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19 pages, 2170 KB  
Article
Long COVID Syndrome Prevalence in 2025 in an Integral Healthcare Consortium in the Metropolitan Area of Barcelona: Persistent and Transient Symptoms
by Antonio Arévalo-Genicio, Mª Carmen García-Arqué, Marta Gragea-Nocete, Maria Llistosella, Vanessa Moro-Casasola, Cristina Pérez-Díaz, Anna Puigdellívol-Sánchez and Ramon Roca-Puig
Vaccines 2025, 13(9), 905; https://doi.org/10.3390/vaccines13090905 - 26 Aug 2025
Abstract
Background: Long COVID can persist for years, but little is known about its prevalence in relation to the number of infections. This study examines the prevalence of long COVID in association with the number of infections and vaccination status. Methods: We analyzed anonymized [...] Read more.
Background: Long COVID can persist for years, but little is known about its prevalence in relation to the number of infections. This study examines the prevalence of long COVID in association with the number of infections and vaccination status. Methods: We analyzed anonymized data on long COVID cases, thrombotic events and polypharmacy from March 2020, provided by the Data Analysis Control Department for the population assigned to the CST (192,651 at March 2025). Additionally, we analyzed responses to a long COVID symptom-specific survey distributed in March 2024 to individuals aged 18 to 75 years from the CST population diagnosed with COVID-19 as of December 2023 (n = 43,398; 3227 respondents). Symptomatic patients suspected of having long COVID underwent blood tests to exclude alternative diagnoses. Results: The overall detected prevalence of long COVID was 2.4‰, with higher frequency among women aged 30–59 years (p < 0.001). The survey, combined with specific blood tests, improved detection rates by 26.3%. Long COVID prevalence was 3–10 times higher in individuals with three or more infections than in those with only one recorded infection (based on survey/CST data, respectively). The absolute number of thrombotic events among individuals aged >60 doubled from 2020 to 2024, occurring in both vaccinated and unvaccinated individuals, as well as in those with or without prior documented COVID-19 infection, including in patients without chronic treatments. Conclusions: We found a link between SARS-CoV-2 reinfection and long COVID, and a post-pandemic rise in thrombotic events across all populations, regardless of vaccination or prior infection. Findings support continued COVID-19 diagnosis in suspected cases and mask use by healthcare workers treating respiratory patients. Full article
(This article belongs to the Section Epidemiology and Vaccination)
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14 pages, 762 KB  
Article
COVID-19 and COVID-19 Vaccinations Lead to Serological Responses in Patients with Inflammatory Bowel Diseases Independent of the Type of Immunomodulatory Medication
by Larissa Kunoff, Martin Kreysing and Annika Gauss
Biomedicines 2025, 13(9), 2072; https://doi.org/10.3390/biomedicines13092072 - 26 Aug 2025
Abstract
Background/Objectives: The COVID-19 pandemic and the development of vaccines provided the opportunity to monitor disease prevalence and outcomes, vaccinations, their side effects and serological responses in patients with inflammatory bowel disease (IBD). Methods: IBD patients of the outpatient clinic at the [...] Read more.
Background/Objectives: The COVID-19 pandemic and the development of vaccines provided the opportunity to monitor disease prevalence and outcomes, vaccinations, their side effects and serological responses in patients with inflammatory bowel disease (IBD). Methods: IBD patients of the outpatient clinic at the University Hospital Heidelberg who completed at least one questionnaire on COVID-19 and related vaccinations from July 2021 to August 2022 were included. Spike-IgG antibody titres were determined. Friedman tests, Wilcoxon signed-rank tests and Kruskal–Wallis tests were used for comparisons. The influence of IBD therapy was analysed using linear models with mixed effects. Results: The cohort included 520 patients (269 females, mean age = 45.3 years, 60.6% with Crohn’s disease, 35.4% with ulcerative colitis, and 4.0% with unclassified IBD). Four hundred eighty patients (92.3%) received at least one COVID-19 vaccination, and 154 patients (29.6%) were infected by SARS-CoV-2. Among all of them, 94.4% achieved seroconversion. Triple-vaccinated patients with additional SARS-CoV-2 infection developed the highest serological responses (χ2 = 16.51, p < 0.001, df = 3). An antibody decay over time was observed after the second (p < 0.001) and third vaccinations (p < 0.001). Regarding individual IBD medications, no differences in mean titres were found after two (χ2 = 6.60, p = 0.36, df = 6) versus three vaccinations (χ2 = 4.97, p = 0.42, df = 5). Linear models with mixed effects revealed no influence of IBD therapies on serological responses. Conclusions: The highest serological responses were observed in IBD patients after three vaccinations plus SARS-CoV-2 infection without significant differences between IBD therapies. Full article
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15 pages, 1151 KB  
Article
Humoral Immune Response Following COVID-19 Vaccination in Multifocal Motor Neuropathy and Chronic Inflammatory Demyelinating Polyneuropathy
by Louise Sloth Kodal, Sonja Holm-Yildiz, Sebastian Rask Hamm, Laura Pérez-Alós, Cecilie Bo Hansen, Mia Marie Pries-Heje, Line Dam Heftdal, Rasmus Bo Hasselbalch, Johannes Roth Madsen, Ruth Frikke-Schmidt, Linda Maria Hilsted, Erik Sørensen, Sisse Rye Ostrowski, Henning Bundgaard, Peter Garred, Kasper Iversen, Susanne Dam Nielsen, John Vissing and Tina Dysgaard
Vaccines 2025, 13(9), 902; https://doi.org/10.3390/vaccines13090902 - 26 Aug 2025
Abstract
Background/Objectives: Multifocal Motor Neuropathy (MMN) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) are immune-mediated polyneuropathies often treated with immunoglobulin therapy. They were prioritized for COVID-19 vaccination during the pandemic. However, their immune response following COVID-19 vaccination remains unclear. We investigated short- and long-term immune [...] Read more.
