participants who did not experience CG. A logistic regression analysis indicated that anxiety/insomnia symptoms, denial as a coping mechanism, and post-traumatic stress symptoms increased the likelihood of CG. For qualitative analyses, the most relevant themes that emerged were distress associated with contagion and illness, hospitalization and access to healthcare services, communication with medical staff, the impact of the news of death, inability to view the body, emotions following the loss, farewell rituals, and coping mechanisms.

COVID doi: 10.3390/covid6050078

Authors: Vidya Keshav Lesley Scott Lucia Hans Wendy Stevens

Rapid antigen tests targeting SARS-CoV-2 nucleocapsid protein were essential for decentralised testing during the COVID-19 pandemic. Independent performance evaluations are essential to support regulatory approval and inform clinical implementation, particularly in resource-limited settings. This study presents a retrospective analytical and operational evaluation of two instrument-based fluorescent immunoassays (FIAs): the PCL COVID-19 Ag Rapid FIA and LumiraDx SARS-CoV-2 Ag Test. Analytical sensitivity was determined using recombinant nucleocapsid protein and viral cultures. Clinical performance was assessed using residual clinical specimens (n = 110) with RT-PCR as a reference, stratified by cycle threshold (Ct). Operational characteristics were assessed using a structured Likert framework. Overall sensitivity was 63% (51–73) for PCL and 95% (88–99) for LumiraDx. For Ct ≤ 25, sensitivity increased to 93% and 100%. Specificity was ≥97% for both. LumiraDx maintained sensitivity (83–94%) at Ct 25–30, whereas PCL did not detect any positives in this range. The limit of detection was 39 pM (PCL) and 0.6 pM (LumiraDx). Operational usability was high for both (90% PCL, 87% LumiraDx). LumiraDx showed higher analytical sensitivity across a broader viral load range, supporting primary diagnostic use, whereas PCL was limited to high viral loads. This evaluation provides a reproducible framework for rapid diagnostic assessment during emerging outbreaks.

COVID doi: 10.3390/covid6050077

Authors: Marina Kloni Alexandros Heraclides Theognosia Panteli Alexios Klonis Panagiotis Rentzias Christos Karagiannis

Background: Post-COVID-19 syndrome (PCS) is associated with impairments in mobility, balance, and physical function, which may reduce quality of life. The 30 s Sit-to-Stand (30STS) and Timed Up and Go (TUG) tests are widely used clinical measures; however, their intra-rater reliability in older adults with PCS has not been established. Reliable outcome measures are essential for clinical assessment and rehabilitation planning. Methods: In this single-center pilot study, nineteen older adults with PCS were recruited as a convenience sample. Participants completed three trials of the 30STS and TUG tests on day one, with the protocol repeated after three days. The 30STS evaluates lower-limb strength and functional performance, while the TUG assesses balance, gait, and fall risk. Intra-class correlation coefficient (ICC), standard error of measurement (SEM), and minimum detectable change (MDC) were calculated. Results: The TUG showed an ICC of 0.995 (95% CI: 0.991–0.998), SEM of 0.48 s, and MDC of 1.33 s. The 30STS showed an ICC of 0.986 (95% CI: 0.973–0.994), SEM of 0.26 repetitions, and MDC of 0.72 repetitions. Conclusions: The TUG and 30STS demonstrate excellent intra-rater reliability and appear to be feasible clinical tools for assessing functional performance in older adults with PCS. However, findings should be interpreted cautiously due to the small, single-center pilot design and single evaluator. Further research is needed to confirm generalizability across broader PCS populations and clinical settings.

COVID doi: 10.3390/covid6050076

Authors: Domna Tichala Dimitrios Papagiannis Ourania S. Kotsiou

Background: Understanding how demographic and clinical factors influence SARS-CoV-2 infection patterns, vaccination uptake and disease outcomes in community settings is essential for effective primary care-based public health planning. Objectives: This study aimed to investigate the distribution of SARS-CoV-2 infections among adults attending Primary Healthcare (PHC) facilities in Giannitsa, Greece, from 2020 to 2024, and to examine associations between demographic and clinical characteristics, vaccination category and disease outcomes. Methods: A retrospective analysis was conducted using data from the National Registry of Patients with COVID-19. The study included 1144 adults diagnosed with SARS-CoV-2 at PHC facilities from 19 November 2020 to 3 October 2024; all cases included in the present analysis had been confirmed by rapid antigen testing. Variables included age, gender, residence, registry-recorded underlying medical conditions, vaccination category, seasonality and clinical outcome. Results: Significant shifts in case distribution were observed across time, with younger adults predominating in 2020–2022 and older adults (61–90 years) in 2023–2024 (p < 0.001). Winter months showed higher case incidence overall (p < 0.001). Vaccination coverage increased annually, reaching 84.8% in 2024 (p < 0.001). Hospitalization/death occurred in 1.7% of patients and was strongly associated with age ≥61 years (6.0% vs. 0.3%), the presence of at least one registry-recorded underlying medical condition (9.2% vs. 0.9%) and vaccination category; specifically, hospitalization/death occurred in 10.4% of individuals diagnosed during the pre-vaccine period, 2.3% of unvaccinated individuals during the vaccination era and 0.9% of vaccinated individuals (all p < 0.001). Conclusions: Older age, underlying medical conditions and a lack of vaccination were key predictors of worse outcomes. The findings underscore the importance of strengthening vaccination outreach and targeted PHC interventions, particularly for high-risk and rural populations.

COVID doi: 10.3390/covid6050075

Authors: George Cătălin Alexandru Doina Chioran Mircea Riviș Cristina Modiga Loredana-Neli Gligor Marius Octavian Pricop Ștefania Dinu Ciprian I. Roi Cristina Dumitrescu Andreea Mihaela Kiș Tudor Rareş Olariu

Background: COVID-19 is primarily a respiratory disease, but increasing evidence suggests possible oral and maxillofacial complications. This study presents a case series of post-COVID maxillary osteonecrosis (PC-RONJ) cases from western Romania and explores the possible association between SARS-CoV-2 infection, its treatment, and this complication. Methods: We conducted a multicenter retrospective case series of two patients with recent PCR-confirmed SARS-CoV-2 infection who subsequently developed maxillary osteonecrosis (ONC) between 2021 and 2023. Clinical examination, CT imaging (including 3D reconstructions), and ENT assessment were used to assess the severity of the disease. All medical records were reviewed to identify comorbidities, details of COVID-19 treatment, and the appearance of maxillofacial symptoms. Results: Both patients had been hospitalized for severe COVID-19 and treated according to the national protocol with systemic corticosteroids, oxygen therapy, anticoagulation, and antivirals. CT scans revealed marked osteolytic destruction of the maxilla and maxillary sinus walls, with extension toward adjacent facial bones. Microbiological analysis revealed a complex polymicrobial profile, including Gram-positive and Gram-negative bacteria as well as opportunistic fungal species, consistent with a chronic biofilm-associated infectious process. Patients received surgical treatment, followed by local care and, in both cases, prosthetic rehabilitation with maxillary obturators, which improved speech, chewing, and oral function. Conclusions: This case series suggests a possible association between severe COVID-19, its treatment, and subsequent maxillary osteonecrosis in susceptible patients; however, the small number of cases precludes causal inference. To our knowledge, this is the first Romanian report describing such cases in patients without prior antiresorptive therapy. These findings highlight the need for careful use of systemic corticosteroids and vigilant post-recovery monitoring of maxillofacial complications. Further studies are required to clarify the underlying mechanisms and risk factors.

COVID doi: 10.3390/covid6050073

Authors: Amanda Caroline Silva Rívolli Isabela Antunes de Souza Lima Camila Candida Compagnoni dos Reis Íngrid Ribeiro Antonio Márcia Marcondes Altimari Samed

Background/Objectives: The COVID-19 pandemic imposed logistical challenges on health systems, particularly for mass vaccination campaigns under emergency conditions. In decentralized health systems, the absence of a structured preparedness phase may compromise coordination, allocation, and operational performance. This study analyzes the vaccination campaign in a municipality in southern Brazil, examining how the overlap of the preparedness and response phases affected outcomes and how alternative logistical scenarios could have altered campaign performance. Methods: An empirical analysis was conducted using scenario-based simulation with stock and flow structures. The model represents vaccine procurement, distribution across national, state, regional, and municipal levels, and municipal vaccination capacity. Real data from the 2021 vaccination campaign in the municipality were used to build a Business-as-Usual scenario, compared with alternative scenarios involving changes in procurement predictability, allocation rules, and operational capacity. Results: Vaccination outcomes were strongly conditioned by upstream allocation decisions, particularly at the national state level. Isolated adjustments at intermediate supply chain levels produced limited improvements when upstream constraints persisted. Scenarios combining improved alignment between forecasted and acquired doses with operational capacity showed higher vaccination potential, revealing a gap between observed performance and system capacity. Conclusions: The findings reinforce that preparedness is a critical determinant of vaccination performance and must precede response in emergency contexts. Supply predictability alone is insufficient without coordinated allocation mechanisms and operational readiness across governance levels. This study provides empirical evidence on how preparation-related decisions shape vaccination outcomes in decentralized health systems and inform logistical coordination in future emergencies.

COVID doi: 10.3390/covid6050074

Authors: Maya Asami Takagi Asef Raiyan Hoque Neli Ragina

The COVID-19 pandemic highlighted substantial variability in public health information environments, yet the relationship between information source, perceived credibility, and behavioral response remains incompletely understood. This study evaluated how information sources influence COVID-19-related knowledge and behaviors and whether targeted educational interventions modify these relationships. We conducted a prospective survey-based study (July–December 2021) among adults recruited from outpatient clinics in Michigan (N = 209). Participants completed pre- and post-intervention surveys assessing information sources, perceived reliability, knowledge, and behaviors, and were randomized to receive either a video or infographic. Social media was the most frequently reported source (n = 95) but had lower perceived reliability (mean 2.97/5), whereas healthcare workers (HCWs) were rated most reliable (mean 4.26/5) despite lower utilization (n = 60). Use of HCWs, print media, and websites was associated with higher baseline knowledge, while television and radio were associated with lower knowledge of vaccine side effects (p = 0.011 and p = 0.003). Educational interventions improved knowledge and attitudes, with differential effects across source groups, while infographic-based interventions were more effective among social media users (p = 0.034). Information sources and perceived credibility significantly shape health knowledge and behavior, highlighting the need for communication strategies that integrate trusted messengers, high-reach platforms, and health literacy to improve public health outcomes.

COVID doi: 10.3390/covid6050072

Authors: Pantea Kiani Dana M. Dijkgraaf Sophie I. Groenewoud Anje A. te Velde Edith J. M. Feskens Aletta D. Kraneveld Johan Garssen Berber J. Vlieg-Boerstra Joris C. Verster

Post-acute sequelae of SARS-CoV-2 infection (PASC), also referred to as Long COVID, affects millions worldwide and is characterized by persistent fatigue, reduced immune fitness, and mood disturbances. The aim of the current study was to identify if immune fitness, mood, fatigue, and quality of life prior to SARS-CoV-2 infection could predict PASC fatigue severity. A retrospective cross-sectional survey was conducted among 299 Dutch PASC patients. Participants completed validated measures of immune fitness, fatigue (assessed with both the Fatigue Severity Scale and a single-item scale), mood (including stress, anxiety, depression, hostility, loneliness, and happiness) and quality of life for the three months prior to SARS-CoV-2 infection. The same assessments were made for the month before survey completion (i.e., during PASC). Correlational and regression analyses were conducted to identify possible predictors of PASC fatigue severity. Participants were predominantly female (90%): mean age 44.1 (SD 11.2) years. Both assessments of PASC fatigue did not correlate significantly with the prior SARS-CoV-2 assessments of immune fitness, fatigue, mood, and quality of life. The regression analyses revealed no significant predictors for PASC fatigue severity. In conclusion, immune fitness, fatigue, mood and quality of life prior to SARS-CoV-2 infection were not identified as independent predictors of PASC fatigue severity.

COVID doi: 10.3390/covid6040071

Authors: Stefan Kurbatfinski Deborah Dewey Nicole Letourneau

Background: The COVID-19 pandemic increased stress experienced by children through individual-, family-, and community-level factors, with potential sex-specific impacts on behavioural outcomes. Children’s resilience may buffer these effects. This exploratory study investigated associations between COVID-19 stress and children’s internalising, externalising, and overall behavioural symptoms, and whether child resilience and sex assigned at birth moderated these associations. Methods: Data (N = 68) came from the longitudinal COVID-19 Impact Study of the Canadian APrON pregnancy cohort of mothers and their children followed for more than 9 years. COVID-19 stress, combining individual-, family-, and community-level stressors, was reported by mothers (mean age = 42.37, SD = 3.72) and their children (53% female; mean age = 10.21 years, SD = 0.43) across three timepoints (October–December 2020; February–May 2021; June–August 2021). Children’s behavioural problems and self-reported resilience were assessed between April and September 2022. Results: COVID-19 stress was not significantly associated with children’s behavioural problems. Moderated-moderation suggested that the association between COVID-19 stress and children’s internalising (T-score estimate = −2.38, 95% CI [−4.08, −0.68]), externalising (T-score estimate = −3.21, 95% CI [−5.09, −1.33]), and overall (T-score estimate = −2.79, 95% CI [−4.45, −1.12]) symptoms may vary by child resilience and child sex assigned at birth. Among females, COVID-19 stress appeared to be associated with more behavioural problems at lower levels of resilience and fewer problems at higher levels of resilience. Significance: The association between COVID-19 stress and children’s behavioural symptoms across children’s resilience levels may vary based on sex assigned at birth, with effects suggested among females. Null findings may reflect the modest sample size and limited statistical power.

COVID doi: 10.3390/covid6040070

Authors: Olga Valderrama-Rios Rosario Miraval-Contreras Noemí Zuta-Arriola Mercedes Ferrer-Mejía Vanessa Mancha-Alvares César Paredes-Román Haydee Paredes-Román María Porras-Roque Lourdes Luque-Ramos Edgar Zárate-Sarapura Evelyn Sánchez-Lévano

This study evaluates the performance of a semi-dynamic negative binomial model with cubic spline smoothing to characterize the spatiotemporal dynamics of COVID-19 mortality in Peru, a setting marked by significant data inconsistency and reporting delays. Using nationwide weekly mortality data, we compared a Poisson regression against a semi-dynamic NB model with a population offset and cubic splines (df = 6). The models were evaluated using Akaike Information Criterion and log-likelihood to handle overdispersion and temporal non-stationarity. The NB model demonstrated a superior fit, reducing the AIC from 136,596.4 to 75,668.25 and improving log-likelihood by over 30,000 points. Demographic analysis revealed an 81.6% higher risk of death in males (IRR = 1.816; 95% CI: 1.753–1.881) and an exponential gradient with age, peaking at an IRR of 4.717 (95% CI: 4.499–4.945) for individuals ≥80 years. Departmental fixed effects identified significant spatial heterogeneity, with higher diffusion in coastal regions. The semi-dynamic NB model with splines provides a robust, parsimonious, and scalable framework for epidemiological surveillance in resource-limited settings. By effectively correcting for overdispersion and stabilizing weekly reporting fluctuations, this approach offers a reliable tool for public health decision making in environments with fragmented data quality.

COVID doi: 10.3390/covid6040069

Authors: Claudine J. Egol Katherine M. Piderman Harold G. Koenig Victor N. Nettey Matthew J. Van Ligten Mohamed Aly Shirshendu Sinha Terry D. Schneekloth Osama A. Abulseoud

Background: Religious affiliation has traditionally served as a coping strategy during stressful events such as the COVID-19 pandemic. Pregnant women faced heightened stress during the pandemic due to concerns about their health as well as that of their fetus. This study examined the prevalence of self-reported religious affiliation among SARS-CoV-2-positive pregnant women and investigated differences in psychiatric diagnoses and pregnancy outcomes based on religious affiliation. Methods: The study included all asymptomatic or mildly symptomatic SARS-CoV-2-positive pregnant women who received care at the Mayo Health System from March 2020 through October 2021 and completed the routine religious affiliation questionnaire. Those selecting “none” were categorized as having no religious affiliation (RA−), whereas those selecting a specific religion were categorized as religiously affiliated (RA+). Results: Among 609 women, 49.6% were RA+ and 50.4% were RA−. RA+ women were more likely to be white, married, college-educated, and have fewer prior abortions. There were no significant differences in rates of depression, anxiety, psychotropic medication use, substance use, or pregnancy and labor complications between RA+ and RA− groups. Conclusions: Half of the women in this cohort reported no religious affiliation. Previously reported protective associations between religiosity and mental health were not observed when religious affiliation alone was examined.

COVID doi: 10.3390/covid6040068

Authors: Salvador Domènech-Montoliu Óscar Pérez-Olaso Diego Sala-Trull Paloma Satorres-Martinez Laura López-Diago Isabel Aleixandre-Gorriz Maria Rosario Pac-Sa Manual Sánchez-Urbano Cristina Notari-Rodriguez Juan Casanova-Suárez Raquel Ruiz-Puig Gema Badenes-Marques Laura Aparisi-Esteve Carmen Domènech-León Maria Angeles Romeu-Garcia Alberto Arnedo-Pena

Background and Objective: After SARS-CoV-2 infection, Long COVID (LC) syndrome has occurred in a high proportion of patients, affecting their health. The aim of this study was to estimate the incidence of LC, as well as its risk and protective factors. Materials and Methods: We conducted a prospective population-based cohort study of the Borriana COVID-19 cohort (Castellon Province, Valencia Community, Spain) from May 2020 to August 2023, with a follow-up of 40 months, using the LC definition given by the World Health Organization. Inverse probability-weighted regression adjustment was applied in the statistical analysis. Results: With a participation rate of 63.8% and a total of 722 participants, the mean age was 37.7 ± 17.4 years, and 460 (62.3%) were female. Among them, 644 had experienced a SARS-CoV-2 infection, and 184 developed LC, corresponding to a cumulative incidence of 28.6%. At the time of follow-up, 135 patients remained affected by LC, and one LC-related death was recorded. Significant risk factors for LC included older age, female sex, being part of a small family, having a chronic disease, SARS-CoV-2 exposure, and disease severity. Asymptomatic COVID-19 infection and SARS-CoV-2 vaccination were significantly protective factors. Conclusions: A substantial incidence of LC was observed, along with a low recovery rate. Several risk and protective factors were identified. Continued follow-up of this cohort, improved medical care for patients with non-recovered LC, ongoing surveillance of SARS-CoV-2 infections, and vaccination of the at-risk populations against SARS-CoV-2 are recommended.

