The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the ongoing need for effective antiviral therapies targeting this now-endemic virus. Ibuzatrelvir, a second-generation SARS-CoV-2 main protease (Mpro) inhibitor, has demonstrated potent antiviral activity without the need for a pharmacokinetic booster such as ritonavir. In the present study, we show that ibuzatrelvir maintains antiviral efficacy against all major SARS-CoV-2 variants circulating between 2020 and 2024 (alpha (α), beta (β), gamma (γ), lambda (λ), delta (δ), mu (μ) and omicron (ο)). Additionally, we characterized the in vitro resistance profile of ibuzatrelvir by selecting for mutations under drug pressure. This approach identified several resistance-associated amino acid changes in Mpro, including T21I, L232R, and S144A, as well as substitution combinations E166V+L232R and S144A+L232R+L253L/F. Among these, the E166V+L232R double substitution conferred the highest level of resistance to ibuzatrelvir. Surveillance studies have shown low prevalence of the E166V substitution in both GISAID datasets and in breakthrough cases from clinical trials. Cross-resistance testing revealed that this double substitution retained susceptibility to remdesivir and also conferred resistance to nirmatrelvir. Ibuzatrelvir and nirmatrelvir remained active against viruses containing the ensitrelvir resistance-associated Mpro substitution, M49L. The sustained efficacy of ibuzatrelvir against circulating variants, combined with the low prevalence of the E166V substitution, supports its continued evaluation in phase 3 studies.

The coronavirus disease 2019 (COVID-19) pandemic, driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need for effective therapeutics, particularly as limitations of existing antiviral treatments persist. Establishing the proper strategy to set target concentrations for human dose projection is essential for any novel drug development project. In this study, we investigated the translatability of various preclinical models, specifically in vitro A549-hACE2 cells and air-liquid interface human nasal epithelial cultures, and in vivo Syrian golden hamsters and K18-hACE2 transgenic mice, using 3-chymotrypsin-like protease (3CLpro) inhibitors as model direct-acting antivirals. We assessed the minimal efficacious concentrations in these models of both ensitrelvir (ETV) and nirmatrelvir (NTV) co-dosed with ritonavir (Paxlovid) and compared this to clinical human data. Notably, in vitro models and the K18-hACE2 mice proved to be the most predictive for human efficacious exposures. Interestingly, lower efficacious exposures were needed in the more severe K18-hACE2 mouse model than in the Syrian golden hamster model for mild infection. Overall, we recommend applying a factor of 4-fold to the in vitro 90% effective concentration (EC90) for a conservative estimate of human efficacious exposure and recommend validation using K18-hACE2 mice. These insights are critical for guiding the development of effective SARS-CoV-2 therapeutics and optimizing clinical trial design.

Enteroviruses (EVs) pose major threats to human health, among which coxsackievirus B4 (CVB4) is particularly notable for its high lethality, increasing prevalence, and the absence of approved targeted therapeutics. Leritrelvir, an approved coronavirus disease 2019 (COVID-19) drug targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease (3CLpro), was investigated for repurposing due to structural and functional homology between the EV 3C protease (3Cpro) and SARS-CoV-2 3CLpro. Molecular docking analyses demonstrated that leritrelvir binds to the CVB4 3Cpro active site in a manner similar to that observed for SARS-CoV-2 3CLpro. In vitro experiments showed that leritrelvir inhibited CVB4 replication in HeLa cells, with a half-maximal effective concentration (EC50) of 12.64nM. The half-maximal cytotoxic concentration (CC50) of leritrelvir in HeLa cells was 572.7μM, yielding a selectivity index (SI=CC50/EC50) of 4.53×104. Among 3-day-old ICR mice infected with CVB4, leritrelvir suppressed viral replication in a dose-dependent manner. Administration of leritrelvir (12mg/kg/day) prevented mortality, alleviated clinical symptoms and weight loss, and attenuated histopathological lesions in virus-targeted organs (e.g., brain, lungs, myocardium, and small intestine). Additionally, leritrelvir effectively suppressed CVB4-induced elevation of interleukin-6. Leritrelvir exhibited superior anti-CVB4 efficacy both in vitro and in vivo compared with the reference drug fluoxetine. Potent activity was observed against CVB4 clinical isolates and 3Cpro mutants, confirming broad-spectrum efficacy against CVB4 variants. In vitro and in silico analyses revealed that leritrelvir exerted robust antiviral effects against EVA71, CVA16, and human rhinovirus 2. These findings support the repurposing potential of leritrelvir against CVB4 and common EVs.

