Search Results (364)

In Ukraine, SARS-CoV-2 detection and national genomic surveillance have been complicated by full-scale war, limited resources, and varying levels of public health infrastructure impacted across the country. Following the Spring of 2022, only a paucity of data have been reported describing the prevalence and variant dynamics of SARS-CoV-2 in the country. Comparative whole genome analysis has overtaken diagnostics as the new gold standard for detecting and tracing emerging variants while showing utility to rapidly inform diagnostics, vaccine strategies, and health policy. Herein, we provide an updated report characterizing the dynamics and prevalence of SARS-CoV-2 in Ukraine from 1 May 2022 to 31 March 2024. The present study extends previous reports for disease incidence Waves 1–4 in Ukraine with the addition herein of Waves 5, 6, and 7, occurring from August to November 2022 (Wave 5), February to May 2023 (Wave 6), and October 2023 to January 2024 (Wave 7). During the study period, the national Case Fatality Rate (CFR) fluctuated between 0.46% and 1.74%, indicating a consistent yet modest rate when compared to the global average. The epidemiological dynamics of Variants of Concern (VOCs) in Ukraine reflected global patterns over this period, punctuated by the rise of the BA.5 lineage and its subsequent replacement by the Omicron subvariants XBB and JN.1. Our analysis of variant dispersal patterns revealed multiple potential spatiotemporal introductions into Ukraine from Europe, Asia, and North America. Our results highlight the importance of ongoing genomic surveillance to monitor variant dynamics and support global efforts to control and mitigate COVID-19 disease risks as new variants arise. Full article

Background/Objectives: For viral entry into host cells, the spike (S) protein of coronavirus (CoV) uses its S1 domain to bind to the host receptor and S2 domain to mediate the fusion between virion and cellular membranes. The S1 domain acquired multiple mutations as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved to give rise to Variant of Concerns (VOCs) but the S2 domain has limited changes. In particular, the stem helix in S2 did not change significantly and it is fairly well-conserved across multiple beta-CoVs. In this study, we generated a murine mAb 7B2 binding to the stem helix of SARS-CoV-2. Methods: MAb 7B2 was isolated from immunized mouse and its neutralization activity was evaluated using microneutralization, plaque reduction and cell–cell fusion assays. Bio-layer interferometry was used to measure binding affinity and AlphaFold3 was used to model the antibody–antigen interface. Results: MAb 7B2 has lower virus neutralizing and membrane block activities when compared to a previously reported stem helix-binding human mAb S2P6. Alanine scanning and AlphaFold3 modeling reveals that residues K1149 and D1153 in S form a network of polar interactions with the heavy chain of 7B2. Conversely, S2P6 binding to S is not affected by alanine substitution at K1149 and D1153 as indicated by the high ipTM scores in the predicted S2P6-stem helix structure. Conclusions: Our detailed characterization of the mechanism of inhibition of 7B2 reveals its distinctive binding model from S2P6 and yields insights on multiple neutralizing and highly conserved epitopes in the S2 domain which could be key components for pan-CoV vaccine development. Full article

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern (VOCs) underscore the critical role of vaccination in pandemic control. These mutations not only enhance viral infectivity but also facilitate immune evasion and diminish vaccine efficacy, necessitating ongoing surveillance and vaccine adaptation. Current SARS-CoV-2 vaccines, including inactivated, live-attenuated, viral vector, protein subunit, virus-like particle, and nucleic acid vaccines, face challenges due to the immune evasion strategies of emerging variants. Moreover, other sarbecoviruses, such as SARS-CoV-1 and SARS-related coronaviruses (SARSr-CoVs) pose a potential risk for future outbreaks. Thus, developing vaccines capable of countering emerging SARS-CoV-2 variants and providing broad protection against multiple sarbecoviruses is imperative. Several innovative vaccine platforms are being investigated to elicit broad-spectrum neutralizing antibody responses, offering protection against both current SARS-CoV-2 variants and other sarbecoviruses. This review presents an updated overview of the key target antigens and therapeutic strategies employed in current SARS-CoV-2 vaccines. Additionally, we summarize ongoing approaches for the development of vaccines targeting infectious sarbecoviruses. Full article

