Search Results (2,368)

SARS-CoV-2, the causative virus of the COVID-19 pandemic, is a highly transmissible, enveloped, single-stranded RNA virus that has mutated into several variants, complicating vaccine strategies and drug resistance. Novel treatment modalities targeting conserved structural vulnerable points are essential to combat these variants. The primary aim of the current study is to test the mechanical vulnerability of the SARS-CoV-2 virus envelope and spike proteins to focused, high-frequency ultrasound waves (25 MHz) in vitro. Utilizing a preliminary pretest and posttest study design, the study was conducted on a virus sample within a distilled water matrix, under controlled laboratory biosafety conditions. Since detailed imaging tools were unavailable, viral disruption was indirectly measured using real-time PCR cycle threshold (Ct) values. Ct values increased significantly after high-frequency ultrasound exposure, indicating a reduction in amplifiable viral genomic material. A paired t-test indicated a significant difference between the pretest and posttest Ct (p < 0.001), which is supported by Monte Carlo test results that revealed statistically significant shifting in viral load categories (p = 0.001, two-sided). Specifically, 85.7% of high-viral-load samples converted to low or moderate content, 46.7% of low or moderate samples were shifted to negative content. This intervention produced a large effect size (Cohen’s d = 2.422). These results indicate that ultrasound may offer a promising non-pharmacological approach to destroy or inactivate SARS-CoV-2 variants in an aqueous environment. Full article

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has had major social and economic consequences worldwide. Whole genome sequencing (WGS) is essential for genomic monitoring, enabling tracking of viral evolution, detection of emerging variants, and identification of introductions and transmission chains to inform timely public health responses. Here, we compile and harmonize SARS-CoV-2 genomic data generated by multiple laboratories across Kazakhstan together with publicly available sequences to provide a national overview of genomic dynamics across successive epidemic waves from 2020 to 2022. We analyzed 4462 genomes deposited in GISAID (including 340 generated in this study), of which 3299 passed Nextclade quality filters, and summarized lineage turnover across major phases (pre-VOC, Alpha, Delta, Omicron BA.1/BA.2, Omicron BA.4/BA.5, and a later recombinant-dominant period). Sequencing intensity varied markedly over time (0.60‰ of confirmed cases during Delta vs. 11.57‰ during the Omicron BA.5 wave), suggesting that lineage diversity and persistence may be underestimated. Pre-VOC circulation included ≥12 Pango lineages with evidence of multiple introductions and sustained local transmission, including a Kazakhstan-restricted B.4.1 lineage that emerged in Nur-Sultan/Astana and disappeared after April 2020. The Tengizchevroil oilfield outbreak comprised B.1.1 viruses with phylogenetic support for ≥three independent introductions. Alpha and Omicron waves were characterized by repeated introductions and heterogeneous origins, whereas Delta was dominated by AY.122 with an additional distinct AY.122 cluster; a notable BF.7 local transmission event was observed during BA.5. We also highlight locally enriched non-lineage-defining mutations. Overall, recurrent importations and variable local amplification shaped SARS-CoV-2 dynamics in Kazakhstan, while interpretation is constrained by strongly time-skewed sequencing. Full article

Background/Objectives: This ecological study aimed to investigate changes in the time-varying reproduction number (Rt) of SARS-CoV-2 across six regions of Massachusetts from 2020 to 2022 and to evaluate the impact of various nonpharmaceutical interventions (NPIs) implemented in 2020 by examining associated changes in the Rt. Methods: COVID-19 incident case data from the Johns Hopkins University database were adjusted for reporting delays using deconvolution and for underreporting via a Poisson-distributed multiplier of 4. Negative and zero counts were corrected using imputation. Rt was estimated using R package EpiEstim (Version 2.2-4) with a 7-day sliding window from 2020 to 2022 and with non-overlapping time windows between policy changes in 2020. Results: From 2020 to 2022, Massachusetts experienced five COVID-19 surges, linked to the wild-type strain and emerging variants, with Rt exceeding 1 during each wave and stabilizing at or dropping below 1 during low-incidence phases. School closure and gathering restrictions, the first major intervention, were associated with a 14.7% statewide reduction in Rt (95% credible interval (CrI): −23.6%, −5.6%), with greater reductions in high-density areas such as Boston (−16.9%; 95% CrI: −26.9%, −7.5%). No statistically significant changes in Rt were found to be associated with other NPIs in 2020, including the mask mandate, reopening phases, travel restrictions and quarantine requirements, and curfews. Conclusions: Our findings highlight the different NPIs’ varying impacts on COVID-19 transmission dynamics across regions in Massachusetts in 2020 and underscore the importance of early interventions for future pandemic preparedness. Full article

