Search Results (1,724)

The clinical severity of COVID-19 is influenced by cellular and humoral immune responses, as well as the dynamics of viral replication. In line with this, the current study examined systemic and mucosal immunity responses alongside viral load in unvaccinated SARS-CoV-2-infected individuals during the period of Omicron predominance. Between 2022 and 2023, when Omicron prevalence was at its peak, 48 SARS-CoV-2-positive cases with varied severity were recruited using positive PCR testing, and 48 negative controls were recruited using negative PCR testing at Moi Teaching and Referral Hospital, Kenya. Severe patients showed higher viral loads and systemic anti-spike IgG levels compared to moderate and asymptomatic individuals. Asymptomatic individuals had higher mucosal anti-spike IgG and receptor-binding domain (RBD) levels compared to severe patients. Systemic IFN-α mRNA transcripts were higher in asymptomatic individuals compared to patients with severe COVID-19 and healthy individuals. Severe patients had significantly lower expression of IFN-γ mRNA transcript levels in both blood and mucosa, as well as significantly lower systemic IFI-16 mRNA transcript levels. These findings reflect associations observed in a cross-sectional design and should not be interpreted as causal mechanisms. Suppressed interferon responses, both mucosal and systemic, were associated with severe disease. In conclusion, high systemic IgG and viral loads and low interferon responses were closely linked to severe COVID-19 outcomes. Full article

To investigate SARS-CoV-2 antibody kinetics and household transmission, infected children along with their families were tested for anti-nucleocapsid antibodies at 1, 3, 6, 9 and 12 months post-SARS-CoV-2 infection during the Ancestral, Alpha, Delta, and Omicron waves. We prospectively included SARS-CoV-2 acute infected children (n = 189). After household recruitment (n = 76 households), the total study population was 228 children and 105 adults. The median age (IQR) of children and adults was 96 (115) months and 504 (96) months, respectively. Anti-nucleocapsid (anti-N) COI (cut-off index) titers peaked at three months post-infection and declined thereafter (p-value < 0.001), and 89.2% remained seropositive at 12 months. Children displayed significantly higher anti-N COI titers than adults during the Delta (p-value: 0.018) and Omicron (p-value: 0.047) periods. Household contact anti-N positivity (evidence of infection) was associated with pediatric index cases (aOR: 1.61, 95% CI: 1.11–2.35; p-value: 0.013) and elevated early anti-N COI titers (aOR: 1.24 per log₁₀ unit, 95% CI: 1.05–1.48; p-value: 0.011). Higher secondary attacks were detected in Delta (aOR: 2.12, 95% CI: 1.19–3.77; p-value: 0.011) and Omicron (aOR: 2.75, 95% CI: 1.44–5.25; p-value: 0.002) compared to Ancestral. Waning of SARS-CoV-2 anti-N titers was faster in secondary cases (aHR: 1.62, 95% CI: 1.01–2.59; p-value: 0.047, Cox model) and during Omicron infection (aHR: 1.74 vs. Ancestral, 95% CI: 1.08–2.79; p-value: 0.023). In contrast, waning was slower in SARS-CoV-2 cases with higher baseline anti-N COI titers (aHR: 0.77, 95% CI: 0.64–0.93; p-value: 0.011). These findings demonstrate variant-specific, age-dependent antibody kinetics, emphasizing that pediatric index cases were associated with higher odds of household infection. Full article