COVID doi: 10.3390/covid6040067

Authors: Boban Stolić Nataša Katanić Bojan Joksimović Jelena Filimonović Ksenija Bojović Aleksandar Pavlović Jasmina Poluga Nikolina Elez-Burnjaković Biljana Mijović Nenad Lalović Milena Anđelković Milica Milentijević Siniša Ristić Miloš Vasiljević Alma Prtina Miljan Adamović Marija Milić

Background: The clinical course of COVID-19 is highly variable, ranging from asymptomatic infection to critical illness with hyperinflammation and multiorgan failure. Oxidative stress plays a central role in COVID-19 pathogenesis, and genetic polymorphisms in glutathione S-transferase (GST) enzymes, particularly GSTM1 and GSTT1 null genotypes, may impair antioxidant defense and exacerbate inflammatory responses. This study aimed to investigate the association of GSTM1 and GSTT1 null genotypes with both disease severity and serum cytokine levels in hospitalized COVID-19 patients. Methods: This cross-sectional study enrolled 137 COVID-19 patients hospitalized during the second pandemic wave (July–September 2020). Patients were stratified into mild (n = 67) and severe (n = 70) groups based on clinical criteria. GSTM1 and GSTT1 polymorphisms were determined by multiplex polymerase chain reaction. Serum levels of 13 cytokines were measured using flow cytometry. Logistic regression analyzed genotype associations with disease severity, and multivariate linear regression assessed relationships between null genotypes and pro-inflammatory cytokine levels (IL-6, TNF-α, IL-17A, IFN-γ), adjusted for age, sex, hypertension, and diabetes. Results: The GSTT1 null genotype was significantly associated with severe COVID-19 (adjusted OR = 2.56, 95% CI: 1.08–6.07, p = 0.032). Severe patients exhibited significantly elevated levels of IL-6 (75.6% increase, p = 0.008), TNF-α (69.4% increase, p = 0.005), IL-17A (54.4% increase, p = 0.016), and IFN-γ (10.1% increase, p = 0.021). Both GSTM1 and GSTT1 null genotypes were associated with higher levels of these cytokines, with stronger effects observed for GSTT1 null. In multivariate analysis, GSTT1 null independently predicted elevated IL-6 (β = 52.6, p = 0.003), TNF-α (β = 13.8, p = 0.002), IL-17A (β = 2.4, p = 0.001), and IFN-γ (β = 56.4, p = 0.012). The combined both null genotype showed the strongest associations but was limited by small sample size (n = 10) and should be interpreted with caution. Conclusions: The GSTT1 null genotype is associated with severe COVID-19 and appears to be associated with heightened pro-inflammatory cytokine responses, particularly IL-6, TNF-α, IL-17A, and IFN-γ. These findings suggest a potential role for genetic impairment of antioxidant defense may contribute to hyperinflammation in COVID-19 hyperinflammation, although validation in larger cohorts is needed.

COVID doi: 10.3390/covid6040066

Authors: Raya Kh. Yashooa Dara K. Mohammad Shawnim M. Maaruf Treska S. Hassan Azhin D. Aziz Wissam Albeer Nooh Ghoorbat A. Mustafa Sevan O. Majed Gaylany H. Abdullah Galawezh O. Othman Suhad A. Mustafa

Coronavirus disease-2019 COVID-19 exhibits marked inter-individual variability in susceptibility and clinical outcomes, suggesting a role for host genetic factors. Vitamin D exerts immunomodulatory effects through the vitamin D receptor (VDR), and genetic variation in the VDR gene may influence host responses to SARS-CoV-2 infection. This study aimed to investigate the association between VDR-gene polymorphisms—FokI (rs2228570), TaqI (rs731236), ApaI (rs7975232), and BsmI (rs1544410)—and COVID-19 susceptibility in the Kurdish population. The FokI polymorphism was significantly associated with COVID-19 susceptibility. Interestingly, the GG-genotype was more frequent among Patients than controls and was associated with increased odds of infection (OR = 9.00; 95% CI: 3.22–25.15; p < 0.0001), whereas the AG-genotype was associated with reduced susceptibility (OR = 0.33; 95% CI: 0.14–0.76; p = 0.001). Additionally, the G-allele was also more prevalent in Patients than controls (OR = 1.87; 95% CI: 1.21–2.89; p = 0.004). Similarly, the TaqI TT-genotype was more frequent among Patients and was associated with increased susceptibility (OR = 36.0; 95% CI: 11.2–115.8; p < 0.0001). In contrast, the ApaI AA-genotype was less frequent among Patients and was associated with reduced odds of COVID-19 susceptibility under a recessive model (OR = 0.15; 95% CI: 0.03–0.68; p = 0.003). Moreover, the BsmI polymorphism was monomorphic in both groups and therefore not informative. Genetic variation in the VDR gene, particularly at the FokI, TaqI, and ApaI loci, was associated with COVID-19 susceptibility in the case–control study, while BsmI showed no variations. These findings suggest that genetic variation in the VDR gene may contribute to inter-individual differences in susceptibility to SARS-CoV-2 infection in the Kurdish population. Larger studies incorporating functional validation and detailed clinical data are required to confirm these associations.

COVID doi: 10.3390/covid6040065

Authors: Miryam Lora-Loza Jean Hernández Angulo José Elías Cabrejo Paredes Maribel Díaz Espinoza Jean Carlos Zapata Rojas

Health crises hinder the provision of intensive care for critical obstetric conditions such as preeclampsia and eclampsia, where timely decision making and system capacity directly impact maternal and fetal outcomes. This study compared the clinical and epidemiological profile and care processes in the ICU for cases of preeclampsia and eclampsia before and during the COVID-19 health crisis in Alto Amazonas, Loreto (Peru), using a comparative mixed-method approach. Quantitative data were obtained from ICU medical records for two periods (2015–2019 and 2020–2022). Categorical variables were compared using exact methods (Fisher’s exact test for 2 × 2 tables and exact procedures for scatter tables with multiple categories), and continuous variables were compared using nonparametric tests where appropriate. The most notable change was an increase in the frequency of cesarean sections during the health crisis, which should be interpreted with caution given the small sample size and potential changes in admission criteria and system limitations. Other clinical indicators and discharge status showed no clear evidence of substantial differences between the periods. Qualitative findings highlighted systemic limitations affecting continuity of care, particularly those related to timely access to safe blood products and referral pathways. These results align with SDG 3 (Good Health and Well-being) and support strengthening preparedness, referral coordination, and the availability of essential resources to protect maternal health during large-scale emergencies.

COVID doi: 10.3390/covid6040064

Authors: Ko Miyazawa Takuya Sakamoto Daisuke Sakamoto Tsugiyasu Kanda Tamaki Takano

The concurrent occurrence of COVID-19 and the 2024 Noto Peninsula earthquake resulted in a “compound disaster” in Japan. This retrospective study, spanning 11 years (2015–2025), examines the impact of these crises on trends in cardiovascular surgery, focusing on infective endocarditis (IE). A total of 2444 surgical cases were analyzed across three distinct periods: pre-pandemic (2015–2019), pandemic (2020–2023), and compound disasters (2024). While overall surgical volumes exhibited fluctuations, there was a notable increase in the number of interventions for IE and renal failure in 2024. Additionally, the 2024 IE cohort revealed a significant epidemiological shift, characterized by a younger median age (56 years compared to 70 years pre-pandemic), absence of pre-existing valvular disease, and a marked rise in blood culture-negative endocarditis (BCNE), which accounted for 83.3% of IE cases. In 2025, the number of surgical IE cases decreased to zero, highlighting the acute nature of the peak in 2024. These findings illustrate that compound disasters can disrupt cardiovascular surgical trends and underscore the susceptibility of IE to compromised healthcare access and environmental stress. The development of resilient diagnostic pathways is essential for managing complex public health emergencies.

COVID doi: 10.3390/covid6040062

Authors: Robert R. Wright Macey Bunnell Given Chatelain Eve McCulloch Alexis L. Soelberg Devon Marrott

For vaccine-preventable diseases, vaccination uptake is among the best public health behaviors to prevent infection, disease and death. However, public confidence in this behavior has waned in recent years alongside the twin respiratory threats of influenza and COVID-19. Moreover, certain populations, such as emerging adults, may be amenable to vaccination attitude and behavior change as they navigate their path between adolescence and adulthood. The current investigation presents two studies that address influenza and COVID-19 vaccination uptake among emerging adults. First, among more than 2000 emerging adults during the years of 2022–2024, we examined rates of vaccination uptake and attitudes, as well as relationships of vaccine rates with other concomitant health behaviors. Second, we explored the efficacy of a classroom-based vaccination promotion experience in altering both attitudes and behaviors regarding vaccination uptake among 275 emerging adults at college. Results highlighted some health behaviors that are related to influenza uptake but not COVID-19 uptake. Moreover, results from Study 2 demonstrated that attitudes, but not behavior, seem to be most amenable to the classroom-based approach to encourage health behavior change, as a significant increase in positive attitudes toward both influenza and COVID-19 vaccines was observed. These findings are discussed further, considering theoretical and practical applications.

COVID doi: 10.3390/covid6040063

Authors: Dartagnan Pinto Guedes Sandro Lucas Sofiati Alessandro Bressan Godoy

Previous studies have suggested that the COVID-19 pandemic exposed children to an increased risk of greater body weight accumulation; however, the evidence found is limited to examining relatively short periods in children from Asian, European, and North American countries and, in most cases, using cross-sectional designs, while studies with longitudinal designs are scarce. To our knowledge, to date, no study involving Brazilian children has examined temporal trends in body weight during the pandemic period using a longitudinal approach. Objective: To report the weight status of children aged 6 to 11 years pre-, during, and post-school closures in response to restrictions imposed by the COVID-19 pandemic, using a six-year school-based longitudinal cohort design (2020–2025). Method: Weight status was analyzed using the body mass index and diagnostic criteria proposed by IOFT. Initial data collection took place in 2020 (baseline—pre-school closures), in 2021 and 2022 (pandemic period—school closures), and in 2023, 2024, and 2025 (post-pandemic period—after the reopening of schools). Results: The data collected confirmed that restrictions imposed to mitigate the adverse impact of the COVID-19 pandemic, including the full or partial closure of schools, substantially increased children’s weight above what would be expected for their gender and age. After two years of the pandemic period, 23% of children identified in the baseline pre-school closures with normal body weight migrated to overweight, while 34% of overweight children became obese. Data equivalent to the post-pandemic period showed signs of a reduction in the excess body weight accumulated during the pandemic; however, the prevalence rates of overweight and obesity remained significantly higher than pre-school closures. Conclusions: The findings suggest that the harmful effects contributing to the greater accumulation of body weight during the COVID-19 pandemic tended not to reverse spontaneously, even five years after its onset. Therefore, specific actions to prevent, combat, and control overweight and obesity are essential to avoid present and future adverse consequences for children’s health.

COVID doi: 10.3390/covid6040061

Authors: Celalettin Topbaş Ayfer Atav Muhsin Ergen

Objective: Dental professionals are routinely exposed to infectious agents through contact with blood, saliva, and aerosols. This cross-sectional survey aimed to evaluate and compare knowledge, attitudes, and self-reported practices related to infectious diseases among dental students and practicing dentists in the post-COVID era. Methods: This web-based cross-sectional survey was conducted between January and March 2024 at a single dental faculty. Fourth- and fifth-year dental students and practicing dentists were invited to participate. A 30-item questionnaire assessed knowledge of infectious disease transmission and immunological markers (Questions Q1–Q19), as well as attitudes and self-reported practices toward patients with infectious diseases (Q20–Q30). Descriptive statistics were calculated, and comparisons between groups were performed using Pearson’s chi-square or Fisher’s exact tests (α = 0.05). Internal consistency of the questionnaire was acceptable (Cronbach’s alpha: 0.81 for knowledge items and 0.88 for attitude/practice items). Results: A total of 221 dental students and 33 dentists were included in the final analysis. Both groups demonstrated high awareness of respiratory transmission routes for COVID-19 and influenza. In contrast, recognition of bloodborne transmission pathways was limited, with approximately half of participants identifying blood contact and blood-contaminated instruments as potential sources of infection. Significant differences were observed between students and dentists in the interpretation of SARS-CoV-2 IgG antibodies, with dentists more frequently associating IgG positivity with prior infection (p = 0.009) and immunity (p < 0.001). Cautious behavior toward treating patients with infectious diseases was common in both groups, whereas reluctance to provide treatment and lower self-perceived knowledge were more frequently reported among students. Conclusions: Despite adequate awareness of respiratory infection transmission, important deficiencies persist in bloodborne pathogen knowledge, serological interpretation, and confidence in managing infected patients, particularly among dental students. These findings underscore the need for targeted, practice-oriented infection control education that integrates immunological principles and hands-on training to enhance clinical preparedness in the post-COVID era.

COVID doi: 10.3390/covid6040060

Authors: Tania Llana Sara Garces-Arilla Marta Mendez

COVID-19 is increasingly recognized as a multisystemic disease with significant neurocognitive consequences. However, its specific impact on spatial memory, a cognitive domain essential for daily navigation and functional independence, remains insufficiently explored. This narrative review provides a critical synthesis of current evidence regarding spatial and visuospatial memory alterations across acute and post-acute phases, and post COVID-19 condition (PCC). Clinical findings, conventional and emerging assessment tools ranging from static tasks to immersive virtual reality environments, as well as potential neurobiological mechanisms, were considered. Results suggested that spatial memory is frequently compromised after COVID-19 disease, with deficits being most pronounced at longer retention intervals and within navigational contexts. Neuroimaging and biomarker data further reveal selective vulnerability in the medial temporal lobe, characterized by hippocampal atrophy, hypoperfusion, and disrupted functional connectivity. Importantly, traditional neuropsychological tools may underestimate these impairments due to limited ecological validity. Therefore, implementing multimodal assessment frameworks that integrate navigational paradigms is essential to enhance diagnostic sensitivity and facilitate the development of targeted rehabilitation strategies for PCC patients.

COVID doi: 10.3390/covid6040059

Authors: Elvira Hasanović Nataša Trifunović Hasiba Erkočević Irma Džambo Zaim Jatić

Background: The COVID-19 pandemic has been associated with increased psychological distress globally. However, the independent psychological impact of prior COVID-19 infection remains heterogeneous, particularly in primary healthcare populations. This study aimed to examine differences in anxiety and depressive symptoms between individuals with and without a history of COVID-19 infection in a primary healthcare setting. Methods: A cross-sectional study was conducted in April 2022 in five family medicine practices in the primary health care facility of Sarajevo Canton. A total of 279 participants without previously diagnosed mental disorders completed an online questionnaire. Anxiety and depressive symptoms were assessed using the GAD-7 and PHQ-9 scales. Multivariable regression models were performed, and propensity score matching (1:1 nearest-neighbor matching, caliper = 0.2) was conducted to address baseline imbalance. Results: No statistically significant independent association was detected between prior COVID-19 infection and anxiety or depressive symptoms in multivariable models. Propensity score matching yielded 84 well-balanced pairs. In the matched sample, no significant differences were observed in GAD-7 (p = 0.229) or PHQ-9 scores (p = 0.139), nor in clinically relevant cut-offs. Female sex and chronic disease were independently associated with higher anxiety levels. Conclusions: In this primary healthcare population, we did not observe an independent association between prior COVID-19 infection and anxiety or depressive symptoms after covariate adjustment and propensity score matching. These findings should be interpreted cautiously given the cross-sectional design, possible exposure misclassification, and residual confounding.

COVID doi: 10.3390/covid6040057

Authors: Stanisław Słyk Jan Kochanowski Michał Białobrzewski Katarzyna Stopińska Viktor Lipko Patryk Sochań Joanna Cegielska Izabela Domitrz

The neuroinvasive and neurotropic character of coronaviruses is a likely reason for neurological complications which may occur during acute COVID illness and sometimes persist or newly emerge in the post-acute phase. Terminology and temporal classification remain heterogeneous. A retrospective case series was conducted in a single center (Department of Neurology, Bielański Hospital, Warsaw, Poland). Medical records from March 2020 to December 2023 were screened. Inclusion criteria: (1) confirmed SARS-CoV-2 infection (polymerase chain reaction or antigen test and radiological findings), (2) new neurological syndrome within acute, post-acute, or post-COVID interval, and (3) diagnostic documentation. Exclusion criteria: alternative established etiology fully explaining the neurological condition. Six cases were selected for detailed analysis due to diagnostic completeness as well as etiological and temporal diversity. Cases included: (1) persistent neurocognitive and sensory symptoms (post-COVID), (2) acute ischemic stroke with internal carotid artery dissection during severe COVID-19, (3) cytotoxic lesion of the corpus callosum (CLOCC) during acute COVID-19, (4) Guillain–Barré syndrome (post-acute), (5) longitudinally extensive transverse myelitis (post-acute), and (6) delayed autoimmune cerebral vasculitis (post-COVID). Neurological presentations ranged from mild persistent symptoms to fatal outcome. Neurological complications span inflammatory, vascular, and autoimmune mechanisms across distinct temporal phases of SARS-CoV-2 infection. Precise temporal classification and systematic diagnostic protocols are essential. Prospective longitudinal studies integrating biomarkers and standardized neuroimaging are required.

COVID doi: 10.3390/covid6040058

Authors: Alice Yip Zoe Tsui Jeff Yip Ka Man Rachel Yip Chun Kit Jacky Chan

The COVID-19 pandemic transformed healthcare education, increasing the shift to digital tools and establishing a hybrid curriculum blending online learning with traditional clinical practice. This study aims to understand how this shift impacts the educational growth and skill building of nursing students. A qualitative approach was conducted to understand the experience of Hong Kong nursing students adapting to online learning during the pandemic and beyond. Fifty nursing students were interviewed, and Colaizzi’s phenomenological method revealed key themes in their learning narratives. The analysis revealed four distinct themes characterizing the students’ experiences: (i) Learning on their terms: the mandated shift in healthcare reflecting a lack of agency during the educational transition; (ii) Knowledge without touch: the perceived incompetence of the COVID-19 nursing cohort, highlighting anxieties regarding a lack of hands-on clinical proficiency; (iii) Words left unsaid: The weight of insecurity, indicating a decline in interpersonal skills due to isolation; and (iv) Beyond the perfect algorithm: the unrehearsed art of care, describing the difficulty in translating digital simulations to complex, human-centric patient care. Findings show that while digital progress ensured continuity in education, it also contributed to reduced clinical confidence, weaker communication skills, and shifts in how nursing students approached their learning. Consequently, the post-COVID environment demands that training programs evolve to address these specific deficits. Advancing the existing pandemic-era nursing literature, this study emphasizes the need for diverse, targeted teaching methods to mitigate these gaps. By intentionally bridging theoretical knowledge with hands-on clinical practice, educators can better support student wellbeing and help restore the confidence and competence required of future graduates.

