Search Results (13,943)

Background: COVID-19 vaccination and subsequent booster doses became critical components of public health strategies to control the pandemic and reduce disease severity, especially in fragile individuals. Among these, subjects undergoing dialysis represent one of the highly vulnerable populations. Methods: We conducted a multicenter case–control study among dialysis patients between March 2021 and May 2022 (study population n = 3264). We evaluated anti-S/RBD-IgG and anti-SARS-CoV-2 neutralizing antibodies before (T3) and after (T4) the third dose in individuals with a COVID-19 diagnosis after the third dose (cases) and in those who did not report infection (controls). Results: The study included 187 cases and 150 controls. Serological analysis showed a significant increase (p < 0.001) in anti-SARS-CoV-2 antibody levels after the third vaccine dose (from T3 to T4) in both groups. At T3, with the same number of days between the second dose and T3, the antibody levels detected were significantly lower in cases as compared to controls. At T4, we observed similar antibody titers in the two groups. Notably, the mean difference in time from the third dose to T4 was significantly greater in controls (73.0 days vs. 36.7, p < 0.001), suggesting a reduced antibody waning in controls. Accordingly, multivariate analysis showed that the risk of infection was considerably reduced by the pre-third-dose antibody levels. Conclusions: This study reinforces the critical role of the humoral response in preventing infections in the vulnerable population of dialysis patients. Regular monitoring of antibody levels and timely administration of booster doses are essential to optimize protection in this group. Full article

The X-linked TLR7 rs179008 T allele has been associated with altered antiviral immunity. Given their shared inflammatory pathways and higher pediatric mortality rates in Brazil during the pandemic, we investigated their association with multisystem inflammatory syndrome in children (MIS-C) together with Kawasaki disease (KS) following SARS-CoV-2 infection. A cross-sectional study (2021–2022) analyzed 73 hospitalized children (<13 years) with confirmed COVID-19. Genotyping for TLR7 rs179008, TLR8 (rs3764879, rs2407992), and TLR3 rs3775291 was performed via PCR and Sanger sequencing. MIS-C/KS cases were identified using CDC criteria, with severity classified by the need for ICU care. Statistical analysis included Fisher’s exact test and relative risk (RR) calculations. Hemizygous boys carrying the TLR7 T allele had a 1.87-fold higher risk of MIS-C/KS (p = 0.007) and a 1.75-fold increased risk of severe or critical outcomes. The T allele frequency was 2.6× higher in MIS-C/KS cases versus other COVID-19 presentations. All fatalities occurred in boys (3/8 MIS-C cases) with one T-allele carrier. No associations were found for TLR8 or TLR3 variants. The TLR7 rs179008 T allele is a potential genetic risk factor for severe post-COVID-19 inflammatory syndromes in boys, likely due to impaired immune signaling. These findings highlight its utility as a biomarker for risk stratification in pediatric populations. Full article

Although acute kidney injury (AKI) is common among patients with coronavirus disease 2019 (COVID-19), there are only limited data on its occurrence at intensive care unit (ICU) admission. Assessing the factors associated with AKI is essential for early diagnosis and intervention. This study aims to compare the clinical and laboratory characteristics and survival outcomes of COVİD-19 patients with and without AKI at ICU admission and determine the factors associated with AKI. In this study, patients with SARS-CoV-2 infection were categorized based on the presence (AKI group) or absence (non-AKI group) of AKI. Clinical and laboratory data and outcomes were analyzed retrospectively. Of the 712 patients included in this study, 198 were assigned to the AKI group and 514 were assigned to the non-AKI group. Patients with AKI had more comorbidities and higher disease severity; higher rates of invasive mechanical ventilation, vasopressor therapy, and mortality; and longer hospital stays (p < 0.05). Our multivariate analysis identified advanced age, a high Acute Physiology and Chronic Health Evaluation II score, a high neutrophil-to-lymphocyte ratio, a low albumin level, and the presence of comorbidities as independent factors associated with AKI. In patients with COVID-19, AKI observed at ICU admission is associated with advanced age and increased disease severity. The early diagnosis and monitoring of patients may improve clinical outcomes. Full article