Background/Objectives: COVID-19 is an infectious disease caused by SARS-CoV-2. The innate immune response constitutes the first line of antiviral defense. Notably, interferon-stimulated genes, such as those belonging to the oligoadenylate synthetase (OAS) family, have been implicated in host susceptibility and the response to SARS-CoV-2 infection. However, the extent to which OAS gene expression varies across SARS-CoV-2 variants remains insufficiently characterized. Its relationship with clinical outcomes in hospitalized patients is also unclear. This study aimed to evaluate OAS gene expression and its association with inflammatory markers and clinical outcomes in patients with severe COVID-19. Methods: An analytical cross-sectional study was conducted in patients hospitalized with severe COVID-19 between October 2021 and February 2022. SARS-CoV-2 infection and viral variants were prescreened at admission. Clinical parameters were recorded, including serum cytokine levels (IL-1β, IL-6, IL-8, MCP-1, IFN-α, IFN-β, IFN-γ, and TNF-α), and hematological indices (neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio). The COVID-GRAM risk score, treatment, and hospitalization outcomes were recorded. Relative mRNA expression of OAS1, OAS2, OAS3, and OAS-L was quantified by quantitative PCR, using TaqMan probes. Results: A total of 76 hospitalized patients with severe COVID-19 were included. In-hospital mortality was 32.9%, with a predominance of male patients (60%). Nearly 50% of non-survivors were infected with the Omicron variant. OAS1, OAS2, and OAS3 were overexpressed in hospitalized patients with severe COVID-19 compared with healthy subjects (HS) (log₂ fold change [95% CI]: OAS2: 4.312 [4.161–4.602], OAS3: 1.660 [1.485–1.916]; p = 0.0040 for both). Expression of OAS2 and OAS3 was significantly increased in survivors compared with HS (log₂ fold change: 4.312 [4.161–4.602] and 1.711 [1.485–1.990], respectively; p = 0.0009 and p = 0.0025). Similar increases were observed in non-survivors (4.554 [4.251–4.743] and 1.640 [1.081–2.301], respectively; p = 0.0002 and p = 0.0061) compared with HS. Conclusions: OAS genes, particularly OAS2 and OAS3, are overexpressed in severe COVID-19. This upregulation was comparable between Delta and Omicron infections, suggesting that the activation of this antiviral pathway is driven more by disease severity than by the specific viral variant. Full article

In the post-pandemic era, monitoring adaptive immunity of the population to emerging SARS-CoV-2 variants remains an important public health priority. To address this need, we developed a test that can simultaneously assess the neutralization ability of three SARS-CoV-2 variants. A panel of lentiviral pseudoviruses, each bearing the S-protein of different SARS-CoV-2 variants (Wuhan-Hu-1, BA.1, and XBB.1.5) and expressing a unique fluorescent protein (Clover, mRhubarb713, or mRuby3) was generated and used to transduce hACE2-overexpressing cells. The percentage of infected target cells for each variant was quantified via flow cytometry. Co-infection led to a minor reduction in the percentage of infected cells compared to mono-infection controls, confirming the robustness of the assay. We then applied the test to the analysis of human sera samples, which were collected in the Sirius Federal Territory (Russian Federation) and revealed the following: (1) sera collected in 2021 neutralized the Wuhan-Hu-1 variant and demonstrated cross-specificity to the BA.1 variant, but not to the XBB.1.5 variant; (2) sera collected after the Omicron emergence point neutralized Wuhan-Hu-1 and BA.1, and possessed a weak ability to neutralize the XBB.1.5. This assay provides a valuable tool for efficient profiling of humoral immunity and monitoring its development in response to ongoing viral diversity. Full article

Clinical, experimental, and computational evidence of COVID-19 virulence and infectivity has been linked to SARS-CoV-2 shell disorder. A strong link was first discovered using an AI disorder-predicting tool, which detected an unusually hard (low disorder) outer shell among all SARS-CoV-2-related viruses but not in the 2003 SARS-CoV-1. This could account for the high infectivity found in SARS-CoV-2—but not in SARS-CoV-1—as it is believed that hard shells protect viral particles from the onslaught of the antimicrobial enzymes present in the respiratory system and saliva. As a result, much larger quantities of particles are shed by COVID-19 patients. Abnormally hard outer shells (M) are associated with burrowing animals, e.g., pangolins, and SARS-CoV-2 likely acquired these shells due to its long-term evolutionary interactions with pangolins. As for virulence, the inner shell of SARS-CoV-2 (N) has been found to exhibit lower disorder than that of SARS-CoV-1. This lower disorder is consistent with the fact that SARS-CoV-2 is less virulent than SARS-CoV-1, as higher disorder in the inner shell is associated with more efficient protein–protein binding during replication. The link between N/M disorder and virulence or infectivity falls under the umbrella of shell disorder models (SDMs), which can connect virulence, infectivity, and long COVID under one coherent concept. Evidence of the reliability and reproducibility of SDMs as applied to COVID-19 is examined. The hard M that is resisting the antimicrobial enzymes in the respiratory system can be extended to immunological enzymes, especially those found in phagocytes such as macrophages, which can therefore become a reservoir for the virus. Full article