Background/Objectives: Multifocal Motor Neuropathy (MMN) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) are immune-mediated polyneuropathies often treated with immunoglobulin therapy. They were prioritized for COVID-19 vaccination during the pandemic. However, their immune response following COVID-19 vaccination remains unclear. We investigated short- and long-term immune responses to COVID-19 vaccination in patients with MMN and CIDP compared to controls. Methods: In a prospective observational study, patients with CIDP or MMN and matched controls were followed over 24 months. Controls were age- and sex-matched 1:9. Participants received COVID-19 vaccines in accordance with the Danish vaccination program. Primary outcomes were levels of SARS-CoV-2 IgG antibodies and virus-neutralizing capacity. A positive vaccine response was defined as IgG > 225 AU/mL and neutralizing capacity ≥ 25%. Results: We included 34 patients and 306 matched controls. While baseline SARS-CoV-2 IgG levels were similar, controls exhibited higher IgG levels at 6- (mean difference, 88%; p = 0.008), 18- (91%; p = 0.023), and 24 months (160%; p < 0.001). Neutralization capacity was also higher in controls at 6 (10%, p = 0.004), 18 (7%, p < 0.001), and 24 months (9%, p = 0.002). Despite this, the proportion of vaccine responders did not differ between the two groups after 24 months (p = 0.196). In patients receiving immunoglobulin therapy, IgG levels were lower than in controls at 24-month follow-up alone (56%, p < 0.001); all demonstrated a positive vaccine response. Conclusions: Patients with CIDP and MMN demonstrated a positive humoral response to COVID-19 vaccination. Although IgG and neutralization levels were lower than in controls, all patients receiving immunoglobulin therapy were vaccine responders. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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17 pages, 1420 KB  
Article
Genomic Evolution of SARS-CoV-2 Variants of Concern Under In Vitro Neutralising Selection Pressure Following Two Doses of the Pfizer-BioNTech BNT162b2 COVID-19 Vaccine
by Kerri Basile, Jessica E. Agius, Winkie Fong, Kenneth McPhie, Danny Ko, Linda Hueston, Connie Lam, David Pham, Sharon C.-A. Chen, Susan Maddocks, Matthew V. N. O’Sullivan, Dominic E. Dwyer, Vitali Sintchenko, Jen Kok and Rebecca J. Rockett
Viruses 2025, 17(9), 1161; https://doi.org/10.3390/v17091161 - 25 Aug 2025
Abstract
We aimed to explore SARS-CoV-2 evolution during in vitro neutralisation using next generation sequencing, and to determine whether sera from individuals immunised with two doses of the Pfizer-BioNTech vaccine (BNT162b2) were as effective at neutralising the variant of concern (VOC) Delta (B.1.617.2) compared [...] Read more.