During the COVID-19 pandemic, SARS-CoV-2 quickly spread all over the world in a pattern of waves. In Mexico, the first wave was from March 2020 to September 2020, and during this time autopsies were forbidden. After that, the postmortem lung samples allowed us to identify histological alterations because of COVID-19. Moreover, SARS-CoV-2 infections are characterized by the manifestation of cytopathic effects like inclusion bodies, and multinucleated cells in alveolar spaces and alveolar walls. Additionally, atypical, enlarged cells, presence of macrophages in alveolar spaces, and congestion of vascular vessels were the other histopathologic alterations of the lung. Our study covered the analysis of nine postmortem lung samples from patients with severe COVID-19 diagnosed by qRT-PCR. The samples were stained with Hematoxylin-Eosin to identify the histological alterations related to lung architecture and cell populations and were subjected to immunohistochemistry for the SARS-CoV-2 Spike and Nucleocapsid proteins. All samples showed alterations associated with diffuse alveolar damage and 1/9 presented no alveolar space, 5/9 presented different levels of pleural fibrosis, and 4/9 presented distention of the small capillaries. Immunohistochemistry results revealed that 4/9 samples showed Spike-positive cytoplasmic inclusion bodies in type I pneumocytes and 2/9 Spike-positive nuclear inclusion bodies in type I pneumocytes. These inclusion bodies were found to be eosinophilic with H&E stains. The H&E results suggest tissue alterations that may contribute to the signs and symptoms of severe COVID-19, as well as the Spike protein expression, as its distribution suggests its participation in pathophysiology. Full article

Mathematical models for infectious diseases, particularly autonomous ODE models, are generally known to possess simple dynamics, often converging to stable disease-free or endemic equilibria. This paper investigates the dynamic consequences of a crucial, yet often overlooked, component of pandemic response: the saturation of public health testing. We extend the standard SIR model to include compartments for ‘Confirmed’ (C) and ‘Monitored’ (M) individuals, resulting in a new SICMR model. By fitting the model to U.S. COVID-19 pandemic data (specifically the Omicron wave of late 2021), we demonstrate that capacity constraints in testing destabilize the testing-free endemic equilibrium ($E_1$). This equilibrium becomes an unstable saddle-focus. The instability is driven by a sociological feedback loop, where the rise in confirmed cases drive testing effort, modeled by a nonlinear Holling Type II functional response. We explicitly verify that the eigenvalues for the best-fit model satisfy the Shilnikov condition (${\lambda }_u>{\lambda }_s$), demonstrating the system possesses the necessary ingredients for complex, chaotic-like dynamics. Furthermore, we employ Stochastic Differential Equations (SDEs) to show that intrinsic noise interacts with this instability to generate ’noise-induced bursting,’ replicating the complex wave-like patterns observed in empirical data. Our results suggest that public health interventions, such as testing, are not merely passive controls but active dynamical variables that can fundamentally alter the qualitative stability of an epidemic. Full article

Background/Objectives: Public healthcare workers face significant occupational stress during crisis situations, yet research on this particular population remains limited compared to other healthcare workers. The aim of this study was to investigate the impact of the COVID-19 pandemic on distress levels and the sense of coherence among public health workers by integrating psychological assessments with physiological markers of stress to identify protective factors against pandemic-related occupational stress. Methods: This longitudinal study was conducted at the Teaching Public Health Institute of Split and Dalmatia County from July 2021 to February 2022 at two time points: the latency phase (between COVID-19 waves) and hyperarousal phase (during an active wave). Fifty-four public health workers participated in the study. There were three questionnaires assessing psychological distress: Kessler Psychological Distress Scale, Impact of Events Scale—Revised and Sense of Coherence Scale-29. Salivary and blood samples were collected at both time points to measure cortisol levels, cortisol awakening response, and interleukin-6 concentrations. Results: The cortisol area under the curve with respect to ground (AUCg) was significantly elevated during the stress phase compared to the latency phase (234.8 vs. 201.8; p = 0.023), indicating heightened physiological stress responses. Epidemiologists demonstrated significantly lower sense of coherence scores compared to non-epidemiologists (117.9 ± 9.1 vs. 125.6 ± 10.5; p = 0.029). A lower sense of coherence was significantly associated with higher psychological distress and post-traumatic stress symptoms. Multiple linear regression analysis revealed that sense of coherence and interleukin-6 levels were significant independent predictors of cortisol changes. Conclusions: The findings demonstrate that public health workers experience measurable physiological stress responses during pandemic peaks, with sense of coherence emerging as a protective psychological factor. Interventions targeting sense of coherence and organizational support may possibly enhance resilience and reduce mental health morbidity in this vulnerable workforce during crisis situations. Full article