Recurrent outbreaks of coronavirus disease 2019 (COVID-19) in Japan highlight the continued need for effective prevention, particularly household transmission. This study clarifies the epidemiological profile of household transmission of COVID-19 and influenza by quantifying transmission rates according to demographic and relational characteristics. An anonymized health insurance claims database was used to identify index patients diagnosed with COVID-19 or influenza between November 2021 and August 2023. Transmission events were defined as cases in which household members were diagnosed with the same infection in the week following the index patient’s diagnosis (Day 1). Analyses were stratified by the age of the index patients and age-based transmission patterns between index patients and household members. A total of 1,001,509 index patients with COVID-19 and 207,090 with influenza met the inclusion criteria. Transmission rates were highest among index patients aged <12 years (COVID-19, 40.17%; influenza, 33.51%). Transmission from children was disproportionately high, while age-combination analysis demonstrated elevated transmission both from and to children for both diseases. COVID-19 exhibited increased transmission among adults. As the primary drivers of household transmission for both COVID-19 and influenza, preventive strategies should be tailored to children. COVID-19 interventions must also address transmission among adults to strengthen household-level infection control. Full article

The SARS-CoV-2 Omicron variant and its descendants accumulated unprecedented numbers of spike substitutions yet remained transmissible, implying compensatory mechanisms that preserve entry while eroding humoral immunity. We analyzed 32 variants for sequence-level mutation, physicochemical profiling, and epitope disruption; 25 had growth-advantage estimates, and 18 underwent molecular dynamics/MM-PBSA simulations. We applied a systems-virology framework to the SARS-CoV-2 receptor-binding domain (RBD), integrating immunodominance-weighted epitope conservation (567 B-cell and 97 T-cell epitopes) across variants (Wuhan-Hu-1 to KP.3) with molecular dynamics, molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) binding energetics, and deep mutational scanning (DMS) benchmarking. B-cell epitope conservation declined from a median of 72.7% in pre-Omicron variants to 28.8% in BA.1 and 10.6% in KP.3, and was strongly inversely associated with a breakthrough-infection proxy (Spearman ρ = −0.8246, p < 0.001), whereas RBD T-cell epitopes remained comparatively conserved (91.5% to 87.2%). Despite the loss of the ancestral K417–ACE2 D30 salt bridge, Omicron reconfigured the interface via alternative electrostatic contacts (Q493R–E35 and Q498R–D38), producing compensatory interactions captured by MM-PBSA, but with only modest agreement with DMS affinity changes (r = 0.682, p = 0.007), consistent with enthalpy–entropy compensation. Finally, mutation tolerance shifted toward stronger epistatic buffering in Omicron (two-fold higher epistasis than pre-Omicron; p = 0.0093), enabling extensive antigenic change without structural collapse. Together, these results support a multi-objective evolutionary strategy—epitope erosion, interface rewiring, and epistatic compensation—that can be operationalized to prioritize emerging lineages for surveillance and to inform vaccine designs that emphasize conserved T-cell targets. Full article