Since the onset of the COVID-19 pandemic, the Republic of Korea has experienced continuous waves of SARS-CoV-2 variants. The current study aimed to analyze the long-term trends of variant prevalence and associated changes in immune responses within the country. Whole-genome sequencing was performed on confirmed patient samples collected from December 2020 to May 2025, and variant distribution, genetic diversity, and neutralization were compared. As a result of analyzing a total of 157,962 gene sequences, various Omicron sub-lineages, including BA.1, BA.2, BA.5, followed by JN.1, KP.3, and NB.1.8.1, were seen to circulate sequentially over time. The nucleotide diversity of the SARS-CoV-2 genome gradually increased after the JN.1 outbreak. Of the tested variants, hamster antiserum neutralization analysis indicated that Omicron NB.1.8.1, which began to circulate in 2025, exhibited the lowest neutralization activity, with an approximately 6.6-fold decrease compared to JN.1. This suggests a potential expansion in the dominance of new variants with enhanced immune evasion. As the transmission of SARS-CoV-2 continues, new variants with novel characteristics may emerge; therefore, continuous national genomic surveillance and immunological characterization are considered crucial for early detection of emerging variants and for guiding effective public health responses. Full article

Background: The COVID-19 pandemic disrupted healthcare systems globally, raising concerns about its negative impact on patients with chronic liver diseases by contributing to hepatic decompensations such as acute variceal bleeding (AVB). This study aimed to evaluate the impact of the COVID-19 pandemic on clinical outcomes in cirrhotic patients with AVB in Germany. Methods: This retrospective national multicenter study compared patients with cirrhosis and AVB treated at four tertiary care centers in Germany before (2016–2020) and during the pandemic (2020–2022). The primary endpoint was 6-week mortality, and secondary outcomes included infections, transfusion requirement and rebleeding. Results: The baseline characteristics of the 247 patients were largely comparable between the two groups, however metabolic dysfunction-associated steatotic liver disease was more prevalent during the pandemic compared to the pre-pandemic period (12.5% vs. 4.8%, p = 0.048). Only one patient tested positive for SARS-CoV-2. Six-week mortality (32.2% vs. 30.1%; p = 0.767) and rebleeding rates (22.8% vs. 22.3%; p = 1.000) did not differ significantly between groups. Interestingly, intubation rates, length of stay on the intensive care unit, post AVB infection rates and types of infection were also comparable (all p >0.05), while transjugular intrahepatic portosystemic shunt placement (TIPS) after bleeding was performed more frequently during the pandemic (23.2% vs. 11.3%, p = 0.019). Conclusions: Relevant patient-related AVB outcomes were unaffected during the COVID-19 pandemic. These findings suggest the resilience of critical AVB management practices in German tertiary centers. The increased use of TIPS and MASLD prevalence during the pandemic may reflect evolving clinical practice and patient profiles warranting further investigation. Full article

