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Search Results (5,473)

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Keywords = COVID-19 symptoms

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24 pages, 2245 KB  
Article
Haptoglobin Phenotypes Stratify Post-Exertional Cognitive Dysfunction Associated with Altered Cerebral Oxygenation and Metabolic Signatures in Long COVID
by Atefeh Moezzi, Wesam Elremaly, Corinne Leveau, Anita Franco, Oleg Nepotchatykh, Christopher W. Armstrong and Alain Moreau
Int. J. Mol. Sci. 2026, 27(15), 7000; https://doi.org/10.3390/ijms27157000 - 4 Aug 2026
Viewed by 1620
Abstract
Long COVID (LC) is a heterogeneous post-infectious syndrome characterized by persistent symptoms, yet the biological basis underlying its interindividual variability remains poorly understood. Given the clinical overlap between LC and myalgic encephalomyelitis (ME), and prior demonstration that haptoglobin (Hp) phenotypes modulate symptom severity [...] Read more.
Long COVID (LC) is a heterogeneous post-infectious syndrome characterized by persistent symptoms, yet the biological basis underlying its interindividual variability remains poorly understood. Given the clinical overlap between LC and myalgic encephalomyelitis (ME), and prior demonstration that haptoglobin (Hp) phenotypes modulate symptom severity in ME, we investigated whether Hp phenotypes similarly stratify post-exertional cognitive dysfunction in LC. In this longitudinal observational study, 44 individuals with LC and 20 short-course COVID controls, who recovered rapidly from SARS-CoV-2 infection without persistent symptoms or sequelae, underwent Hp phenotyping alongside metabolomic and physiological profiling before and after a standardized 90 min passive post-exertional challenge. Hp phenotypes identified clinically distinct LC subgroups. Compared with Hp1-1 individuals, Hp2 allele carriers exhibited greater fatigue, poorer physical function, and more severe post-exertional symptoms. Immediately following the challenge, Hp2-2 participants with LC showed significant cognitive decline, whereas Hp1-1 individuals demonstrated cognitive resilience and more favorable longitudinal cognitive trajectories. This differential susceptibility was accompanied by higher post-exertional cerebral fractional tissue oxygen extraction in the right hemisphere in Hp1-1 individuals and by distinct metabolic signatures, with Hp2 allele carriers exhibiting lower post-exertional plasma concentrations of citric acid, isethionate, and glucosamine. Lower metabolite levels were associated with poorer cognitive performance. These findings support Hp phenotypes as promising candidate biomarkers for biological stratification in Long COVID, pending validation in larger independent cohorts. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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16 pages, 2180 KB  
Article
NeuroCOVID Burden and Functional Impairment in Adults with Long COVID: A Secondary Analysis of an Italian Cohort
by Angelo Cianciulli, Emanuela Santoro, Roberta Manente, Mariachiara Figura, Antonietta Pacifico and Giovanni Boccia
J. Clin. Med. 2026, 15(15), 6027; https://doi.org/10.3390/jcm15156027 - 3 Aug 2026
Viewed by 202
Abstract
Background/Objectives: Long COVID is frequently characterized by neurological, cognitive, neuropsychiatric, and autonomic symptoms (NeuroCOVID). However, their impact on daily functioning remains insufficiently investigated. This study evaluated the association between NeuroCOVID burden and functional impairment among Italian Long COVID survivors. Methods: A [...] Read more.
Background/Objectives: Long COVID is frequently characterized by neurological, cognitive, neuropsychiatric, and autonomic symptoms (NeuroCOVID). However, their impact on daily functioning remains insufficiently investigated. This study evaluated the association between NeuroCOVID burden and functional impairment among Italian Long COVID survivors. Methods: A secondary cross-sectional analysis was conducted on 250 adults using a validated Italian Long COVID questionnaire. A NeuroCOVID Burden Score (10 symptom domains) and a Functional Impairment Score (daily activities) were constructed and analyzed using correlation and multivariable linear regression. Results: The sample (mean age 33.2 years; 63.6% female) demonstrated high internal consistency for both scores. A strong positive correlation was found between NeuroCOVID burden and functional impairment (r = 0.703; p < 0.001). Conclusions: Persistent NeuroCOVID burden was strongly associated with greater limitations in daily activities. In multivariable regression, NeuroCOVID Burden Score remained independently associated with functional impairment (B = 0.671; 95% CI 0.566–0.776; p < 0.001), together with acute COVID-19 severity (B = 0.156; 95% CI 0.055–0.257; p = 0.003). The final model explained 52.5% of the variance in functional impairment (R2 = 0.525). Full article
(This article belongs to the Section Clinical Rehabilitation)
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18 pages, 4357 KB  
Article
Clinical and Hospital Trajectory of Fatal COVID-19 Cases in Campo Grande, Brazil, During 2021–2022
by Nayara de Lira Esteves Pimenta, Fabio Antonio Venancio and Valter Aragão do Nascimento
Sci 2026, 8(8), 190; https://doi.org/10.3390/sci8080190 - 1 Aug 2026
Viewed by 213
Abstract
Understanding the clinical and hospital trajectory of fatal COVID-19 cases is essential to clarify disease progression and support healthcare planning. This study analyzed the temporal trajectory of patients with confirmed COVID-19 who died in Campo Grande, Brazil, during 2021–2022. A retrospective observational study [...] Read more.