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global public health emergency in humans from 2020 to 2023 and was associated with over 7 million human deaths. Besides humans, SARS-CoV-2 has been detected in a wide range of animals, including companion, farm, zoo, and wild animals. At least 61 animal species from 29 animal families of 12 animal orders have tested SARS-CoV-2 positive. Documented evidence reported that not only human-to-animal transmission but also animal-to-human transmission events occurred. During the course of the pandemic progression in humans, SARS-CoV-2 strains in animals evolved in parallel with those in humans. Continued monitoring of SARS-CoV-2 in animals is needed to safeguard both human and animal health. In this study, we report investigation of two outbreaks of SARS-CoV-2 Omicron variant infection in tigers and gorillas in two zoological institutions. In the first zoo, six tigers tested positive by SARS-CoV-2 real-time RT-PCR and shed viral nucleic acid in feces for up to two weeks. Three of the tigers showed intermittent shedding patterns, while the other tigers shed only for 7–10 days. No other species, including cheetah, otter, lion, anteater, gibbon, and tamarin, tested positive. During the outbreak at the second zoo, a total of six gorillas were tested positive for SARS-CoV-2, while other primates housed in the same building (colobus and orangutan) tested negative. Follow-up testing revealed that two gorillas tested positive for SARS-CoV-2 over a one-month period (30 and 33 days, respectively), while the other four gorillas had positive SARS-CoV-2 PCR results for 14 to 25 days. Four gorillas had intermittent shedding patterns. Notably, compared to tigers, gorillas had a prolonged duration of fecal viral shedding. Sequencing was performed on the positive samples, and analysis indicated that strains detected in tigers and gorillas belonged to SARS-CoV-2 Omicron BQ.1.10 and XBB.1.16, respectively. Overall, this study offers valuable insights into the duration of viral RNA shedding for SARS-CoV-2 Omicron in zoo animals, facilitating accurate diagnostic evaluation and management of infected tigers and gorillas. Full article

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) remains a major cause of both community-onset and hospital-acquired infections, yet longitudinal data from Latin American hospitals spanning the COVID-19 pandemic are scarce. We characterized temporal trends, seasonality, and the impact of the COVID-19 pandemic on MRSA prevalence and incidence density among clinical S. aureus isolates at a tertiary-care hospital in western Mexico over 9.5 years. Methods: We analyzed 6625 non-duplicate clinical S. aureus isolates (6609 with valid resistance data) from June 2016 to December 2025. Temporal trends were assessed using Mann–Kendall tests, Theil–Sen estimation, and binomial generalized linear models. Seasonality was evaluated through STL decomposition, generalized additive models, and Fourier analysis. An interrupted time series (ITS) model with GLS-AR(1) and Newey–West corrections compared three COVID-19 phases: pre-pandemic (2016–2020), high viral circulation (2020–2022), and post-peak stabilization (2022–2025). Exposure-adjusted incidence densities (per 1000 patient-days) were analyzed in parallel. Results: MRSA prevalence declined from 28.1% pre-pandemic to 14.0% post-peak (Mann–Kendall z = −9.03, p < 0.001; OR = 0.85 per year, 95% CI: 0.829–0.871). MRSA incidence density decreased by 50%, from 1.27 to 0.63 per 1000 patient-days, while aggregate S. aureus incidence density remained stable (z = −0.17, p = 0.868). The ITS joint Wald test confirmed a significant cumulative shift in MRSA trajectory post-pandemic (p = 0.019 counts; p = 0.012 incidence density), with a significant post-peak level drop (p = 0.008). S. aureus exhibited moderate seasonality peaking in May–July (GAM edf = 7.26, p < 0.001), whereas MRSA showed only marginal seasonal variation. Conclusions: MRSA declined markedly across the study period, with the steepest reduction following the Omicron peak. The decline persisted after adjustment for pandemic-related fluctuations in hospital volume, supporting periodic reassessment of empiric anti-MRSA prescribing policies in similar settings. Full article

Background: The spike D614G substitution became globally dominant early in the COVID-19 pandemic, and reversion to ancestral D614 is expected to be rare once D614G is fixed. SARS-CoV-2 sequences lacking D614G detected later raise questions about the origin of these reversions. Methods: We analyzed spike protein amino-acid sequences from 22 SARS-CoV-2 Variants of Concern (VOCs) deposited in the NCBI GenBank database, screening for sequences carrying ancestral D614 and comparing their distributions across VOCs. Results: D614 reversions (reverse mutations of D614G) were not evenly distributed across VOCs but were strongly enriched in Delta (B.1.617.2) and Omicron BA.2, reaching levels statistically inconsistent with other VOCs. In both lineages, D614-containing sequences showed limited mutational diversity and pronounced geographic clustering within specific U.S. regions. Conclusions: These non-random patterns are difficult to reconcile with spontaneous reverse mutation arising and spreading through typical community transmission and are more consistent with localized reintroduction of an older genetic background. Further investigation is warranted to assess whether laboratory-associated events could be involved. Full article