Background: The SARS-CoV-2 Omicron variant became the dominant driver during the COVID-19 pandemic due to its high transmissibility and immune escape potential. Although clinical outcomes are generally mild to moderate, the inflammatory mechanisms triggered by Omicron subvariants remain poorly defined. The goal of this study was to consider both viral evolution and the host immune response by assessing plasma cytokine levels in patients infected with SARS-CoV-2 Omicron subvariants. Methods: A total of 115 individuals were recruited, including 40 with laboratory-confirmed SARS-CoV-2 infection by RT-qPCR. Demographic, clinical, and comorbidity data were collected. Plasma levels of IL-6, TNF, IFN-γ, IL-4, IL-2, IL-10, and IL-17A were quantified using Cytometric Bead Array. Subvariant data were obtained from GISAID records and grouped into early (BA.1-lineage) and late (BA.4/BA.5-lineage) Omicron clusters. Statistical analysis included non-parametric and parametric tests, correlation matrices, and multivariate comparisons. Results: Pharyngitis, nasal discharge, cough, and headache were the most common symptoms among infected individuals. Despite no significant variation in symptom distribution across subvariants, infected patients showed higher levels of IFN-γ, TNF, IL-10, IL-4, and IL-2 compared to non-SARS-CoV-2 infected controls (p < 0.05). IL-4 and IL-10 levels were significantly higher in early Omicron infections. No associations were observed between cytokine levels and comorbidities. A significant correlation was found between reporting fewer symptoms and having received three vaccine doses. Conclusions: Infection with Omicron subvariants elicits a strong yet balanced cytokine response. Despite genetic divergence between lineages, immune and clinical patterns remain conserved, with vaccination appearing to mitigate the symptom burden. Full article

The global impact of COVID-19 was staggering, with millions of cases and related mortality reported worldwide. Genetic variations play a significant role in determining an individual’s susceptibility to SARS-CoV-2 infection and progress to severe disease. This pilot study provides an experimental approach using WES to identify certain rare and novel genetic variants that might affect an individual’s susceptibility to the risk of SARS-CoV-2 infection, offering an initial exploration of these genetic variants. In the study cohort with 16 patients, the mortality rate was higher in male patients due to severe disease. There was a substantial burden of comorbidity, including hypertension, ischemic heart disease, and T2DM, conditions which independently increase the risk of adverse outcomes in COVID-19 patients. A total of 4478 variants were identified, distributed across 322 genes within the cohort. The majority of these variants were missense substitutions along with frameshift variants, inframe insertions/deletions (indels), and nonsense variants. The variants were further categorized by types to include single-nucleotide polymorphisms (SNPs), deletions (DEL), and insertions (INS). The gene with the highest number of variants was HLA-DRB1, followed by HLA-B, ABO, HPS4, and SP110 displaying both common polymorphisms and rare variants. Moreover, the HLA-B gene exhibited the highest number of rare candidate variants, followed by AK2, IRF7, KMT2D, TAP1, and HLA-DRB1. Several genes harbored multiple novel variants, including TAP1, AK2, G6PC3, HLA-B, IL12RB2, and ITGB2. The frequencies of the identified variants were found to be either zero or extremely low (below 1% threshold) in the Middle Eastern or in the overall combined population, suggesting that these are indeed rare and do not represent common indigenous polymorphisms. Functional enrichment analysis of the constructed protein–protein interaction network in our preliminary findings revealed that the identified genes are primarily enriched in pathways associated with immune deficiency and DNA repair. This initial exploration of genetic variants in COVID-19 susceptibility provides a foundation for future large-scale studies. Full article

Background: Atherosclerosis is a chronic inflammatory condition that underlies both cardiovascular and cerebrovascular complications. Emerging evidence suggests that COVID-19 may play a role in its progression. Purpose: The aim of the study was to evaluate the potential impact of SARS-CoV-2 infection on the development of atherosclerosis. Patients and Methods: Common carotid artery (CCA) intima media thickness (IMT) was measured by ultrasonography twice, 12–18 months apart, in a cohort of 92 patients (47 with COVID-19 and 45 controls). Clinical data were collected from medical histories, physical examinations, and laboratory findings. Results: Baseline IMT values were comparable between the study groups (0.85 mm vs. 0.78 mm). However, the COVID-19 group exhibited a significantly greater increase in IMT over time, with a median change of 0.13 mm compared to 0.05 mm in the controls (p = 0.018). Furthermore, 69.2% of COVID-19 patients exceeded the median IMT progression threshold compared to 36% in the control group (p = 0.017). An elevated level of C-reactive protein (CRP) and a higher triglyceride (Tg)-to-High-Density Lipoprotein Cholesterol (HDL) ratio were significantly associated with increased IMT in the COVID-19 group. Age and heart rate were identified as significant predictors of IMT progression across both groups. Conclusion: COVID-19 may accelerate the progression of subclinical atherosclerosis. The strong associations of CRP and the TG/HDL ratio with IMT highlight the potential roles of chronic inflammation and metabolic dysregulation in driving these vascular changes. Further large-scale, multicenter studies are needed to elucidate the underlying mechanisms, confirm these observations, and guide targeted preventive and therapeutic strategies for individuals with an increased cardiovascular and cerebrovascular risk. Full article