Understanding the clinical and hospital trajectory of fatal COVID-19 cases is essential to clarify disease progression and support healthcare planning. This study analyzed the temporal trajectory of patients with confirmed COVID-19 who died in Campo Grande, Brazil, during 2021–2022. A retrospective observational study was conducted using secondary data from 3572 fatal cases. Time intervals between symptom onset, hospitalization, intensive care unit (ICU) admission, and death were calculated. Survival analyses were performed using Kaplan–Meier curves and Cox proportional hazards regression. Most patients were aged 61–80 years (48%), male (55%), and had at least one reported risk factor (86%). The most frequent comorbidities were cardiopathy (56%), diabetes mellitus (35%), and obesity (20%). The mean time from symptom onset to hospitalization was 7.70 days, while the mean time from symptom onset to death was 22.87 days. Survival analyses showed significant differences according to age, neurologic disease, pneumopathy, and obesity. In the multivariable Cox model, age remained independently associated with shorter survival time. Fatal COVID-19 cases were characterized by a relatively short interval from symptom onset to hospitalization and a prolonged in-hospital course until death. By characterizing the timing of clinical deterioration, ICU admission, and death, these findings may inform regional assessments of critical care demand, expected ICU bed occupancy, and capacity planning during periods of increased healthcare demand. Full article
(This article belongs to the Section Clinical Medicine and Healthcare)
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20 pages, 388 KB  
Review
Neurodegenerative and Cognitive Consequences of Long COVID
by Luiza Marek-Józefowicz, Alina Borkowska, Bogusław Nedoszytko, Wiesław Jerzy Cubała, Dorota Purzycka-Bohdan and Michał Bohdan
Int. J. Mol. Sci. 2026, 27(15), 6897; https://doi.org/10.3390/ijms27156897 - 1 Aug 2026
Viewed by 357
Abstract
The SARS-CoV-2 virus has infected approximately 778 million people worldwide since the pandemic. Patients who have survived coronavirus disease (COVID-19) may experience long-term symptoms related to cognitive deficits, mood changes, and depressive disorders. The mechanisms underlying the long-term effects of COVID-19 on the [...] Read more.
The SARS-CoV-2 virus has infected approximately 778 million people worldwide since the pandemic. Patients who have survived coronavirus disease (COVID-19) may experience long-term symptoms related to cognitive deficits, mood changes, and depressive disorders. The mechanisms underlying the long-term effects of COVID-19 on the brain are being actively investigated. SARS-CoV-2 infection triggers various mechanisms, such as hyperstimulation of the immune response, which may lead to changes in the central nervous system. In this article, we review the evidence linking COVID-19 to neurodegenerative disorders and cognitive impairment. Current research indicates that patients with pre-existing cognitive and neuropsychiatric deficits have a poorer prognosis after SARS-CoV-2 infection, and patients who have survived COVID-19 may be at increased risk of developing dementia and mood disorders. We analyse the available evidence regarding SARS-CoV-2 brain infection, induction of inflammation, coagulopathy, and blood–brain barrier (BBB) dysfunction as possible mechanisms underlying the disorders in the acute phase of COVID-19 disease and contributing to the development of neurodegenerative disorders in long COVID. Viral infection can trigger inflammation of the central nervous system (CNS), leading to damage and contributing to the development of cognitive dysfunction. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology (7th Edition))
16 pages, 790 KB  
Article
The Impact of Long COVID on Cognitive Functioning
by Karen L. Siedlecki and Veronika Kobrinsky
J. Intell. 2026, 14(8), 157; https://doi.org/10.3390/jintelligence14080157 - 1 Aug 2026
Viewed by 237
Abstract
This study systematically examined whether long COVID negatively impacts subjective and objective measures of cognition in a community-based sample of 251 participants. Participants completed a battery of neurocognitive tasks (including assessments of short-term memory, working memory, episodic memory, processing speed, executive functioning, and [...] Read more.