We aimed to explore SARS-CoV-2 evolution during in vitro neutralisation using next generation sequencing, and to determine whether sera from individuals immunised with two doses of the Pfizer-BioNTech vaccine (BNT162b2) were as effective at neutralising the variant of concern (VOC) Delta (B.1.617.2) compared to the earlier lineages Beta (B.1.351) and wild-type (A.2.2) virus. Using a live-virus SARS-CoV-2 neutralisation assay in Vero E6 cells, we determined neutralising antibody titres (nAbT) against three SARS-CoV-2 strains (wild type, Beta, and Delta) in 14 participants (vaccine-naïve (n = 2) and post-second dose of BNT162b2 vaccination (n = 12)), median age 45 years [IQR 29–65]; the median time after the second dose was 21 days [IQR 19–28]. The determination of nAbT was based on cytopathic effect (CPE) and in-house quantitative reverse transcriptase real-time quantitative polymerase chain reaction (RT-qPCR) to confirm SARS-CoV-2 replication. A total of 110 representative samples including inoculum, neutralisation breakpoints at 72 h, and negative and positive controls underwent genome sequencing. By integrating live-virus neutralisation assays with deep sequencing, we characterised both functional antibody responses and accompanying viral genetic changes. There was a reduction in nAbT observed against the Delta and Beta VOC compared with wild type, 4.4-fold (p ≤ 0.0006) and 2.3-fold (p = 0.0140), respectively. Neutralising antibodies were not detected in one vaccinated immunosuppressed participant and the vaccine-naïve participants (n = 2). The highest nAbT against the SARS-CoV-2 variants investigated was obtained from a participant who was vaccinated following SARS-CoV-2 infection 12 months prior. Limited consensus level mutations occurred in the various SARS-CoV-2 lineage genomes during in vitro neutralisation; however, consistent minority allele frequency variants (MFV) were detected in the SARS-CoV-2 polypeptide, spike (S), and membrane protein. Findings from countries with high COVID-19 incidence may not be applicable to low-incidence settings such as Australia; as seen in our cohort, nAbT may be significantly higher in vaccine recipients previously infected with SARS-CoV-2. Monitoring viral evolution is critical to evaluate the impact of novel SARS-CoV-2 variants on vaccine effectiveness, as mutational profiles in the sub-consensus genome could indicate increases in transmissibility and virulence or suggest the development of antiviral resistance. Full article
(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology 2.0)
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19 pages, 1262 KB  
Review
Aerobiology of Respiratory Infectious Viruses: Recent Paradoxes, Mechanistic Insights, and Future Perspectives
by Kavita Ghosal and Atin Adhikari
Aerobiology 2025, 3(3), 7; https://doi.org/10.3390/aerobiology3030007 - 25 Aug 2025
Abstract
Since the emergence of SARS-CoV-2, the interplay of human behavior, environmental factors, viral evolution, and public health interventions has resulted in unexpected changes in the timing, intensity, and geography of respiratory virus outbreaks. For example, respiratory syncytial viruses (RSV) exhibited a surge during [...] Read more.
Since the emergence of SARS-CoV-2, the interplay of human behavior, environmental factors, viral evolution, and public health interventions has resulted in unexpected changes in the timing, intensity, and geography of respiratory virus outbreaks. For example, respiratory syncytial viruses (RSV) exhibited a surge during atypical summer months in several countries. Influenza, on the other hand, nearly vanished in the early years of the pandemic, but returned with unusual strength and altered seasonal patterns. Concurrently, new variants of concern in coronaviruses have demonstrated increased airborne transmissibility, greater resilience to environmental conditions, and the ability to evade both natural and vaccine-induced immunity. In this review article, we have synthesized the current understanding of the aerobiology of respiratory infectious viruses, with a particular emphasis on the paradoxical trends observed in recent years. We examined various aspects, including viral morphology and environmental survivability, shifts in seasonality, the drivers of mutation and resistance, and the impact of environmental and climatic factors. Key issues we explored include viral morphology adaptation in response to airborne selective pressures and climate variability influence on the ecology of airborne viruses. Lastly, we investigated future risks and proposed an interdisciplinary framework for monitoring and mitigating airborne viral threats in an ever-changing world. Full article
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15 pages, 1092 KB  
Review
From Acute Carditis, Rheumatic Carditis, and Morphologic Cardiac Reactions to Allergic Angina, Allergic Myocardial Infarction, and Kounis Syndrome: A Multidisciplinary and Multisystem Disease
by Nicholas G. Kounis, Alexandros Stefanidis, Ming-Yow Hung, Uğur Özkan, Cesare de Gregorio, Alexandr Ceasovschih, Virginia Mplani, Christos Gogos, Stelios F. Assimakopoulos, Christodoulos Chatzigrigoriadis, Panagiotis Plotas, Periklis Dousdampanis, Sophia N. Kouni, Grigorios Tsigkas, Nicholas Patsouras, Gianfranco Calogiuri, Soheila Pourmasumi and Ioanna Koniari
J. Cardiovasc. Dev. Dis. 2025, 12(9), 325; https://doi.org/10.3390/jcdd12090325 - 25 Aug 2025
Abstract
This narrative review explains the history of anaphylactic or hypersensitivity reactions, their connection to the cardiovascular system, and Kounis syndrome, which is linked to hypersensitivity. Additional subjects discussed include immunoglobulin E and serum tryptase, common pathways of allergic and nonallergic cardiovascular events, current [...] Read more.