This narrative review consolidates existing evidence about the interaction between Epstein-Barr virus (EBV) and SARS-CoV-2 in cancer development. EBV is a recognized oncogenic driver, whereas COVID-19 may heighten cancer risk by immunological dysregulation, persistent inflammation, and reactivation of latent viruses. We underscore molecular similarities (e.g., NF-κB activation, T-cell exhaustion) and clinical ramifications for high-risk individuals, stressing the necessity for interdisciplinary research to alleviate dual viral risks. EBV, a well-known oncogenic virus, has been linked to numerous malignancies, including lymphomas, nasopharyngeal carcinoma, and gastric cancer. Through the production of viral proteins that interfere with immune evasion, cellular signaling, and genomic integrity, it encourages malignant transformation and ultimately results in unchecked cell proliferation. Because of its capacity to induce tissue damage, immunological dysregulation, and chronic inflammation, COVID-19, which is brought on by the SARS-CoV-2 virus, has become a possible carcinogen. The virus’s influence on cellular pathways and its long-term effects on the immune system may raise the chance of malignancy, particularly in people with pre-existing vulnerabilities, even if direct correlations to cancer are still being investigated. When two viruses co-infect a host, the review highlights the possibility of synergistic effects that could hasten the development of cancer. It describes how overlapping mechanisms like inflammation, immune suppression, and viral reactivation may be used by a combined EBV and COVID-19 infection to exacerbate carcinogenic processes. Gaining an understanding of these relationships is essential for creating tailored treatment plans and enhancing cancer prevention in high-risk groups. Full article

The COVID-19 pandemic has caused over 7 million deaths, but its legacy extends beyond mortality. SARS-CoV-2 infection induces immune alterations that persist post-recovery, manifesting not only in long COVID (LC) but also in healthy individuals. Cytokines serve as critical orchestrators of these processes. The goal of this study is to investigate post-pandemic immune remodeling through cytokine assessment in both patients with LC and healthy donor, and to compare the post-pandemic population with pre-pandemic controls to find changes in the immune responses and cytokine profiles. A panel of 47 immune mediators (cytokines, chemokines, and growth factors) was measured with the MAGPIX multiplex analysis. LC was characterized by an increase in IL-7, IL-8, IL-17F, IL-18, EGF, FGF-2, PDGF-AA, sCD40L, and MCP-3 and a decrease in IL-4, IL-13, IL-22, IL-27, and FLT-3L. Comparing post-pandemic recovered individuals with pre-pandemic healthy cohort, we saw an upregulation of IL-13 and MCP-3 and a downregulation of MDC, M-CSF, IL-12, and IL-17F. While LC is characterized by persistent immune imbalance—particularly in cytokine networks—our data emphasize the critical need to study healthy donors in both pre- and post-pandemic eras when analyzing and interpreting these changes. Full article