COVID doi: 10.3390/covid6040056

Authors: Murat Razi Manuel Graña

Objectives: While the previous literature has established that meteorological conditions are associated with COVID-19 mortality fluctuations, the relative effect of each of these highly correlated factors remains unclear. This study aims to conduct a comparative analysis to determine which of three main meteorological variables—Ambient Temperature, Ultraviolet (UV) Index, and Sunlight Duration—have the strongest negative association with COVID-19 mortality. The objective is to quantify and rank their impact over a 7-to-21-day biological exposure window. Methods: We conducted retrospective spatiotemporal analyses in the form of panel Poisson Distributed Lag Models (PDLMs) regression using daily data from 21 January 2020 to 10 January 2023, spanning 129 distinct geographical regions worldwide. To ensure a direct and fair comparison of effect sizes, all meteorological and environmental variables were Z-score standardized. We estimated three independent PDLMs—each focusing separately on UV Index, Ambient Temperature, and Sunlight Duration—with lags ranging from 7 to 21 days. These models controlled for overarching time trends and utilized a categorical variable to account for Region Fixed Effects modeling time-invariant regional health and socioeconomic determinants (e.g., obesity, age demographics, healthcare capacity). Furthermore, distributed lags of daily PM2.5 (air pollution) and relative humidity were explicitly included in each model as dynamic confounders. Results: The comparison of PDLM results reveals that the UV Index has the strongest negative association with COVID-19 mortality. A one standard deviation increase in the UV Index corresponds to a massive, highly significant cumulative reduction in deaths observed 1 to 3 weeks later (p < 0.001). Sunlight Duration is the second-strongest protective meteorological factor, whereas Ambient Temperature has the weakest effect. The distributed lags of particulate matter (PM2.5) and relative humidity were found to be statistically insignificant when modeled alongside the meteorological variables. Conclusions: After standardizing variables and controlling for dynamic environmental confounders like air pollution and humidity, the study findings provide robust empirical evidence that meteorological conditions have a strong significant association with COVID-19 mortality fluctuation with a temporal delay, overcoming the confounding effects of merely dry or clear-air conditions.

COVID doi: 10.3390/covid6030055

Authors: Andrada Todor Raluca Lupusoru Tudor Moga Paul Tirla Anca Voron Camelia Nica Teofana Bizerea-Moga Mickael Naassila Melena Dreinaza Roxana Sirli Alina Popescu

Background: The COVID-19 pandemic significantly altered the daily routines of young adults. This study investigated alcohol consumption patterns and associated factors among young adults in Romania during this period. Method: A cross-sectional study was conducted using an online survey. Participants were asked to retrospectively report their alcohol consumption patterns before and during the COVID-19 pandemic, including the period of university campus closures. A cohort of 249 young adults (68.6% female) participated in an online survey focused on their alcohol consumption patterns, utilizing the standardized AUDIT-C questionnaire and some modified questions to better establish the habit of drinking. Results: In total, 41.7% of the included subjects were in medical school, 10% in IT, and 44% in various areas of work. Most respondents were female, between 20 and 25 years old (65%) and living in urban areas, with wine being the most favorable drink. Regarding AUDIT scores, approximately 90% fall into low-risk drinking or even abstinence, 10% belong to the high-risk group of alcohol consumption, and 3 people have a high score, which suggests drinking abuse and the likelihood of developing alcohol dependence. A comparison of pre- to post-closure drinking among medical students showed statistically significant changes in the typical number of drinks per week (from 11.5 to 9.9) and maximum drinks per day (from 4.9 to 3.3) and a slight increase in typical drinking days per week (from 3 to 3.2), p < 0.05, outlining a decrease in alcohol consumption. Conclusions: The study highlights specific drinking patterns during the pandemic. While some individuals decreased consumption, a significant portion remained at risk for alcohol-related complications, emphasizing the need for targeted screening and prevention programs.

COVID doi: 10.3390/covid6030054

Authors: Hae-Jin Park Jung Min Cho Eun-Mi Ahn Jaehoon Bae

The COVID-19 pandemic has led to an unprecedented global health crisis, with millions recovering from acute infection but experiencing lingering symptoms, collectively referred to as post-acute sequelae of COVID-19 (PASC), or “long COVID.” While the precise mechanisms underlying long COVID remain elusive, one hypothesis gaining traction is the persistence of viral reservoirs in various tissues. Despite evidence of viral RNA and proteins detected in post-acute patients, the concept of viral reservoirs in the context of long COVID remains a subject of debate. This review explores the current scientific evidence for the existence of persistent SARS-CoV-2 in human tissues beyond the acute infection phase, focusing on the molecular mechanisms by which the virus may evade immune surveillance. We examine the role of immune dysregulation, chronic inflammation, and viral persistence in tissues such as the lungs, heart, brain, and gut. Additionally, we explore how these persistent viral elements may be associated with ongoing symptoms in long COVID and discuss the biological plausibility of these links. Finally, we discuss the clinical implications of viral persistence in post-COVID care, potential therapeutic strategies, and the need for further research to resolve the open questions surrounding this phenomenon.

COVID doi: 10.3390/covid6030053

Authors: Elisa Perego

Long COVID is the disease entity triggered and potentially driven by SARS-CoV-2 infection. It is an heterogeneous condition characterized by dozens of different symptoms, signs and sequelae, which can affect all organs and body systems and evolve over the disease course. Clinical manifestations of Long COVID can vary from individual to individual and across the broader patient population. Pathology can range from asymptomatic and subclinical manifestations to fatal outcomes. Over 400 million people worldwide are estimated to suffer, or have suffered, from Long COVID, making the sequelae of SARS-CoV-2 infection one of the greatest public health challenges of the 21st century. This article provides an updated overview of epidemiology, definitions, main concepts and terminology for Long COVID. It also summarizes key evidence of pathology and disease mechanisms in major organs and body systems, such as the immune system, cardiovascular system, endothelium, heart, lungs, central nervous system, peripheral nervous system, gastrointestinal system, hapatobiliary system, pancreas and kidney. Heterogeneity in manifestations, potential risk of death and the degree of disability in several disease subsets call for timely diagnosis of each Long COVID types and a fuller understanding of their pathophysiological underpinnings. Further research is recommended to better understand pathobiology, develop effective clinical trials, and identify treatments and scalable biomarkers.

COVID doi: 10.3390/covid6030052

Authors: Eili Y. Klein Alexander Tulchinsky Fardad Haghpanah Gary Lin Wilbur H. Chen Jacky M. Jennings

In the early stages of the COVID-19 pandemic, uncertainty around the extent of SARS-CoV-2 spread hampered policymakers’ understanding of the epidemic’s extent. Mathematical models, which proved vital for aiding decision-making, relied primarily on reported cases that were unreliable due to significant underdetection and underreporting. While serological data was used to improve understanding of the epidemiology, it can be costly and difficult to implement without bias. To counter these issues, we integrated serological data from 7229 remnant serum samples collected in 15 Maryland emergency departments (EDs) in Maryland between August and December 2020 into a Bayesian modeling approach to derive an estimate of the incidence of infection and the case fatality rate during the pandemic’s initial wave. We estimated that 5.2% (95% CI, 3.7–7.2%) of the population of Maryland had been infected by late fall 2020. The inferred reporting rate that was estimated started low (<10% in March 2020) and increased to 32% (95% HDI = 26–41%) by the fall, while the estimated infection fatality rate was likely initially higher but fell to 0.51% (95% HDI = 0.43–0.68%) after 1 September 2020. These results demonstrate how existing ED infrastructure can be leveraged to generate less biased, more accurate estimates of the true prevalence of a disease, improving the ability to make decisions and allocate resources under uncertainty.

COVID doi: 10.3390/covid6030051

Authors: Rebeccah M. Ayako Kirtika Patel Isaac Ndede Simeon K. Mining Jonas Klingström Johan Nordgren Marie Larsson

The clinical severity of COVID-19 is influenced by cellular and humoral immune responses, as well as the dynamics of viral replication. In line with this, the current study examined systemic and mucosal immunity responses alongside viral load in unvaccinated SARS-CoV-2-infected individuals during the period of Omicron predominance. Between 2022 and 2023, when Omicron prevalence was at its peak, 48 SARS-CoV-2-positive cases with varied severity were recruited using positive PCR testing, and 48 negative controls were recruited using negative PCR testing at Moi Teaching and Referral Hospital, Kenya. Severe patients showed higher viral loads and systemic anti-spike IgG levels compared to moderate and asymptomatic individuals. Asymptomatic individuals had higher mucosal anti-spike IgG and receptor-binding domain (RBD) levels compared to severe patients. Systemic IFN-α mRNA transcripts were higher in asymptomatic individuals compared to patients with severe COVID-19 and healthy individuals. Severe patients had significantly lower expression of IFN-γ mRNA transcript levels in both blood and mucosa, as well as significantly lower systemic IFI-16 mRNA transcript levels. These findings reflect associations observed in a cross-sectional design and should not be interpreted as causal mechanisms. Suppressed interferon responses, both mucosal and systemic, were associated with severe disease. In conclusion, high systemic IgG and viral loads and low interferon responses were closely linked to severe COVID-19 outcomes.

COVID doi: 10.3390/covid6030050

Authors: Maha Ouarab Zineb Rhazzar Nadia Touil Elmostafa El Fahime

Vaccines worldwide reduce severe coronavirus disease 2019 (COVID-19) consequences; however, viral evolution escapes immunity, raising global concerns about vaccine protection and requiring monitoring. Bioinformatics is crucial for studying vaccine escape, speeding up variant detection, mapping antibody evasion epitopes and ensuring updated vaccines and public health responses. This study combines bibliometric analysis of the Scopus literature (n = 416) on SARS-CoV-2 immune evasion using bioinformatics tools with descriptive analysis of the top ten most highly cited original articles. Our results showed the United States (USA) as the dominant contributor, leading in publication output, citation impact and collaboration networks. The key themes identified were immune evasion, spike protein mutations, and viral evolution, highlighting the structural, functional and immune evasion mechanisms of spike mutations. Leading authors and journals reveal a globally connected research community that is making advances in our understanding of SARS-CoV-2 vaccine evasion, and supporting the development of future treatments and vaccines. The top ten articles showed molecular docking, dynamics simulations, and protein modeling as crucial to studying vaccine escape. In conclusion, global research led mainly by the USA and supported by active contributions has used bioinformatics to elucidate SARS-CoV-2 immune evasion, guiding variant future vaccine and treatment development, variant monitoring, and preparedness for emerging variants.

COVID doi: 10.3390/covid6030049

Authors: Pattharawin Pattharanitima Suthiya Anumas Manoch Rattanasompattikul Sukit Raksasuk Suchai Sritippayawan Thatsaphan Srithongkul

Background: During the COVID-19 pandemic, Thailand prioritized hemodialysis patients for vaccination. Due to limited supply, heterologous regimens were used. This study evaluates the mortality rate and risk factors in hemodialysis patients who received heterologous versus homologous vaccine regimens. Methods: We retrospectively reviewed data of hemodialysis patients in Thailand from January 2021 to December 2022, using data from the Department of Medical Sciences, Ministry of Public Health, and Thailand Renal Replacement Therapy Registry. Mortality was defined as death within 30 days of a positive RT-PCR or rapid antigen test for SARS-CoV-2. Multivariate logistic regression was used to identify mortality risk factors. Results: The associated risks of mortality in hemodialysis patients with COVID-19 were female sex, age ≥ 50 years, diabetes, and BMI ≥ 25.0 kg/m2. Regarding vaccination regimens, the inactivated–Viral vector–mRNA regimen was associated with lower mortality compared with the mRNA–mRNA regimen (OR 0.29, 95% CI 0.08–0.99). In contrast, no vaccination (OR 16.95, 95% CI 7.86–36.54) and single-dose vaccination with inactivated vaccine (OR 17.54, 95% CI 7.01–43.88) or Viral vector vaccine (OR 20.74, 95% CI 9.38–45.86) were associated with markedly higher mortality risk. Conclusion: The inactivated–Viral vector–mRNA vaccine regimen was associated with a decreased mortality risk among this population.

COVID doi: 10.3390/covid6030048

Authors: Padmakumar Krishnankutty Nair Russell F. Dsouza Ivone Duarte Rui Nunes

Introduction: Healthcare institutions and care providers, including medical professionals, were at the forefront of the rapid response to the challenges of the pandemic. As medical professionals across the country actively fought the COVID-19 pandemic, many ethical, social, and legal challenges arose that had not been previously encountered. This study was conducted to determine the ethical challenges and dilemmas faced by medical professionals during the COVID-19 pandemic. Materials and Methods: A descriptive cross-sectional questionnaire-based survey was conducted among the registered medical practitioners in the year 2022. The study setting included health care institutions in India where COVID patients were treated. Results: 558 participants took part in this study. The availability of personal protective equipment was sufficient in 519 (93%) of cases, while 39 (7%) of respondents reported insufficient quantities of personal protective equipment. Overall, 318 (56.99%) respondents were comfortable with their duty patterns, and 435 (77.96%) medical professionals received clear-cut and updated guidelines for practicing safely; 534 (95.70%) completed both doses of vaccines available at that time in India. Conclusions: Indian medical professionals experienced substantial ethical, occupational, and psychological challenges during the COVID-19 pandemic, despite the high availability of protective equipment and vaccination coverage. Resource allocation dilemmas, demanding duty patterns, and psychological distress during quarantine underscore the need for stronger institutional support, clear guidelines, and mental health interventions during future public health crises.

COVID doi: 10.3390/covid6030047

Authors: Malvina Todorova Victoria Tsvetkova Milena Atanasova Adelaida Ruseva Katya Todorova

Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation and immune dysregulation, potentially affecting hypothalamic–pituitary–adrenal (HPA) axis function and glucocorticoid signaling. However, the dynamics and clinical relevance of these alterations across different disease phases remain insufficiently defined. In this cross-sectional observational study, 101 participants were divided into three groups: patients with active COVID-19 (n = 33), individuals ≥ 6 months post-COVID-19 (n = 35), and a reference group of healthy individuals (n = 33). Serum cortisol, circulating glucocorticoid receptor alpha (GRα), and selected cytokines were measured. Statistical analysis included parametric and non-parametric tests, multivariable generalized linear models adjusted for age and sex, correlation analysis, and receiver operating characteristic (ROC) analysis. Lower serum cortisol levels were observed in approximately two-thirds of patients during the acute phase. Circulating GRα concentrations demonstrated a significant gradient across groups, with the lowest levels in active infection and partial restoration post-COVID. Active COVID-19 status remained independently associated with reduced GRα levels after adjustment for age and sex. The cytokine profile, including interleukin-17A (IL-17A), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10), provided a mechanistic context for inflammation-associated modulation of glucocorticoid signaling, most evident during acute infection. Significant correlations between cortisol, GRα, and inflammatory mediators were observed only in this phase. ROC analysis demonstrated a high degree of statistical separation between active COVID-19 and healthy individuals (AUC 0.942; 95% CI: 0.878–1.000). Given the predefined group structure and modest sample size, these findings should be considered exploratory. Overall, the results support the presence of dynamic and potentially reversible immune–endocrine dysregulation during and after SARS-CoV-2 infection. Further validation in larger prospective cohorts is required.

COVID doi: 10.3390/covid6030046

Authors: Roberto Surek Gonçalves da Silva Nathalia Marçallo Peixoto Souza Christiane Mayrhofer Grocoske de Lima Paula Rothbarth Silva Ademir Luiz do Prado Meri Bordignon Nogueira Indianara Rotta Gislaine Custódio Marcel Henrique Marcondes Sari Geraldo Picheth Fabiane Gomes de Moraes Rego

Infection with SARS-CoV-2, the virus responsible for COVID-19, is associated with cytokine storm, an excessive immune response. Interleukin-6, a multifunctional cytokine, is involved in the COVID-19 immune response. Functional polymorphisms in the interleukin-6 gene promoter, namely rs1800796, rs1800797, and rs2069845, may contribute to individual susceptibility to or severity of COVID-19. In this study, 106 healthy SARS-CoV-2-negative individuals (controls) and 106 patients with severe COVID-19 (COVID-19 group), confirmed by qPCR or rapid antigen tests, were genotyped using fluorescent probes for polymorphisms. All participants were from southern Brazil. Groups were matched for sex and body mass index, with a median age of 56–57 years. The COVID-19 group exhibited blood biomarker concentrations consistent with severe disease. No significant differences were detected in genotypic or allelic frequencies between groups, and all polymorphisms conformed to the Hardy–Weinberg equilibrium. The control group minor allelic frequencies for rs1800796 (allele C, 11.3%; 95% CI, 7–16), rs1800797 (allele A, 28.3%; 95% CI, 22–34), and rs2069845 (allele G, 36.8%; 95% CI, 30–50) were similar to those of African, American, and European populations. The polymorphisms investigated were not associated with severe COVID-19 in this cohort.

COVID doi: 10.3390/covid6030045

Authors: Vaidyanathan Gowri Marwa Al-Riyami Deepthy Geetha Shadia Al-Sinawi Khalfan Al Jabri Younis Al-Mufargi Nadia Al-Abri Adham Al-Rahbi Srinivasa Rao Sirasanagandla

Background: Autophagy is a conserved intracellular degradation pathway essential for maintaining cellular homeostasis by recycling damaged organelles and proteins. Dysregulation of autophagy has been implicated in pregnancy-related complications such as preeclampsia and fetal growth restriction, underscoring its importance in maternal and fetal health. However, the autophagy status in the placental tissue of COVID-19-infected pregnant women remains unknown. Objective: To investigate autophagy activity in term placentas from pregnant women infected with COVID-19 compared to those from uninfected control pregnant women. Methods: In this prospective cross-sectional single-center study, 15 COVID-19-positive and 15 COVID-19-negative term pregnant women who delivered at Sultan Qaboos University Hospital between January 2020 and December 2022 were included. Immediately after delivery, the placental tissue samples were collected and assessed for autophagy activity using immunohistochemistry for LC3B and p62 markers, histopathological examination, and transmission electron microscopy. The proportion and intensity of LC3B and p62 staining were quantified. Statistical analysis was performed using the Mann–Whitney U test. Results: There was a significant reduction in p62 and LC3B expression in both the proportion and intensity in COVID-19 placentas compared to the control group. The proportion of p62 (p = 0.001) and LC3B (U = 46.000, p = 0.003) was significantly reduced in infected placentas. Similarly, intensity levels of both markers showed significant differences (p < 0.05), supporting the evidence of reduced LC3B/p62, suggesting autophagy modulation in COVID-19 patients’ placentas. Additionally, abnormal ultrastructural changes were observed in COVID-19–positive placentas, including mitochondrial injury, endoplasmic reticulum stress, microvillus loss, and basement membrane thickening. Conclusion: The study results from a limited sample size demonstrate a significantly altered autophagy flux in the placental tissues of term pregnant women with COVID-19 infection. These findings highlight the potential impact of COVID-19 infection on placental function and fetal development and underscore the need for further investigation into autophagy-modulating strategies to improve maternal–fetal health.

COVID doi: 10.3390/covid6030044

Authors: Paulina Bartoszek Emilie Ates Pauline Sambon Lucie Pothen Alexandra Kozyreff

An 87-year-old woman was referred to our ophthalmology ward due to decreased visual acuity and intense right orbital pain, which had been present for four weeks. The anamnesis was not contributory, except that she had been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) four weeks prior to symptom onset. Her best-corrected visual acuity was hand movements in the right eye and 20/20 in the left eye. Intra-ocular pressure was 34 mmHg and 16 mmHg, respectively. Right eye slit lamp examination revealed palpebral oedema, chemosis, and temporal scleral thickening with conjunctival injection. The cornea was edematous with endothelial precipitates. The anterior chamber was shallow with a closed angle, associated with grade 1+ cells and 1+ flare, according to the SUN grading system. Mild vitreous inflammation was present (grade 0.5+ vitreous cells), and a total choroidal detachment was visible. In the absence of any other plausible cause, unilateral choroidal effusion with secondary angle-closure due to severe panuveitis was considered a possible adverse event following vaccination against SARS-CoV2.