This narrative review explains the history of anaphylactic or hypersensitivity reactions, their connection to the cardiovascular system, and Kounis syndrome, which is linked to hypersensitivity. Additional subjects discussed include immunoglobulin E and serum tryptase, common pathways of allergic and nonallergic cardiovascular events, current perspectives on Kounis syndrome, allergic myocardial infarction, allergic angina, and the impact of COVID-19 and its vaccination on Kounis syndrome. Kounis syndrome is a distinct kind of acute vascular disease that affects the coronary, cerebral, mesenteric, peripheral, and venous systems. Kounis syndrome is currently used to describe coronary symptoms linked to disorders involving mast cell activation and inflammatory cell interactions, such as those involving T-lymphocytes and macrophages, which further induce allergic, hypersensitive, anaphylactic, or anaphylactic insults. Platelet activating factor, histamine, neutral proteases like tryptase and chymase, arachidonic acid products, and a range of cytokines and chemokines released during the activation process are among the inflammatory mediators that cause it. Proinflammatory cytokines are primarily produced by mast cells in COVID-19 infections. Mast cell-derived proteases and eosinophil-associated mediators are also more prevalent in the lung tissues and sera of COVID-19 patients. As a modern global threat to civilization, COVID-19 is linked to chemical patterns that can activate mast cells; therefore, allergic stimuli are usually the reason. Virus-associated molecular patterns can activate mast cells, but allergic triggers are typically the cause. By activating SARS-CoV-2 and other toll-like receptors, a variety of proinflammatory mediators, including IL-6 and IL-1β, are released, potentially contributing to the pathology of COVID-19. Full article
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12 pages, 779 KB  
Article
Epidemiological-Based Study of SARS-CoV-2 in Faisalabad
by Sana Ullah, Muhammad Waseem Khan, Qurat-ul-Ain, Khushbu Farva, Niaz Muhammad Khan and Hayat Ullah
Zoonotic Dis. 2025, 5(3), 23; https://doi.org/10.3390/zoonoticdis5030023 - 25 Aug 2025
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raced around the world across different populations; there needs to be a consolidated effort to understand the divergence of the epidemiology of SARS-CoV-2. Population-based epidemiological characteristics studies measure the extent of SARS-CoV-2 infection in a country. [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raced around the world across different populations; there needs to be a consolidated effort to understand the divergence of the epidemiology of SARS-CoV-2. Population-based epidemiological characteristics studies measure the extent of SARS-CoV-2 infection in a country. The current research study was designed to report epidemiological data from Pakistan. For this purpose, 246 SARS-CoV-2-infected patients were included in the study. For SARS-CoV-2 confirmation, viral samples were collected from all the study participants; SARS-CoV-2 infection was confirmed by viral nucleic acid detection using a nucleic acid detection kit. After SARS-CoV-2 confirmation, all the study participants were interviewed for epidemiological data through a detailed questionnaire. The study results showed that the disease ratio was higher between 30 and 59 years (51.21%) of age. The male ratio (55.28%) was higher compared to the female ratio (44.71%). The patients’ illiteracy and low socioeconomic status were 32.52% and 59.75%, respectively. The majority of the patients (97.56%) had cough, smell or taste disturbance (79.67%), or fever (76.42%), and 70.73% had fatigue. For comorbidities, a higher ratio was observed for diabetes (38.61%), hypertension (36.17%), and respiratory disease (16.26%). The vaccination status analysis revealed that 51.21% of patients had not received routine immunizations, and 65.5% were un-vaccinated against SARS-CoV-2. Notably, not a single patient was vaccinated for influenza vaccine. The current research study concluded that SARS-CoV-2 was more prevalent in individuals who were middle aged, male, and had low socio-economic status. The most common symptoms were cough, smell or taste disturbance, and fever. The patients’ vaccination status highlights a critical gap in preventive healthcare and shows the need to strengthen vaccination awareness and accessibility in the population to reduce vulnerability to future outbreaks. Future research should focus on investigating the impact of COVID-19 outcomes on comorbidities such as diabetes and hypertension. Full article
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4 pages, 312 KB  
Editorial
pDNA Impurities in mRNA Vaccines
by Luca Roncati, Nazha Ghaleb, Joya Ghaleb and Karl Kfoury
Microorganisms 2025, 13(9), 1975; https://doi.org/10.3390/microorganisms13091975 - 24 Aug 2025
Viewed by 99
Abstract
Funded during the emergency phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, messenger RNA (mRNA) vaccines are single-stranded, 5′-capped mRNAs produced using a cell-free in vitro transcription from the corresponding plasmid DNA (pDNA) templates, encoding the viral spike (S) protein [...] Read more.