This study systematically examined whether long COVID negatively impacts subjective and objective measures of cognition in a community-based sample of 251 participants. Participants completed a battery of neurocognitive tasks (including assessments of short-term memory, working memory, episodic memory, processing speed, executive functioning, and reasoning) and provided self-ratings of their cognition (mental fatigue and subjective cognitive difficulties), depressive symptoms, the impact of symptoms on their life, and completed surveys assessing other psychosocial outcomes. Subgroups included individuals with no known lifetime history of COVID-19 illness (n = 66), those who had recovered from a short-term COVID infection (n = 119), and those who had been diagnosed with long COVID (n = 62). Analyses indicated that long COVID was associated with worse performance on measures of processing speed and executive functioning. In addition, those with a history of long COVID reported higher levels of mental fatigue and subjective cognitive difficulties compared to the other subgroups. Analyses within the long COVID subsample indicated that after controlling for covariates, depressive symptoms were significantly associated with mental fatigue and self-reported cognitive difficulties, and ratings of symptom impact also significantly predicted mental fatigue. These findings reinforce the value of incorporating both subjective and objective assessments when evaluating cognitive outcomes in long COVID, as each captures distinct aspects of functioning. Furthermore, these findings underscore the importance of assessing subjective cognitive concerns and functional symptom burden in clinical encounters, even when objective performance is generally unimpaired. Full article
20 pages, 1593 KB  
Article
Potential Adjunctive Effects of Quercetin–Curcumin Co-Supplementation in Adults with Mild-to-Moderate Long COVID: Results from a Pragmatic Exploratory Real-World Clinical Study
by Amjad Khan, Fazle Rabbani, Sami Ullah Mumtaz, Roha Javed, Ikram Ujjan, Ayesha Kanwal and Gabriele Conti
Pharmaceuticals 2026, 19(8), 1202; https://doi.org/10.3390/ph19081202 - 31 Jul 2026
Viewed by 234
Abstract
Background/Objectives: Long COVID is characterised by persistent symptoms such as fatigue, pain, cognitive impairment, sleep disturbances, and reduced quality of life (QoL) following SARS-CoV-2 infection. Proposed mechanisms include persistent immune activation, chronic inflammation, oxidative stress, endothelial dysfunction, mitochondrial disturbances, and virus-induced cellular [...] Read more.
Background/Objectives: Long COVID is characterised by persistent symptoms such as fatigue, pain, cognitive impairment, sleep disturbances, and reduced quality of life (QoL) following SARS-CoV-2 infection. Proposed mechanisms include persistent immune activation, chronic inflammation, oxidative stress, endothelial dysfunction, mitochondrial disturbances, and virus-induced cellular senescence. Current management is largely supportive, highlighting the need for complementary strategies targeting these pathways. Natural polyphenols such as quercetin and curcumin possess anti-inflammatory, antioxidant, immunomodulatory, and potential senolytic properties that may modulate multiple pathways implicated in Long COVID. This study aimed to explore the potential complementary effects of oral quercetin–curcumin co-supplementation, administered alongside usual symptomatic management, in adults with persistent Long COVID symptoms. Methods: This single-centre, open-label, single-arm, pragmatic exploratory study enrolled 15 adults with Long COVID in an outpatient real-life clinical practice setting. Participants received a nutraceutical formulation containing quercetin (65 mg) and Curcuma longa extract standardised to provide 42 mg curcumin (Nasafytol®), administered as two capsules twice daily for 8 weeks in addition to standard care. The primary endpoint was change in overall symptom burden assessed using the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS). Secondary outcomes included fatigue (Fatigue Severity Scale, FSS), pain (Brief Pain Inventory—Short Form, BPI-SF), cognitive function (Patient-Reported Outcomes Measurement Information System Cognitive Function Short Form 8a, PROMIS-CF-8a), mood (Hospital Anxiety and Depression Scale, HADS), sleep quality (Pittsburgh Sleep Quality Index, PSQI), autonomic symptoms (Composite Autonomic Symptom Score-31, COMPASS-31), and health-related QoL (Medical Outcomes Study 36-Item Short-Form Health Survey, SF-36). Results: After 8 weeks, overall symptom burden significantly decreased (C19-YRS median 50 to 32; q = 0.018). Significant reductions were observed in patient-reported fatigue (q = 0.006), pain severity and interference (q = 0.006), and improved physical health-related QoL (SF-36 PCS; q = 0.025). Numerically favourable changes were also observed in cognitive function, anxiety, sleep quality, and autonomic symptoms, although these did not reach statistical significance. The supplementation was generally well tolerated with no serious adverse events. Conclusions: Quercetin–curcumin co-supplementation was associated with lower patient-reported symptom burden, fatigue, and pain and better physical health-related QoL after 8 weeks of supplementation in adults with Long COVID. These observed findings represent treatment-associated changes within this uncontrolled exploratory study and should be interpreted cautiously. Further evaluation in adequately powered randomised placebo-controlled trials is warranted. Trial registration: ClinicalTrials.gov (ID NCT06974058). Full article
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28 pages, 1609 KB  
Review
SARS-CoV-2 Point-of-Care Testing Modalities: Integrating Molecular, Immunological, Biosensor, and AI Approaches
by Helal F. Hetta, Rehab Ahmed, Abdul Haseeb, Salwa Qasim Bukhari, Zinab Alatawi, Ahmad J. Mahrous, Mahmoud E. Elrggal, Mohammad Al Masri and Ahmed A. Kotb