COVID doi: 10.3390/covid6030043

Authors: Subhasree Basu Roy

This paper studies the mental health impacts of the COVID-19 pandemic on older adults with a particular focus on the role of technology use. We use nationally representative individual-level survey data from a random sample of 3257 community-dwelling older Americans (65+) from the National Health and Aging Trends Study (NHATS) COVID-19 supplement (2020). We empirically estimate the impact of COVID-19 (under three alternative specifications) on the five mental health outcomes while controlling other confounding factors. The mental health indicators include feelings of loneliness, anxiety, feeling sad or depressed, poor sleep quality, and not feeling hopeful about the future. The confounding control factors in our empirical model are age, gender, race, financial difficulty, physical health, area of residence, and living arrangement. We further examine whether the mental health effects differ between the technology users and the non-users of technology. Our findings indicate a lower likelihood of adverse health outcomes among technology users (compared to the non-users of technology) during the pandemic. These results validate the potential use of technology for healthcare delivery, mental health therapy, and other lifestyle interventions to improve the quality of life in the older population.

COVID doi: 10.3390/covid6030042

Authors: Rami Bzeih MacKenzie Mayo Twylla Tassava Abdulhameed Aziz

Background: Patients diagnosed with Acute Respiratory Distress Syndrome (ARDS) who require Intensive Care Unit (ICU) admission often require invasive vascular access including central venous catheters and arterial lines. Early reports of excessive thrombosis combined with the severity of illness in COVID-19 could lead to more line-related thrombosis and infections, requiring more line replacements. This retrospective cohort study explores differences in vascular access usage and line-related complications between patients with COVID-19 ARDS and non-COVID-19 ARDS. Methods: A cohort of patients with COVID-19 ARDS (n = 81) was compared to a cohort of patients with non-COVID-19 ARDS (n = 46). We compared baseline characteristics, total number and placement rate of lines (arterial lines, central venous catheters, and dialysis catheters), and incidence of line-related complications (bleeding, thrombosis, or infection). Statistical analysis was performed utilizing Excel software, with associations assessed using Chi-squared, Fisher’s exact, and t-tests. A p-value < 0.05 was considered statistically significant. Results: The COVID-19 cohort had significantly greater total number of lines per patient (4.00 vs. 2.76, p < 0.001). This was due to more arterial (2.17 vs. 1.41, p = 0.003) and dialysis lines (0.43 vs. 0.13, p = 0.002) per patient. There was no significant difference in the number of central venous catheters. When adjusted for length of stay in the ICU, the rate of line placement was not significantly different between groups. The COVID-19 cohort had a significantly greater number of line-related complications defined as thrombosis, bleeding, and infections (18 vs. 2, p = 0.008). Conclusions: The significantly greater total number of lines in the COVID-19 group was likely attributable to COVID-19 patients’ longer lengths of stay in the ICU. Patients with COVID-19 appear to have significantly more line-related complications, which may be due to the greater total number of lines, the longer lengths of stay, and inherent demographic and comorbid differences. Future studies are needed to assess methods for prevention of line-related complications in patients with COVID-19 ARDS.

COVID doi: 10.3390/covid6030041

Authors: Assel Izekenova Dinara Sukenova Ardak Nurbakyt Maimakova Akmaral Aigulsum Izekenova Filip Milanovic Irena Lazic Dejan Nikolic

The aim of this study was to examine the factors associated with COVID-19-related fear in older adults from Kazakhstan, and to explore its associations with sociodemographic characteristics, health status and multiple domains of quality of life in a regional context. A total of 445 individuals aged 60 and above from both urban and rural locations in Kazakhstan participated in this cross-sectional study. To assess the quality of life among older people we used the OPQoL (Older People’s Quality of Life) Scale. Further variables were evaluated: sociodemographic (age, gender, education level, marital status, and place of residence); health-related (self-reported overall health, hypertension, diabetes, cerebrovascular disease, cardiovascular disease, and chronic obstructive pulmonary disease (COPD); and COVID-19-related fear variable. Female gender (OR = 2.344; p = 0.001), present hypertension (OR = 2.106; p = 0.008), the specialized secondary educational level (OR = 2.321; p = 0.012) and at the border of significance university educational level (OR = 1.832; p = 0.051) were variables significantly associated with the COVID-19-related fear in older adults. For individuals with reported COVID-19-related fear, advanced age was significantly negatively associated with leisure and activities domain (B = −0.747; p = 0.020) of OPQoL; better self-reported overall health was significantly positively associated with life overall domain (B = 0.691; p < 0.001), health domain (B = 1.320; p < 0.001), psychological and emotional well-being domain (B = 0.395; p = 0.001), home and neighborhood domain (B = 0.249; p = 0.036), independence, control over life and freedom domain (B = 1.082; p < 0.001), financial circumstances domain (B = 1.132; p < 0.001), and leisure and activities domain (B = 0.556; p = 0.026) of OPQoL; present hypertension was significantly negatively associated with health domain (B = −0.888; p = 0.004) of OPQoL; present cardiovascular disease was significantly negatively associated with life overall domain (B = −0.588; p = 0.027), health domain (B = −0.967; p = 0.009), and independence, control over life and freedom domain (B = −0.542; p = 0.039) of OPQoL; being single was significantly negatively associated with life overall domain (B = −0.481; p = 0.033), social relations domain (B = −0.671; p = 0.014) and financial circumstances domain (B = −0.694; p = 0.036) of OPQoL; and urban place of residency was significantly positively associated with health domain (B = 0.735; p = 0.011) and psychological and emotional well-being domain (B = 0.483; p = 0.010) of OPQoL. Our findings pointed that numerous variables were associated with the COVID-19-related fear and quality of life domains regarding COVID-19-related fear in older adults from Kazakhstan during pandemics.

COVID doi: 10.3390/covid6030040

Authors: Joseph Musonda Chalwe Retsilisitsoe Raymond Moholisa Ndimo Rahab Modipane Saidon Herbert Mbambara Relebohile Matobole Boitumelo Moetlhoa Mike Machaba Sathekge Mankgopo Kgatle

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), exploits angiotensin-converting enzyme 2 (ACE2) for cell entry, implicating the renin–angiotensin system (RAS) in disease pathogenesis. Hypertension (HT), a major comorbidity, is strongly influenced by genetic factors within RAS, including angiotensin ii receptor type 1 (AGTR1) and ACE2) polymorphisms. However, data on these variants in African populations remain scarce. This study investigated associations between AGTR1 and ACE2 single-nucleotide polymorphisms (SNPs), HT, and COVID-19 severity in patients at a Tshwane Academic Hospital. Methods: We genotyped AGTR1 and ACE2 SNPs in 94 PCR-confirmed COVID-19 patients using Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF) mass spectrometry. Clinical data were extracted from hospital records. Ordinal logistic regression models assessed relationships between SNPs, HT, and COVID-19 severity. Results: The cohort (mean age: 53.9 years; HT prevalence: 54.9%) exhibited mild (54.9%), moderate (18.6%), and severe (26.5%) COVID-19. Although the rs2106809 A genotype appeared to be associated with lower odds of severe disease (OR = 0.39, 95% CI: 0.14–1.08, p = 0.04), this observation should be interpreted with caution given the limited sample size of this study. Other SNPs and clinical variables showed no significant associations. Conclusions: This exploratory study represents the first description of AGTR1 and ACE2 SNP patterns in COVID-19 patients from Tshwane. While the rs2106809 variant may indicate a possible protective trend, the evidence remains preliminary. Age correlated with severity. Larger, multi-ethnic studies are needed to confirm these findings.

COVID doi: 10.3390/covid6030039

Authors: Matheus Torres Giulia Davanço Isabela de Paula Destro Neif Murad Glaucia Luciano da Veiga Pedro Henrique Alves Reis Renata de Lion Botero Martins Beatriz da Costa Aguiar Alves Rodrigo Daminello Raimundo Juliana Zangirolami-Raimundo Fernando Luiz Affonso Fonseca

Long COVID is a complex condition characterized by persistent symptoms following SARS-CoV-2 infection. Understanding its biochemical mechanisms is essential for effective management and treatment strategies. Objective: This study investigated biochemical alterations associated with long COVID in unvaccinated individuals presenting symptoms persisting for more than six months, highlighting the prolonged nature of the condition and its systemic and neurological manifestations. A cross-sectional study was conducted with 60 unvaccinated patients at least six months post-COVID-19 infection. Serum biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), N-terminal pro-brain natriuretic peptide (NT-proBNP), and irisin, were analyzed. Correlations between these biomarkers and persistent symptoms were assessed using statistical regression models. Elevated CRP levels were significantly associated with persistent respiratory and musculoskeletal symptoms, suggesting ongoing inflammation. Increased IL-6 levels correlated with fatigue and musculoskeletal complaints. NT-proBNP elevations were linked to cardiovascular manifestations, including dyspnea and chest pain. A positive correlation between irisin and persistent sensory impairments, such as anosmia and dysgeusia, indicates potential neuroinflammatory mechanisms. This study highlights that persistent inflammation plays a critical role in long-term (>6 months) post-COVID manifestations. Monitoring biomarkers such as CRP, IL-6, NT-proBNP, and irisin may enhance understanding and management of prolonged post-COVID conditions.

COVID doi: 10.3390/covid6030038

Authors: María F. González-Delgado Alberto González-Zamora José J. Alba-Romero Edgar H. Olivas-Calderón Rebeca Pérez-Morales

Respiratory viral infections such as influenza and SARS-CoV-2 induce complex immune responses characterized by dysregulated cytokine production, which may influence disease severity and lead to post-infection immunometabolic alterations. However, comparative data on local epithelial and systemic immune responses during acute infection and recovery remain limited. Objective: To evaluate the expression of IFN-γ, TNF-α, and interleukins IL-2, IL-4, IL-6, and IL-10 in nasopharyngeal epithelial cells from patients with influenza and SARS-CoV-2 infection, as well as in peripheral blood mononuclear cells (PBMCs) from individuals who recovered from COVID-19. Methods: A total of 120 participants were distributed into four groups (control, influenza, asymptomatic SARS-CoV-2 infection, and symptomatic COVID-19; n = 30 per group), in addition to 90 individuals who had recovered from COVID-19. COVID-19 and influenza diagnoses were established by the treating physician based on clinical presentation and confirmed by RT–qPCR. Cytokine gene expression was quantified by real-time PCR, and hematological and biochemical parameters were measured using automated analyzers. Results: The asymptomatic SARS-CoV-2 group showed significantly increased expression of IFN-γ (p = 0.0001), TNF-α (p = 0.0007), and IL-4 (p = 0.01). Individuals who recovered from COVID-19 exhibited elevated erythrocyte and leukocyte counts, along with increased glucose, glycated hemoglobin, triglycerides, and very-low-density lipoprotein levels, while no significant alterations in liver function markers were observed. Conclusions:Influenza and SARS-CoV-2 infections are associated with distinct epithelial cytokine expression profiles during acute infection, and COVID-19 recovery is characterized by persistent immunometabolic alterations, suggesting prolonged systemic effects beyond viral clearance.

COVID doi: 10.3390/covid6030037

Authors: Leyi Wang Sandipty Kayastha Anne Burgdorf-Moisuk Xufang Deng Matthew Allender Karen Terio

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global public health emergency in humans from 2020 to 2023 and was associated with over 7 million human deaths. Besides humans, SARS-CoV-2 has been detected in a wide range of animals, including companion, farm, zoo, and wild animals. At least 61 animal species from 29 animal families of 12 animal orders have tested SARS-CoV-2 positive. Documented evidence reported that not only human-to-animal transmission but also animal-to-human transmission events occurred. During the course of the pandemic progression in humans, SARS-CoV-2 strains in animals evolved in parallel with those in humans. Continued monitoring of SARS-CoV-2 in animals is needed to safeguard both human and animal health. In this study, we report investigation of two outbreaks of SARS-CoV-2 Omicron variant infection in tigers and gorillas in two zoological institutions. In the first zoo, six tigers tested positive by SARS-CoV-2 real-time RT-PCR and shed viral nucleic acid in feces for up to two weeks. Three of the tigers showed intermittent shedding patterns, while the other tigers shed only for 7–10 days. No other species, including cheetah, otter, lion, anteater, gibbon, and tamarin, tested positive. During the outbreak at the second zoo, a total of six gorillas were tested positive for SARS-CoV-2, while other primates housed in the same building (colobus and orangutan) tested negative. Follow-up testing revealed that two gorillas tested positive for SARS-CoV-2 over a one-month period (30 and 33 days, respectively), while the other four gorillas had positive SARS-CoV-2 PCR results for 14 to 25 days. Four gorillas had intermittent shedding patterns. Notably, compared to tigers, gorillas had a prolonged duration of fecal viral shedding. Sequencing was performed on the positive samples, and analysis indicated that strains detected in tigers and gorillas belonged to SARS-CoV-2 Omicron BQ.1.10 and XBB.1.16, respectively. Overall, this study offers valuable insights into the duration of viral RNA shedding for SARS-CoV-2 Omicron in zoo animals, facilitating accurate diagnostic evaluation and management of infected tigers and gorillas.

COVID doi: 10.3390/covid6030036

Authors: Ebtisam Aldaais Munthir Aldukhi Hind Alotaibi Heba Mofleh Alzabni Subha Yegnaswamy Nada F. Alahmady

Rapid antigenic drift in the coronavirus spike protein motivates alternative antiviral strategies. We target the conserved nucleocapsid (N) protein—central to RNA binding, genome packaging, and replication—and perform a comparative, cross-species 3D structure-based in silico evaluation. A library of 494 compounds (natural, phytochemical, synthetic) was docked with AutoDock Vina against the MERS-CoV N–terminal RNA–binding domain (NTD; PDB 7DYD) and the C–terminal dimerization domains (CTD) of SARS-CoV (2CJR) and SARS-CoV-2 (8R6E), reflecting the availability of high-resolution, functionally relevant domain structures for each virus. Top-ranked poses underwent ADME profiling and 100 ns GROMACS molecular-dynamics (MD) simulations. Myricetin 3-O-β-D-Galactopyranoside (myricetin) showed the most favorable predicted docking scores across targets (−8.9 kcal/mol, MERS–NTD; −10.1, SARS–CTD; −9.8, SARS-CoV-2 CTD). Curcumin showed moderate predicted affinity (−7.1 to −8.1), while MCC950 achieved consistently favorable docking score (−7.9 to −9.0). ADME results highlighted a trade-off: glycosylated flavonoids offered rich interaction networks but violated oral drug-likeness criteria (e.g., high TPSA), whereas MCC950 met Lipinski/Veber guidelines, supporting translational potential. MD analyses revealed ligand- and target-specific stability: myricetin maintained persistent binding over 100 ns in the SARS-CoV-2 CTD with lower RMSD than comparators; curcumin exhibited transient stability (~30 ns) in MERS- and SARS-bound complexes; MCC950 showed intermittent interactions. Collectively, these findings suggest that the conserved N protein RNA-binding groove represents a resistance-resilient target for broad-spectrum antiviral discovery. Natural flavonoids provide promising scaffolds for optimization, and MCC950 warrants further exploration given its drug-like profile. As this study is purely computational, the results are hypothesis-generating and should be validated via RNA-binding disruption assays, antiviral cell studies, and in vivo models.

COVID doi: 10.3390/covid6030035

Authors: Karla Farmer-Diaz Makeda Matthew-Bernard Sonia Cheetham Kerry Mitchell Calum N. L. Macpherson Maria E. Ramos-Nino

Wastewater-based epidemiology (WBE) allows for early surveillance of viral pathogens, including SARS-CoV-2. Simplified low-cost approaches are needed to deploy WBE surveillance in resource-limited small-island settings, where high sensitivity must be maintained. In this study, we optimized key upstream steps in an electronegative membrane virus adsorption–elution (VIRADEL) workflow, including sample acidification, composite sampling duration, and RT-qPCR inhibition mitigation. Wastewater influent was sampled at a pump station in Grenada using 12 h and 24 h time-weighted composite samples, concentrated using electronegative membrane VIRADEL with and without sample acidification (pH 3.5), and used Phi 6 (enveloped virus) and MS2 (non-enveloped virus) bacteriophages as process controls and PMMoV as a fecal-derived normalization target. Targets for SARS-CoV-2 N1 and a non-enveloped virus surrogate were measured by RT-qPCR. Quantitative wastewater data were compared to reported clinical cases in the community. Sample acidification significantly increased recovery of the enveloped process control, Phi 6 (p < 0.01) indicating improved efficiency in capturing enveloped viral targets during filtration. Twelve-hour composite samples had a false-negative percentage of 88%, while 24 h samples had only 6% false negatives and were able to mirror clinical case trends. Wastewater viral signals were detected 3–5 days prior to an increase in clinical cases. Hydraulic travel time within the contributing sewer network was not directly measured; therefore, the reported 3–5 day lead time reflects the combined effect of shedding dynamics, sampling integration, and sewer transport. This optimized workflow was deployed for nine months showing sustained analytical performance and operational feasibility.

COVID doi: 10.3390/covid6030034

Authors: Lenny Phulong Mamaro

The COVID-19 pandemic disrupted traditional financing channels, accelerating the adoption of crowdfunding as an alternative capital-raising mechanism across Africa. Limited access to finance for women entrepreneurs remains a pivotal issue globally, particularly in Africa, where most women are significantly underrepresented. This study investigates the role of gender differences in campaign design, communication, and signalling in crowdfunding success during the COVID-19 pandemic, rather than focusing on gender as a direct factor. Guided by signalling, Congruity, Feminist Economics, and Social Network theories, the research investigates whether gender-related differences in campaign presentation and communication strategies contributed to variations in funding outcomes. A quantitative research approach was adopted to analyse reward-based crowdfunding campaigns launched between March 2020 and December 2020. The study measures success through funding attainment ratios and goal achievement rates. The findings reveal nuanced gender effects, with male-led campaigns exhibiting strengths in social engagement and narrative appeal, while female-led campaigns demonstrated advantages in higher average contribution sizes. This awareness contributes to the literature on gender and entrepreneurial finance in crisis contexts, offering practical implications for platform design, policy interventions, and inclusive funding strategies in Africa’s evolving crowdfunding ecosystem. In line with the empirical results, the impact of gender is mostly indirect and mediated by campaign variables such as updates, videos, and engagement intensity.

COVID doi: 10.3390/covid6030033

Authors: Dorothy Wallis

Treatment seeking among individuals who misuse substances can be a complex process, with many factors contributing to treatment seeking. Guided by Gelberg–Andersen’s Behavioral Model for Vulnerable Populations, this research seeks to establish predisposing, enabling, and need factors contributing to treatment seeking during COVID-19. A total of 201 individuals participated in the study. Contrary to existing literature, no predisposing factors were associated with treatment seeking during COVID-19. However, variations were seen in enabling and need factors. Perceiving a need for treatment and having reliable transportation to treatment were associated with treatment seeking during COVID-19, underlying the importance of addressing both physical barriers to treatment and readiness for treatment. Additional enabling factors contributing to treatment seeking were a history of past treatment and differing types of recovery supports, underscoring the importance of addressing structural access barriers and individual-level determinants of treatment seeking. More research is needed on individual differences in perception of need that lead to treatment seeking.