Prolonged severe acute respiratory syndrome coronavirus 2 infection and intrahost viral evolution in a severely immunocompromised patient with human immunodeficiency virus infection: A whole-genome sequencing study.

An observational retro-prospective study on patients with head and neck cancer who contracted COVID-19 (HERODOTUS: head and neck cancERs international cOviD-19 collabOraTion).

We evaluated the effectiveness of a community research partnership focused on improving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing for New York City residents during the pandemic. We employed interviews, a focus group, and a survey to evaluate partnership characteristics, engagement, and future collaboration. Qualitative analysis revealed five core themes: committee identity, collective goals, information sharing, adaptability, and trust. The findings highlight the importance of flexibility, shared goals, diverse representation, open communication, and trust in effective multisector community health partnerships. (Am J Public Health. 2026;116(4):431-436. https://doi.org/10.2105/AJPH.2025.308358).

Deep Venous Thrombosis in Patients Recovered from COVID-19: A Long-Term Sequel.

To explore the mechanisms underlying ocular infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we conducted a comprehensive review of current literature, focusing on viral entry pathways, receptor expression in ocular tissues, and associated clinical manifestations. This review encompasses studies published within the last five years with a focus on original research and systematic reviews that provide molecular, histological, or clinical evidence. The findings show that SARS-CoV-2 can infect ocular tissues through multiple receptors beyond angiotensin-converting enzyme 2 (ACE2), including transmembrane serine protease 2 (TMPRSS2), CD147, alanyl aminopeptidase N (ANPEP), dipeptidyl peptidase 4 (DPP4), angiotensin II receptor type 2 (AGTR2), and polymeric immunoglobulin receptor (PIGR), which are expressed in retinal, conjunctival, corneal, limbal, and photoreceptor cells. The virus may also reach ocular structures via neurovascular invasion. Clinically, patients with coronavirus disease 2019 (COVID-19) may present with a broad spectrum of ophthalmic manifestations, including conjunctivitis, hyperreflective lesions in the inner retinal layers, flame-shaped hemorrhages, cotton-wool spots, retinal pallor, hard exudates, and various forms of maculopathy, such as paracentral acute middle maculopathy and acute macular neuroretinopathy (AMN). These signs reflect both direct viral damage and secondary effects of systemic inflammation and microvascular injury. Understanding the molecular and clinical spectrum of ocular involvement is essential for early diagnosis, appropriate ophthalmologic care, and the prevention of long-term visual sequelae in patients affected by COVID-19.

A Randomized Trial of Vitamin D Supplementation and COVID-19 Clinical Outcomes and Long COVID: The Vitamin D for COVID-19 Trial.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has underscored an urgent need for rapid, accurate, and accessible diagnostic tools to detect infections, facilitate timely quarantine, and inform therapeutic decisions. Fabricating nanostructures on biosensors can enhance biomolecule orientation, minimize steric hindrance, and reduce non-specific binding, resulting in improved signal-to-noise ratios and high sensitivity, making them promising point-of-care diagnostic. However, clinical translation remains limited by challenges in scalable and reproducible fabrication and insufficient diagnostic validation. Here, we introduce a nanowell biosensor (NW-Biosen) fabricated via semiconductor manufacturing, enabling scalable production and yields >1000 electrodes with reproducible properties. NW-Biosen detects SARS-CoV-2 antigens from patient nasal swabs within ∼10 min, with high sensitivity and minimal interference from other coronavirus recombinant proteins, respiratory pathogens, bacteria, and environmental substances, while maintaining consistent reproducibility with different batches. We validated NW-Biosen through two independent clinical trials involving 249 retrospective and 243 prospective patient samples. In prospective cohort, NW-Biosen achieved 93.02% sensitivity, 98.73% specificity, and a Cohen's kappa of 0.927, indicating near-perfect agreement with RT-PCR and superior sensitivity compared to commercially available colorimetric kits. Thus, NW-Biosen enables rapid, highly sensitive, reproducible, and cost-effective at-home detection, with real-time data transmission to public health authorities via mobile app integrated with a miniature potentiostat.