We present several remarks on the spread of the COVID-19 epidemics in Bulgaria. The remarks are based on the hypothesis that the spread of the infection exhibits scaling properties similar to the scaling in urban dynamics. The corresponding mathematical theory leads us to a relationship for a power-law dependence of the number of infected in a certain region on the corresponding homochrony number. We prove the correctness of the mathematical theory on the basis of data for several Bulgarian regions for the first large COVID-19 wave in 2020. We observe a collapse of the real data along a single straight line. Full article

Standard epidemiological models often treat human behavior as static, failing to capture the dynamic feedback loops that shape epidemic waves. To address this, we developed a compartmental model of COVID-19 that couples the disease dynamics with two co-evolving behavioral games governed by imitation dynamics: an altruistic self-isolation game for infected individuals and a self-interested vaccination game for susceptible individuals. Our simulations reveal a fundamental behavioral paradox: strong adherence to self-isolation, while effective at reducing peak infections, diminishes the perceived risk of disease, thereby undermining the incentive to vaccinate. This dynamic highlights a critical trade-off between managing acute crises through non-pharmaceutical interventions and achieving long-term population immunity. We conclude that vaccination has a powerful stabilizing effect that can prevent the recurrent waves often driven by behavioral responses to non-pharmaceutical interventions. Public health policy must therefore navigate the tension between encouraging short-term mitigation behaviors and communicating the long-term benefits of vaccination to ensure lasting population resilience. Full article

Background/Objectives: Long COVID (LC) has been linked to fatigue, exercise intolerance, and autonomic dysfunction, but sex-stratified data on cardiovascular responses to maximal exercise—an essential component of personalized medicine—are scarce. This study aimed to examine hemodynamic, autonomic, and functional responses during and up to 24 h after a cardiopulmonary exercise test (CPET) in young adults with and without Long COVID (LC). Methods: In this cross-sectional study, we assessed 38 physically active adults, who were allocated into four subgroups stratified by clinical condition (LC or control) and biological sex: control–female (CON-F; n = 10), LC–female (LC-F; n = 10), control–male (CON-M; n = 10), and LC–male (LC-M; n = 8). Outcomes included systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), cardiac output (CO), total (TPR) and peripheral vascular resistance (PVR), pulse wave velocity (PWV), augmentation index (AIx@75), and heart rate variability (HF, LF, LF/HF), assessed at rest, peak effort, recovery (1, 3, 5, 10, 30, and 60 min), and through 24 h ambulatory blood pressure monitoring (ABPM) after CPET. Results: SBP increase appropriately during exercise, with higher peaks in males (p < 0.01), and returned to baseline within 5 min across all groups. HR recovery was preserved; however, LC-F showed lower values than CON-F at 3, 5, and 10 min (126 vs. 144 bpm, p = 0.020; 119 vs. 136 bpm, p = 0.020; 94 vs. 109 bpm, p = 0.011), though all groups normalized by 60 min. PWV, AIx@75, TPR and PVR exhibited expected sex-related patterns without LC-related impairments. HRV indices showed transient post-exercise shifts (HF↓, LF↑, LF/HF↑). Ambulatory monitoring confirmed preserved circadian modulation, with normal systolic dipping (11–13%) and no abnormal nocturnal patterns. Conclusions: Young physically active adults with LC showed preserved hemodynamic, autonomic, and vascular responses during and after maximal exercise. These findings contribute to personalized medicine by showing that individualized, sex-stratified cardiovascular assessments reveal no clinically relevant impairments in this population, supporting tailored clinical decision making and exercise prescription. Full article

COVID-19 has raised significant concern regarding its neurological impact, particularly during the early pandemic waves when severe systemic inflammation and neuroimmune dysregulation were more common. Although SARS-CoV-2 has been extensively studied, the precise mechanisms underlying its neurological effects remain incompletely understood, and much of the available evidence is derived from early variants with higher pathogenicity. Current research indicates that neuroinflammatory processes—driven primarily by systemic cytokine elevation, microglial activation, and blood–brain barrier dysfunction—contribute to a wide range of neurological symptoms. Severe complications such as encephalopathy, stroke, and cognitive impairment were predominantly reported in critically ill patients infected with the Wuhan, Alpha, or Delta variants, while such manifestations are considerably less frequent in the Omicron era. Most proposed mechanisms, including ACE2-mediated viral entry into the central nervous system, are supported mainly by experimental or preclinical studies rather than definitive human evidence. Biomarkers such as IL-6 and TNF-α, along with neuroimaging modalities including MRI and PET, offer useful but indirect indicators of neuroinflammation. Therapeutic approaches continue to focus on controlling systemic inflammation through immunomodulatory agents, complemented by targeted non-pharmacological strategies—such as physical rehabilitation, cognitive support, and psychological interventions—for the minority of patients with persistent neurological deficits. Overall, current evidence supports a variant-dependent neuroinflammatory profile and underscores the need for longitudinal, mechanism-focused studies to better characterize long-term neurological outcomes and refine therapeutic strategies. Full article

