Search Results (18,458)

Background/Objectives: Precautionary health behaviours (PHBs), such as hand-washing or self-isolation, are non-pharmaceutical interventions used to reduce SARS-CoV-2 transmission. We investigated the potential confounding by PHBs of COVID-19 vaccine effectiveness (VE) estimates in a subset of study participants enrolled in id.DRIVE. Methods: The id.DRIVE COVID-19 VE study (formerly COVIDRIVE) is a European multicentre test-negative case–control study estimating COVID-19 VE against hospitalisation due to laboratory-confirmed SARS-CoV-2 in patients with severe acute respiratory infection. All adults (≥18 y) prospectively enrolled between 16 November 2021 and 16 August 2023 at three sites were invited to complete a PHB survey capturing indicators of PHBs in the 3 months preceding admission. Fisher’s exact test with Bonferroni-adjusted threshold was used to measure the level of association between PHB indicators and both COVID-19 vaccine status and SARS-CoV-2 test result. VE estimates were generated with and without adjustment for PHBs. Results: PHBs were modified over time, with higher precautionary attitudes in the first COVID-19 vaccine booster season (2021–2022) compared to the second one (2022–2023). For the first booster season, PHBs were positively associated with exposures (vaccination status) and outcomes (case or control status). Adjusting for PHBs led to a 6 to 9 percentage-point increase in VE estimates. Conversely, no confounding by PHBs was observed in the second booster season. Conclusions: PHBs should be considered a possible confounder of COVID-19 VE studies. Further research is needed to define when PHBs should be integrated into VE models, as the level of confounding may differ according to the study population and the epidemiological context. Full article

The Jurubatiba Sandbank National Park (PARNA Jurubatiba) is an ecological reserve characterized by harsh environmental conditions, including low rainfall, high sun exposure, and sandy soil. Among its native vegetation, Eremanthus crotonoides stands out for its richness in flavonoids, phenolic compounds, and sesquiterpene lactones. The objective of this study was to isolate and quantify sesquiterpene lactones from this species using ¹H NMR and to investigate their anti-SARS-CoV-2 potential and cytotoxicity against cancer cells. UPLC-(ESI)-MS/MS analyses enabled metabolite annotation, and semi-preparative HPLC-DAD allowed the isolation of centratherin and goyazensolide, which were identified by 1D and 2D NMR. In vitro assays showed that centratherin at 10 µM concentration reduced the viability of PC-3 and HCT-116 cancer cells by 100%, while goyazensolide had no noteworthy effects. Furthermore, enzymatic inhibition assays on SARS-CoV2 targets revealed that centratherin exhibited a lower apparent IC₅₀ of 12 µM against PL^pro, while goyazensolide was more active against 3CL^pro, with an IC₅₀ of 71 µM. Notably, the dichloromethane fraction demonstrated promising activity against both enzymes, with IC₅₀ values of 30 µM for PL^pro and 11 µM for 3CL^pro. This study reports, for the first time, the isolation of goyazensolide from E. crotonoides and highlights the potential of both sesquiterpene lactones as SARS-CoV-2 enzyme inhibitors. In contrast to centratherin, goyazensolide fortunately had almost no cytotoxic effects at inhibition concentration on the cells tested. This shows that anticancer and anti-SARS effects can be separated and should have different SARs, an important prerequisite for further development. Full article

