Search Results (1,346)

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 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

A comprehensive analysis of the molecular epidemiology of SARS-CoV-2 in the Kandy District of Sri Lanka from November 2020 to March 2022 was conducted to address the limited genomic surveillance data available across the country. The study investigated the circulating SARS-CoV-2 lineages, their temporal dynamics, and the associated mutational profiles in the study area. A total of 280 SARS-CoV-2-positive samples were selected, and 252 complete genomes were successfully sequenced using Oxford Nanopore Technology. Lineage classification was performed using the EPI2ME tool, while phylogenetic relationships were inferred through maximum likelihood and time-scaled phylogenetic trees using IQ-TREE2 and BEAST, respectively. Amino acid substitutions were analyzed to understand lineage-specific mutation patterns. Fifteen SARS-CoV-2 lineages were identified, and of those B.1.411 (36%) was the most prevalent, followed by Q.8 (21%), AY.28 (9.5%), and the Delta and Omicron variants. The lineage distribution showed a temporal shift from B.1.411 to Alpha, Delta, and finally the Omicron, mirroring the global trends. Time to the most recent common ancestor analyses provided estimates for the introduction of major variants, while mutation analysis revealed the widespread occurrence of D614G in the spike protein and lineage-specific mutations across structural, non-structural, and accessory proteins.Detection of the Epsilon variant (absent in other national-level studies) in November 2020, highlighted the regional heterogeneity viral spread. This study emphasizes the importance of localized genomic surveillance to capture the true diversity and evolution of SARS-CoV-2, to facilitate containment strategies in resource-limited settings. 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

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

Background/Objectives: The aim of this analysis of data from the multi-year nationwide SARSTer program in Poland was to compare the clinical presentation and course of COVID-19 in the last two infectious seasons. Methods: Clinical data from 719 consecutive patients hospitalized between April 2023 and March 2024 were compared with data from 360 patients hospitalized between 1 April 2024 and 31 March 2025. Results: In the 2023/2024 season, hospitalizations due to COVID-19 occurred primarily between September and January, and in the 2024/2025 season, the majority of hospitalizations occurred between July and November. In the 2024/2025 season, we documented a change in the age structure, with an increasing predominance of hospitalized patients over 70 years of age (68% vs. 60% in 2023/2024), a milder disease manifestation, reflected in a significantly lower percentage of patients with pulmonary lesions (19% vs. 24%), an improvement in the clinical course of the disease, reflected in a halving of the number of hospitalizations, a significantly higher percentage of patients with clinical improvement in subsequent weeks of hospitalization, including those discharged from the hospital within the first week (39% vs. 30%), and a significantly lower mortality rate (4.7% vs. 7.9%), especially among patients over 70 years of age (5.4% vs. 10.4%). This indicates that the trend of a milder disease course initiated by the emergence of the Omicron variant continues. Conclusions: In conclusion, our findings provide real-world clinical evidence of the evolution of the COVID-19 situation in the post-pandemic era. Full article

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

The COVID-19 pandemic has prompted the scientific community to develop new weapons against the SARS-CoV-2 spike protein. The study of its mutations is important to understand how it interacts with human receptors and how to prevent a future pandemic. In this study, four mutations of the Omega variant, along with those from the SARS-CoV-1 and MERS variants, were analyzed in complex with the angiotensin-converting enzyme 2 (ACE2) receptor. In silico studies were carried out to demonstrate that these mutations affect the interaction with the compounds under investigation. The ligands studied are heterocyclic compounds previously considered as potential inhibitors. Our results show that these compounds interact well with the spike protein and provide insights into how mutations, especially in the RBD region, can lead to perturbations in ligand–protein interactions. Full article

Natural products possess a wide range of biological and biochemical potentials, with plant-derived compounds being significant sources for discovering new drugs. In this study, extracts of Vitex negundo and Macaranga tanarius prepared with different solvents were tested for their antiviral activity against the original SARS-CoV-2 Wuhan strain and its variants using plaque assay, quantitative real time RT-PCR, and immunofluorescence assay (IFA). Our results showed that at their maximum non-toxic concentrations, Vitex-Dichloromethane (DCM) and Macaranga extracts significantly inhibited SARS-CoV-2 Wuhan strain growth in Vero E6 cells, showing a 5-log reduction in plaque assay and confirmed by IFA. Meanwhile, Vitex-Hexane showed moderate activity with a 2-log decrease. The inhibition was shown in a dose-dependent manner. The antiviral efficacy of these extracts was further demonstrated against various SARS-CoV-2 variants including Alpha, Beta, Delta, and Omicron. Both Vitex-DCM and Macaranga showed strong virucidal activity. In addition, Vitex-DCM and Macaranga inhibited the transcriptional activity of purified SARS-CoV-2 RdRp, indicating that RdRp inhibition may contribute to viral suppression as shown at the post-infection stage. Furthermore, combining Vitex-DCM or Macaranga with remdesivir showed a synergistic effect against SARS-CoV-2. These results suggest that Vitex negundo and Macaranga tanarius extracts are promising candidates for anti-SARS-CoV-2 treatments. Their synergy with remdesivir also underscores the potential of drug combinations in fighting SARS-CoV-2 and preventing the emergence of mutant variants. Full article