Diagnostics 2026, 16(15), 2402; https://doi.org/10.3390/diagnostics16152402 - 30 Jul 2026
Viewed by 342
Abstract
The coronavirus disease 2019 (COVID-19) pandemic highlighted the critical need for rapid, accessible, and accurate diagnostic tools to support timely clinical decision-making, outbreak control, and public health surveillance. Point-of-care testing (POCT) has emerged as an essential component of decentralized healthcare by enabling diagnostic [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic highlighted the critical need for rapid, accessible, and accurate diagnostic tools to support timely clinical decision-making, outbreak control, and public health surveillance. Point-of-care testing (POCT) has emerged as an essential component of decentralized healthcare by enabling diagnostic testing outside conventional laboratory settings. This review was based on a structured literature search of PubMed, Scopus, and Web of Science databases covering studies published between January 2020 and January 2026. The review evaluates current advances in COVID-19 POCT technologies, including molecular assays, antigen-based tests, antibody-based assays, biosensor platforms, and artificial intelligence (AI)-assisted diagnostic approaches. Molecular POCT methods, including rapid reverse transcription polymerase chain reaction (RT-PCR), loop-mediated isothermal amplification (LAMP), and CRISPR-based technologies, provide high analytical sensitivity and specificity and are increasingly suitable for decentralized diagnostic applications. Antigen-based assays offer rapid and cost-effective screening solutions, although diagnostic performance may vary depending on viral load, symptom onset, and circulating variants. Antibody-based POCT remains valuable for seroprevalence studies, retrospective diagnosis, and immune-response monitoring rather than acute infection detection. Emerging biosensor technologies and AI-enabled diagnostic systems demonstrate promising analytical capabilities and operational advantages; however, many remain at the prototype or early-validation stage and require further clinical evaluation before widespread implementation. The findings indicate that no single POCT modality is optimal for all clinical scenarios. Instead, molecular, antigen, antibody, biosensor, and AI-assisted approaches provide complementary strengths that support different diagnostic and public health objectives. Continued advances in assay design, digital connectivity, multiplex testing, and variant-resilient detection strategies are expected to further enhance the role of POCT in COVID-19 management and future infectious disease preparedness. Full article
(This article belongs to the Special Issue Point-of-Care Testing (POCT) for Infectious Diseases)
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18 pages, 359 KB  
Article
Cancer Survivorship After COVID-19: Psychological Burden, Symptom Experience, and Social Support
by Anna Tsiakiri, Pinelopi Vlotinou, Konstantinos Tzanas, Despoina Chrisostomidou, Sevasti Chatzifotiou, Maria Lavdaniti and Evangeli Bista
Medicina 2026, 62(8), 1475; https://doi.org/10.3390/medicina62081475 - 30 Jul 2026
Viewed by 238
Abstract
Background and objectives: Cancer survivors continue to face significant psychological and quality-of-life challenges following the COVID-19 pandemic. This study aimed to investigate levels of depression, anxiety, stress, quality of life, and perceived social support among patients with cancer during the post-COVID-19 period [...] Read more.
Background and objectives: Cancer survivors continue to face significant psychological and quality-of-life challenges following the COVID-19 pandemic. This study aimed to investigate levels of depression, anxiety, stress, quality of life, and perceived social support among patients with cancer during the post-COVID-19 period and to examine their interrelationships. Materials and Methods: A cross-sectional study was conducted among 162 Greek adults with cancer. Participants completed questionnaires assessing psychological distress (Depression Anxiety Stress Scale-21), health-related quality of life (EORTC QLQ-C30), and perceived social support. Descriptive statistics, factor analysis, group comparisons, and correlation analyses were performed. Results: High levels of psychological distress were observed, with 32.1% of participants reporting severe or extremely severe depression, 40.1% severe or extremely severe anxiety, and 29.0% severe or extremely severe stress. Quality of life was moderate, with emotional and social functioning being the most impaired domains, while fatigue, insomnia, and financial difficulties were the most prominent symptoms. Depression, anxiety, and stress were strongly associated with poorer quality of life and greater symptom burden. Higher perceived social support, particularly from family and friends, was associated with better quality of life and lower psychological distress. Conclusions: These findings highlight the need for comprehensive oncology care that incorporates routine psychological assessment and psychosocial support to improve cancer survivorship outcomes. Full article
(This article belongs to the Special Issue Palliative Care in Oncology: Innovations and Challenges)
17 pages, 4551 KB  
Article
Determinants and Consequences of Long Impact of COVID-19: A National Cross-Sectional Study in Saudi Arabia
by Abdulaziz Alshomrani, Anum S. Hussaini and Elhadi Miskeen
J. Clin. Med. 2026, 15(15), 5902; https://doi.org/10.3390/jcm15155902 - 28 Jul 2026
Viewed by 416
Abstract
Background: The post-acute consequences of prolonged Coronavirus Disease 2019 (COVID-19) infection are a major public health problem characterized by long-lasting, multisystem manifestations. There is limited evidence from Saudi Arabia, particularly from nationally representative studies using standard case definitions. Objective: This study aimed to [...] Read more.