COVID doi: 10.3390/covid6030032

Authors: Katarzyna Kieruzal Joanna Ciećwierz Daniel Śliż

The COVID-19 pandemic revealed substantial variation in vaccine attitudes and susceptibility to misinformation, raising concerns from an occupational health perspective about potential differences across employment sectors. This study examined associations between employment category and pandemic-related changes in mental health, and vaccine-related misinformation among adults in Poland. Data were collected between 13 January and 14 February 2022 using a cross-sectional online survey. Complete questionnaires from 7018 respondents were analyzed. Employment category (services, industry, agriculture, unemployed) was examined in relation to self-reported changes in sleep, mental health, physical activity, and diet. A misinformation index was constructed based on agreement with eight vaccine-related misinformation statements. Overall, 81.8% of participants reported being vaccinated. Employment category was significantly associated with perceived changes in sleep, mental health, and diet. The misinformation index was consistently higher among unvaccinated individuals across all employment groups, with the largest differences observed among the unemployed and agricultural workers. These findings show a strong link between vaccine misinformation and remaining unvaccinated, highlighting the need for targeted occupational health education and reliable health information. Increasing vaccination coverage therefore requires not only vaccine availability but also systematic efforts to counteract misinformation and strengthen digital health literacy across occupational groups.

COVID doi: 10.3390/covid6020031

Authors: Israel Anibal Vega Maximiliano Giraud-Billoud

Wastewater-Based Epidemiology (WBE) has emerged as a critical tool for monitoring SARS-CoV-2 circulation at the community level. This study assessed spatiotemporal viral dynamics in Las Heras, Mendoza, Argentina, by comparing wastewater samples from six sewer maintenance holes and three wastewater treatment plants (WWTPs) between January and June 2021, and by conducting long-term surveillance at Campo Espejo WWTP during epidemic (2020–2021) and endemic (2024–2025) phases of COVID-19. Viral particles from sewer manholes and WWTPs samples were concentrated by polyethylene glycol precipitation or aluminum polychloride adsorption–precipitation methods, and then SARS-CoV-2 RNA was quantified by reverse transcription quantitative polymerase chain reaction targeting N1 and N2 nucleocapsid viral markers. Results showed consistent detection of viral RNA across all sites, with peaks in wastewater preceding diagnosed COVID-19 cases increases, confirming WBE as an early-warning system. Localized sewer sampling identified urban hotspots, while WWTPs monitoring captured broader epidemiological trends. Recently, COVID-19 surveillance showed lower and intermittent viral loads, decoupled from diagnosed cases, compared to epidemic phase, indicating a transition to endemic circulation. Overall, combining upstream and downstream WBE enhanced spatial and temporal resolution, demonstrating its utility for public health monitoring during both epidemic and endemic phases.

COVID doi: 10.3390/covid6020030

Authors: Ramosaj Morina Atifete Beqiraj Qendresa Gjaka Petrit Keka Sylaj Alije Baloku Zejnullahu Arbana

A rare but potentially fatal hyperinflammatory disease that develops following SARS-CoV-2 infection is called multisystem inflammatory syndrome in children (MIS-C). Mucocutaneous manifestations are common and frequently overlap with other pediatric inflammatory illnesses, including Kawasaki disease, and may serve as early diagnostic indicators. We describe a 6-year-old girl who was previously healthy but was hospitalized in the pediatric intensive care unit due to a high-grade fever, toxic appearance, and quickly progressing mucocutaneous symptoms, such as bilateral non-purulent conjunctivitis and broad maculopapular rash. Myocardial dysfunction, severe anemia and thrombocytopenia, respiratory failure necessitating mechanical ventilation, and hypotensive shock complicated the clinical course. Laboratory tests showed positive SARS-CoV-2 serology and significantly increased inflammatory markers. Several microbiological tests came up negative. Bacterial sepsis and Kawasaki diseases were not included. A diagnosis of MIS-C was made based on clinical, laboratory, and epidemiological data. In addition to supportive intensive care, the patient received systemic corticosteroids and intravenous immunoglobulin. After two weeks, she was released in a stable condition after gradually improving clinically and biochemically. This instance emphasizes how crucial it is to identify noticeable mucocutaneous manifestations as early warning signs of MIS-C. Immunomodulatory therapy must be started as soon as possible in order to minimize serious consequences and enhance the prognosis of afflicted infants.

COVID doi: 10.3390/covid6020029

Authors: Muhammad Rauf Shaker Clifford Schexnayder Byungik Chang

The COVID-19 pandemic disrupted the global construction industry, resulting in workforce shortages, project delays, and contractual disputes. This study used an online survey of private engineering and construction companies to assess their responses to the challenges posed by COVID-19. The survey focused on workforce management, technological advancements, safety protocols, and project execution. Workforce adaptations, particularly the shift to telework, saw 66% of respondents reporting partial telework and 22% indicating that telework became permanent after the pandemic. Technological advancements were crucial for maintaining operations during the pandemic, with 82% of respondents reporting the adaptation of new digital tools. These included widespread adoption of Microsoft Teams and Zoom by both office and field staff. Training was identified as essential for the effective implementation of these technologies, enabling employees to maximize their benefits. The pandemic affected project design and construction activities, with 69% of respondents reporting delays during the design phase and 70% during construction. Cost overruns of up to 25% were reported in the public sector and 67% of respondents in the private sector reported cost overruns, highlighting the financial impact of the pandemic. The findings provide insights into organizational resilience strategies adopted by private firms and offer lessons that can inform preparedness for future disruptions.

COVID doi: 10.3390/covid6020028

Authors: Aisha T. Kekere-Ekun Adam Webb Manish Pareek Lieve Gies Christopher D. Bayliss

University students are a major target population for infectious disease prevention programmes. Understanding the barriers to implementation of these programmes, and specifically vaccines, among student populations is critical for effective health prevention strategies. To assess changes in COVID-19 vaccine hesitancy and vaccine delivery programmes, we compared questionnaire-based survey data of two cohorts of first year students from two points, July and October 2021, during the COVID-19 vaccine rollout in the United Kingdom. We observed a highly significant increase in vaccine uptake without any alteration in vaccine hesitancy, as measured using a modified VAX score between the two survey dates. The October survey confirmed an association of vaccine hesitancy with the Non-White ethnic group and specifically identified concerns with the plurality of vaccine testing as a potential cause of this hesitancy. University pop-ups for COVID-19 vaccine delivery were not extensively utilised but were deemed as strongly or weakly favourable by 28.3% of students. Survey responses indicated that on-campus pop-ups for delivery of MMR and MenACWY were also supported by a significant minority of students.

COVID doi: 10.3390/covid6020027

Authors: James Dafydd Ainsworth Aung Min Saw Keith Morris Suresh Pillai

Coronavirus disease 2019 (COVID-19) has caused substantial global health and economic disruption, and identifying factors associated with adverse outcomes remains essential. This study is a first-wave observational study and examined risk factors and outcomes among patients admitted with COVID-19 to a non-acute hospital during the first wave of the pandemic, with particular focus on social deprivation and frailty. We conducted a retrospective review of clinical notes for 205 patients admitted between December 2019 and June 2020. Frailty was assessed using the Clinical Frailty Score and the Charlson Comorbidity Index, and social deprivation was evaluated using the Welsh Index of Multiple Deprivation. Although more women than men were admitted, mortality rates were similar across sexes. Older age was associated with increased mortality, and ischaemic heart disease was the most common comorbidity, occurring more frequently among patients who died. Those who died also demonstrated greater frailty, reflected in higher frailty and comorbidity scores. Most patients, irrespective of survival, were from less deprived areas, and greater social deprivation was not associated with increased admission or mortality. These findings indicate that older age, frailty, and ischaemic heart disease are important predictors of mortality in non-acute hospital settings, while social deprivation did not appear to influence admission risk or outcomes in this cohort. As this cohort predates widespread vaccination and antiviral therapy, these findings provide insight into baseline risk factors for COVID-19 mortality in frail populations during the first pandemic wave.

COVID doi: 10.3390/covid6020026

Authors: Brandt Wiskur Kavya Boyina Bijay Rimal Katrin Gaardbo Kuhn Kelly Garrett Blake T. Hilton Gargi Deshpande Maria Trapp Michael W. Brand

The COVID-19 pandemic (2020–2023) profoundly disrupted healthcare systems and imposed sustained psychological burdens on healthcare professionals and trainees. Reliable instruments are essential for assessing these impacts. This study evaluated the construct validity and reliability of the Fear of COVID-19 Scale (FCV-19S) in a convenience sample of 1761 healthcare professionals, trainees, and academic staff at a single U.S. academic health sciences center (the University of Oklahoma Health Campus). Participants completed the FCV-19S; confirmatory factor analysis (CFA) examined its dimensional structure; and internal consistency was assessed using Cronbach’s α and McDonald’s ω. The one-factor model demonstrated good internal consistency (α = 0.89; ω = 0.89) but exhibited sub-optimal model fit (CFI = 0.89; TLI = 0.83; SRMR = 0.06; RMSEA = 0.18). The two-factor model, distinguishing emotional and somatic fear, showed substantially improved fit (CFI = 0.97; TLI = 0.96; SRMR = 0.03; RMSEA = 0.09) and acceptable internal consistency for both factors (α = 0.85 and 0.86; ω = 0.85 and 0.87), although RMSEA remained above conventional thresholds for close fit. Overall, findings support a two-factor structure as a comparatively superior and more nuanced representation of fear responses among an academic health workforce. The validated FCV-19S offers a reliable tool for assessing COVID-19-related distress in clinical and educational health settings, informing targeted interventions to strengthen workforce resilience.

COVID doi: 10.3390/covid6020025

Authors: Ligia Rodina Vlad Monescu Lavinia Georgeta Caplan Maria Elena Cocuz Victoria Bîrluțiu

Background: Endocrine disturbances are increasingly recognized as components of long COVID, yet long-term data remain limited. This study evaluated the prevalence of dysglycemia and thyroid autoimmunity four years after SARS-CoV-2 infection in adults without previously known endocrine disease. Methods: We conducted a retrospective longitudinal 4-year evaluation of adults hospitalized for COVID-19 between 2020 and 2021. Of 1009 eligible patients without prior diabetes or thyroid disease, 96 completed a standardized 4-year post-infection evaluation. Acute-phase data included COVID-19 severity, admission glucose, inflammatory markers, imaging findings, and treatments. The 4-year evaluation comprised fasting plasma glucose, thyroid function tests, anti-thyroid antibodies (anti-TPO, anti-Tg), and thyroid ultrasonography. Baseline HbA1c, thyroid autoantibodies, and thyroid imaging were not available. Results: At four years post-infection, 27.1% of patients exhibited dysglycemia compatible with type 2 diabetes mellitus, 41.6% showed thyroid autoimmunity, and 15.6% presented with both conditions. Overall, 47.9% developed at least one endocrine alteration. Admission hyperglycemia strongly predicted long-term dysglycemia (OR 6.67; 95% CI: 1.45–30.58), and diabetes prevalence increased with acute disease severity. Thyroid autoimmunity was frequent but not associated with initial COVID-19 severity. Conclusions: Four years after SARS-CoV-2 infection, a substantial proportion of patients exhibited persistent metabolic and autoimmune alterations, supporting a long COVID immunometabolic phenotype. In the absence of baseline endocrine data, the reported findings reflect long-term endocrine alterations identified at the 4-year evaluation, with a potential role of SARS-CoV-2 infection. These findings highlight the importance of baseline metabolic and thyroid assessment—including HbA1c and thyroid autoantibodies—in hospitalized COVID-19 patients and underscore the need for structured long-term endocrine monitoring.

COVID doi: 10.3390/covid6020024

Authors: Anna Puigdellívol-Sánchez

Although self-administered antigen tests are widely available, anatomical knowledge of nasal anatomy in the general population is limited. Cerebrospinal fluid leakage has been reported in multiple cases following damage to the roof of the nasal cavity due to accidental penetration of the cribriform plate of the ethmoid bone. Methods: Images of anatomical prosections used for teaching in the Dissection Room of the Faculty of Medicine of the University of Barcelona were obtained to illustrate the viable pathway to the nasopharynx through the inferior meatus, below the inferior turbinate. Screenshots from publicly available videos produced by the author demonstrating perpendicular swab insertion were analyzed, and multiethnic illustrative images were taken from staff volunteers. Publicly available instructions for patients included in the first eight nasal antigen tests for self-diagnosis authorized in Spain in 2021 were reviewed. Results: Most of the initially authorized antigen tests (all but one) still recommended in 2025 a vertical swab insertion. However, successful insertion into the inferior meatus towards the nasopharynx can be achieved with a perpendicular approach. A schematic illustration for free use is provided. Conclusion: Swab instructions should indicate an insertion perpendicular to the face to access the inferior meatus safely and reduce the risk of injury to the ethmoidal cells.

COVID doi: 10.3390/covid6010023

Authors: Natália Milan Carlos Laranjeira Stéfane Lele Rossoni Amira Mohammed Ali Feten Fekih-Romdhane Wanessa Baccon Lígia Carreira Maria Aparecida Salci

One of the challenges post-COVID-19 is reducing the negative impacts on quality of life, performance, and independence in activities of daily living. Assessing functional dependence in adults one year after acute infection can help to understand the long-term consequences, evaluate the impact on quality of life, plan rehabilitation and healthcare, identify the most vulnerable groups, measure the socioeconomic impact, and support public policies and clinical decisions. Objectives: The objectives of this study are as follows: (a) to assess the prevalence of functional dependence in Brazilian adults with COVID-19; (b) to analyze the association between the study variables; and (c) to determine the factors associated with functional dependence. Methods: This was an observational, cross-sectional study with 987 adults (18 to 59 years old) living in the State of Paraná (Brazil) hospitalized for COVID-19 between March and December 2020. Data were collected by telephone 12 months after the acute infection using an instrument to retrieve sociodemographic and health information, and a functional dependence scale to assess dependence before COVID-19 retrospectively (using participant recall information) and at the time of the interview. Data were analyzed using penalized logistic regression after imputing missing data. Data were analyzed using penalized logistic regression after imputing missing data. Results: Functional dependence after COVID-19 was 5.0% and was associated with low levels of education, not having a partner, living with someone, not owning a home, experiencing job changes, requiring care, obesity, smoking, multimorbidity, ICU admission in the acute phase, use of invasive ventilation, or having Long COVID. Individuals who required care or used invasive ventilation support were, respectively, 9.3 and 6.5 times more likely to develop dependence after COVID-19. Despite adjustment for multiple factors, the magnitude of the observed effects warrants cautious interpretation, as unmeasured or residual confounding effects may still be present. Sample recall bias due to collection after 12 months and the presence of the alpha variant without COVID-19 vaccination coverage may limit data generalization. Conclusions: The results highlight the need to emphasize the public health implications of identifying functional dependence. In this vein, it is necessary to implement preventive measures, identify and monitor more vulnerable groups, plan rehabilitation programs, and develop public health policies.

COVID doi: 10.3390/covid6010022

Authors: Jose Carlos Nóbrega Júnior Daniella Brandão Daiara Xavier Roberta Torres Simone Soares Brandão Magno Formiga James B. Fink Arzu Ari Shirley Campos Armèle Dornelas de Andrade

Background and Purpose: Post-COVID-19 syndrome significantly impacts respiratory function and quality of life. Inspiratory muscle training (IMT) has been proposed as a potential intervention to improve respiratory muscle strength and overall recovery. This study aimed to evaluate the effects of IMT on respiratory muscle performance, lung function, functional capacity, sleep quality, and quality of life in individuals with post-COVID-19 syndrome. Methods: Nineteen individuals with post-COVID-19 syndrome were randomized into an IMT group (N = 10) or a sham group (N = 9). The IMT group performed eight weeks of training at 50% of maximal inspiratory pressure (MIP), while the sham group used a non-load device. Outcomes included MIP (cm H2O), functional capacity (6MWT), lung function (spirometry), sleep quality (PSQI), and quality of life (SF-36). Results: The IMT group showed significant improvements in MIP (125.50 ± 22.50 vs. 93.67 ± 20.87 cm H2O; p = 0.036; Cohen’s d = 0.50), PSQI (4.40 ± 2.50 vs. 9.00 ± 2.80; p = 0.011; Cohen’s d = 0.60), and SF-36 (p = 0.030). The IMT group also increased 6MWT distance by 58.36 ± 25.10 m. Conclusions: IMT significantly improved respiratory muscle strength, sleep quality, and quality of life in post-COVID-19 syndrome. These findings suggest that IMT may be an effective intervention, warranting further studies to confirm long-term benefits.

COVID doi: 10.3390/covid6010021

Authors: Ming Zheng

Influenza is typically framed as an acute respiratory infection, yet accumulating evidence suggests that—like SARS-CoV-2—it may trigger persistent, multi-organ morbidity consistent with a post-acute infection syndrome (“long flu”). Leveraging the nationwide FinnGen registry infrastructure, we conducted a temporally stratified disease-wide association study (DWAS) to map antecedent risk factors and long-term sequelae following clinically diagnosed influenza and COVID-19. We assembled an exposed cohort comprising 9204 individuals with influenza (ICD-10 J09–J11) and 4258 individuals with COVID-19 (ICD-10 U072) recorded in specialist inpatient/outpatient care between 1998 and 2021, and an unexposed comparator cohort of 420,005 individuals with no recorded influenza or pneumonia (J09–J18) across their available medical history. Across harmonized clinical endpoints, we fitted age- and sex-adjusted Cox proportional hazards models and controlled for multiple testing using a stringent false discovery rate threshold (FDR-adjusted p < 0.001), further interrogating temporal persistence within 1-, 5-, and 15-year windows. The DWAS revealed that both infections are associated with broad, system-spanning disease signatures extending beyond the respiratory tract, including circulatory, neurological, metabolic, musculoskeletal, digestive, mental/behavioural, ocular, and oncologic endpoints. Predisposition analyses demonstrated that infection risk is concentrated in individuals with substantial pre-existing multimorbidity, most prominently cardiovascular disease, alongside cardiometabolic, respiratory, renal, neuropsychiatric, and inflammatory conditions. Post-infection analyses identified a durable burden of incident multi-system morbidity after influenza, with particularly robust and persistent cardiovascular and neurological signatures—encompassing thromboembolic disease and major adverse cardiovascular outcomes, as well as migraine, neurodegenerative disorders, and depression—together with metabolic and renal sequelae that, in subsets, extended across multi-year horizons. Collectively, these longitudinal findings reframe influenza as a systemic event embedded within a chronic disease continuum, motivate recognition of “long flu” as a clinically meaningful post-viral risk landscape, and support intensified prevention and risk-stratified surveillance strategies alongside analogous efforts for long COVID.