Background: Systematic studies providing differentiated insight into the contribution of immunity directed against conserved and non-conserved epitopes of SARS-CoV-2 Spike on long-term protection are rare and insufficiently guide future pan-variant vaccine research. The present observational cohort study aimed to evaluate the correlation of neutralizing antibody levels and cellular immunity against the Spike protein with symptomatic Omicron breakthrough infection. Methods: Neutralizing antibody levels against multiple (sub)variants were analyzed 6 months following the second wild-type mRNA vaccination and 6 months after booster in 107 subjects using a multiplex surrogate virus neutralization assay. To assess cellular immunity, cytokine mRNA expression levels were determined after peptide pool stimulation in whole blood samples of a study subgroup. Results: Neutralizing antibody titers were found to serve as a reasonably reliable correlate of protection prior to booster immunization. However, the predictive power of neutralizing antibody titers was diminished after boosting. This loss appears to be due to a critical remodeling of the antibody repertoire—a process that was dose-dependent on pre-boost humoral immunity. Vaccination against Omicron infection was most effective when a balanced immune response to both conserved and non-conserved epitopes of the viral Spike protein was induced. While neutralizing antibodies against receptor-binding domain epitopes affected by mutations were specifically associated with protection from symptomatic variant infection, cellular immunity was most effective when targeting conserved Spike epitopes. Conclusions: Optimal long-term protection against Omicron infection requires balanced immunity to both conserved and non-conserved epitopes of the viral Spike protein. The limited availability of cross-neutralizing antibodies targeting non-conserved epitopes and their inherently lower efficacy renders them a limiting factor as humoral immunity wanes over time. Future pan-SARS-CoV-2 variant vaccines that primarily target conserved epitopes may therefore provide less effective long-term protection against symptomatic variant infection than vaccines targeting a broader epitope spectrum including both conserved and non-conserved epitopes. Full article

Background: Preschool-aged children can have difficulty adhering to infection control measures and were affected during the Omicron wave of the coronavirus disease 2019 (COVID-19) pandemic. However, the impacts of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination on viral load in this age group remain poorly understood. This study aimed to investigate the relationship between previous SARS-CoV-2 infection, COVID-19 vaccination, and viral load or clinical severity in preschool-aged children infected during the Omicron variant epidemic in Japan. Methods: This prospective observational study investigated 107 children aged 1–75 months who were diagnosed with COVID-19 between May and September 2023. Rapid antigen (Ag) tests were performed on days 1 and 5 or 6, and results were visually graded into four categories (–, ±, 1+, or 2+). Ag results were validated against quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) cycle threshold (Ct) values. Clinical parameters, including vaccination status, previous infection, age, maximum body temperature, and fever duration, were analyzed using multivariate regression models. Results: Higher Ag loads (1+/2+) were more frequently observed in younger children who had not experienced prior infection or full vaccination. Prior infection and vaccination were independently linked to lower Ag loads and reduced maximum body temperature. Many unvaccinated and infection-naïve children continued to show elevated Ag levels on day 5 or 6, corresponding to Ct values suggestive of potential infectivity. Conclusions: Prior SARS-CoV-2 infection and vaccination were linked to lower viral loads and milder febrile responses among preschool-aged children. These findings enhance our understanding of infection dynamics in this age group and may inform future discussions on public health strategies in pediatric settings. Full article

SARS-CoV-2 undergoes frequent mutations that drive viral evolution and genomic diversity, influencing transmissibility, immune escape, and disease severity. In this study, we performed whole-genome sequencing on SARS-CoV-2 isolates from patients in New York City and identified several globally rare mutations across multiple viral lineages. The isolates analyzed for rare mutations belonged to three lineages: B.1.1.7 (Alpha), B.1.526 (Iota), and B.1.623. We identified 16 rare mutations (global incidence <1000) in non-structural protein genes, including nsp2, nsp3, nsp4, nsp6, nsp8, nsp13, nsp14, ORF7a, and ORF8. Three of these mutations—located in nsp2, nsp13, and ORF8—have been reported in fewer than 100 individuals worldwide. We also detected five rare mutations in structural proteins (S, M, and N), including two—one in M and one in N—previously reported in fewer than 100 cases globally. We present clinical profiles of three patients, each infected with genetically distinct viral isolates from the three lineages studied. Furthermore, we illustrate a local transmission chain inferred from unique mutation patterns identified in the Omicron genome. These findings underscore the importance of whole-genome sequencing for detecting rare mutations, tracking community spread, and identifying emerging variants with clinical and public health significance. Full article