Background: The post-acute consequences of prolonged Coronavirus Disease 2019 (COVID-19) infection are a major public health problem characterized by long-lasting, multisystem manifestations. There is limited evidence from Saudi Arabia, particularly from nationally representative studies using standard case definitions. Objective: This study aimed to estimate the prevalence of Long COVID, characterize its symptoms, identify risk factors, and assess disease burden and healthcare utilization among Saudi adults. Methods: Between June 2023 and December 2024, we conducted a national cross-sectional mixed-methods study among 1790 adults with PCR-confirmed COVID-19 infection in all 13 regions of Saudi Arabia. Long COVID was defined using the WHO consensus case definition (symptoms persisting ≥ 3 months post-infection not attributable to alternative diagnoses). Results: The prevalence of Long COVID was 32.0% (95% CI 29.8–34.3). The most common symptoms were fatigue (68%), dyspnea (45%), and cognitive impairment (39%). Independent predictors included female sex (adjusted odds ratio [aOR] 1.8, 95% CI 1.4–2.3), moderate-to-severe acute infection (aOR 2.5, 95% CI 2.0–3.1), incomplete vaccination (aOR 1.6, 95% CI 1.2–2.1), metabolic disorders (aOR 1.6, 95% CI 1.2–2.1), and obesity (aOR 1.5, 95% CI 1.2–1.9). Among Long COVID patients, 41% required specialty care and 12% reported work disability. Conclusions: Long COVID affects approximately one-third of COVID-19 survivors in Saudi Arabia, imposing a significant healthcare and socioeconomic burden. These findings highlight the need for swift action and policy implementation within the health care system to mitigate long-term consequences. Full article
(This article belongs to the Section Infectious Diseases)
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22 pages, 2101 KB  
Article
Safety and Immunogenicity of an Additional Dose of Thailand Government Pharmaceutical Organization (GPO) Inactivated NDV-HXP-S COVID-19 Vaccine (HXP-GPOVac) Administered After Primary Vaccination with HXP-GPOVac or BNT162b2: An Open-Label Phase II Extension Trial in Thai Adults
by Prabda Praphasiri, Darunee Ditsungneon, Anusak Kerdsin, Sutthichai Nakphook, Jiraphut Kittiwatanachod, Kanlaya Sornwong, Suriya Naosri, Sarunpattori Khunarsa, Ponthip Wirachwong, Isariya Techatanawat, Piengthong Narakorn, Somchaiya Surichan, Jorge Flores, Laina D. Mercer, Christina S. Polyak, Bruce L. Innis, Rama Raghunandan, Chakrarat Pittayawonganon, Sopon Iamsirithaworn, Supakit Sirilak and Kriengkrai Prasertadd Show full author list remove Hide full author list
Vaccines 2026, 14(8), 660; https://doi.org/10.3390/vaccines14080660 - 28 Jul 2026
Viewed by 311
Abstract
Background/Objectives: Waning immunity after primary COVID-19 vaccination supports evaluation of additional doses. HXP-GPOVac is an egg-based, inactivated Newcastle disease virus (NDV)-vectored vaccine expressing a prefusion-stabilized SARS-CoV-2 HexaPro spike antigen. We evaluated the safety, tolerability, and immunogenicity of a single additional 10 µg dose [...] Read more.