Several researchers have documented the occurrence of the unfamiliar severe acute respiratory syndrome coronavirus 2 ribonucleic acid (also known as SARS-CoV-2 RNA) in various raw wastewater (WW) samples analyzed globally. The efficiency of strategic WW-based epidemiology (WBE) approach as a timely cautioning tool for human coronavirus disease-2019 (COVID) and other similar outbreaks is highly promising. This strategy offers a cost-effective, population-wide surveillance tool that can detect rising case trends, from days to weeks before clinical reports, thus enabling proactive public health interventions. This study aimed to detect the occurrence of the viral genome in WW over four seasons, which contributes to the database for multi-plant surveillance research in South Africa. About 480 WW influent samples were amassed from ten sampling points situated in nine wastewater treatment facilities (WWTFs) in Amathole District Municipality (ADM) located in the Province of Eastern Cape (EC), South Africa (SA). The study was carried out for a period of one year. Quantitative real-time polymerase chain reaction (i.e., RT-PCR) was operated to identify the viral genomes in the respective total RNA samples. Of the 480 extracted RNA samples, 210 (44%) were positive with viral genome copies (gc) that ranged from 700 to 40,000 GC/mL. Our results were contrasted with existing COVID-19-positive cases throughout the COVID omicron wave in the ECP. Variations in gc were observed across different seasons, with the highest GC observed in winter. In contrast, there were significant inconsistencies in the existing data of COVID-19 clinical cases, thus indicating no connection between both data. However, with more similar studies, advanced innovative WBE strategies could possibly act as prompt warning tools to signal public health officials about potential future outbreaks. Full article

The continuous evolution of SARS-CoV-2 affects its infectivity and ability to evade the immune system. The XBB.1.5 subvariant carries numerous mutations compared to previous Omicron variants and exhibits significant evasion of polyclonal neutralizing antibodies. In this study, the mechanistic effects of mutations in the XBB.1.5 spike protein on structural stability, antigenic markers, and antibody epitopes were analyzed using homology modeling, epitope prediction, protein stability analysis, coarse-grained dynamic simulations, and chain-specific interface mapping. Thirty-eight amino acid substitutions were identified relative to Wuhan-Hu-1, including 22 in the receptor-binding region. The prefusion trimeric fold was conserved, with localized rearrangements in the N-terminal domain, receptor-binding domain, and S1/S2 region. Linear B-cell epitope prediction yielded similar epitope counts and length distributions in wild-type and XBB.1.5, but only moderate residue-level overlap (Jaccard ≈ 0.40–0.62), indicating epitope turnover and alteration of four conserved antigenic determinants. Functional screening suggested that ~45% of substitutions could affect protein function. Chain-specific interface analysis of the A–B protomer interface indicated preserved inter-protomer coupling with modest repacking of the polar/directional contacts. Overall, XBB.1.5 appears to maintain ACE2 engagement while redistributing antibody targets, underscoring the need for updated vaccine formulations and therapeutic antibodies. Full article

With the ongoing emergence of SARS-CoV-2 variants, continued surveillance of antiviral susceptibility remains critical for detecting resistance that could compromise treatment efficacy. This study evaluated the activity of 2 SARS-CoV-2 RNA-dependent RNA polymerase (Nsp12) inhibitors against emerging Omicron variants: remdesivir (RDV), an approved antiviral for the treatment of COVID-19, and obeldesivir (ODV), an oral prodrug that shares the same parent nucleoside as RDV. Both RDV and ODV were shown to retain antiviral activity against the Omicron subvariants BA.2.86.1, JN.1.7, KP.2, KP.3.1.1, KP.3.3, LP.8.1, NB.1.8.1, XBB.2, XEC, and XFG compared with wild-type reference strains. Only 1 new lineage-defining Nsp12 substitution, D284Y (detected in NB.1.8.1), was observed. Phenotypic analysis demonstrated that a replicon containing this substitution remained susceptible to both RDV and ODV. These findings are consistent with previous studies showing that RDV and ODV retain potent activity against previously identified Omicron variants, support the continued clinical use of RDV against circulating SARS-CoV-2 variants, and reinforce the potential of ODV as an oral antiviral therapeutic. Full article