Background and Objectives: Healthcare-associated infections (HAIs) significantly increase morbidity and mortality in critically ill patients, and their burden became more pronounced during the COVID-19 pandemic. However, data describing the temporal evolution of HAIs, pathogen distribution, and associated risk factors across consecutive pandemic waves remain limited. This study aimed to characterize the epidemiology, microbiology, and outcomes of HAIs in COVID-19 intensive care units (ICU) patients and to identify clinical and laboratory predictors of mortality. Materials and Methods: This retrospective observational study included adult patients with RT-PCR–confirmed COVID-19 who developed at least one HAI ≥ 48 h after ICU admission between March 2020 and December 2020, encompassing the first three pandemic waves in Türkiye, in a tertiary-care ICU. Demographic, clinical, laboratory, and microbiological data were collected. Inflammatory markers and severity scores (SAPS-II, MCCI, and NLR) were analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for mortality prediction. Results: Among the 1656 ICU admissions, 145 patients (8.7%) developed HAIs; after exclusions, 136 patients were included in the final analysis. Bloodstream infections were the most frequent HAI (57%), followed by urinary tract infections (31%), ventilator-associated pneumonia (9%), and surgical site infections (1%). Klebsiella pneumoniae was the predominant pathogen, followed by Candida albicans and Acinetobacter baumannii. Multidrug-resistant organisms, including MRSA and VRE, showed variable distribution across pandemic periods. Overall in-hospital mortality was 74.3%. Non-survivors had significantly higher SAPS-II, MCCI, and NLR values. ROC analysis identified NLR > 38.8 and SAPS-II > 35.5 as mortality-predictive thresholds. Dynamic inflammatory marker patterns correlated with infection timing, and early peaks of CRP, WBC, and IL-6 were associated with worse outcomes. Conclusions: HAIs imposed a substantial clinical burden on critically ill COVID-19 patients, with high mortality driven predominantly by multidrug-resistant bloodstream infections. Severity indices and inflammation-based biomarkers demonstrated strong prognostic value. Temporal shifts in pathogen ecology across pandemic waves underscore the need for adaptive infection-prevention strategies, continuous microbiological surveillance, and strengthened antimicrobial stewardship in critical care settings. Full article

Background/Objectives: Oral health-related quality of life (OHRQoL) may influence mental health outcomes, yet longitudinal evidence on its association with depression remains limited. This study aimed to examine whether oral health status and OHRQoL are associated with a change in self-reported depression status among adults in Japan. Methods: We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), conducted in 2022 and 2023. A total of 15,068 participants aged ≥20 years without depression at baseline were included. Depression status was identified by self-reported measures between the two survey waves. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for change in self-reported depression status in relation to OHRQoL and oral health status, adjusting for sociodemographic and behavioral factors. Results: During follow-up, 218 participants (1.45%) reported a change in self-reported depression status. Poorer OHRQoL was significantly associated with a change in self-reported depression status (OR: 1.018; 95% CI: 1.001–1.036; p = 0.039). Additional risk factors included younger age (OR: 0.974; 95% CI: 0.964–0.985), participation in hobbies and cultural activities (OR: 2.224; 95% CI: 1.498–3.302), habitual use of sleeping pills or anxiolytics (current use OR: 3.512; 95% CI: 2.267–5.442), increased loneliness (OR: 1.217; 95% CI: 1.140–1.299), lower life satisfaction (OR: 0.900; 95% CI: 0.836–0.969), and poor self-rated health (OR: 2.921; 95% CI: 1.810–4.715). Conclusions: Impaired OHRQoL was associated with a change in self-reported depression status, potentially through psychosocial mechanisms. These findings suggest that oral health and OHRQoL may be relevant factors to consider in integrated oral and mental health approaches in clinical practice. Full article