Background/Objectives: Waning immunity after primary COVID-19 vaccination supports evaluation of additional doses. HXP-GPOVac is an egg-based, inactivated Newcastle disease virus (NDV)-vectored vaccine expressing a prefusion-stabilized SARS-CoV-2 HexaPro spike antigen. We evaluated the safety, tolerability, and immunogenicity of a single additional 10 µg dose of HXP-GPOVac administered to adults previously primed with two doses of either HXP-GPOVac or BNT162b2. Methods: Study GPO NDV-HXP-S 203 was an open-label phase II extension enrolling adults (18–75 years) who previously completed a two-dose primary series in Study 202 with either HXP-GPOVac or BNT162b2 (Pfizer–BioNTech; Comirnaty). All participants received a single additional 10 µg intramuscular dose of HXP-GPOVac ≥ 6 months after their second primary dose. Solicited local/systemic adverse events (AEs) were recorded for 7 days, unsolicited AEs through Day 28, and serious AEs (SAEs) and adverse events of special interest (AESIs) throughout follow-up. Neutralizing antibody titers (pseudovirus 50% neutralization titer, NT50) and anti-spike IgG (BAU/mL) were assessed pre-dose (Day 1) and post-vaccination through 12 months; a predefined subset underwent IFN-γ and IL-5 ELISpot. SARS-CoV-2 infection during follow-up was assessed using anti-nucleocapsid (anti-N) IgG. Symptomatic COVID-19 was identified through symptom-reported, symptom-triggered RT-PCR testing; sequencing was performed when feasible. Results: All 219 participants received HXP-GPOVac (167 primed with HXP-GPOVac and 52 with BNT162b2). Any solicited local reaction occurred in 22.2% (37/167) of HXP-GPOVac-primed and 26.9% (14/52) of BNT162b2-primed participants; any solicited systemic reaction occurred in 10.8% (18/167) and 13.5% (7/52), respectively. No vaccine-related unsolicited AEs or AESIs were reported. Three deaths occurred during the 12-month follow-up; one (a sudden cardiac death in an HXP-GPOVac-primed participant) was assessed by the safety medical team as possibly related to vaccination, and two were assessed as not related. Neutralizing antibody GMTs increased from 46.33 at baseline to 1569.04 at Day 15 in HXP-GPOVac-primed participants and from 77.25 to 841.34 in BNT162b2-primed participants; corresponding SCRs were 78.8% and 76.9%. Anti-spike IgG GMCs increased from 48.79 to 1480.14 BAU/mL and from 194.48 to 1547.88 BAU/mL, respectively. Responses declined over time but remained above baseline through 12 months. In the cellular immunity subset, post-vaccination IFN-γ responses increased, with comparatively modest IL-5 responses and no pattern suggestive of Th2 predominance. Conclusions: A single additional dose of HXP-GPOVac administered ≥6 months after primary vaccination with HXP-GPOVac or BNT162b2 was generally well tolerated and elicited robust recall humoral responses, with supportive findings of cellular immunity. Trial registration: Thai Clinical Trials Registry, TCTR20230213001. Full article
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8 pages, 210 KB  
Commentary
Beyond Fatigue: The Fatigue Assessment Scale as a Potential Indicator of Long COVID Severity
by Giulia Del Duca, Marta Franco, Lorenzo Talamanca, Andrea Antinori and Marta Camici
J. Clin. Med. 2026, 15(15), 5878; https://doi.org/10.3390/jcm15155878 - 28 Jul 2026
Viewed by 251
Abstract
Patient-reported outcomes (PROs) are often regarded in clinical practice as less reliable than biomarkers because they are patient-dependent and not objectively measurable in the same way as circulating molecules or imaging findings. This view may be reductive. Biomarkers are frequently considered reliable because [...] Read more.
Patient-reported outcomes (PROs) are often regarded in clinical practice as less reliable than biomarkers because they are patient-dependent and not objectively measurable in the same way as circulating molecules or imaging findings. This view may be reductive. Biomarkers are frequently considered reliable because they are easily quantifiable, yet biological meaning does not depend solely on measurement. In precision and personalized medicine, the absolute level of a circulating hormone, cytokine, or metabolite is often insufficient unless interpreted in relation to how a given patient, at a given time, responds to that molecular signal. If biomarkers are considered less absolute and more context-dependent, the relevance of PROs becomes clearer. Standardized PROs capture the subjective impact of disease on the patient system in a reproducible and clinically interpretable manner. This is particularly relevant in Long COVID, where no validated diagnostic biomarker is currently available, and severity stratification cannot rely exclusively on objective biological measures. Among available tools, the Fatigue Assessment Scale (FAS) may be particularly useful for quantifying the fatigue burden in Long COVID, including both physical and mental components. Moreover, FAS scores have been shown to correlate with the number of symptoms reported by patients, suggesting that this scale may help stratify patients not only according to fatigue severity but also according to overall symptom burden. Greater standardization of clinical characterization through instruments such as the FAS may improve comparability across cohorts and facilitate interpretation of data from different clinical trials. Full article
12 pages, 514 KB  
Article
Adverse Events in Following Immunization with Inactivated SARS-CoV-2 Vaccines (TURKOVAC and CoronaVac) in PCR-Positive Asymptomatic or Mildly Symptomatic Individuals Compared to PCR-Negative Recipients
by Ateş Kara, İhsan Ateş, Sebahat Tekcan, Seçil Uysal, Yüksel Hakan Aydoğmuş, Mine Durusu Tanrıöver, Aykut Özdarendeli, Erdogan Oz and Muhammed Emin Demirkol
Vaccines 2026, 14(8), 657; https://doi.org/10.3390/vaccines14080657 - 27 Jul 2026
Viewed by 215
Abstract
Background/Objectives: COVID-19 vaccines may be given without requiring a negative test or absence of symptoms; however, this recommendation needs further safety evaluation. This study aimed to compare the adverse events following immunization (AEFI) between PCR-positive (asymptomatic/mildly symptomatic) and PCR-negative individuals at the [...] Read more.