Background: COVID-19 is associated with coagulopathy and increased mortality. The ABO blood group system has been implicated in modulating susceptibility to SARS-CoV-2 infection and disease severity, but its relationship with viral RNAemia, spike gene mutations, and thrombosis remains underexplored. Methods: We analyzed 446 hospitalized COVID-19 patients between 2021 and 2022. SARS-CoV-2 RNAemia was assessed via RT-qPCR on whole blood, and spike gene mutations were identified through whole-genome sequencing in RNAemia-positive samples. ABO blood groups were determined by agglutination testing, and thrombotic events were evaluated using coagulation markers. Statistical analyses included chi-square tests and Kruskal–Wallis tests, with significance set at p < 0.05. Results: RNAemia was detected in 26.9% of patients, with no significant association with ABO blood group (p = 0.175). Omicron was the predominant variant, especially in blood group A (62.5%). The N501Y mutation was the most prevalent in group O (53.2%), and K417N was most prevalent in group B (36.9%), though neither reached statistical significance. Thrombotic events were significantly more common in blood group A (OR = 2.08, 95% CI = 1.3–3.4, p = 0.002), particularly among RNAemia-positive patients. Conclusions: ABO blood group phenotypes, particularly group A, may influence thrombotic risk in the context of SARS-CoV-2 RNAemia. While no direct association was found between blood group and RNAemia or spike mutations, the observed trends suggest potential host–pathogen interactions. Integrating ABO typing and RNAemia screening may enhance risk stratification and guide targeted thromboprophylaxis in COVID-19 patients. Full article

Background: Since the COVID-19 pandemic, managing acute infections in symptomatic individuals, regardless of vaccination status, has been widely debated and extensively studied. Even more concerning, however, is the impact of COVID-19 on pregnant women—especially its effects on fetuses and newborns. Several studies have documented complications in both expectant mothers and their infants following infection. Methods: In our previous works, we provided scientific evidence of the bacteriophage behavior of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). This demonstrated that a well-defined combination of two antibiotics, amoxicillin and rifaximin, is associated with the same statistics for subjects affected by severe cases of SARS-CoV-2, regardless of vaccination status. We considered the few cases in the literature regarding the management of pregnancies infected with SARS-CoV-2, as well as previous data published in our works. In this brief case series, we present two pregnancies from the same unvaccinated mother—one prior to the COVID-19 pandemic and the other during the spread of the Omicron variant—as well as one pregnancy from a mother vaccinated against COVID-19. We describe the management of acute maternal infection using a previously published protocol that addresses the bacteriophage and toxicological mechanisms associated with SARS-CoV-2. Results: The three pregnancies are compared based on fetal growth and ultrasound findings. This report highlights that, even in unvaccinated mothers, timely and well-guided management of symptomatic COVID-19 can result in positive outcomes. In all cases, intrauterine growth remained within excellent percentiles, and the births resulted in optimal APGAR scores. Conclusions: This demonstrates that a careful and strategic approach, guided by ultrasound controls, can support healthy pregnancies during SARS-CoV-2 infection, regardless of vaccination status. Full article

Background/Objectives: mRNA vaccines introduced during the COVID-19 pandemic were a significant step forward in the rapid development and deployment of vaccines in a global pandemic context. These vaccines showed good protective efficacy, but—due to limited breadth of the immune response—they required frequent boosters with manufactured spike sequences that often lagged behind the circulating strains. In order to enhance the breadth, durability, and magnitude of immune responses, we studied the effect of combining priming with an RNA vaccine technology with boosting with protein/adjuvant using a TLR4-agonist based adjuvant. Methods: Specifically, four proprietary adjuvants (EmT4^TM, LiT4Q^TM, MiT4^TM, and AlT4^TM) were investigated in combination with multiple modes of SARS-CoV-2 vaccination (protein, peptide, RNA) for their effectiveness in boosting antibody responses to SARS-CoV-2 spike protein in murine models. Results: Results showed significant improvement in immune response strength and breadth—especially against more distant SARS-CoV-2 variants such as Omicron—when adjuvants were used in combination with boosters following an RNA vaccine prime. Conclusions: The use of novel TLR4 adjuvants in combination with protein or RNA vaccinations presents a promising strategy for improving the efficacy of vaccines in the event of future pandemics, by leveraging rapid response using an RNA vaccine prime and following up with protein/adjuvant-based vaccines to enhance the breadth of immunity. Full article