Background/Objectives: Bitter Taste Receptors (encoded by TAS2R genes) are expressed in mucosal and bronchial epithelia, as well as in immune cells, contributing to defense against airborne pathogens such as SARS-CoV-2. Data on single-nucleotide polymorphisms (SNPs) in TAS2R genes or pseudogenes in COVID-19 are limited. This study examined the association between TAS2R SNPs and COVID-19 infection and seroconversion in European individuals participating in the Canadian Longitudinal Study on Aging. Methods: Data from the Genome-wide Genetic Data, Comprehensive Baseline (version 7.0), Follow-up 2 (version 1.1), COVID-19 Questionnaire Study (4-2020 to 12-2020), and COVID-19 Seroprevalence (Antibody) Study (11-2020 to 7-2021) datasets were accessed. Associations of TAS2R SNPS with COVID-19 infection or seroconversion were determined using logistic regression adjusted for sociodemographics, genetic principal components, smoking, vaccine doses, and chronic medical conditions (diabetes, immune-mediated inflammatory diseases (IMIDs), respiratory disease, and cardiovascular disease). Results: In the COVID-19 Questionnaire Study (N = 14,073), the rs117458236 (C) variant in TAS2R20 showed a trend toward an association with COVID-19 infection (OR = 1.95; 95% Confidence Interval (CI): 0.98, 3.51). In the COVID-19 Antibody Study (N = 8313), the rs2234235(G) variant in TAS2R1 was associated with anti-nucleocapsid (OR = 1.55; CI: 1.06, 2.20) and anti-spike response (OR = 0.74; CI: 0.57, 0.98); the rs2234010(A) variant in TAS2R5 was associated with anti-nucleocapsid (OR = 1.56; CI: 1.08, 2.19); and the rs34039200(A) variant in TAS2R62P was associated with anti-spike (OR = 0.86; CI: 0.77, 0.97). In a subgroup analysis, the rs2234235(G) variant in TAS2R1 was associated with a decreased anti-spike response to infection or vaccination in individuals with IMIDs or respiratory disease and an increased risk of SARS-CoV-2 infection. Conclusions: TAS2R variants are associated with COVID-19 infection and vaccine response. These data may inform personalized management and vaccination strategies. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) closely interacts with host cellular mechanisms, with mitochondria playing a crucial role in this process. As essential organelles that control cellular energy production, apoptosis, reactive oxygen species (ROS) metabolism, and innate immune responses, mitochondria are vital to the development of COVID-19. However, the exact molecular interactions between mitochondria and SARS-CoV-2 remain under active investigation. Gaining a comprehensive understanding of mitochondrial involvement in SARS-CoV-2 infection is therefore essential for uncovering complex disease mechanisms, identifying prognostic biomarkers, and developing effective treatments. Ultimately, exploring these virus–host interactions may provide new insights into the fundamental and complex aspects of mitochondrial physiology and pathophysiology. Full article

Respiratory viral infections are a major cause of morbidity and mortality worldwide. The COVID-19 pandemic has evidenced the need for broad-spectrum antivirals and improved preclinical models that more accurately recapitulate human respiratory disease. These new strategies should also involve the search for drug targets in the infected cell that hamper the development of resistance and of potential efficacy against diverse viruses. Since many viruses reprogram cellular metabolism to support viral replication, we performed a comparative analysis of inhibitors targeting the PI3K/AKT/mTOR pathway, central to virus-induced metabolic adaptations, using MRC5 lung fibroblasts and Huh7 hepatoma cells. HCoV-229E infection in MRC5 cells caused the expected shift in the energy metabolism but the inhibitors had markedly different effects on the metabolic profile and antiviral activity in these two cell lines. Dichloroacetate (DCA), a clinically approved inhibitor of aerobic glycolysis, showed antiviral activity against HCoV-229E in MRC5 cells, but not in Huh7 cells, underscoring that the screening model is more critical than previously assumed. We further tested DCA in polarized human small airway epithelial cells cultured in air–liquid interface, a 3D model that mimics the human respiratory tract. DCA reduced the viral progeny of HCoV-229E, SARS-CoV-2, and respiratory syncytial virus by 2–3 orders of magnitude, even when administered after infection was established. Our work reinforces the need for advanced human preclinical screening models to identify antivirals that target host metabolic pathways frequently hijacked by respiratory viruses, and establishes DCA as a proof-of-concept candidate. Full article

Background: In the Kingdom of Saudi Arabia, various COVID-19 vaccines were administered during the pandemic. However, region-specific real-word comparative data on their immunogenicity remain limited. This study aimed to assess the serological responses to Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and AstraZeneca (ChAdOx1 nCoV-19) vaccines in a diverse population living in KSA. Methods: This observational study included 236 adults recruited from vaccination sites in Riyadh. Participants provided serum samples at predefined intervals: before the first dose, after the first dose, after the second dose, and post-vaccination infection (if applicable). IgG and neutralising antibodies were quantified using ELISA assays. Demographic and vaccination data, and their associations with antibody responses, were evaluated. Results: At baseline, 75.4% of participants were positive for SARS-CoV-2 IgG, suggesting high prior exposure. Marked incremental increases in IgG levels were observed after each vaccine dose. Both Moderna and Pfizer elicited stronger responses, with Pfizer inducing the strongest early response and Moderna achieving the highest overall titres. Among IgG-positive individuals, neutralising antibodies were detected in 98.1%. There were no statistically significant differences by age or gender, although males tended to show higher mean titres. Heterologous vaccine schedules induced comparable or enhanced immunogenicity relative to homologous schedules, supporting their use in flexible immunisation strategies. Conclusions: All COVID-19 vaccines administered in Saudi Arabia elicited robust antibody responses, particularly the mRNA-based vaccines. Our findings support their continued use and justify varied vaccination approaches, including mix-and-match booster strategies, to enhance community immunity. Full article