Funded during the emergency phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, messenger RNA (mRNA) vaccines are single-stranded, 5′-capped mRNAs produced using a cell-free in vitro transcription from the corresponding plasmid DNA (pDNA) templates, encoding the viral spike (S) protein of SARS-CoV-2 [...] Full article
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12 pages, 2421 KB  
Article
Titers of IgG, IgM, and IgA Against SARS-CoV-2 in Healthcare Workers from a General Hospital in Mexico City
by Nelly Raquel González-Arenas, Mariana Dinazar Chavez-Vargas, Hector Prado-Calleros, Juan Pablo Ramírez-Hinojosa, Fernando Martinez-Hernandez, Angélica Olivo-Díaz, Pablo Maravilla, Mirza Romero-Valdovinos and Guillermina Ávila-Ramírez
Diseases 2025, 13(9), 276; https://doi.org/10.3390/diseases13090276 - 22 Aug 2025
Viewed by 127
Abstract
Objectives: The aim of the present study was to better understand the antibody concentrations in healthcare workers (HCWs) from a hospital in Mexico City with a high density of COVID-19 patients. Methods: Up to 243 HCWs were recruited in 2020 and 2022 and [...] Read more.
Objectives: The aim of the present study was to better understand the antibody concentrations in healthcare workers (HCWs) from a hospital in Mexico City with a high density of COVID-19 patients. Methods: Up to 243 HCWs were recruited in 2020 and 2022 and were sorted into three groups: hybrid immunity (HI, natural infection plus vaccination), vaccine-induced immunity (VI), and unvaccinated but RT-qPCR negative at the beginning of the pandemic (UV). Peripheral blood and nasopharyngeal swab samples were obtained; additionally, saliva samples were obtained from the UV group. The titers of IgG, IgM, and IgA against the SARS-CoV-2 receptor-binding domain (RBD) and nucleocapsid (NCP) proteins were assessed using an in-house ELISA, and positivity to the virus was determined via RT-qPCR. Results: Most HI and VI participants were positive for serum anti-RBD IgG (92.8% and 100%, respectively), while 26.6% (for HI) and 19% (for VI) were positive for anti-NCP IgG. Regarding serum anti-RBD IgA, the VI and HI groups had positive rates of 87.3% and 66%, respectively. In contrast, the UV group showed a rate of 5.7% but the positivity for IgA in saliva was higher (52% for RBD and 35% for NCP). In addition, the highest antibody titers were obtained for anti-RBD IgG and IgA in the HI and VI groups, respectively. In saliva, the IgA antibody titer was higher for the RBD antigen (1:1280). Conclusions: These results strengthen our understanding of antibody concentrations in HCWs during two critical years of the pandemic in a general hospital with many COVID-19 patients. Full article
(This article belongs to the Section Infectious Disease)
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16 pages, 3670 KB  
Article
Sex-Specific Longitudinal Changes in Metabolic, Endocrine, Renal, Cardiovascular, and Inflammatory Biomarkers of Vaccinated COVID-19 Survivors: 30-Month Follow-Up Study
by Ceren Gur, Sezen Kumas Solak, Erdal Gundogan, Fatih Pektas and Hafize Uzun
Medicina 2025, 61(9), 1510; https://doi.org/10.3390/medicina61091510 - 22 Aug 2025
Viewed by 123
Abstract
Objectives: Sex-based disparities in COVID-19 outcomes are well-documented, with men experiencing greater acute severity and women showing increased vulnerability to post-viral syndromes. However, longitudinal immunometabolic trajectories in vaccinated individuals remain underexplored. In this study, sex-based differences in long-term metabolic, endocrine, renal, cardiovascular, [...] Read more.