Background/Objectives: COVID-19 vaccines may be given without requiring a negative test or absence of symptoms; however, this recommendation needs further safety evaluation. This study aimed to compare the adverse events following immunization (AEFI) between PCR-positive (asymptomatic/mildly symptomatic) and PCR-negative individuals at the time of vaccination, with a secondary objective of comparing the two vaccines (TURKOVAC and CoronaVac). Methods: This descriptive study was a secondary analysis of phase III clinical trials. Individuals who were positive for SARS-CoV-2 PCR at the time of vaccination constituted the PCR(+) group and those who tested negative or became positive after the 4th day following vaccination constituted the PCR(−) group. Whether participants had a history of COVID-19 was not considered. Results: Data from 5207 individuals were analyzed. AEFIs were more frequent in the PCR(+) group than PCR(−) group: site pain (24.5% vs. 16.7%, p < 0.001), arm pain (9.5% vs. 7.8%, p = 0.008), headache (14.8% vs. 10.0%, p < 0.001), fatigue (14.5% vs. 8.9%, p < 0.001), myalgia (12.3% vs. 7.5%, p < 0.001), sore throat (11.9% vs. 8.1%, p < 0.001), cough (7.9%; 11.1% vs. 6.9%, p < 0.001). These AEFIs were more frequent in the PCR(+) group with both vaccine groups separately. The distribution of AEFIs over time followed similar patterns in PCR(+) and PCR(−) individuals. Local AEFIs were slightly more common with the TURKOVAC, systemic AEFIs with the CoronaVac. Conclusions: While AEFIs were more common among PCR(+) group, they were mild, tolerable, and easily manageable. Our results support the suggestion that routine PCR testing prior to vaccination may not be warranted solely to mitigate concerns about anticipated adverse events. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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32 pages, 759 KB  
Systematic Review
The Impact of Pulmonary Rehabilitation in Patients with Post-COVID-19 Syndrome: A Systematic Review
by Vlad-Florin Oiegar, Cristina Călărașu, Paraschiva Postolache, Constantin Ghimuș, Mara-Amalia Bălteanu, Simona Pătru, Dănuț Caimac, Ana Maria Bumbea, Simona-Maria Roșu and Ionela Alina Croitoru
Med. Sci. 2026, 14(4), 443; https://doi.org/10.3390/medsci14040443 - 27 Jul 2026
Viewed by 256
Abstract
Background: Post-COVID-19 syndrome represents a global health problem, manifesting with persistent multiple organ symptoms, including respiratory ones. This review aimed to evaluate the efficacy of different pulmonary rehabilitation interventions in the management of the disease, including its particularities. Methods: This systematic review was [...] Read more.
Background: Post-COVID-19 syndrome represents a global health problem, manifesting with persistent multiple organ symptoms, including respiratory ones. This review aimed to evaluate the efficacy of different pulmonary rehabilitation interventions in the management of the disease, including its particularities. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) statement and prospectively registered in the PROSPERO database (CRD420261292824). PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 2021 to January 2026. Two reviewers independently screened studies, extracted data, and assessed methodological quality using the Cochrane Risk of Bias 2 (RoB 2) tool. Twenty randomized controlled trials involving 2101 adult patients with post-COVID-19 syndrome met the eligibility criteria and were included in the qualitative synthesis. Results: Pulmonary rehabilitation (PR) demonstrated significant improvements in exercise capacity, with notable increases in 6MWT and VO2max. Respiratory and peripheral muscle strength significantly increased. The quality of life, dyspnea and fatigue consistently improved. The results for intrinsic pulmonary function, anxiety, and depression were heterogeneous, suggesting benefits more related to reconditioning. Conclusions: Pulmonary rehabilitation is an essential and efficient component in post-COVID-19 syndrome, improving physical function, respiratory and peripheral muscle strength, the quality of life, fatigue and dyspnea. Telerehabilitation is a viable alternative. Adapting protocols is crucial, recognizing that most benefits derive from physical reconditioning and muscle training, not necessarily from major structural pulmonary changes. Full article
(This article belongs to the Section Pneumology and Respiratory Diseases)
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13 pages, 2204 KB  
Article
Mediterranean Diet, Redox Biomarkers, and Body Composition in ICU Post-COVID-19 Patients
by Fernandes Daieni, Berbigier Marina Carvalho, Soares Cássia Medino, Spritzer Poli Mara, Marschner Rafael Aguiar, Wajner Simone Magagnin, Ferreira Samanta Catherine and Dall Alba Valesca
Nutrients 2026, 18(15), 2420; https://doi.org/10.3390/nu18152420 - 24 Jul 2026
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Abstract
Background: Post-COVID-19 condition (PCC) remains a public health concern due to persistent metabolic and inflammatory alterations, especially among ICU survivors. Oxidative stress is involved in PCC pathophysiology, and the Mediterranean diet may be associated with redox balance. Objective: To evaluate the [...] Read more.