Background: Pre-exposure passive immune prophylaxis (PrEP) might contribute to improve hematologic malignancy (HM) outcomes; however, there are currently no specific guidelines to inform patient selection. Methods: A literature review and a Delphi consensus process were used to identify COVID-19 risk factors, critical COVID-19 outcomes, and efficacy of PrEP against SARS-CoV-2 in HMs. An analytic hierarchy process was used to assign a priority score to candidate outcomes and to determine the PrEP indications. For these decisions, the experts assumed adequate compliance with anti-COVID-19 vaccination and acknowledged the effectiveness of PrEP in reducing SARS-CoV-2-related mortality and hospital admissions. Results: Based on the literature review, the expert panel identified 80 risk categories among patients with HM and prioritized eight clinical outcomes related to SARS-CoV-2 PrEP. The highest mean priority scores were observed for HM-related mortality (7.0), intensive care unit admission (6.7), and delays in anti-HM treatment (6.6). Based on such a framework, the experts deemed that if there was a variant-specific PrEP promptly available, it would be considered mandatory for all candidates receiving allogeneic hematopoietic cell transplantation, CAR-T therapy, or bispecific antibodies, regardless of local viral epidemiology. During epidemiological waves, variant-specific PrEP would also be recommended for patients with HMs at high risk of unfavorable COVID-19 clinical outcomes. Conclusions: This study identified PrEP indications for patients with HM receiving appropriate active immunization against COVID-19. Full article

Teacher occupational health is a critical issue worldwide that COVID-19 has worsened. While previous research has highlighted the impact of chronic work-related stress and limited personal resources on burnout, much of this research relies on cross-sectional data that do not capture how these effects develop over time. Additionally, the role of positive organizational factors remains underexplored. Our study examined burnout trajectories among 101 Portuguese elementary teachers (94.1% women, M = 46.03 years, 85.6% enrollment rate) over five data collection points spanning the 1st and 2nd COVID-19 waves (2019–2021) and investigated the impact of organizational climate on teacher burnout indicators. Main work-related stressors were identified through an open-ended question. Trajectories of occupational stress and burnout were analyzed using independent ANOVAs, and moderation analyses tested the relationship between organizational climate, occupational stress, and burnout indicators. Results showed a significant drop in perceived personal accomplishment during the first lockdown. Key stressors included greater job demands and more strained interpersonal relationships. Organizational climate significantly moderated the effect of work-related stress on emotional exhaustion, while having a positive main effect on personal accomplishment. This research contributes to a strengthened theoretical understanding of burnout as a dynamic, context-sensitive process, offering new empirical evidence, especially in underrepresented educational systems like Portugal. It emphasizes the importance of addressing contextual factors when working to reduce teacher burnout. Rethinking professional development and workplace relationships is essential for supporting teachers’ occupational health in today’s uncertain educational environments. Full article

Background: Evidence on COVID-19 convalescent plasma (CCP) is mixed. We examined associations between CCP administration and in-hospital outcomes among patients hospitalized during early pandemic waves in Poland. Methods: We conducted a retrospective, single-center cohort study of adults hospitalized with COVID-19 between October 2020 and January 2021. Patients receiving CCP were compared with contemporaneous controls without CCP. Primary outcomes were in-hospital mortality and discharge alive. Requirement for invasive mechanical ventilation/intubation was summarized descriptively because timing of intubation was not reliably available. Group comparisons used χ²/Fisher’s exact tests and t-test/Mann–Whitney U tests as appropriate. Associations with mortality and discharge were evaluated using logistic regression: (i) a prespecified age-adjusted model and (ii) an exploratory prognostic model including in-hospital treatments and severity markers (systemic glucocorticoids, remdesivir, oxygen therapy, and antibiotic use), interpreted prognostically rather than causally. Results: The cohort included 224 patients (CCP, n = 92; controls, n = 132); outcome status was missing for eight controls. Baseline demographics, comorbidities, and admission laboratory values were broadly comparable between groups. Crude in-hospital mortality was 25% in the CCP group (23/92) versus 42% in controls (52/124; p = 0.010), and discharge alive occurred in 66% versus 50%, respectively (p = 0.022). Invasive mechanical ventilation/intubation was required in 12.0% of CCP recipients and 4.5% of controls (p = 0.071). In age-adjusted models, CCP was associated with lower odds of in-hospital death. In exploratory prognostic models incorporating systemic glucocorticoids, remdesivir, oxygen therapy, and antibiotic use, CCP remained associated with lower odds of death and higher odds of discharge alive. Conclusions: In this early-wave retrospective cohort, CCP administration was associated with lower in-hospital mortality and higher discharge rates. Exploratory analyses adjusted for concomitant in-hospital therapies and severity markers should be interpreted as prognostic associations rather than evidence of causal efficacy. Full article