Objectives: Sex-based disparities in COVID-19 outcomes are well-documented, with men experiencing greater acute severity and women showing increased vulnerability to post-viral syndromes. However, longitudinal immunometabolic trajectories in vaccinated individuals remain underexplored. In this study, sex-based differences in long-term metabolic, endocrine, renal, cardiovascular, and inflammatory responses were investigated among vaccinated individuals recovering from SARS-CoV-2 infection. Methods: This retrospective single-center cohort study included 426 adults (199 females, 227 males) with PCR-confirmed symptomatic COVID-19 and at least two vaccine doses. Serial assessments were conducted at baseline, 18-, 24-, and 30-month post-infection. Parameters included fasting glucose, HbA1c, lipid profile, thyroid function, renal markers, CRP, D-dimer, fibrinogen, troponin, and hematologic indices. Statistical analyses assessed longitudinal changes and sex-stratified correlations. Results: Fasting glucose and HbA1c levels significantly declined over time, more prominently in males. Glucose correlated with age and BMI only in females. Lipid levels remained largely unchanged, although males had higher baseline triglycerides. Females showed rising TSH levels and persistently lower free T3; males exhibited higher creatinine, urea, and troponin levels throughout. Inflammatory markers declined significantly in both sexes, with males displaying higher CRP and troponin, and females showing sustained fibrinogen elevation and a temporary lymphocyte surge. D-dimer was elevated in females at the 30-month point. Conclusions: Sex-specific physiological recovery patterns were evident among vaccinated COVID-19 survivors. Males exhibited earlier metabolic and cardiac alterations, while females had more persistent endocrine and inflammatory shifts. These findings underscore the need for sex-tailored long-term monitoring strategies prioritizing early metabolic and cardiac screening in men and prolonged immunoendocrine surveillance in women. Full article
(This article belongs to the Section Epidemiology & Public Health)
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20 pages, 3581 KB  
Article
Long-Term Durability and Variant-Specific Modulation of SARS-CoV-2 Humoral and Cellular Immunity over Two Years
by Lilia Matei, Mihaela Chivu-Economescu, Laura Denisa Dragu, Camelia Grancea, Coralia Bleotu, Raluca Hrișcă, Corneliu Petru Popescu, Carmen C. Diaconu and Simona Maria Ruţă
Int. J. Mol. Sci. 2025, 26(16), 8106; https://doi.org/10.3390/ijms26168106 - 21 Aug 2025
Viewed by 283
Abstract
There is an increasing need to understand the long-term dynamics and quality of SARS-CoV-2 immune memory—both humoral and cellular—particularly with emerging variants. This study aimed to evaluate immune durability and variant-specific modulation through a longitudinal analysis of individuals with diverse SARS-CoV-2 exposure histories, [...] Read more.
There is an increasing need to understand the long-term dynamics and quality of SARS-CoV-2 immune memory—both humoral and cellular—particularly with emerging variants. This study aimed to evaluate immune durability and variant-specific modulation through a longitudinal analysis of individuals with diverse SARS-CoV-2 exposure histories, over two years after infection and/or vaccination. The study involved assessing anti-spike IgG and IgA levels over time and analyzing their relationship with neutralizing activity against both ancestral and Omicron SARS-CoV-2 variants. Persistence of T cell responses was evaluated using intracellular cytokine staining (ICS) and activation-induced marker (AIM) assays. Anti-S IgG levels remained stable over time and increased after each immune stimulation, suggesting cumulative immune memory. Neutralizing capacity correlated strongly with IgG levels, showing long-term stability for pre-Omicron variants, but a moderate decline for Omicron. CD4+ and CD8+ T cell responses persisted across all groups, largely unaffected by Omicron mutations. However, cytokine profiles revealed subtle, variant-dependent changes. These findings underscore the durability of cellular immunity and the comparatively reduced robustness of Omicron-specific humoral responses. Such insights are crucial for understanding long-term protection against evolving SARS-CoV-2 variants and guiding public health strategies. Full article
(This article belongs to the Special Issue COVID-19: Molecular Research and Novel Therapy)
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10 pages, 545 KB  
Article
Anti-SARS-CoV-2 Antibodies in Urine of Individuals Vaccinated with Janssen AD26.COV2.S COVID-19 Vaccine
by Marina F. N. Melo, Rômulo C. D. Lira, Raquel S. B. Câmara, Isabela A. G. Pereira, Fernanda F. Ramos, Carolina S. F. Costa, Laura F. Amorim, Quezia D. Teixeira, Flávio G. da Fonseca, Vandack Nobre, Flavia G. F. Ferreira, Jorge Pinto, Eduardo A. F. Coelho, Fernanda Ludolf and Júlia F. M. Caporali
Pathogens 2025, 14(8), 827; https://doi.org/10.3390/pathogens14080827 - 21 Aug 2025
Viewed by 265
Abstract
Urine-based immunoassay is a non-invasive method with demonstrated utility in detecting anti-SARS-CoV-2 antibodies in unvaccinated patients with COVID-19. To evaluate urine’s potential for serological surveys in a real-world setting, SARS-CoV-2 serology was performed on urine samples from vaccinated individuals, both with and without [...] Read more.