Air pollution is an escalating global concern with significant implications for human health and athletic performance. This narrative review synthesizes and critically compares the current literature on the impact of air pollution on health and football performance, elucidates the physiological mechanisms involved, and evaluates available mitigation strategies. Comparative studies consistently demonstrate that football players—who frequently engage in high-intensity outdoor exercise—are particularly susceptible to the harmful effects of airborne pollutants such as particulate matter (PM), volatile organic compounds (VOCs), nitrogen dioxide (NO₂), ozone (O₃), and carbon monoxide (CO). These pollutants bypass natural respiratory defenses due to increased pulmonary ventilation during exercise, reaching deeper lung regions and triggering oxidative stress, inflammation, and impaired lung function. Evidence across studies indicates that poor air quality is associated with decreased football performance, including reduced distance covered, fewer high-intensity efforts, elevated physiological strain, and diminished training adaptation. Long-term exposure exacerbates respiratory conditions, suppresses immune function, and heightens the risk of illness and injury. Furthermore, comparative genetic research highlights inter-individual variability in pollution sensitivity, with specific gene variants conferring either increased vulnerability or resilience to adverse effects. This review also explores practical and emerging mitigation strategies—such as timing training to avoid peak pollution, utilizing air quality monitoring and antioxidant-rich diets, and promoting sustainable infrastructure—to safeguard athlete health and optimize performance. Novel approaches including respiratory training, anti-smog masks, indoor sessions, and personalized recovery protocols offer additional protection and recovery support. Full article

SARS-CoV-2 remains a severe threat to worldwide public health, particularly as the virus continues to evolve and diversify into variants of concern (VOCs). Among these VOCs, Omicron variants exhibit unique phenotypic traits, such as immune evasion, transmissibility, and severity, due to numerous spike protein mutations and the rapid subvariant evolution. These Omicron subvariants have more than 15 mutations in the receptor-binding domain (RBD), a region of the SARS-CoV-2 spike protein that is important for recognition and binding with the angiotensin-converting enzyme 2 (ACE2) human receptor. To address the impact of these high numbers of Omicron mutations on the binding process, we have developed a novel method to precisely quantify amino acid interactions via the amino acid–amino acid bond pair (AABP). We applied this concept to investigate the interface interactions of the RBD–ACE2 complex in four Omicron Variants (BA.1, BA.2, BA.5, and XBB.1.16) with its Wild Type counterpart. Based on the AABP analysis, we have identified all the sites that are affected by mutation and have provided evidence that unmutated sites are also impacted by mutation. We have calculated that the binding between RBD and ACE2 is strongest in OV BA.1, followed by OV BA.2, WT, OV BA.5, and OV XBB.1.16. We also present the partial charge values for all 311 residues across these five models. Our analysis provides a detailed understanding of changes caused by mutation in each Omicron interface complex. Full article

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating the severity of clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have been developed to this effect, including BioNTech-Pfizer and Moderna’s mRNA vaccines, as well as adenovirus vector-based vaccines such as Oxford–AstraZeneca. However, the emergence of new variants and subvariants of SARS-CoV-2, characterized by enhanced transmissibility and immune evasion, poses significant challenges to the efficacy of current vaccination strategies. In this review, we aim to comprehensively outline the landscape of emerging SARS-CoV-2 variants of concern (VOCs) and sub-lineages that have recently surfaced in the post-pandemic years. We assess the effectiveness of existing vaccines, including their booster doses, against these emerging variants and subvariants, such as BA.2-derived sub-lineages, XBB sub-lineages, and BA.2.86 (Pirola). Furthermore, we discuss the latest advancements in vaccine technology, including multivalent and pan-coronavirus approaches, along with the development of several next-generation coronavirus vaccines, such as exosome-based, virus-like particle (VLP), mucosal, and nanomaterial-based vaccines. Finally, we highlight the key challenges and critical areas for future research to address the evolving threat of SARS-CoV-2 subvariants and to develop strategies for combating the emergence of new viral threats, thereby improving preparedness for future pandemics. Full article

Mutation is one of the most important drivers of viral evolution and genome variability, allowing viruses to potentially evade host immune responses and develop drug resistance. In the context of COVID-19, local genomic surveillance of circulating virus populations is therefore critical. The goals of this study were to describe the distribution of different SARS-CoV-2 lineages, assess their genomic differences, and infer virus importation events in Bangladesh. We individually aligned 1965 SARS-CoV-2 genome sequences obtained between April 2020 and June 2021 to the Wuhan-1 sequence and used the resulting multiple sequence alignment as input to infer a maximum likelihood phylogenetic tree. Sequences were assigned to lineages as described by the hierarchical Pangolin nomenclature scheme. We built a phylogeographic model using the virus population genome sequence variation to infer the number of virus importation events. We observed thirty-four lineages and sub-lineages in Bangladesh, with B.1.1.25 and its sub-lineages D.* (979 sequences) dominating, as well as the Beta variant of concern (VOC) B.1.351 and its sub-lineages B.1.351.* (403 sequences). The earliest B.1.1.25/D.* lineages likely resulted from multiple introductions, some of which led to larger outbreak clusters. There were 570 missense mutations, 426 synonymous mutations, 18 frameshift mutations, 7 deletions, 2 insertions, 10 changes at start/stop codons, and 64 mutations in intergenic or untranslated regions. According to phylogeographic modeling, there were 31 importation events into Bangladesh (95% CI: 27–36). Like elsewhere, Bangladesh has experienced distinct waves of dominant lineages during the COVID-19 pandemic; this study focuses on the emergence and displacement of the first wave-dominated lineage, which contains mutations seen in several VOCs and may have had a transmission advantage over the extant lineages. Full article