COVID doi: 10.3390/covid6010020

Authors: Asongwe Lionel Ateh Tantoh Makhutsisa Charlotte Mokoatle Thokozani P. Mbonane

Numerous factors contributed to coronavirus 2019 (COVID-19) disease recovery and death rates. In many countries, socioeconomics, morbidities, the experience of symptoms and access to healthcare services are major contributors to recovery and death rates. A retrospective cohort study was conducted to determine the morbidity, mortality, survival probability, and risk factors associated with COVID-19 among children in the Free State province, South Africa. A total of 846 patients’ records were used in the study. Using SPSS version 28 software, survival probability was determined using Kaplan–Meier estimation curves and Cox regression was used to determine the effect of sociodemographics and clinical manifestation information on time of death. The COVID-19 mortality rate was 13.12% in our study. There were more female patients (60%) than male patients (40%). In total, 71 patients had two or more morbidities, while 414 patients were asymptomatic. Patients between 5 and 18 years old were at twice the risk of dying of COVID-19, and male children were at a higher risk as well. Having more than one symptom was also a risk for dying in this study. Severe COVID-19 is attributed to numerous factors, and these are closely associated with surrounding environments and public health systems. The findings are important for the clinical management of similar diseases and circumstances in the future.

COVID doi: 10.3390/covid6010019

Authors: Monther Abuhantash Luca Ramelli Ashley Stewart-Tufescu Tamara Taillieu Isuru Dharmasena Ian Laxdal James McCammon Tracie O. Afifi

There is a paucity of evidence informing our understanding of how the COVID-19 pandemic affected pediatric trauma in Manitoba, Canada. The aim of this retrospective cohort study was to analyze the effect of the pandemic on pediatric trauma and its association with patients’ demographic characteristics. Pre-pandemic and pandemic patient cohorts were created, and the rates of these injuries were compared by patients’ sex, age, and area of residence. During the pre-pandemic period, ED presentations with an MSK or head injury were lower in patients from rural communities compared to urban communities (RR: 0.68, p < 0.001, RR: 0.51, p < 0.001). Hospitalizations with an MSK or head injury were higher in patients from rural communities (RR: 1.78, p < 0.001, RR: 1.14, p = 0.62). During the pandemic, MSK injury ED presentations (RR: 1.14, p = 0.037) and hospitalizations (RR: 1.78, p < 0.001) were higher in patients from rural communities. Patients from rural communities had a lower rate of head injury ED presentations (RR: 0.81, p < 0.001), but higher hospitalization rate (RR:1.96, p = 0.001). Differences in the rates of pediatric MSK and head injuries could be attributed to the limited healthcare resources in underserved rural communities. Efforts should be made to rectify these inequities to ensure fair access to healthcare for these patients.

COVID doi: 10.3390/covid6010018

Authors: Sidiane Rodrigues Bacelo Vagner Ferreira do Nascimento Anderson Reis de Sousa Sabrina Viegas Beloni Borchhardt Luciano Garcia Lourenção

The COVID-19 pandemic exacerbated structural, social, economic, and racial inequalities affecting immigrant, refugee, and asylum-seeking men—vulnerable populations often overlooked in men’s health research. This study investigated the health conditions of immigrant, refugee, and asylum-seeking men during the COVID-19 pandemic. A scoping review was conducted following Joanna Briggs Institute guidance, and a qualitative lexical analysis (text-mining of standardized study syntheses) was performed in IRaMuTeQ using similarity analysis, descending hierarchical classification, and factorial correspondence analysis. We identified 93 studies published between 2020 and 2023 across 35 countries. The evidence highlighted vaccine hesitancy, high epidemiological risks (infection, hospitalization, and mortality), barriers to accessing services and information, socioeconomic vulnerabilities, psychological distress (e.g., anxiety and depression), and structural inequalities. Findings were synthesized into four integrated thematic categories emphasizing the role of gender constructs in help-seeking and gaps in governmental responses. Most studies focused on immigrants, with limited evidence on refugees and especially asylum seekers; therefore, conclusions should be interpreted cautiously for these groups. Overall, the review underscores the urgency of multisectoral interventions, universal access to healthcare regardless of migration status, culturally and linguistically appropriate outreach, and gender-sensitive primary care strategies to support inclusive and resilient health systems.

COVID doi: 10.3390/covid6010017

Authors: Honglun Xu Andrews T. Anum Michael Pokojovy Sreenath Chalil Madathil Yuxin Wen Md Fashiar Rahman Tzu-Liang (Bill) Tseng Scott Moen Eric Walser

The COVID-19 pandemic has highlighted the importance of rapid clinical decision-making to facilitate the efficient usage of healthcare resources. Over the past decade, machine learning (ML) has caused a tectonic shift in healthcare, empowering data-driven prediction and decision-making. Recent research demonstrates how ML was used to respond to the COVID-19 pandemic. This paper puts forth new computer-aided COVID-19 disease screening techniques using six classes of ML algorithms (including penalized logistic regression, random forest, artificial neural networks, and support vector machines) and evaluates their performance when applied to a real-world clinical dataset containing patients’ demographic information and vital indices (such as sex, ethnicity, age, pulse, pulse oximetry, respirations, temperature, BP systolic, BP diastolic, and BMI), as well as ICD-10 codes of existing comorbidities, as attributes to predict the risk of having COVID-19 for given patient(s). Variable importance metrics computed using a random forest model were used to reduce the number of important predictors to thirteen. Using prediction accuracy, sensitivity, specificity, and AUC as performance metrics, the performance of various ML methods was assessed, and the best model was selected. Our proposed model can be used in clinical settings as a rapid and accessible COVID-19 screening technique.

COVID doi: 10.3390/covid6010016

Authors: Patchareeya Amput Weerasak Tapanya Noppharath Sangkarit Sirima Wongphon

This study aims to evaluate the reliability and minimal detectable change (MDC) of the 2 min marching test (2MMT) for cardiovascular response, as well as to compare its outcomes with those of the 6 min walk test (6MWT), in youth recovering from post-COVID-19 condition. Forty-four youth with post-COVID-19 condition underwent two assessment sessions, separated by five days, utilizing both the 6MWT and 2MMT to measure cardiorespiratory response parameters. Test–retest reliability was found to be excellent for the 6MWT (ICC = 0.83; MDC95 = 8.06%) and good for the 2MMT (ICC = 0.78; MDC95 = 15.61%) between initial and follow-up measurements. The 2MMT demonstrates good reliability and validity for assessing cardiovascular response in youth with post-COVID-19 condition. The reported MDC values provide clinically meaningful thresholds that enable clinicians to distinguish true changes in performance from measurement error. These findings support the use of the 2MMT as a practical tool for clinical assessment, providing preliminary guidance for interpreting changes in performance. However, longitudinal monitoring of patient progress was not directly assessed in this study.

COVID doi: 10.3390/covid6010015

Authors: Laura Smolski dos Santos Genifer Erminda Schreiner Elizandra Gomes Schmitt Mariana Larré da Silveira Camila Berny Pereira Luana Tamires Maders Silvia Muller de Moura Mohammad Prudêncio Mustafá Itamar Luís Gonçalves Ilson Dias da Silveira Vanusa Manfredini

Background: In 2019, a new virus caused by SARS-CoV-2, called COVID-19, spread throughout the world, causing a pandemic state. As the pandemic progressed and cases continued to increase, safe vaccines were developed for the entire population. In Brazil, AstraZeneca® (ChAdOx1-S) and Pfizer® (BNT162b2) vaccines were among those administered to the population. Objectives: The objective of this study was to analyze whether immunoglobulin G (IgG) is produced for COVID-19 in individuals immunized with two doses of AstraZeneca (ChAdOx1-S) and Pfizer (BNT162b2) vaccines and to evaluate several parameters in order to understand how our bodies respond to this immunization. Methods: The study involved the participation of 120 individuals: 49 in the control group, 44 vaccinated with the AstraZeneca vaccine, and 27 the vaccinated with Pfizer vaccine. Results: Hematological, biochemical, inflammatory, and oxidant/antioxidant parameters and the production of IgG antibodies were analyzed. An increase in some inflammatory parameters was observed in vaccinated individuals, which may have been caused by an immune reaction after vaccination. In terms of hematological parameters, the changes caused by vaccination appear to be transient and quickly resolved after immunization. In terms of biochemical parameters, an increase in IgG antibodies was observed in the group vaccinated with the Pfizer® vaccine; however, the AstraZeneca® and control groups also produced IgG, although to a lesser extent. In terms of the remaining parameters, there was little change after vaccination. Regarding the levels of oxidants/antioxidants, it was observed that there was a compensation by antioxidants due to the increase in oxidant parameters, which may act as corrective mechanism. Conclusions: Both the AstraZeneca® and Pfizer® vaccines induced anti-SARS-CoV-2 IgG production, accompanied by inflammatory, hematological, and oxidative changes.

COVID doi: 10.3390/covid6010014

Authors: Marta Domínguez Gallego Paula Panos Basterra Alba Somovilla Alicia Gonzalez-Martinez Carmen Ramos Ana Belen Lopez-Rodriguez Álvaro Morales Caballero Amparo López-Guerrero Almansa Manuela García Cebrián Jose Vivancos Mora Ana Beatriz Gago-Veiga

Headache is a common symptom during SARS-CoV-2 infection and may persist beyond three months. Both tension-type and migraine-like headaches have been described during SARS-CoV-2 infection and after immunization. The main objective was to characterize headache phenotype during SARS-CoV-2 infection and its relationship with headache recurrence following reinfection and COVID-19 vaccination in a cohort of healthcare professionals. Secondary aims included profiling primary headaches and identifying predictors of post-COVID-19 headache persistence. We included 109 participants (86.2% women, mean age 45.3 ± 2.5 years). During infection, 49.5% met ICHD-3 criteria for tension-type headache and 12.8% for migraine. Headache recurred in 62.5% after reinfection and 59.2% after vaccination. A primary-headache history was present in 77.9% of sampled patients (25.9% migraine, 47.1% tension-type). The COVID-19 headache phenotype typically mirrored patients’ previous headache type during reinfection and post-vaccination. Persistent headache beyond three months from SARS-CoV-2 infection occurred in 22.9% and was associated with fibromyalgia and obesity. These findings suggest that COVID-19-related headache often mirrors the patient’s pre-existing primary headache and tends to recur with the same phenotype following reinfection or vaccination.

COVID doi: 10.3390/covid6010013

Authors: Jenny Bernard Jazmin Cascante Themba Nyirenda Aimee Gabuya Victor Carrillo

Vulnerable populations experience higher mortality and readmission after hospital discharge. We sought to evaluate the impact of the Transitions Of Care Bundle (TOCB™) on COVID-19 patient outcomes post-discharge compared to a control cohort. This retrospective study used electronic health record data collected for 243 COVID-19 patients (65 TOCB™, 178 control) during the initial pandemic months at a large academic facility in Northeast New Jersey (NJ). Data included demographics, comorbidities, readmissions, mortality, and payor. The TOCB™ cohort had proportionally more Hispanic patients (56.92% vs. 48.3%, p = 0.0885). All TOCB™ patients were discharged home without needing additional services, compared to only 36% of the control group. The implementation of TOCB™ was associated with shorter hospital stays, a potential decrease in readmission rates, and fewer emergency department visits. These results imply that well-coordinated post-discharge services are linked to a diminished risk of mortality, possible hospital readmission, and other adverse health outcomes.

COVID doi: 10.3390/covid6010012

Authors: Anasuya K. Lingappa Bhaavya Maheshwari Asish Oommen Mathew

Local Owner-Operated Retail Outlets (LOOROs) in India faced unprecedented disruption during the COVID-19 pandemic, with digital transformation emerging as both a challenge and an opportunity. The growing dominance of larger online and offline competitors, who swiftly adopted digital payments, posed a threat to traditional business models of these small neighborhood retailers. This study employs the Stimulus–Organism–Response (S-O-R) framework to examine the antecedents shaping LOORO owners’ attitudes toward digital payment practices and how these attitudes influence their intention and actual adoption. A survey of 175 LOOROs in Navi Mumbai was analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). The findings revealed that resource availability and customer care significantly influenced adoption, whereas competitor and customer pressure had little effect. Overall, LOORO owners demonstrated a positive outlook toward integrating digital payment systems, indicating their adaptive capacity to navigate the digital shift accelerated by the COVID-19 pandemic.

COVID doi: 10.3390/covid6010011

Authors: Roseane Lima Santos Porto Sonia Oliveira Lima Cristiane Costa da Cunha Oliveira Vera Lúcia Corrêa Feitosa Raissa Pinho Morais Aline de Siqueira Alves Lopes Ana Jovina Barreto Bispo Francisco Prado Reis

COVID-19 in newborns presents a multifaceted clinical spectrum, with the potential for severe outcomes. This study aimed to evaluate the clinical evolution and hospital outcomes of neonates with a molecular diagnosis of COVID-19. A case-control study was conducted in a public referral maternity hospital for high-risk pregnancies. Two controls were selected for each case, matched by sex and gestational age. Variables related to birth data, symptoms, and clinical progression were collected from medical records and analyzed statistically, with crude and adjusted relative risks calculated using Poisson regression with robust standard errors. A total of 25 neonates with confirmed SARS-CoV-2 infection were identified among 875 newborns. Compared with controls, infected neonates had a longer hospital stay (median of 19 days vs. 8 days; p < 0.001) and higher readmission rates (16% vs. 0%; p = 0.03). After adjusting for potential confounders, COVID-19 infection was associated with a 2.41-fold higher risk of neonatal death (95% CI: 1.24–4.67; p = 0.009). No evidence of vertical transmission was found. These findings suggest that neonates with COVID-19 may experience longer hospitalizations and an adjusted higher risk of mortality, emphasizing the need for vigilant surveillance and supportive care. However, given the observational design of the study, these results indicate associations rather than causal relationships. Understanding the clinical behavior of COVID-19 in this population—characterized by inherently low immunity—and recognizing its interaction with other neonatal conditions are essential for improving hospital management and outcomes.

COVID doi: 10.3390/covid6010010

Authors: Johanna Kämpe Jesper Eisfeldt Per Nordberg Agneta Nordenskjöld Magnus Nordenskjöld Miklos Lipcsey Michael Marks-Hultström Robert Frithiof Jonathan Grip Olav Rooijackers Hugo Zeberg Anders Kämpe

Background: Several genes and genomic regions have been implicated in COVID-19 susceptibility and severity, but their clinical relevance remains uncertain. We comprehensively assessed both copy number variants (CNVs) and single-nucleotide variants (SNVs) disrupting genes implicated in COVID-19 in a Swedish cohort of ICU-treated COVID-19 patients with detailed phenotype data. Methods: Patients (n = 301) with severe COVID-19 treated in intensive care units (ICU) between March 2020 and January 2021 at two large Swedish university hospitals were included. Whole exome sequencing (WES) was performed to identify both large copy number variations (CNVs) and single-nucleotide variants (SNVs), including small indels, using the Genome Analysis Toolkit (GATK) pipelines. We focused our analyses on variants disrupting coding genes implicated in severe COVID-19, but also assessed variants known to cause human disease. Results: We identified 11 rare CNVs and several SNVs potentially linked to severe COVID-19. Patients carrying a CNV spanning a COVID-19-implicated gene had higher levels of the heart failure marker NT-proBNP (median 4440 [1558–8160] vs. 1170 [329–3152], p = 0.017), worse renal function at ICU admission (p = 0.0026), and a higher need for continuous renal replacement therapy (CRRT) (28% vs. 10%, p = 0.045) compared to patients without a potentially damaging CNV. Conclusions: Although patients with a potentially damaging CNV or SNV exhibited some differences in cardiac and renal markers, our findings do not support broad genetic screening as a predictive tool for COVID-19 severity.

COVID doi: 10.3390/covid6010009

Authors: Nancy Esmeralda Sánchez-Duarte Michelle Valencia-Arreola Maribel Pallanez-Murrieta Mabeth Burgos-Hernández Hugo César De La Torre-Valdez Daniel Morales-Romero

It is imperative that society becomes aware of ergonomic risks, not only in an occupational place but also in everyday contexts where they can go unnoticed, such as the educational sector, and in the specific case of students. To identify this risk, an ergonomic assessment was conducted on students in Mexico during remote learning due to COVID-19. To this end, a survey was applied, and the ROSA (Rapid Office Strain Assessment) method was used. According to the survey results, the students reported adopting inappropriate postures during online classes and suffering from musculoskeletal pains. Furthermore, they showed a strong interest in learning about ergonomics and improving their postures. In addition, the application of the ROSA method yielded a significant result 60% of the evaluated students are at high or very high ergonomic risk. Regardless of their profession, ergonomics should be integrated as part of educational programs. This measure would help prevent musculoskeletal disorders once students transition into their respective work environments.

COVID doi: 10.3390/covid6010008

Authors: Ido Narpati Bramantya Ratna Sutanto Callistus Bruce Henfry Sulay Gilbert Sterling Octavius

Posterior Reversible Encephalopathy Syndrome (PRES) is a rare but potentially reversible neurological manifestation associated with Multisystem Inflammatory Syndrome in Children (MIS-C). We report an eight-year-old boy who developed PRES secondary to MIS-C following asymptomatic SARS-CoV-2 exposure. The patient presented with fever, seizures, decreased consciousness, and visual disturbances. MRI revealed characteristic bilateral parieto-occipital and posterior temporal cortical–subcortical hyperintensities, while CT scans were normal. The patient achieved full neurological recovery with corticosteroid therapy, blood pressure control, and supportive management. This case underscores the importance of early MRI in detecting PRES when clinical or CT findings are inconclusive, emphasizing the need for heightened awareness among pediatric clinicians to prevent irreversible neurological sequelae.

COVID doi: 10.3390/covid6010007

Authors: Gabrielle Humphreys Ethan Berry Lawrence D. Hayes Sam Jensen Roisin Moodley Nilihan E. M. Sanal-Hayes

Background: According to the National Institute for Health and Care Excellence (NICE), long COVID refers to symptoms persisting for four weeks or more after acute infection, with over 100 identified, including fatigue, cognitive dysfunction, and breathlessness. Women aged 45–54 are disproportionately affected, overlapping with the typical age for perimenopause and menopause. This scoping review aimed to provide an overview of existing research on the intersection between long COVID and the menopausal transition. Methods: Five database (CINAHL ultimate, MEDLINE, ScienceDirect, Cochrane, and Scopus) searches yielded 387 articles; after removing 40 duplicates and screening 347 titles and abstracts, fourteen studies were reviewed in full, with seven meeting the inclusion criteria (examined both long COVID and menopause in their scope and are written in English language). Results: This scoping review identified a significant symptomatic overlap between long COVID and menopause reported by participants, particularly fatigue, cognitive difficulties, mood changes, and sleep disturbances. Preliminary evidence also suggests that hormonal fluctuations may influence symptom severity, though biological mechanisms remain insufficiently understood. Methodological limitations restrict generalisability, underscoring the need for longitudinal symptom tracking, diverse samples, and biomarker-informed studies. Recognising the intersection of long COVID and menopausal transition is essential for improving assessment, management, and targeted care for affected women.