Urine-based immunoassay is a non-invasive method with demonstrated utility in detecting anti-SARS-CoV-2 antibodies in unvaccinated patients with COVID-19. To evaluate urine’s potential for serological surveys in a real-world setting, SARS-CoV-2 serology was performed on urine samples from vaccinated individuals, both with and without prior confirmed COVID-19. (1) Methods: An in-house indirect ELISA was used to measure antibodies against recombinant spike (S) and nucleocapsid (N) proteins of SARS-CoV-2 in urine and paired serum from 149 individuals vaccinated with Janssen AD26.COV2.S, an S protein-based COVID-19 vaccine. (2) Results: Anti-S and anti-N levels were higher in the urine and serum of participants with confirmed prior COVID-19 compared to those without prior infection. Urinary anti-S effectively distinguished vaccinated individuals with (AUC = 0.96) and without (AUC = 0.88) prior infection from negative controls (non-vaccinated, non-previously infected individuals) (p < 0.0001). Among vaccinated participants, urinary anti-S and anti-N identified prior infection, with AUC values of 0.73 (p < 0.0001) and 0.60 (p = 0.03), respectively, being recorded. (3) Conclusions: Findings indicate that urinary anti-SARS-CoV-2 antibodies reflect AD26.COV2.S vaccination and previous COVID-19. To further advance the methodology, studies with larger sample sizes and a greater diversity of COVID-19 vaccines are required. Full article
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11 pages, 807 KB  
Article
Human Metapneumovirus Infection in Adults and Its Role in Differential Diagnosis of COVID-19
by Lerzan Dogan, Neval Yurtturan Uyar and Sesin Kocagoz
COVID 2025, 5(8), 137; https://doi.org/10.3390/covid5080137 - 20 Aug 2025
Viewed by 131
Abstract
Introduction: Human metapneumovirus (HMPV), though commonly perceived as a pediatric pathogen, significantly impacts adults, yet its role in acute respiratory tract infections (ARTIs) remains underappreciated. The COVID-19 pandemic has reshaped respiratory virus epidemiology and amplified the need for comprehensive differential diagnosis. This study [...] Read more.
Introduction: Human metapneumovirus (HMPV), though commonly perceived as a pediatric pathogen, significantly impacts adults, yet its role in acute respiratory tract infections (ARTIs) remains underappreciated. The COVID-19 pandemic has reshaped respiratory virus epidemiology and amplified the need for comprehensive differential diagnosis. This study aimed to comprehensively investigate the prevalence, clinical characteristics, and post-COVID-19 trends of HMPV infection in adults and to elucidate its critical role in the differential diagnosis of ARTIs by distinguishing it from other common viral pathogens. Methods: This was a retrospective, multicenter study conducted across six hospitals within the Acibadem Hospitals Group in Istanbul, Turkey. Data were collected from two periods: January 2016 to January 2020 (pre-COVID-19) and January 2021 to September 2023 (post-COVID-19), excluding the peak pandemic phase (March 2020 to May 2021). Respiratory samples (sputum, BAL, nasopharyngeal/nasal/throat swabs) were analyzed using multiplex PCR (Seegene RV12-ACE), with an expanded panel including SARS-CoV-2 in the post-COVID-19 era. Demographic data, comorbidities, symptoms, hospitalization, and ICU admission rates were collected. Results: In the post-COVID-19 period, 2197 positive viral panels were recorded, an increase from 1357 in the pre-COVID period, reflecting enhanced testing. HMPV prevalence reached 9.7% post-COVID-19, making it the fourth most common respiratory virus in adults (8.7% of 644 positive adult tests), following SARS-CoV-2 (26.4%), influenza A (21.3%), and rhinovirus (17.5%). The average age of HMPV-infected adults was 52.14 years (18–90 years); 64% were female. While 52% had no comorbidities, common underlying conditions included hypertension (24%), cancer (12%), and diabetes (10%). Weakness (34%), lower respiratory symptoms (16%), and fever (12%) were frequent. A significant proportion of HMPV patients required hospitalization (34%) and ICU admission (18%), with 40% receiving antibiotics. Despite potential severity, the mortality rate was low (2.8%). No significant difference in severity was observed between HMPV monoinfection and co-infected groups (e.g., with influenza A, rhinovirus, SARS-CoV-2, parainfluenza virus 2). Conclusion: Our findings establish HMPV as a significant and increasingly prevalent respiratory pathogen among adults in Istanbul in the post-COVID-19 era. Its non-specific clinical presentation underscores the critical importance of multiplex PCR for accurate differential diagnosis, enabling appropriate patient management and antimicrobial stewardship. While HMPV can lead to severe outcomes requiring hospitalization and ICU admission, particularly in patients with comorbidities, the overall mortality rate remains low. Given the lack of specific antiviral treatments and vaccines, sustained surveillance and continued research into targeted interventions are crucial. Full article
(This article belongs to the Section COVID Clinical Manifestations and Management)
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26 pages, 3939 KB  
Article
Clinical and Proteomic Associations of SARS-CoV-2 Infection and COVID-19 Vaccination in Multimorbid Patients: A Cross-Sectional Observational Study
by Anett Hudák, Aladár Pettko-Szandtner, Annamária Letoha and Tamás Letoha
Int. J. Mol. Sci. 2025, 26(16), 8007; https://doi.org/10.3390/ijms26168007 - 19 Aug 2025
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Abstract
Vaccines played a crucial role in the COVID-19 pandemic, but their long-term biological effects and efficacy in vulnerable populations remain under intensive investigation. This study assessed clinical outcomes, comorbidities, and systemic biomarker and proteomic profiles in 366 multimorbid patients, stratified into four groups [...] Read more.