Background: Host genetic factors significantly influence individual susceptibility to severe COVID-19, potentially explaining the observed disparities in clinical outcomes across populations. One of the key effectors in innate immunity and antiviral defense is the CD209 gene. This study explored the potential correlation of the CD209 gene SNP rs2287886 with diverse COVID-19 patient outcomes. Materials and Methods: A total of 176 patients (87 in the moderate group and 89 in the severe/critical/death group) were included in the study. Genotyping of patients was performed using the qPCR methodology, through the TAQMAN system. The results were analyzed adopting a significance level of p < 0.05. Results: The GG genotype (compared to AG + AA) and the G allele (compared to the A allele) of the rs2287886 SNP were significantly associated with an increased severity of COVID-19 (p = 0.0005 and p < 0.0001, respectively). The G allele was more frequent in individuals with more severe clinical outcomes (49.43% vs. 25.28%). Furthermore, expression quantitative trait loci (eQTL) analysis indicated that the GG genotype of rs2287886 is associated with higher CD209 gene expression. Furthermore, the observed interaction analysis suggests that the interactions between CD209 and its associated proteins may play a role in modulating the immune response. Conclusions: Our findings suggest that Brazilian patients homozygous for the GG genotype of the rs2287886 polymorphism in the CD209 gene may be at increased risk of severe COVID-19 in the Brazilian population and may act as a potential prognostic marker of disease severity. Full article

A novel skin test for an in vivo assessment of SARS-CoV-2-specific T-cell immunity was developed using CoronaDermPS, a multiepitope recombinant polypeptide encompassing MHC II–binding CD4+ T-cell epitopes of the SARS-CoV-2 structural proteins (S, E, M) and full length nucleocapsid (N). In silico epitope prediction and modeling guided antigen design, which was expressed in Escherichia coli, was purified (>95% purity) and formulated for intradermal administration. Preclinical evaluation in guinea pigs, mice, and rhesus macaques demonstrated a robust delayed type hypersensitivity (DTH) response at optimal doses (10–75 µg), with no acute or chronic toxicity, mutagenicity, or adverse effects on reproductive organs. An integrated clinical analysis included 374 volunteers stratified by vaccination status (EpiVacCorona, Gam-COVID-Vac, CoviVac) prior to COVID-19 infection (Wuhan/Alpha, Delta, Omicron variants), and SARS-CoV-2–naïve controls. Safety assessments across phase I–II trials recorded 477 adverse events, of which >88% were mild and self-limiting; no severe or anaphylactic reactions occurred. DTH responses were measured at 24 h, 72 h, and 144 h post-injection by papule and hyperemia measurements. Overall, 282/374 participants (75.4%) exhibited a positive skin test. Receiver operating characteristic analysis yielded an overall AUC of 0.825 (95% CI: 0.726–0.924), sensitivity 79.5% (95% CI: 75.1–83.3%), and specificity 85.5% (95% CI: 81.8–88.7%), with comparable diagnostic accuracy across vaccine, and variant subgroups (AUC range 0.782–0.870). CoronaDerm-PS–based skin testing offers a simple, reproducible, and low-cost method for qualitative evaluation of T-cell–mediated immunity to SARS-CoV-2, independent of specialized laboratory equipment (Eurasian Patent No. 047119). Its high safety profile and consistent performance across diverse cohorts support its utility for mass screening and monitoring of cellular immune protection following infection or vaccination. Full article

Background/Objectives: Low levels of lysophosphatidylcholine (LPC) in the blood can be used as a diagnostic marker for sepsis. SARS-CoV-2 infection, a more recent cause of sepsis, shares similarities with non-SARS-CoV-2 sepsis but also exhibits distinct features. We have recently shown that plasma cholesteryl ester levels are higher in patients with SARS-CoV-2 infection than in patients without, and this study analysed whether this may extend to differences in LPC, a bioactive constituent of lipoproteins. Methods: The plasma levels of 13 LPC species were measured by flow injection analysis tandem mass spectrometry (FIA-MS/MS) in 157 patients with systemic inflammatory response syndrome (SIRS), sepsis or septic shock. Of these patients, 24 had SARS-CoV-2 infection. Results: Patients with SIRS exhibited higher plasma levels of the minor LPC species LPC 15:0 and 22:4 compared to those with sepsis or septic shock. Five LPC species were also reduced in the plasma of 31 patients with liver cirrhosis; therefore, patients with cirrhosis or SIRS were excluded from subsequent analyses. Compared to 76 non-COVID-19 patients with sepsis or septic shock, SARS-CoV-2 infection in 21 patients was associated with significantly higher plasma levels of ten individual LPC species and total LPC concentration. In patients with sepsis/septic shock, LPC species showed negative correlations with procalcitonin and interleukin-6, and positive correlations with gamma-glutamyltransferase and cholesteryl ester levels. In contrast, no significant associations were observed between LPC levels and C-reactive protein, aminotransferases, or free cholesterol. Conclusions: Differential LPC levels, despite comparable disease severity, may serve as metabolic biomarkers to distinguish SARS-CoV-2 sepsis from other causes of sepsis and inform targeted therapeutic approaches. Full article