Current SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccines have shown robust induction of neutralizing antibodies and CD4+ T cell activation; however, CD8+ responses are variable, and the duration of immunity and protection against variants are limited. Here we repurpose our DNA origami vaccine nanotechnology DoriVac to target infectious viruses, namely, SARS-CoV-2, HIV and Ebola. The DNA origami nanoparticle, conjugated with infectious-disease-specific heptad repeat 2 peptides, which act as highly conserved antigens, and CpG adjuvant at precise nanoscale spacing, induces neutralizing antibodies, Th1 CD4+ T cells and CD8+ T cells in naive mice, with significant improvement over a bolus control. Pre-clinical studies using lymph-node-on-a-chip systems validate that DoriVac, when conjugated with antigenic peptides or proteins, induces promising cellular and humoral immune responses in human cells. Moreover, DoriVac bearing full-length SARS-CoV-2 spike protein achieves immune responses comparable to current mRNA vaccine platforms while potentially reducing storage constraints. These results suggest that DoriVac holds potential as a versatile, modular vaccine platform, capable of inducing both humoral and cellular immunities, underscoring its potential future use.

Antibody engineering is often achieved through laborious mutagenesis and screening. However, the physicochemical basis of cross-reactivity-enhancing mutations remains unclear. We computationally redesigned the severe acute respiratory syndrome coronavirus (SARS-CoV)-1 neutralizing antibody m396 to recognize the SARS-CoV-2 receptor-binding domain (RBD) and characterized its biophysical properties. A first-generation variant carrying three light-chain substitutions (S30LW, S93LI, and S94LF) acquired detectable SARS-CoV-2 RBD binding, while strengthening its affinity for the SARS-CoV RBD. A second-generation variant carrying two substitutions (T52HL and L54HW) further improved SARS-CoV-2 binding with a low micromolar affinity, predominantly driven by an approximately 200-fold increase in the association rate. Circular dichroism spectra indicated preserved global folding across the variants, whereas differential scanning calorimetry revealed stepwise decreases in lower-temperature unfolding transitions. Hydrogen-deuterium exchange mass spectrometry showed increased dynamics of CDR-L1 and localized rigidification near CDR-H2 in the second variant. These results suggest a biophysical model in which a small number of mutations reprogram cross-recognition by redistributing the local conformational dynamics.

In order to diagnose COVID-19, severe acute respiratory syndrome-Corona Virus-2 (SARS-CoV-2) must be positively identified. When the epidemic first began, medical personnel had little understanding of the condition and course of treatment for COVID-19 patients. The World Health Organization (WHO) recommended that it is important to have laboratory attached to management. In order to analyze the various laboratory findings in COVID-19 diagnosis observed at the Isolation Centre of the Fevers Unit of Korle-Bu Teaching Hospital, a retrospective analysis study of various documented laboratory results captured. A total of 54 patients were hospitalized at the COVID-19 ICU of the Korle-Bu Teaching Hospital. Women accounted for 57% (31/54) positivity and men, 43% (23/54). The mean (SD) age was 47.1(17.9) years. The age distribution showed that the largest percentage of people, 26.4% (14/54), were in the 60+ age group, followed by the 40-49 age group (22.6%) (12/54), and the 30-39 age group (18.9% (10/54).Over 56% of patients had hypertension, making it the most prevalent disease condition. Hematological parameters like HB for patients (n=24) were 10.5±2.5, cardiac parameters like albumin for patients (n=18) were 24.4±13.7, and biochemical parameters like ALT for patients (n=21) were 63.21 ±65. Inflammatory parameters, like CRP (n=12), recorded a mean of 23.5, while coagulation parameters, like D-DIMER, for patients (n=18) were 4.7±8.4.According to the list of comorbidities noted, the kidney, lungs, and liver were the organs most affected in the study.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in approximately 778 million reported cases and over 7 million deaths worldwide as of August 2025 (WHO COVID-19 Dashboard), predominantly due to variable acute and chronic lung infections accompanied by inflammatory responses within the pulmonary tract and vasculature. Despite ongoing research, no definitive cure has been identified. Preventive measures, including vaccines and monoclonal antibody-based interventions, have been developed to protect vulnerable populations, and hundreds of therapeutic candidates have been evaluated worldwide. Complementing these strategies, vitamin D and zinc (Zn) supplementation have emerged as promising, accessible adjunctive strategies due to their immunomodulatory and anti-inflammatory properties. This review synthesizes current experimental, clinical, and epidemiological evidence on the roles of vitamin D and Zn in modulating immune responses relevant to SARS-CoV-2 infection. Available data suggest that adequate vitamin D and Zn status may support immune function, reduce excessive inflammation, and potentially mitigate disease severity, particularly in deficient individuals. However, clinical trial outcomes remain heterogeneous. Overall, vitamin D and Zn supplementation may be considered supportive, adjunctive preventive measures. Further well-designed randomized controlled trials are required to define their optimal use in COVID-19 prevention and management.