COVID doi: 10.3390/covid6010006

Authors: Sonia López-Gómez Carolina Lechosa-Múñiz Verónica Vejo-Landaida Sonia Mateo-Sota María Jesús Cabero Carmen Sarabia-Cobo

Background: The COVID-19 pandemic exacerbated pre-existing inequities in maternity care, particularly among culturally diverse and migrant women. Although data were collected during the early pandemic phase, revisiting these experiences offers valuable insights for strengthening equity, cultural safety, and system preparedness in maternal healthcare. Methods: A qualitative phenomenological–hermeneutic study was conducted in a tertiary maternity hospital in Spain. Semi-structured interviews were carried out with six women from diverse cultural backgrounds. Data were analysed inductively through thematic analysis, followed by a secondary interpretive review in 2024 to identify enduring implications for culturally safe, equitable, and crisis-resilient maternity care. Results: Four main themes emerged: (1) heightened fear and uncertainty surrounding hospital care; (2) emotional distress linked to restrictions on companionship and support; (3) disruption of culturally embedded postpartum practices, resulting in isolation; and (4) health literacy barriers and dependence on informal information sources. Despite these challenges, participants demonstrated notable adaptability and resilience. Conclusions: COVID-19 amplified structural inequities in maternity care for culturally diverse mothers. The findings highlight the need to reinforce cultural safety, health literacy support, language mediation, family-centred care, and emotional wellbeing. These insights may inform efforts to strengthen resilient and equitable maternal health systems and improve preparedness for future public health emergencies.

COVID doi: 10.3390/covid6010005

Authors: Lolita Rapolienė Giedrė Taletavičienė Aelita Bredelytė Antonella Fioravanti Arvydas Martinkėnas

Background: Balneotherapy (BT) has been proposed as a supportive intervention for post-COVID-19 musculoskeletal (MSK) and fatigue-related symptoms; however, comparative evidence across different BT delivery modes remains limited. This study aimed to evaluate the long-term effects of a BT-based treatment program on MSK health and related functional outcomes in individuals with a history of COVID-19. Methods: This secondary analysis was derived from a multicenter, randomized, controlled, single-blinded trial conducted from January to September 2023 across six Lithuanian medical spa centers. Participants with a self-reported history of COVID-19 and persistent multisystem symptoms were assigned to one of three BT modalities or a control group. Primary outcomes included MSK pain, muscle tension and spasm, handgrip strength, and trunk flexibility. Secondary outcomes included fatigue, sleep, quality of life, and analgesic use. Assessments were performed at baseline, post-treatment, and at three- and six-month follow-ups. The 2-week BT program consisted of daily sessions of light pool exercise, mineral baths, sapropel body wraps, and halotherapy. Data were analyzed using repeated-measures GLM in IBM SPSS Statistics (version 28.0). Results: Significant time effects were observed for MSK pain, muscle tension, spasms, fatigue, sleep disturbance, flexibility, and quality of life (all p < 0.05). Improvements occurred primarily within groups and were most pronounced immediately post-treatment, with partial maintenance at 3–6 months. Between-group differences were modest; however, ambulatory BT, inpatient BT, and BT combined with nature therapy demonstrated greater long-term improvements in several outcomes. Conclusions: BT was associated with beneficial changes across MSK and psychosocial domains in individuals recovering from COVID-19, although differences between BT modalities were limited. These findings support BT as a complementary component within multimodal post-COVID rehabilitation frameworks and highlight the need for further research on long-term maintenance and individualized treatment strategies.

COVID doi: 10.3390/covid6010004

Authors: Victoria Tsvetkova Malvina Todorova Milena Atanasova Irena Gencheva Katya Todorova

Introduction: Immune dysfunction plays a significant role in Metabolic syndrome, contributing to both insulin resistance and chronic low-grade inflammation. This immune dysfunction is characterized by overproduction of inflammatory cytokines among which of primary importance are tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and (MCP-1), whereas others such as interferon gamma (IFN-γ), IL-17A, and the anti-inflammatory IL-10 appear to be of secondary importance. Cytokines also play a significant role in Post-COVID disorders contributing to prolonged immune dysregulation and persistent subclinical inflammation. However, their role in the newly emerging metabolic disorders following infection remains poorly defined. Methods and materials: In the current study 78 patients (26 men and 52 women) were included, divided into two groups—group 1 (individuals with newly diagnosed carbohydrate disorders after proven COVID-19 or Post-COVID group; n = 35) and group 2 (COVID-19 negative persons with Metabolic Syndrome; n = 33). They were further divided into several subgroups according to type of metabolic disorder present. Standard biochemical, hormonal and immunological parameters were measured using ELISA and ECLIA methods, as well as some indices for assessment of insulin resistance were calculated using the corresponding formula. Results: Patients from both groups demonstrate similar metabolic parameters including BMI and unadjusted lipid and uric acid levels (p > 0.05). After adjustment for age, sex, and BMI revealed significant differences, Post-COVID status independently predicted higher fasting glucose, HbA1c, total cholesterol, LDL-cholesterol, triglycerides, uric acid, and insulin-resistance indices, indicating substantially impaired glycemic and metabolic control beyond traditional risk factors. Furthermore, the Post-COVID cohort demonstrated marked cytokine dysregulation, with significantly elevated levels of TNF-α, IFN-γ, IL-17A, and IL-10 after adjustment. Conclusions: The observed changes in both metabolic and immune parameters studied among the two groups show many similarities, but some significant differences have also been identified. Together, these findings indicate that Post-COVID metabolic dysfunction is characterized by inflammation-driven dyslipidemia, heightened oxidative stress, and persistent immune activation, distinguishing it from classical Metabolic syndrome.

COVID doi: 10.3390/covid6010003

Authors: Elena Moreno-Guillamont Amparo Moret Tatay Mar Tripiana Rallo María Auxiliadora Dea-Ayuela Nadia San Onofre Jose M. Soriano

Background: Elderly individuals represent one of the populations most affected by COVID-19, exhibiting high vulnerability to malnutrition, sarcopenia, and poor clinical outcomes. The association between nutritional status and disease progression highlights the need for standardized assessment and targeted nutritional interventions. Methods: A systematic review was performed using PubMed, Cochrane Library, and Google Scholar, covering studies published between January 2020 and October 2025. The review followed PRISMA guidelines and included studies evaluating nutritional status, screening tools, and nutritional support strategies for the elderly population (≥65 years old) with COVID-19 across inpatient, outpatient, and institutional care settings. Results: A total of seven studies met the inclusion criteria. Reported malnutrition prevalence ranged from 25% to 65%, increasing with both age and COVID-19 severity. The most frequently applied tools were the Mini Nutritional Assessment–Short Form (MNA-SF), the Global Leadership Initiative on Malnutrition (GLIM) criteria, and the Geriatric Nutritional Risk Index (GNRI). New evidence supports early nutritional screening, high-protein supplementation, and individualized dietary strategies to reduce complications and improve recovery trajectories. Conclusions: Nutritional risk screening and timely intervention are essential in the management of elderly patients with COVID-19. Standardized assessment tools and multidisciplinary nutrition approaches enhance clinical outcomes, minimize disease burden, and should remain integral components of geriatric care in infectious and post-pandemic contexts.

COVID doi: 10.3390/covid6010002

Authors: Jan Catindig John Atkinson Ana Llamas Maria Eugenia Fernandez-Esquer

This study examined the relationship between trust in COVID-19 information sources and self-rated health (SRH) among Latino Day Laborers (LDLs) and whether mental health mediated this association. Participants (N = 300) recruited at 18 job-seeking locations were interviewed in Spanish during November and December 2021. Validated scales were used to measure trust in formal (e.g., broadcast news, newspapers, and radio) and informal sources (e.g., friends, family, and social media) and mental health (depression, anxiety, and stress), with SRH measured with a single item. Mediation analysis was conducted using Hayes’ SPSS PROCESS macro. Higher trust in formal sources of information was related to lower SRH, but this relationship was not mediated by mental health. However, depression and anxiety were associated with a decrease in SRH. There were no significant direct or indirect effects between trust in informal sources and SRH. Depression and anxiety remained significant predictors of lower SRH. Further research is warranted on the mechanisms underlying these associations and the differential impact of information sources on vulnerable populations, such as LDLs, during health crises.

COVID doi: 10.3390/covid6010001

Authors: Rachael K. Raw Jon Rees Amy Pearson David R. Chadwick

Objectives: Neurodivergent (ND) individuals (e.g., autistic people) are more likely to experience health problems that are characterised by ‘Central Sensitisation’ (CS). Recent research suggests that a so-called ‘Long-COVID’ syndrome might also be explained by a heightened response to internal physiological stimuli, much like in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The primary objective of this study was to establish whether individuals who scored highly on a measure of CS would be more likely to experience long-term symptoms of COVID-19. A secondary aim considered if having a Type D personality was also linked to ongoing COVID-19 symptoms. Method: Using a standardised assessment tool, we examined whether traits associated with autism would predict long-term COVID-19 symptoms in 267 Healthcare Workers (HCWs). We also used a measure of Type D personality to establish if negative affect and social inhibition were related to Long-COVID. Results: A higher number of autistic traits predicted COVID-19 symptoms that lasted more than 12 weeks regardless of formal autism diagnosis. A personality measure also showed that negative affect was associated with experiencing COVID-19 symptoms for 4–12 weeks, though the direction of causality in this case is uncertain. Conclusions: Our main findings were (i) more HCWs scored above threshold for neurodivergence than those who were self-declared as having been diagnosed as neurodivergent; (ii) while there was no association between long-term COVID-19 and self-declared neurodivergent status, scores for the ‘sensory reactivity’ item of a standardised autism scale was predictive of COVID-19 symptoms lasting beyond 12 weeks post-infection; and (iii) HCWs with Type D Personality were not more likely to experience long-term COVID-19.

COVID doi: 10.3390/covid5120208

Authors: Fabiana Rodríguez-Pastene Sara Sorza Pablo J. Castro-Carrasco Claudia Carrasco-Aguilar Verónica Gubbins Vladimir Caamaño-Vega Martina Zelaya

This study examines how the explanations about school violence are constructed in Chilean online newspapers after the country—which had the longest period of school closures—returned to in-person classes. During early 2022, several complaints of school violence surged compared to the lockdown years, prompting questions about how the media shaped public interpretations of this rise. Using a content analysis of three Chilean online newspapers (“SoyChile”, “ElMostrador”, and “LUN”), this study reconstructed the Subjective Theories (STs) conveyed in their coverage. All articles (n = 50) published during three strategic periods of the 2022 school year were analyzed to identify explicit and implicit theories about the causes, intervening conditions, and strategies for addressing school violence. The most prevalent ST framed school violence as a structural problem, appearing 27 times. This narrative portrays the phenomenon as both inevitable and beyond the control of key actors, such as caregivers, teachers, school leaders, authorities, and students, ultimately reducing perceived accountability and agency in prevention or intervention efforts. Media discourse tended to legitimize explanations that locate school violence outside the sphere of individual or institutional responsibility.

COVID doi: 10.3390/covid5120207

Authors: Muhammad Danial Che Ramli Beevenna Kaur Darmindar Singh Zakirah Zainal Abidin Athirah Azlan Amanina Nurjannah Zaw Myo Hein Che Mohd Nasril Che Mohd Nassir Rajesh Thangarajan Noor Aishah Bt. Mohammed Izham Suresh Kumar

The COVID-19 pandemic has demonstrated that its effects go far beyond the initial respiratory illness, with many survivors experiencing lasting neurological problems. Some patients develop a condition known as Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), which includes current issues such as reduced cognitive function, chronic headaches, depression, neuropathic pain, and sensory disturbances. These symptoms can severely disrupt daily life and overall well-being. In this narrative review, we provide an overview of current understanding regarding the neurological effects of COVID-19, with a focus on Long COVID. We discuss possible underlying mechanisms, including direct viral invasion of the nervous system, immune-related damage, and vascular complications. We also summarize findings from cohort studies and meta-analyses that explore the causes, symptom patterns, and frequency of these neurological issues. Approximately one-third of people who have had COVID-19 report neurological symptoms, especially those who experienced severe illness or were infected with pre-Omicron variants. Emerging research has identified potential biomarkers such as neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) that may help in diagnosis. Treatment approaches under investigation include antiviral medications, nutraceuticals, and comprehensive rehabilitation programs. Factors like older age, existing health conditions, and genetic differences in ACE2 and TMPRSS2 genes may affect an individual’s risk. To effectively address these challenges, current research is essential to improve diagnostic methods, develop targeted treatments, and enhance rehabilitation strategies. Ultimately, a coordinated, multidisciplinary effort is crucial to reduce the neurological impact of Long COVID and support better recovery for patients.

COVID doi: 10.3390/covid5120206

Authors: Yu Chen Zhao Xinan Wang Yujia Lu Rounak Dey Yuchen Liu Francesca Giacona Elizabeth A. Abe Emma White Li Su Qingyi Wei Xihong Lin Lorelei A. Mucci Jehan Alladina David C. Christiani

Importance: The coronavirus disease 2019 (COVID-19) was the third leading cause of mortality in the United States for three years in a row. The genetic contributions to disease severity remain unclear and many previously identified single nucleotide polymorphisms (SNPs) have not been replicated nor linked with functional significance. Objective: To identify SNPs associated with mortality among hospitalized COVID-19 patients supplemented by expression quantitative trait loci (eQTL) evidence to infer plausible functional mechanisms related to COVID-19 severity. Design: A quality-controlled genome-wide association study (GWAS) supported by robust gene-level omnibus kernel association tests (SKAT-O), functional prediction, and eQTL analyses of the top GWAS signal. Setting: Massachusetts General Hospital (MGH). Participants: 370 adult ICU patients with SARS-CoV-2 infection and acute hypoxemic respiratory failure and floor patients with mild hypoxemia managed with supplemental oxygen consecutively admitted to MGH between March and June 2020 (Surge 1), and January and March 2021 (Surge 2) with baseline clinical characteristics and demographics collected. Exposures: Low-pass genotyped SNPs from whole blood and aggregated SNP-sets of potential disease susceptibility loci with ±500 kb flanking regions. Main Outcomes & Measures: Genome-wide individual SNP associations and SNP-set associations with mortality outcomes from 370 severe COVID-19 cases. Results: After LD pruning (<0.8) and false discovery rate adjustment (<0.05), we identified rs7420371 G>A of the receptor transporter protein 5 (RTP5) gene as the top independent signal significantly associated with 30- and 60-day mortality among severe COVID-19 patients (OR, 2.32; 95% CI, 1.59–3.39; p = 4.92 × 10−9 and OR, 2.06; 95% CI, 1.43–2.97; p = 5.43 × 10−8, respectively). SKAT-O analyses on the RTP5 SNP-set showed associations with both mortality outcomes (p = 5.90 × 10−5 and 6.17 × 10−5, respectively). eQTL analysis showed rs7420371 A allele significantly upregulated the mRNA expression of RTP5 in 266 cerebellum tissues, in 277 cerebellar hemisphere tissues, and in 270 cerebral cortex samples. Conclusions & Relevance: We discovered a novel, independent, and potentially functional SNP RTP5 rs7420371 G>A to be significantly associated with COVID-19 mortality. The A allele is significantly associated with elevated mRNA expression of RTP5 in the brain, an important protein coding gene that modulates olfactory binding and taste perceptions in response to SARS-CoV-2 infection.

COVID doi: 10.3390/covid5120205

Authors: Leonard A. Jason Jacob Furst Lauren Ruesink Ben Z. Katz

Efforts have been made to develop a case definition for Long COVID, with results differing on whether the case definition should be specific and exclusive, or broad and easily generalizable. Each of these methods has been subject to limitations. As most efforts have focused on symptoms, inclusion criteria have often relied on the binary occurrence of a symptom. The current study uses a more detailed measure that considers the frequency and severity of symptoms in a sample of individuals with Long COVID and matched controls who recovered from acute SARS-CoV-2 infection. Patients were diagnosed with Long COVID in a systematic process involving their completion of quantitative questionnaires, qualitative interviews, a physical examination, and general laboratory testing to rule out other diagnoses. Since samples were comparatively small given the number of symptoms investigated, Leave One Out Cross-Validation (LOOCV) was used to develop LASSO regression models to determine which symptoms best distinguished Long COVID from recovered controls. An ideal threshold for classifying Long COVID based on symptomatology was developed using a receiver operator characteristics (ROC) curve. The model presented in this article identified Long COVID with high accuracy. The importance of smell/taste was lessened in the current study, and gastrointestinal symptoms took on greater prominence in our study. It is possible to achieve high accuracy in differentiating those with Long COVID from those who have recovered. It is important to specify criteria of Long COVID and to measure symptoms comprehensively to identify those with Long COVID. Reliably identifying those who have developed Long COVID will help in the formulation of treatment strategies.

COVID doi: 10.3390/covid5120204

Authors: Eduardo Tuta-Quintero Alirio Bastidas Esteban García-Gallo Emilio Díaz María Bodí Jordi Solé-Violán Ricard Ferrer Antonio Albaya-Moreno Lorenzo Socias Ángel Estella Ana Loza-Vazquez Ruth Jorge-García Isabel Sancho Ignacio Martin-Loeches Alejandro Rodriguez Luis Felipe Reyes

Background: This study aimed to assess whether methylprednisolone treatment, while effective in reducing COVID-19 mortality, increases the risk of intensive-care-unit-acquired respiratory tract infections (RTI-ICU) in critically ill patients. Methods: This was a multicenter prospective cohort study conducted in ten countries across Latin America and Europe. It included patients over 18 years of age with confirmed SARS-CoV-2 infection who required ICU admission. A multivariable logistic regression analysis and propensity score matching (PSM) were performed to determine the association between methylprednisolone treatment and RTI-ICU. Results: A total of 3239 patients were included, of whom 1527 patients (47.1%) were treated with methylprednisolone. Methylprednisolone treatment was associated with a higher risk of developing RTI-ICU (OR = 1.59; 95% CI: 1.33–1.91). Patients with RTI-ICU had a significantly higher average number of days on invasive mechanical ventilation (IMV) (24.6, SD: 15.9 vs. 9.5, SD: 11.7; p < 0.001), longer hospital stays (40 days, SD: 24.9 vs. 24.4 days, SD: 18.7; p < 0.001), and higher ICU mortality (39.2%, 259/660 vs. 29.2%, 754/2579; p < 0.001). Conclusions: Methylprednisolone treatment is associated with an increased risk of RTI-ICU in critically ill patients with COVID-19. RTI-ICU was linked to higher mortality, a greater need for invasive mechanical ventilation, prolonged ICU stay, elevated leukocyte and C-reactive protein levels, and a higher comorbidity burden. However, methylprednisolone may not be the sole factor explaining these differences, as residual confounding related to baseline disease severity and comorbidities could have influenced the outcomes.