Background: Post-COVID-19 condition (PCC) remains a public health concern due to persistent metabolic and inflammatory alterations, especially among ICU survivors. Oxidative stress is involved in PCC pathophysiology, and the Mediterranean diet may be associated with redox balance. Objective: To evaluate the association between Mediterranean diet adherence (main exposure variable) and oxidative stress/redox stress biomarkers (primary outcomes) in ICU survivors with persistent symptoms after severe COVID-19. Additionally, body composition and inflammatory markers were explored as secondary outcomes related to redox status. Methods: This cross-sectional study included 123 adult ICU survivors with PCC (51 ± 13.2 years; 53% men; 75% with obesity). Protein carbonyls, TBARS, sulfhydryl groups, glutathione, CRP, albumin, and IL-6 were measured. Diet adherence during post-COVID-19 outpatient follow-up was assessed using MEDAS, and body composition by DXA. Participants were categorized by the median score, and Poisson regression models were applied. Results: The median MEDAS total score was 4 (IQR 2–5), indicating overall low adherence to the Mediterranean diet. Lower adherence was associated with higher glutathione levels (p = 0.04), with no differences in pro-oxidant markers. Higher sulfhydryl levels were associated with lower body fat, higher appendicular skeletal muscle mass, and lower CRP and IL-6. Conclusions: Low adherence was frequent and associated with antioxidant differences. Redox status was also associated with body composition and inflammatory markers. Full article
(This article belongs to the Section Clinical Nutrition)
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24 pages, 1555 KB  
Review
Blood–Brain Barrier Changes and Related Microvascular Outcomes in Long-COVID: A Comprehensive Review
by Marcella Chagas-Sena, Wei Ling Lau, Thomas Edward Lane, Paola Cristina Resende and Ane Claudia Fernandes Nunes
Life 2026, 16(8), 1227; https://doi.org/10.3390/life16081227 - 24 Jul 2026
Viewed by 1509
Abstract
Caused by the SARS-CoV-2 virus, the COVID-19 pandemic is still considered a complex challenge, with manifestations not only of respiratory issues, but also conditions related to chronic cerebrovascular damage. Endothelial biomarkers, neuropathological and neuroimaging findings indicate endothelial dysfunction, microthrombosis, and disruption of the [...] Read more.
Caused by the SARS-CoV-2 virus, the COVID-19 pandemic is still considered a complex challenge, with manifestations not only of respiratory issues, but also conditions related to chronic cerebrovascular damage. Endothelial biomarkers, neuropathological and neuroimaging findings indicate endothelial dysfunction, microthrombosis, and disruption of the blood–brain barrier (BBB) are central mechanisms for acute and chronic ischemic and hemorrhagic cerebral events. Understanding these mechanisms is vital to reducing their impact on population health, whether through treatment or prevention of adverse outcomes. The objective of this study is to perform a review of the scientific literature on the post-infection effects of SARS-CoV-2 affecting the cerebral endothelium and the BBB, correlating them with potential clinical outcomes. Material and Methods: Analysis of studies extracted from the PubMed database using the following terms: Long-COVID “AND” SARS-CoV-2 “AND” blood–brain barrier. Inclusion criteria: keywords, publications related to the topic, and primary studies published after peer review. Exclusion criteria: preprint studies, publication outside of the timeframe 2020–2025, study design not compatible with this research, and full text not available. Results: An initial 121 studies were identified, of which 105 were excluded due to not meeting all inclusion criteria and 6 studies were inaccessible due to not being in the English language and full-text access limitations. Fifteen articles were included in the analysis, for topics as expression of viral receptors in the endothelium, markers of their activation, cerebral microvascular injury and coagulopathies. To clarify the pathogenic cascade, the evidence was stratified by biological model where in vitro evidence demonstrates that the Spike protein induces direct endothelial toxicity and platelet aggregation, establishing the primary molecular insult. Animal models confirm the translation of this insult into structural degradation of the BBB and pericyte loss. Clinically, infection-phase findings, characterized by multifocal microthrombosis and permeability spikes, act as the determining event that predisposes to the persistent neuroinflammatory environment. Biomarkers of BBB disruption and neuronal damage were consistently reported, with persistence of BBB dysfunction modifying risk stratification and rehabilitation efforts. Reported cases of Long-COVID demonstrated normalization of BBB markers without correlation with long-term symptoms, suggesting that other mechanisms are involved in Long-COVID. Conclusion: Cerebral endotheliopathies and BBB dysfunction in patients with COVID-19 continue to impact the health of the population. The scientific literature indicates that SARS-CoV-2 induces cerebral endothelial injury, BBB disruption, and an increased risk of vascular events related to endotheliopathy, inflammation, and hypercoagulability. Understanding the impact of COVID-19 pathology on the population and developing prospective studies is essential to quantify the prevalence and mechanisms of brain injury. The identification of molecular targets and infection pathways are promising toward defining both preventive and therapeutic strategies to improve outcomes in the Long-COVID population. Full article
(This article belongs to the Special Issue Outlook for Cerebrovascular Damage Research)
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