Vaccines played a crucial role in the COVID-19 pandemic, but their long-term biological effects and efficacy in vulnerable populations remain under intensive investigation. This study assessed clinical outcomes, comorbidities, and systemic biomarker and proteomic profiles in 366 multimorbid patients, stratified into four groups based on SARS-CoV-2 infection and vaccination status (COV+ vac+, COV+ vac−, COV− vac+, COV− vac−). Clinical and laboratory data, including comorbidities and relevant biomarkers, were collected. Proteomic analysis using mass spectrometry was performed to identify molecular changes associated with infection and vaccination. Statistical analyses examined associations between clinical status, biomarkers, and patient outcomes. As most participants received mRNA-based vaccines, the results primarily reflect responses to spike protein-expressing platforms. Biomarkers of cardiac and renal stress—namely proBNP and carbamide—were elevated in vaccinated individuals. Five deaths occurred in the COV+ vac+ group and two in the COV+ vac− group, most of which were attributed to exacerbations of pre-existing chronic diseases rather than to COVID-19 pneumonia. Protection against breakthrough infections waned over time, particularly beyond 200 days post-vaccination. Mass spectrometry identified proteins such as actin, fibrinogen chains, and SAA2 as potential diagnostic targets. Although the cross-sectional observational design limits the ability to draw causal inferences, the observed waning immunity and potential systemic alterations in vaccinated multimorbid patients highlight the importance of longitudinal follow-up to guide tailored immunization strategies and post-vaccination monitoring in high-risk groups. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19): Pathophysiology (6th Edition))
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14 pages, 1644 KB  
Article
Exploring TREC and KREC Levels in Nursing Home Residents and Staff and Their Association with SARS-CoV-2 Antibody Response After Vaccination
by Eline Meyers, Natalja Van Biesen, Liselore De Rop, Tine De Burghgraeve, Marina Digregorio, Laëtitia Buret, Samuel Coenen, Beatrice Scholtes, Jan Y. Verbakel, Stefan Heytens and Piet Cools
Vaccines 2025, 13(8), 874; https://doi.org/10.3390/vaccines13080874 - 19 Aug 2025
Viewed by 374
Abstract
Background: T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) are markers of recent thymic and bone marrow output, respectively. As they have previously been associated with immunosenescence, we aimed to investigate their association with anti-spike SARS-CoV-2 (S1RBD) IgG antibody response [...] Read more.
Background: T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) are markers of recent thymic and bone marrow output, respectively. As they have previously been associated with immunosenescence, we aimed to investigate their association with anti-spike SARS-CoV-2 (S1RBD) IgG antibody response after COVID-19 vaccination in nursing home residents (NHRs) and staff (NHS). Methods: We measured TREC and KREC levels and S1RBD IgG antibody levels from dried blood spots (DBSs) using in-house qPCRs and a commercial ELISA kit, respectively, in 200 participants (50 NHRs and 150 NHS). DBSs were collected in April 2021, approximately two months after primary course COVID-19 vaccination (BNT162b2). We assessed the association between TREC and KREC as dependent variables and age, sex, infection-priming status, and post-vaccination S1RBD-specific IgG concentrations as independent variables by simple and multiple linear regression. Results: TREC and KREC levels were significantly lower in NHRs compared with NHS and were negatively correlated with age (p < 0.001). Neither TREC nor KREC levels were significantly associated with SARS-CoV-2 antibody concentrations (p > 0.05). Conclusions: In our study population, TREC and KREC levels decreased with age and were statistically significantly lower in NHRs than NHS. They were, however, not associated with the antibody response after COVID-19 vaccination. Yet, additional research is warranted to explore their potential relevance in cellular immune responses or in combination with other biomarkers of immune function. Full article
(This article belongs to the Special Issue Understanding Immune Responses to COVID-19 Vaccines)
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