Viral metagenomic next-generation sequencing (vmNGS) has transformed our capacity for the untargeted detection and characterisation of (re)emerging zoonotic viruses, surpassing the limitations of traditional targeted diagnostics. In this review, we critically evaluate the current landscape of vmNGS, highlighting its integration within the One Health paradigm and its application to the surveillance and discovery of (re)emerging viruses at the human–animal–environment interface. We provide a detailed overview of vmNGS workflows including sample selection, nucleic acid extraction, host depletion, virus enrichment, sequencing platforms, and bioinformatic pipelines, all tailored to maximise sensitivity and specificity for diverse sample types. Through selected case studies, including SARS-CoV-2, mpox, Zika virus, and a novel henipavirus, we illustrate the impact of vmNGS in outbreak detection, genomic surveillance, molecular epidemiology, and the development of diagnostics and vaccines. The review further examines the relative strengths and limitations of vmNGS in both passive and active surveillance, addressing barriers such as cost, infrastructure requirements, and the need for interdisciplinary collaboration. By integrating molecular, ecological, and public health perspectives, vmNGS stands as a central tool for early warning, comprehensive monitoring, and informed intervention against (re)emerging viral threats, underscoring its critical role in global pandemic preparedness and zoonotic disease control. Full article

Background/Objectives: In response to the COVID-19 pandemic, we developed a vaccine candidate against SARS-CoV-2. Spike Ferritin Nanoparticle (SpFN) comprises 24 identical prefusion-stabilized spike proteins anchored to a self-assembled nanoparticle. Organized along the three-fold axis of the ferritin particle, eight SARS-CoV-2 spike trimers are presented per nanoparticle. Methods: Here, we describe the CGMP processes for manufacturing SpFN using transient transfection of Expi293F cells. Results: The final yield of SpFN was ~10 mg per liter of media supernatant. The resulting protein is stable in cold storage for two years at −20 °C, as well as for a month at room temperature, and can withstand multiple freeze/thaw cycles. SpFN material produced using the CGMP protocols adjuvanted with Army Liposomal Formulation-QS-21 (ALFQ) elicited potent neutralizing antibodies against WA-1, Alpha, Beta, and Delta variants in mice as measured by a pseudovirus neutralization assay. Conclusions: This work demonstrates rapid development and scaled-up production of clinical-grade SARS-CoV-2 vaccine protein material, allowing permissive storage and transport conditions, and serves as a framework for recombinant protein production for future emergent pathogens. Full article

Background/Objectives: Multisystem inflammatory syndrome in children (MIS-C), a rare but serious post-acute hyperinflammatory condition that occurs in children 2–6 weeks after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection or exposure, varies between countries. Despite its serious nature, most children recover without any sequelae. The most frequently reported long-term sequelae are coronary artery aneurysms. This study aimed to describe the epidemiological profile, clinical characteristics (including cardiac manifestations), treatment, and outcomes of multisystem inflammatory syndrome in children (MIS-C) under 14 years of age with SARS-CoV-2 between February 2020 and November 2021 in Kuwait. Methods: Data on sociodemographic factors, co-morbidities, presenting signs and symptoms, as well as laboratory and echocardiography findings were retrieved from the Pediatric COVID registry (PCR-Q8 registry). Results: Of the one hundred and two patients with a provisional diagnosis of MIS-C, eighty-three patients fulfilled the WHO criteria of MIS-C. Thirty-nine of the MIS-C patients were admitted to the intensive care unit, and only one child died due to cardiogenic shock. Sixteen patients from the pediatric MIS-C cohort were diagnosed with cardiac abnormalities. Sixteen patients from the pediatric MIS-C cohort were diagnosed with cardiac abnormalities. Most (63% (10/16)) of the patients had coronary abnormalities, nine patients (56%) had myocardial dysfunction, and six patients (38%) had dual pathologies. Pericarditis occurred in three patients only, whilst six patients (38%) had dual pathologies. Pericarditis occurred in three patients only. Conclusions: MIS-C appears to affect younger children in Kuwait than in other countries; however, the clinical pattern is consistent with other countries. Further studies of an analytical nature are recommended to identify the risk factors associated with MIS-C and its cardiac sequalae to allow for proactive risk reduction. Full article