Wastewater surveillance has become a valuable tool to monitor the emergence of SARS-CoV-2 variants of concern (VOCs) at the community level. In this study, we aimed to evaluate the presence of Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1617.2), and Omicron (B.1.1.529) VOCs in samples from the inlet of a wastewater treatment plant (WWTP) as well as from two different sewer interceptors (SI-1 and SI-2) from the urban sewage system in Santiago de Compostela (Galicia, NW of Spain) throughout 2021 and January 2022. For this purpose, detection and quantification of the four VOCs was performed using four duplex SARS-CoV-2 allelic discrimination RT-qPCR assays, targeting the S-gene. An N1 RT-qPCR gene assay was used as a reference for the presence of SARS-CoV-2 RNA in wastewater samples. All VOCs were detected in wastewater samples. Alpha, Beta, Delta, and Omicron VOCs were detected in 45.7%, 7.5%, 66.7%, and 72.7% of all samples, respectively. Alpha VOC was dominant during the first part of the study, whereas Delta and Omicron detection peaks were observed in May–June and December 2021, respectively. Some differences were observed among the results obtained for the two city sectors studied, which could be explained by the differences in the characteristics of the population between them. Wastewater-based epidemiology allowed us to track the early circulation and emergence of SARS-CoV-2 variants at a local level, and our results are temporally concordant with clinical data and epidemiological findings reported by the health authorities. Full article

Background: The rapid genetic evolution of SARS-CoV-2 has led to the emergence of immune-evading, highly transmissible variants of concern (VOCs). This prompts the need for next-generation vaccines that elicit robust mucosal immunity in the airways to directly curb viral infection. Objective: Here, we investigate the impact of heterologous variant prime–boost regimens on humoral responses, focusing on intramuscular (IM) and intranasal (IN) routes of administration. Using a murine model, we assessed the immunogenicity of unadjuvanted protein boosts with Wu-1, Omicron BA.4/5, or Wu-1 + BA.4/5 spike antigens following monovalent or bivalent IM priming with mRNA-LNP vaccines. Results: IM priming induced strong systemic total and neutralizing antibody responses that were further enhanced by IN boosts with BA.4/5. IN boosting achieved the broadest serum neutralization across all VOCs tested. Notably, bivalent mRNA-LNP IM priming induced robust, cross-variant serum neutralizing antibody production, independent of subsequent IN boost combinations. Conclusions: Our findings highlight the benefit of including distinct antigenic variants in the prime vaccination followed by a variant-tailored IN boost to elicit both systemic and mucosal variant-specific responses that are potentially capable of reducing SARS-CoV-2 transmission. Full article

The Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2), a causative agent of the COVID-19 disease, has been constantly evolving since its first identification. Mutations that are embedded in the viral genomic RNA affect the properties of the virus and lead to the emergence of new variants. During the COVID-19 pandemic, the World Health Organization has identified more than ten variants of the SARS-CoV-2 virus. Five of these—Alpha, Beta, Gamma, Delta, and Omicron—were classified as variants of concern (VOCs), as they caused significant outbreaks of the disease. Additionally, two progeny variants of Omicron, designated JN.1 and KS.1, are still causing new waves of infections. Due to the emergence of various SARS-CoV-2 variants, in some cases, it has become important to identify a particular variant in a sample. Here, we have developed a multiplexed probe-based real-time PCR system for the identification of SARS-CoV-2 VOCs (Alpha, Beta, Gamma, Delta, Omicron B.1.1.529/BA.1, and Omicron BA.2), as well as modern Omicron variants JN.1 and KS.1. The sensitivity and specificity of the PCR system have been tested using isolated viral genomes and RNA preparations from human nasopharyngeal swabs. The system allows for rapid identification of coronavirus variants in the cryopreserved and fresh samples. Full article

COVID-19, first identified in December 2019 in Wuhan, China, is caused by the SARS-CoV-2 virus, a pathogen that primarily targets the respiratory system and can lead to severe conditions such as acute respiratory distress syndrome (ARDS). Among the seven coronaviruses known to infect humans, three—SARS-CoV, MERS-CoV, and SARS-CoV-2—are associated with severe illness and significant morbidity. SARS-CoV-2 is an enveloped, single-stranded RNA virus that utilizes the angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry. The genetic sequence of SARS-CoV-2 is highly mutable, leading to the emergence of variants that alter disease pathology and transmission dynamics. The World Health Organization (WHO) has classified these mutations into variants of concern (VOCs), variants of interest (VOIs), and variants under monitoring (VUMs). This review provides an in-depth analysis of both historical and emerging SARS-CoV-2 variants, summarizes recent advancements in diagnostic methods for SARS-CoV-2 detection, and discusses current therapeutic strategies for COVID-19, with a particular focus on virus-like particle (VLP) vaccines developed in recent years. Additionally, we highlight ongoing therapeutic approaches and their implications for managing COVID-19. Full article