Enantioenriched vinyl sulfinamides with chiral-at-sulfur chirality are medicinally valuable but have limited accessibility with conventional strategies. Here we disclose an organocatalytic approach via enantioselective C-S bond formation between Morita-Baylis-Hillman esters and sulfinylamines catalysed by a designed chiral organophosphine. The structural rigidity of this catalyst is crucial for not only the excellent chemo-, enantio- and diastereoselectivities in this process but also its extraordinary air stability. Density functional theory and experimental studies indicated that the phosphonium species probably serves as the catalyst resting state, and the sulfinylamine may play a dual role as both reaction partner and promoter for the formation of the key phosphonium intermediate. The cyclic vinyl sulfinamides showed promising binding affinity to the mutant spike of severe acute respiratory syndrome coronavirus 2 and ENV of human immunodeficiency virus-1, suggesting that this less-explored chemical space has great potential for further antiviral drug development.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells via its spike (S) protein, which binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Glycans are thought to influence this interaction by modulating the binding affinity between the S protein and its receptor. In this study, we screened 300 carbohydrate species using a glycan array to identify potential ligands that interact with the S proteins of the Delta and Omicron variants. Among the identified candidates, two aminoglycoside antibiotics, tobramycin and sisomicin, exhibited notable binding to the S protein. Surface plasmon resonance (SPR), circular dichroism (CD), and in silico docking analyses confirmed direct interactions between these aminoglycosides and the S protein, revealing distinct binding characteristics. Nuclear magnetic resonance (NMR) analysis further localized the tobramycin-binding site within the receptor-binding domain (RBD) of the S protein. Tobramycin and sisomicin showed a tendency to inhibit SARS-CoV-2 replication in human induced pluripotent stem cell (hiPSC)-derived lung organoids, though the effect did not reach statistical significance. Docking simulations using the trimeric S model suggested that aminoglycosides bind at an inter-subunit interface. These findings demonstrate that aminoglycosides can directly interact with the SARS-CoV-2 S protein and may serve as scaffolds for developing host-independent antiviral agents against SARS-CoV-2 and its variants.

Background: Coronavirus disease 2019 is characterized by causing thromboembolic events due to a procoagulant state. The possible relationship between lupus anticoagulant and patient's procoagulant state is controversial and no study has specifically evaluated the impact of lupus anticoagulant on noninvasive mechanical ventilation. Objectives: The aim of our study was to analyze the association between lupus anticoagulant and the need for noninvasive mechanical ventilation in 44 consecutive patients hospitalized for Severe acute respiratory syndrome Coronavirus 2 pneumonia. Methods: This was a prospective, multicenter, observational study conducted between January 1 and March 31, 2022, which included a total of 44 consecutive patients, > 18 years old and admitted for severe Severe acute respiratory syndrome Coronavirus 2 pneumonia. The following characteristics were determined: age, gender, blood group and Rh factor, plasma levels of Interleukin-6, Von Willerbrand Factor, lupus anticoagulant at admission, presence of venous thromboembolic disease, need for noninvasive mechanical ventilation, and intensive care unit admission. The relationship between the need for noninvasive mechanical ventilation and the levels of Von Willerbrand Factor and lupus anticoagulant was performed by T-student and its cutoff point was defined by ROC curve. Multivariate analysis was performed to establish worse prognosis factors. SPSS 27.0 statistical software was used, and an alpha error of 0.05 was established. Results: 44 patients hospitalized with severe Severe acute respiratory syndrome Coronavirus 2 pneumonia (56.8% male, 68.5±17.9 years). 88.6% showed elevated Von Willerbrand Factor. Lupus anticoagulant levels were higher in patients requiring mechanical ventilation versus oxygen therapy (1.32±0.27 vs 1.12±0.17, p=0.011). The cutoff point for lupus anticoagulant levels that were associated with mechanical ventilation was 0.792 AUC (p=0.01). The predictors of noninvasive mechanical ventilation in the multivariate analysis were intensive care unit admission (p=0.02). Conclusions: Plasma levels of Von Willerbrand Factor, lupus anticoagulant and Interleukin-6 can be a very useful prognostic tool for assessing the need for hospital admission to the critical care unit and the need for noninvasive mechanical ventilation. It would be interesting to include these determinations as routine assessments in patients with severe pneumonia.