Wild-type transthyretin amyloidosis is an underdiagnosed condition that significantly contributes to mortality in the elderly population. This histopathological study describes autopsy findings in patients with severe clinical course of COVID-19 and ATTR not identified during life. Autopsy findings in the myocardium were analyzed in 19 patients with pre-existing ATTR who died from severe COVID-19. RT PCR was used for pre- and post-mortem detection of SARS-CoV-2 RNA. Immunohistochemical typing was performed with a broad panel of antibodies against different amyloid types. Autopsy specimens from the myocardium and lungs were positive for SARS-CoV-2 RNA in 10 (53%) cases. Microscopic examination of the myocardium revealed focal cardiosclerosis and cardiomyocyte dissociation in 15 (68%) cases, hypertrophy and atrophy of cardiomyocytes in 17 (77%) and 7 (32%), respectively, and myocarditis in 4 (18%) cases. Immunohistochemical analysis determined ATTR amyloidosis in all cases. In patients with rapidly progressive heart failure, the postmortem examination revealed multiple sites of interstitial amyloid deposits and focal cardiosclerosis in the myocardium. Pre-existing cardiac amyloidosis contributes to the aggressive clinical course of COVID-19. Coupled with the toxic effect of the SARS-CoV-2 virus on the myocardium, the disease may lead to progressive heart failure and poor outcomes. Full article

The disease COVID-19, which has befallen mankind in recent years, was a challenge that we had not faced for centuries. The first registered patient case was in China. This review is performed by the inspection of a large body of worldwide investigations conducted in the peak period of the disease’s progress. The disease is spread by airborne droplets and develops mainly with fever, cough, sputum, and shortness of breath. Laboratory tests show leukopenia, lymphopenia, a decrease in the levels of sodium, potassium, and calcium, and an increase in the levels of CRP, LDH, and D-dimer. Radiological changes in most cases are bilateral and of the “ground glass” type in the lower parts of the lungs. The most severe complication of COVID-19 pneumonia is ARDS. The risk groups are people with chronic lung diseases, the elderly, and those who are overweight. This article analyzes and summarizes the main characteristics of SARS-CoV-2 pneumonia in order to better understand and apply better clinical management of this condition. Full article

The breach of an interspecies barrier by RNA viruses has facilitated the emergence of lethal hCoVs, particularly SARS-CoV-2, resulting in significant socioeconomic setbacks and public health risks globally in recent years. Moreover, the high evolutionary plasticity of hCoVs has led to the continuous emergence of diverse variants, complicating clinical management and public health responses. Studying the evolutionary trajectory of hCoVs, which provides a molecular roadmap for understanding viruses’ adaptation, tissue tropism, spread, virulence, and immune evasion, is crucial for addressing the challenges of zoonotic spillover of viruses. Tracing the evolutionary trajectory of lethal hCoVs provides essential genomic insights required for risk stratification, variant/sub-variant classification, preparedness for outbreaks and pandemics, and the identification of critical viral elements for vaccine and therapeutic development. Therefore, this review examines the evolutionary landscape of the three known lethal hCoVs, presenting a focused narrative on SARS-CoV-2 variants under monitoring (VUMs) as of May 2025. Using advanced bioinformatics approaches and data visualization, the review highlights key spike protein substitutions, particularly within the receptor-binding domain (RBD), which drive transmissibility, immune escape, and potential resistance to therapeutics. The article highlights the importance of real-time genomic surveillance and intervention strategies in mitigating emerging variant/sub-variant risks within the ongoing COVID-19 landscape. Full article