APOBEC3B (A3B) has been implicated in host–virus interactions, but its role in SARS-CoV-2 infection is unclear. Here, we demonstrate that A3B is overexpressed in bronchoalveolar lavage fluid (BALF) cells from severe COVID-19 patients compared to those with mild disease. A3B knockdown in Caco-2 cells significantly reduces SARS-CoV-2 infectivity, likely through attenuation of the PKR-mediated integrated stress response, a pathway proposed to promote SARS-CoV-2. Single-cell RNA sequencing (scRNA-seq) data suggest that BALF cells from severe COVID-19 patients exhibit a repressed state for cellular translation, potentially mediated by eIF2α phosphorylation. However, in A549-ACE2 cells, SARS-CoV-2 does not activate PKR, but A3B knockdown still reduces SARS-CoV-2 infectivity, suggesting an alternative mechanism of action in different cellular contexts. To further investigate A3B’s role in severe COVID-19, we employed Geneformer, a transformer-based machine learning model, which predicted that A3B knockout would perturb AMPD2 (adenosine monophosphate deaminase 2), a key enzyme in purine metabolism and immune regulation. We validated this prediction using bulk RNA-seq and clinical scRNA-seq data, confirming that AMPD2 expression is downregulated in severe COVID-19 but restored upon A3B knockdown. Together, these findings suggest that A3B plays a proviral role in SARS-CoV-2 infection by modulating translational control and immune regulatory networks, warranting further studies to elucidate the underlying mechanistic details. Full article

The emergence of the SARS-CoV-2 JN.1 lineage in late 2023 marked a major shift in viral evolution. By January 2024, it had displaced XBB variants to become the dominant strain worldwide. JN.1 and its descendants are antigenically distinct from earlier Omicron subvariants, with approximately 30 additional spike mutations compared to XBB-derived viruses. The combination of these features alongside growing evidence of considerable immune evasion prompted the FDA to recommend that vaccine formulations be updated to target JN.1 rather than XBB.1.5. The continued dominance of JN.1-derived variants necessitates the characterization of viral infection in established animal models to inform vaccine efficacy and elucidate host–pathogen interactions driving disease outcomes. In this study, transgenic mice expressing human ACE2 were infected with SARS-CoV-2 subvariants JN.1, KP.2, and EG.5.1 to compare the pathogenicity of JN.1-lineage and XBB-lineage SARS-CoV-2 viruses. Infection with JN.1 and KP.2 resulted in attenuated disease, with animals exhibiting minimal clinical symptoms and no significant weight loss. In contrast, EG.5.1-infected mice exhibited rapid progression to severe clinical disease, substantial weight loss, and 100% mortality within 7 days of infection. All variants replicated effectively within the upper and lower respiratory tracts and caused significant lung pathology. Notably, EG.5.1 resulted in neuroinvasive infection with a significantly high viral burden in the brain. Additionally, EG.5.1 infection resulted in a significant increase in CD8⁺ T cell and CD11b⁺ CD11c⁺ dendritic cell populations in infected lungs. Full article