Remdesivir is recommended for hospitalized patients with severe COVID-19 and for those at high risk of progression. Real-world Omicron-era data on incidental COVID-19 and high-risk outpatients remain limited. We conducted a multicenter retrospective cohort study (ReEs-COVID19) in Greece (June–December 2022) including adults with PCR-confirmed SARS-CoV-2 infection who received remdesivir. Hospitalized patients with incidental COVID-19 (Group A, n = 138) and high-risk outpatients (Group B, n = 312) were analysed. Outcomes included clinical deterioration, mortality, and adverse events. Group A patients were older with more comorbidities. Remdesivir was initiated earlier in Group A (median 1 vs. 2 days) but with a more heterogeneous duration (48.9% vs. 97.8% in Group B, which received the standard 3-day regimen). Clinical deterioration due to COVID-19 occurred in 5.8% vs. 0.6%, and 30-day mortality was 18.1% (25/138) in Group A, including 10 COVID-19-related deaths (7.2%). Group B had two deaths (0.6%), none COVID-19-related. Adverse events were uncommon, with mild kidney injury in 3.6% of Group A and hepatotoxicity in 2.2% vs. 0.3%. In high-risk outpatients, the ReEs-COVID19 study confirmed the effectiveness and safety of remdesivir’s profile. Among incidental cases, two distinct disease patterns were identified, associated with different remdesivir regimens and highlighting the importance of comorbidities and the need for tailored clinical interventions. Full article

Background: The U.S. Food and Drug Administration (FDA) conducted a benefit–risk assessment for Moderna’s COVID vaccine mRNA-1273 prior to its full approval, announced 31 January 2022. The FDA’s assessment focused on males 18–64 years old because its risk analysis was limited to vaccine-attributable myocarditis/pericarditis (VAM/P), given the excess risk among males. The FDA’s analysis concluded that vaccine benefits outweighed risks, even for 18–25-year-old males (those at highest VAM/P risk). We reanalyze the FDA’s benefit–risk assessment using information available through the third week of January 2022 and focusing on 18–25-year-old males. Methods: We develop a benefit–risk model, extending the FDA’s, that can stratify benefits and risks of vaccination by prior-infection and comorbidity status. We use the FDA’s framework but apply our model to account for benefits derived from prior COVID infection, while also accounting for finer age stratification in COVID-hospitalization rates, incidental hospitalizations (those of patients who test positive for COVID but receive treatment for something else), more realistic projections of Omicron-infection rates, and more accurate VAM/P rates. Results: With hospitalizations as the principal endpoint of the analysis (those prevented by vaccination vs. those caused by VAM/P), our model finds vaccine risks outweighed benefits for 18–25-year-old males, except in scenarios projecting implausibly high Omicron-infection prevalence. Our assessment suggests that mRNA-1273 vaccination of 18–25-year-old males generated between 8% and 52% more hospitalizations for VAM/P compared to COVID hospitalizations prevented (over a five-month period of vaccine protection assumed by the FDA). The preceding assessment uses model inputs based on data available at the time of the FDA’s mRNA-1273 assessment. Moreover, these inputs as well as model outputs are validated by subsequently available data. Conclusions: The outcome of a vaccine benefit–risk assessment may be dramatically impacted by accounting for the benefits derived from prior infection by the vaccine-targeted disease. To increase public confidence in vaccines and thereby reduce vaccine hesitancy, public-health agencies should employ benefit–risk models capable of supporting stratification of vaccination recommendations not only based on age and sex but also on prior-infection and comorbidity status. Full article