Background/Objectives: The interplay between asthma and COVID-19 raises critical clinical questions, particularly regarding the risk of hematological complications in patients affected by both conditions. While COVID-19 is known to cause coagulopathy and thromboembolic events, it remains unclear whether asthma independently influences these risks. This systematic review aimed to synthesize existing evidence on hematological abnormalities—including D-dimer elevation, thrombocytopenia, and venous thromboembolism (VTE)—in asthmatic patients with confirmed SARS-CoV-2 infection. Methods: A systematic search was conducted in PubMed and Web of Science databases for studies published between January 2020 and May 2025. Inclusion criteria were studies reporting hematologic outcomes in asthmatic patients with COVID-19. After duplicate removal, 139 unique articles were screened, with 40 studies meeting inclusion criteria. These included observational cohorts, retrospective analyses, and clinical investigations. Data were synthesized in a systematic review with qualitative synthesis due to heterogeneity in design and reporting. Results: The review identified variable patterns of D-dimer elevation and thrombotic events among asthmatic COVID-19 patients. Some studies reported a higher incidence of ICU admission, elevated inflammatory and coagulation markers, and increased thromboembolic risk in asthmatic individuals—particularly those with poor disease control or non-allergic phenotypes. However, findings were inconsistent and often limited by the absence of asthma stratification, standardized outcome measures, and prospective designs. Conclusions: Current evidence does not support a definitive link between asthma and increased thrombotic risk in COVID-19. Further research with prospective, phenotype-stratified methodologies and harmonized hematologic endpoints is needed to clarify whether asthma modifies the hematologic trajectory of SARS-CoV-2 infection. Full article

Background: Due to the wide host range of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccination has been recommended for susceptible species in zoological collections, particularly to protect endangered species. The Zoetis^® Experimental Mink Coronavirus Vaccine (Subunit) was temporarily authorized in 2021–2024 for emergency use in North America for this purpose. However, there are limited data regarding its safety or efficacy in non-domestic mammals. The present study was conducted to assess the ability of this vaccine to elicit serum neutralizing titers against SARS-CoV-2 in selected animals from the Toronto Zoo (TZ) vaccinated during 2022. Methods: Serum samples were collected from 24 individuals across four families (Cervidae, Felidae, Ursidae, and Hyaenidae) and tested using a surrogate virus neutralization test (sVNT) and a plaque-reduction neutralization test (PRNT). Results: The results showed that all species developed some neutralizing titers after at least one vaccine dose, except for polar bears, which showed no seroconversion. Felids and hyenas had the highest neutralizing titers, which peaked at 3 and declined between 4 and 6 months after boost. These differences may stem from species-specific immune responses or lack of vaccination protocols tailored to individual species. Conclusions: While natural infection with SARS-CoV-2 could not be ruled out in the cohort of this study, insights from our results have the potential to inform future vaccine recommendations for non-domestic species. Furthermore, our study highlighted the value of competitive assays in assessing serological responses across a broad range of exotic species, for which reagents, such as anti-isotype antibodies, are often unavailable. Full article

Bats host a wide range of viruses, including several high-profile pathogens of humans and other animals. The COVID-19 pandemic raised the level of concern regarding the risk of spillover of bat-borne viruses to humans and, conversely, human-borne viruses to bats. From August 2020 to July 2021, we conducted viral surveillance on 254 bats from 10 species across urban, periurban, and rural environments in New Mexico, USA. We used a pan-coronavirus RT-PCR to assay rectal swabs and performed metagenomic sequencing on a representative subset of 14 rectal swabs and colon samples. No coronaviruses were detected by either RT-PCR or metagenomic sequencing. However, four novel viruses were identified: an adenovirus (proposed name lacepfus virus, LCPV), an adeno-associated virus (AAV), an astrovirus (AstV), and a genomovirus (GV). LCPV, detected in a big brown bat (Eptesicus fuscus), is more closely related to canine adenoviruses than to other bat adenoviruses, suggesting historical transmission between bats and dogs. All virus-positive bats were either juvenile or adult individuals captured in urban environments; none exhibited obvious clinical signs of disease. Our findings suggest limited or no circulation of enzootic coronaviruses or SARS-CoV-2 in southwestern U.S. bat populations during the study period. The discovery of a genetically distinct adenovirus related to canine adenoviruses highlights the potential for cross-species viral transmission and underscores the value of continued virome surveillance in animals living with and near humans. Full article