Rohingya Myanmar nationals are at high risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to densely populated camp areas with inadequate water, sanitation, and hygiene (WASH) infrastructure, along with limited awareness of hygiene practices. This study aimed to characterize the longitudinal SARS-CoV-2 antibody dynamics among Rohingya refugees in Cox's Bazar to inform vaccination strategies and public health preparedness in humanitarian settings. Reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 positive cases and their household members were enrolled and followed at multiple time points to monitor the IgG antibody response against the SARS-CoV-2 receptor binding domain (RBD) of the spike (S) protein. A total of 194 primary SARS-CoV-2 RT-PCR-positive cases were enrolled at baseline, of whom 47% were symptomatic, with the highest burden observed among individuals aged 18-55 years. At enrollment, 56% of primary cases had detectable IgG antibodies (≥ 500 ng/mL). Seropositivity increased to 80%, 88%, and 93% at days 30, 180, and 360, respectively. Among unvaccinated participants, RBD-specific IgG titers peaked at one month and remained detectable up to 12 months following natural infection. Among household members, seropositivity increased from 57% at enrollment to 71% at the one-month follow-up. Among vaccinated primary cases, antibody titers peaked at 1-2 months after vaccination and declined markedly within 4-5 months. This study demonstrates robust antibody responses following natural SARS-CoV-2 infection and a marked rise-but rapid decline-of vaccine-induced immunity among Rohingya refugees. The findings highlight the need for timely booster doses, strengthened vaccination coverage, and continued serological monitoring to maintain protective immunity in high-density humanitarian settings. These insights can support targeted public health interventions and pandemic preparedness strategies for displaced and vulnerable populations.

Understanding the duration of the humoral immune response after coronavirus disease 2019 infection is critical for assessing vaccination strategies. This study aimed to evaluate the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in patients from Northern Jordan 1 year after infection. A descriptive cross-sectional study was conducted at King Abdullah University Hospital in Irbid, Jordan, from January to March 2021. Participants who were infected with the early SARS-CoV-2 variants circulating in Jordan (B.1, B.1.1, and B.1.1.312) prior to the emergence of the Alpha variant and unvaccinated were tested for antibodies against recombinant spike (S) and nucleocapsid (N) proteins using the quantitative Elecsys Anti-SARS-CoV-2 S and the qualitative Elecsys Anti-SARS-CoV-2 assays, respectively (Roche Diagnostics GmbH, Mannheim). Data were analyzed using Statistical Package for Social Sciences, and chi-square tests were applied to identify associations. Among 122 participants (62 males, 60 females), more than 50% of the patients retained detectable antibodies 1 year postinfection. Spike protein antibodies showed a more consistent long-term presence compared to nucleocapsid antibodies. Blood group O individuals showed the lowest seropositivity rates (P = .06). Other variables, including age, gender, comorbidities, smoking status, and symptom severity, did not show a significant correlation with antibody persistence. SARS-CoV-2 antibodies persist in more than 50% of patients for at least 1 year postinfection, particularly against the spike protein. These findings support the potential for long-term immune protection and may inform vaccination policies, particularly in resource-limited settings.

ABSTRACT Aims/Background Medical events during birth and self-reported birth experience may influence early relational health (ERH) in the postpartum period. Limited longitudinal work has been conducted in this area, particularly among women who gave birth during the COVID-19 pandemic. The goal of this study was to assess labour and delivery characteristics and maternal birth satisfaction as predictors of ERH domains of mother-reported bonding and observed emotional connection in the first year of life among women who gave birth during the COVID-19 pandemic. Design/Methods Participants included mothers (n = 384) with and without SARS-CoV-2 infection during pregnancy who gave birth at three U.S.-based academic medical centres who were enrolled in the Epidemiology of Severe Acute Respiratory Syndrome Coronavirus-2 in Pregnancy and Infancy COVID-19 Mother Baby Outcomes (ESPI COMBO) Study. Labour and delivery information was abstracted from medical records. Mothers completed surveys assessing birth satisfaction (2 months) and bonding (4 months postpartum). A remote (Zoom) video visit was conducted at 4–6 months postpartum and observed mother–infant emotional connection was coded using the Welch Emotional Connection Screen. We evaluated study aims using structural equation models. Results Maternal and infant medical risks (e.g. maternal complications, unplanned caesarean deliveries, care escalation) were associated with lower maternal birth satisfaction, which in turn predicted lower mother-reported bonding and observed emotional connection in infancy. Conclusion Results provide insight into perinatal determinants of early relational health among infants born during the COVID-19 pandemic and inform transdisciplinary clinical care approaches to support families and children in the transition to motherhood.