The emergence of SARS-CoV-2 variants has significantly impacted the global response to the COVID-19 pandemic. This review examines the genetic diversity of SARS-CoV-2 variants, their roles in epidemiological tracking, and their influence on viral fitness. Variants of concern (VOCs) such as Alpha, Beta, Gamma, Delta, and Omicron have demonstrated increased transmissibility, altered pathogenicity, and potential resistance to neutralizing antibodies. Epidemiological tracking of these variants is crucial for understanding their spread, informing public health interventions, and guiding vaccine development. The review also explores how specific mutations in the spike protein and other genomic regions contribute to viral fitness, affecting replication efficiency, immune escape, and transmission dynamics. By integrating genomic surveillance data with epidemiological and clinical findings, this review provides a comprehensive overview of the ongoing evolution of SARS-CoV-2 and its implications for public health strategies and new vaccine development. Full article

The evolutionary origin of the variants of concern (VOCs) of SARS-CoV-2, characterized by a large number of new substitutions and strong changes in virulence and transmission rate, is intensely debated. The leading explanation in the literature is a chronic infection in immunocompromised individuals, where the virus evolves before returning into the main population. The present article reviews less-investigated hypotheses of VOC emergence with transmission between acutely infected hosts, with a focus on the mathematical models of stochastic evolution that have proved to be useful for other viruses, such as HIV and influenza virus. The central message is that understanding the acting factors of VOC evolution requires the framework of stochastic multi-locus evolution models, and that alternative hypotheses can be effectively verified by fitting results of computer simulation to empirical data. Full article

We have previously shown that the hepatitis C virus (HCV) E1E2 envelope glycoprotein can regulate HIV-1 long-terminal repeat (LTR) activity through disruption to NF-κB activation. This response is associated with upregulation of the endoplasmic reticulum (ER) stress response pathway. Here, we demonstrate that the SARS-CoV-2 S, M, and E but not the N structural protein can perform similar downmodulation of HIV-1 LTR activation, and in a dose-dependent manner, in both HEK293 and lung BEAS-2B cell lines. This effect is highest with the SARS-CoV-2 Wuhan S strain and decreases over time for the subsequent emerging variants of concern (VOC), with Omicron providing the weakest effect. We developed pseudo-typed viral particle (PVP) viral tools that allowed for the generation of cell lines constitutively expressing the four SARS-CoV-2 structural proteins and utilising the VSV-g envelope protein to deliver the integrated gene construct. Differential gene expression analysis (DGEA) was performed on cells expressing S, E, M, or N to determine cell activation status. Gene expression differences were found in a number of interferon-stimulated genes (ISGs), including IF16, IFIT1, IFIT2, and ISG15, as well as for a number of heat shock protein (HSP) genes, including HSPH1, HSPA6, and HSPBP1, with all four SARS-CoV-2 structural proteins. There were also differences observed in expression patterns of transcription factors, with both SP1 and MAVS upregulated in the presence of S, M, and E but not the N protein. Collectively, the results indicate that gene expression patterns associated with ER stress pathways can be activated by SARS-CoV-2 envelope glycoprotein expression. The results suggest the SARS-CoV-2 infection can modulate an array of cell pathways, resulting in disruption to NF-κB signalling, hence providing alterations to multiple physiological responses of SARS-CoV-2-infected cells. Full article

The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is in its sixth year and is being maintained by the inability of current spike-alone-based COVID-19 vaccines to prevent transmission leading to the continuous emergence of variants and sub-variants of concern (VOCs). This underscores the critical need for next-generation broad-spectrum pan-Coronavirus vaccines (pan-CoV vaccine) to break this cycle and end the pandemic. The development of a pan-CoV vaccine offering protection against a wide array of VOCs requires two key elements: (1) identifying protective antigens that are highly conserved between passed, current, and future VOCs; and (2) developing a safe and efficient antigen delivery system for induction of broad-based and long-lasting B- and T-cell immunity. This review will (1) present the current state of antigen delivery platforms involving a multifaceted approach, including bioinformatics, molecular and structural biology, immunology, and advanced computational methods; (2) discuss the challenges facing the development of safe and effective antigen delivery platforms; and (3) highlight the potential of nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNP) as the platform that is well suited to the needs of a next-generation pan-CoV vaccine, such as the ability to induce broad-based immunity and amenable to large-scale manufacturing to safely provide durable protective immunity against current and future Coronavirus threats. Full article