COVID doi: 10.3390/covid5120203

Authors: Sreelakshmi Kalayakkattil Ananthakrishnan Anil Indu Punya Sunil Haritha Nekkanti Smitha Shet Ranajit Das

SARS-CoV-2, the virus responsible for COVID-19, disrupts human cellular pathways through complex protein–protein interaction, contributing to disease progression. As the virus has evolved, emerging variants have exhibited differences in transmissibility, immune evasion, and pathogenicity, underscoring the need to investigate their distinct molecular interactions with host proteins. In this study, we constructed a comprehensive SARS–CoV–2–human protein–protein interaction network and analyzed the temporal evolution of pathway perturbations across different variants. We employed computational approaches, including network-based clustering and functional enrichment analysis, using our custom-developed Python (v3.13) pipeline, BioEnrichPy, to identify key host pathways perturbed by each SARS-CoV-2 variant. Our analyses revealed that while the early variants predominantly targeted respiratory and inflammatory pathways, later variants such as Delta and Omicron exerted more extensive systemic effects, notably impacting neurological and cardiovascular systems. Comparative analyses uncovered distinct, variant-specific molecular adaptations, underscoring the dynamic and evolving nature of SARS-CoV-2–host interactions. Furthermore, we identified host proteins and pathways that represent potential therapeutic vulnerabilities, which appear to have co-evolved with viral mutations.

COVID doi: 10.3390/covid5120202

Authors: Kento Fukano Junko S. Takeuchi Azusa Kamikawa Wataru Sugiura Junko Terada-Hirashima Moto Kimura

Saliva specimens are widely used for coronavirus disease 2019 (COVID-19) testing using RT-qPCR due to their advantages over nasopharyngeal swabs of being non-invasive and self-collectable. However, saliva collection can be time-consuming in individuals with reduced saliva secretion, including those with diabetes, diseases involving salivary glands such as Sjögren’s syndrome, and older adults. In this study, we evaluated the diagnostic performance of mouth rinse specimens, which can be easily collected even from individuals with reduced saliva secretion, as an alternative to saliva for RT-qPCR COVID-19 testing. Among the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive specimens analyzed, 88.2% were derived from patients possessing risk factors associated with reduced salivary secretion, including diabetes, use of medications such as anticholinergics or antihistamines, smoking, and older age. The analysis results of mouth rinse specimens demonstrated 96.7% overall agreement with those of saliva specimens, with a sensitivity of 94.1% and specificity of 100%; however, the viral load in the mouth rinse specimens was lower than that in saliva because of sample dilution. These findings suggest that mouth rinse specimens are a practical, versatile, and reliable alternative specimen for RT-qPCR COVID-19 testing.

COVID doi: 10.3390/covid5120201

Authors: Dovilė Važgėlienė Raimondas Kubilius Indre Bileviciute-Ljungar

Objective: To compare self-reported functioning, disability, and health care-seeking behavior of previously healthy and unhealthy participants after SARS-CoV-2 infection. Design: Cross-sectional design conducted in 2021–2022. Subjects/Patients: Participants 18 years or older were asked to participate in an anonymous survey after acute SARS-CoV-2 infection (at least 28 days passed). Methods: The survey was conducted using an Internet-based questionnaire distributed through Lithuanian websites, including Facebook groups, city/town/district hospitals, and media outlets. Results: The final cohort consisted of 1945 participants, almost 90% being women with higher education and approximately 89% working at the time of survey. The mean age was 43 years. Among them, 53% reported to be healthy before SARS-CoV-2 infection and 5% were hospitalized during acute infection. Individuals with chronic diseases prior to infection rated their health status significantly lower but reported similar functional capacity before infection. After infection, they reported more restricted activities and more often sought health care due to remaining symptoms. In total, 16% of the cohort applied for rehabilitation services and only 7% were accepted, more often those with chronic diseases before infection. Conclusions: Results indicate a small proportion of participants receiving rehabilitation services, more often these with prior chronic diseases. The results increase awareness of rehabilitation needs after infection, particularly for previously unhealthy people.

COVID doi: 10.3390/covid5120200

Authors: Hadassa Yuef Martínez-Padrón Ariadne Guadalupe Quintero-Zapata Ares Duvaliere Buenfild-Saldivar Jorge Luis Valdéz-Báez Elsa Verónica Herrera-Mayorga Rodrigo Vargas-Ruiz

Background: Women are at increased risk of developing severe morbidity and mortality during pregnancy, childbirth, and the puerperium, especially in developing countries. In Mexico, during 2020, 27.5% of maternal deaths were attributed to COVID-19. The aim of this study was to describe the sociodemographic and clinical characteristics of maternal deaths among patients with and without COVID-19 in the state of Tamaulipas. Materials and Methods: A non-probabilistic sampling approach was used in this observational, cross-sectional, descriptive, retrospective study of obstetric patients. Results: One hundred and six obstetric patient records were evaluated. Eleven patients died directly from COVID-19 complications. The mean age of the population was 29.5 years, with 7.54% suffering from type 2 diabetes mellitus and 5.66% systemic arterial hypertension. Obstetric complications were late surgical puerperium (11.32%), physiological puerperium (9.43%), and obstetric hemorrhage (7.54%). Lung complications were community-acquired pneumonia (20.75%), of which 50% were due to COVID-19 (10.37%) and respiratory distress syndrome (15.09%). Systemic complications were hypovolemic shock (16.98%), septic shock (15.09%), and multiple organ failure (12.26%). Conclusions: Mortality from COVID-19 in obstetric patients was 10.37%, and 89.63% died from gynecological, lung, and systemic complications.

COVID doi: 10.3390/covid5120199

Authors: Chia Siang Kow Dinesh Sangarran Ramachandram Barbara R. Conway Syed Shahzad Hasan

The COVID-19 pandemic initially focused clinical efforts on hospitalized patients. However, as the pandemic progressed, attention shifted to outpatients who often experience milder symptoms yet still contribute to viral transmission. This scoping review aimed to document and evaluate the clinical outcomes assessed in randomized controlled trials (RCTs) involving outpatients with COVID-19, identifying gaps and areas for improvement in trial design. This review followed the PRISMA-ScR guidelines. A comprehensive search of four electronic databases (PubMed, Scopus, Cochrane CENTRAL, and Web of Science) was conducted for RCTs published between December 2019 and December 2023. Studies were included if they involved outpatients with confirmed COVID-19 and reported clinical outcomes. Data were extracted from eligible studies, and outcomes were categorized using the COMET taxonomy. A total of 91 studies were included, representing a wide geographical distribution, with the USA, Iran, and Brazil contributing the most studies. The most frequently investigated treatments included hydroxychloroquine, fluvoxamine, convalescent plasma, and ivermectin. Key outcomes focused on hospitalization rates, symptom resolution, and disease progression. Mortality, although less common in outpatients, was reported in 65 studies, underscoring the importance of outpatient interventions. This review highlights the need for standardized outcome measures in outpatient COVID-19 trials.

COVID doi: 10.3390/covid5120198

Authors: Aung Du Andrew Dang Khai Nguyen

Long COVID, a condition marked by persistent symptoms following COVID-19 infection, poses significant challenges in regard to clinical management. While emerging pharmacological treatments have demonstrated limited benefits in isolated studies, clinical experience and the literature suggest that low-dose naltrexone (LDN) may be a promising therapeutic option. Therefore, in this systematic review, we aim to synthesise findings from the available literature and evaluate the overall safety and efficacy of LDN as a potential treatment for long COVID. A literature search was conducted using a combination of key terms—‘COVID’, ‘COVID-19’, ‘SARS-COV-2’, and ‘Naltrexone’— and the following databases: MEDLINE, Web of Science (Clavirate), Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Cumulative Index in Nursing and Allied Health Literature (CINAHL). The methodology is available on the PROSPERO database (CRD42025630362). Screening identified five eligible articles. Four studies were included, but only two provided comparable data suitable for meta-analysis. Meta-analysis demonstrated statistically significant improvements in fatigue, brain fog, and headaches. Preliminary evidence suggests LDN has potential benefits in the treatment of long COVID, particularly with respect to fatigue, brain fog, and headaches, but more robust studies, such as randomised controlled trials, are urgently needed to confirm LDN’s safety and efficacy.

COVID doi: 10.3390/covid5120197

Authors: Venera Kudabaeva Timur Tastaibek Almagul Mansharipova Arystan Seidalin Nargiza Nassyrova

Background: Diagnosing post-COVID syndrome (PCS) in older adults with hypertension is difficult due to heterogeneity and multimorbidity. We aimed to identify factors associated with PCS. Methods: An observational study was conducted from June 2024 to April 2025. Patients aged 60–89 years with arterial hypertension were enrolled; PCS was verified according to the national protocol. Between-group comparisons used standard tests. Multivariable logistic regression with pre-specified clinical predictors estimated independent associations. Results: A total of 291 patients with arterial hypertension were included in the study. Patients were grouped by PCS status (PCS = 101; controls = 190). In multivariable analysis, female sex (OR 3.64; 95% CI 1.22–10.82), younger age (OR 0.93; 95% CI 0.89–0.98), lower systolic blood pressure (SBP) (OR 0.98; 95% CI 0.96–1.00), and rhythm disturbances (OR 2.63; 95% CI 1.07–6.49) were associated with PCS; other predictors were not significant. Model discrimination was moderate (AUC 0.728; 95% CI 0.668–0.787; Brier score 0.193) with positive net benefit across thresholds ~0.10–0.65. Conclusions: In older hypertensive adults, female sex, younger age, lower SBP, and rhythm disturbances indicate higher PCS likelihood, supporting risk-stratified monitoring and management.

COVID doi: 10.3390/covid5120196

Authors: Nilihan E. M. Sanal-Hayes Kate Slade Marie Mclaughlin Ethan Berry Emma Swift Lawrence D. Hayes

The cumulative global incidence of long COVID is around 400 million individuals, yet effective treatment options remain limited. A recent systematic review published in 2025 highlighted promising results for non-invasive brain stimulation in alleviating long COVID symptoms. Given the growing use of repetitive transcranial magnetic stimulation (rTMS) for people with long COVID, a focused meta-analysis on the therapeutic effectiveness of rTMS is warranted. To address this gap, this protocol outlines the planned procedures for a systematic review and meta-analysis. A comprehensive search will be conducted across CINAHL Ultimate, MEDLINE, ScienceDirect, and Scopus. Retrieved studies will be managed using Rayyan, with two independent reviewers screening titles and abstracts, followed by full-text review. Data extraction will follow PRISMA and Cochrane guidelines using a standardised form, with dual independent extraction and reconciliation of discrepancies. Risk of bias will be assessed using Cochrane RoB 2.0. Meta-analytical procedures will include calculation of standardised effect sizes (e.g., Hedges’ g), use of random-effects models, and assessment of heterogeneity via I2, Cochran’s Q, and tau2. Subgroup and moderator analyses will explore variations in rTMS protocols, participant characteristics, and symptom domains. Sensitivity analyses and meta-regression will be conducted where data permit. Results will be visualised using forest and funnel plots, and the GRADE framework will be used to assess the quality of evidence.

COVID doi: 10.3390/covid5120195

Authors: Claus Rinner

Attitudes towards COVID-19 and lived experiences during the pandemic depended greatly on people’s level of education. This study extends a previous analysis of vaccine hesitancy as a function of formal education and examines additional indicators from the COVID-19 Trends and Impacts Survey for the United States during 2021–2022. The monthly values for social and health-related activities and constraints, testing and vaccination decisions, and information-seeking behaviours, as well as trust and beliefs, often varied markedly between education-defined classes. Many indicators present a significant gap between the attitudes and experiences of better-educated groups, represented by college/university graduates and those with post-graduate studies, on the one hand, and less-educated groups, including those with only high school or some college education, on the other hand. These patterns suggest that the academic and professional-managerial classes, which supply the vast majority of societal decision-makers, may be ill-equipped to understand and respect the needs and worries of the working class in an emergency situation such as the COVID-19 pandemic. Given growing concerns about the benefit–harm balance of many government policies, a more inclusive pandemic response could have been achieved by respecting and adopting the common sense, scepticism, and outright opposition of the less-educated groups vis-a-vis restrictions and public health measures.

COVID doi: 10.3390/covid5120194

Authors: Rahima Jahic Mustafa Asim Demirkol Sefika Umihanic Jasmina Smajic Sekib Umihanic Alma Trnacevic Amra Adrovic Yildiz Kamber Kasali Ayhan Olcay Nejra Selak Onur Yolay

During the early months of the COVID-19 pandemic, treatment protocols varied substantially among countries and even between hospitals. This study compared the clinical characteristics, management strategies, and outcomes of hospitalized COVID-19 patients treated in tertiary centers in Türkiye and Bosnia and Herzegovina. We retrospectively analyzed 1338 adults hospitalized with laboratory-confirmed SARS-CoV-2 infection: 657 patients in Tuzla (Bosnia and Herzegovina, June–December 2020) and 681 in İstanbul (Turkiye, April–May 2020). Demographic, clinical, and laboratory data, treatment details (including favipiravir use), need for invasive or non-invasive mechanical ventilation, and in-hospital mortality were extracted from medical records. Patients in Bosnia and Herzegovina were older (61.6 ± 14.4 vs. 56.9 ± 15.8 years; p < 0.001) and had longer hospital stays (9.0 ± 5.5 vs. 7.7 ± 6.1 days; p < 0.001). In the Bosnian cohort, leukocyte, neutrophil, platelet, ferritin, CRP, troponin, creatinine, AST, and ALT levels were significantly higher, whereas hemoglobin and D-dimer levels were lower. The need for ventilatory support was greater in Bosnia and Herzegovina (15.1% vs. 12.2%, p < 0.001), and overall mortality was higher (25.7% vs. 9.3%, p < 0.001). No mortality difference was observed between patients treated and not treated with favipiravir. Despite similar inclusion criteria, patients in Bosnia and Herzegovina exhibited more severe disease, greater organ involvement, and higher mortality than those in Turkiye. Favipiravir use did not influence survival. Inter-country comparisons highlight how differing patient profiles and treatment protocols may impact COVID-19 outcomes; however, interpretation should consider that the two centers contributed data from different phases of the 2020 pandemic, and that country-level differences in circulating variants, healthcare capacity, hospital strain, and evolving clinical guidelines may also have influenced the observed patterns.

COVID doi: 10.3390/covid5110193

Authors: Miltiadis Georgiadis Nuriye Akyol Lars Kamper Nima Nadem-Boueini Athanasios Ziakos Patrick Haage Melchior Seyfarth Nadine Abanador-Kamper

After SARS-CoV-2 infection, a subset of patients experience persistent cardiac symptoms, yet data on long-term cardiac involvement and clinical outcomes in the post-COVID-19 condition remain limited. This study aimed to investigate myocardial abnormalities using advanced cardiovascular magnetic resonance (CMR) imaging techniques in patients with ongoing cardiac symptoms for at least three months following COVID-19 diagnosis, and to assess their clinical outcomes. Between January 2021 and March 2022, 94 post-COVID-19 patients were examined at a median of 99 days (IQR 92–110) after diagnosis and compared to 100 controls. The CMR assessment included the left ventricular ejection fraction (LVEF), myocardial T2 signal, late gadolinium enhancement (LGE), and myocardial strain parameters. Follow-up for major adverse cardiac events (MACEs) was conducted at a median of 269 days (IQR 144–352). While no significant differences in LVEF were observed, post-COVID-19 patients demonstrated significantly reduced peak radial and circumferential strain values, suggesting subclinical myocardial dysfunction. Additionally, these patients exhibited a higher event rate compared to controls (0.063 vs. 0; p = 0.029). These findings indicate that patients with cardiac symptoms following COVID-19 may exhibit subtle but measurable myocardial changes and an increased risk of adverse outcomes. The observed alterations in myocardial strain most likely reflect mild, subclinical myocardial involvement within the spectrum of post-COVID-19 effects, rather than a direct cause of persistent symptoms. Further research is warranted to determine the prognostic significance of these findings.

COVID doi: 10.3390/covid5110192

Authors: Cláudia P. M. Araújo Carolina M. Vieira Ketlen C. Ohse Alessandra S. Silva Sofia A. Cavalcante Felipe G. Naveca Fernanda N. Oliveira James L. Crainey Marcus V. G. Lacerda Gisely C. Melo Vanderson S. Sampaio Michel Batista Amanda C. Camillo-Andrade Marlon D. M. Santos Diogo B. Lima Juliana de S. G. Fischer Paulo C. Carvalho Priscila F. Aquino

This study investigated proteomic differences in nasopharyngeal swabs of SARS-CoV-2-infected patients from Manaus (Brazil) who were hospitalized during the devastating first wave of the COVID-19 pandemic, before the emergence of the deadly P1 SARS-CoV-2 strain. LC-MS/MS proteomic analysis compared 16 matched COVID-19 patient profiles: eight survivors and eight fatalities. A total of 1604 proteins were identified in fatality swabs, and 981 in the swabs of survivors. Our study provides new insights into the cellular mechanisms underlying first-wave COVID-19 deaths from Manaus and identifies hypoxia-related HYOU1, endothelial injury-associated S100A10, and some viral replication proteins (DDX1/17, XPO1) as potential biomarkers of fatal infections. The proteomic profiles of the swabs taken from patients that died collectively suggest that many of the first wave COVID-19 fatalities in Manaus suffered immune-system collapse. Survivor patient swabs showed elevated levels of immune defense proteins (FN1, C4BPA, IGKV1-5), indicating effective antiviral responses. Gene ontology analysis revealed dysregulated secretory pathways in fatalities and did not detect the defense-response pathways in fatality-group datasets that were observed in survivor protein datasets. Interestingly, the NOS2 protein, previously associated with first-wave fatalities, was found exclusively in our fatality swabs.

COVID doi: 10.3390/covid5110191

Authors: Patchareeya Amput Arunrat Srithawong Ajchamon Thammachai Sirima Wongphon

Background: This cross-sectional study reports exploratory observations on respiratory symptom patterns in individuals with prior coronavirus disease 2019 (COVID-19), evaluating associations with exercise habits, number of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection episodes, vaccine doses received, body mass index (BMI), age, sex, and comorbidities. Methods: A total of 240 participants were assessed for age, sex, height, weight, BMI, comorbidities, SARS-CoV-2 infection episodes, vaccine doses received, and exercise habits; the self-reported duration of symptomatic periods was summarized descriptively and was not modeled as an exposure or outcome. Results: Compared with the first SARS-CoV-2 infection episode (reference), patients who experienced a second episode had higher odds of dyspnea (adjusted odds ratio; OR = 7.61; 95% confidence interval CI = 1.54–37.66). In univariate analysis, patients who received three vaccine doses had lower odds of dyspnea than those who received two doses (OR = 0.39; 95% CI = 0.16–0.98), but this association was not significant after adjustment (adjusted OR = 0.46; 95% CI = 0.13–1.63). After adjustment, patients who exercised had lower odds of secretion compared with those who did not (adjusted OR = 0.30; 95% CI = 0.12–0.73). Conclusions: These cross-sectional, hypothesis-generating observations suggest higher adjusted odds of dyspnea among individuals with repeat infection and lower adjusted odds of sputum among those reporting regular exercise; estimates are imprecise and subject to residual confounding due to unbalanced group sizes. Confirmation in larger, longitudinal cohorts is required.