Project description:BackgroundMany new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been termed variants of concern/interest (VOC/I) because of the greater risk they pose due to possible enhanced transmissibility and/or severity, immune escape, diagnostic and/or treatment failure, and reduced vaccine efficacy.AimsWe sought to review the current knowledge of emerging SARS-CoV-2 variants, particularly those deemed VOC/Is: B.1.351, B.1.1.7, and P.1.SourcesMEDLINE and BioRxiv databases, as well as the grey literature, were searched for reports of SARS-CoV-2 variants since November 2020. Relevant articles and their references were screened.ContentMutations on the spike protein in particular may affect both affinity for the SARS-CoV-2 cell receptor ACEII and antibody binding. These VOC/Is often share similar mutation sets. The N501Y mutation is shared by the three main VOCs: B.1.1.7, first identified in the United Kingdom, P.1, originating from Brazil, and B.1.351, first described in South Africa. This mutation likely increases transmissibility by increasing affinity for ACEII. The B.1.351 and P.1 variants also display the E484K mutation which decreases binding of neutralizing antibodies, leading to partial immune escape; this favours reinfections, and decreases the in vitro efficacy of some antibody therapies or vaccines. Those mutations may also have phenotypical repercussions of greater severity. Furthermore, the accumulation of mutations poses a diagnostic risk (lowered when using multiplex assays), as seen for some assays targeting the S gene. With ongoing surveillance, many new VOC/Is have been identified. The emergence of the E484K mutation independently in different parts of the globe may reflect the adaptation of SARS-CoV-2 to humans against a background of increasing immunity.ImplicationsThese VOC/Is are increasing in frequency globally and pose challenges to any herd immunity approach to managing the pandemic. While vaccination is ongoing, vaccine updates may be prudent. The virus continues to adapt to transmission in humans, and further divergence from the initial Wuhan sequences is expected.
Project description:hACE2 transgenic mice were infected with the original SARS-CoV-2 strain (B.1) and the Beta (B.1.351) variant. Lung and spleen samples were collected 1 day post infection (DPI), 3 DPI and 5 DPI, and mRNA was sequenced.
Project description:BackgroundThe rapid development of safe and effective vaccines against the SARS-CoV-2 virus has been a singular scientific achievement. Confounding due to health seeking behaviours, circulating variants, and differential testing by vaccination status may bias analyses towards an apparent increase in infection severity following vaccination.MethodsWe used data from Ontario, Canada's Case and Contact Management database, merged to a provincial vaccination dataset (COVaxON) to create a time-matched cohort of individuals who were hospitalized with SARS-CoV-2 infection. Vaccinated individuals were matched to up to five unvaccinated individuals based on test date. Risk of ICU admission and death were evaluated using conditional logistic regression. Unmatched exploratory analyses were performed to identify sources of heterogeneity in vaccine effects.ResultsIn 20,064 individuals (3,353 vaccinated and 16,711 unvaccinated) hospitalized with infection due to SARS-CoV-2 between January 1st, 2021 and January 5th, 2022, vaccination with 1, 2, or 3 doses significantly reduced the risk of ICU admission and death. An inverse dose-response relationship was observed between vaccine doses received and both outcomes (adjusted odds ratio (aOR) per additional dose for ICU admission: 0.66, 95% CI 0.62 to 0.71; aOR for death: 0.78, 95% CI 0.72 to 0.84). Reduction in risk was greater for ICU admission than for death (P for heterogeneity <0.05).InterpretationWe identified decreased virulence of SARS-CoV-2 infections in vaccinated individuals, even when vaccines failed to prevent infection sufficiently severe to cause hospitalization. Even with diminished efficacy of vaccines against infection with novel VOCs, vaccines remain an important tool for reduction of ICU admission and mortality.
Project description:SARS-CoV-2 has produced various variants during its ongoing evolution. The competitive behavior driven by the co-transmission of these variants has influenced the pandemic transmission dynamics. Therefore, studying the impact of competition between SARS-CoV-2 variants on pandemic transmission dynamics is of considerable practical importance. In order to formalize the mechanism of competition between SARS-CoV-2 variants, we propose an epidemic model that takes into account the co-transmission of competing variants. The model focuses on how cross-immunity influences the transmission dynamics of SARS-CoV-2 through competitive mechanisms between strains. We found that inter-strain competition affects not only both the final size and the replacement time of the variants, but also the invasive behavior of new variants in the future. Due to the limited extent of cross-immunity in previous populations, we predict that the new strain may infect the largest number of individuals in China without control interventions. Moreover, we also observed the possibility of periodic outbreaks in the same lineage and the possibility of the resurgence of previous lineages. Without the invasion of a new variant, the previous variant (Delta variant) is projected to resurgence as early as 2023. However, its resurgence may be prevented by a new variant with a greater competitive advantage.
Project description:The increased transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated variants of concern (VOCs) throughout the pandemic, responsible for waves of cases worldwide. To monitor mutations in the S gene of SARS-CoV-2 in different variants, we evaluated 1497 individuals with COVID-19 in western Amazonia in the period April 2021 to July 2022. The epidemiological and clinical data of the individuals were collected; subsequently, the samples were extracted using a commercial kit, the viral load was assessed, and viral genomes were sequenced. We analyzed the quality and mutations of the genomes and maximum likelihood phylogenetic inference. However, 3 main clusters were observed, referring to Gamma (52.91%), Delta (24.38%), and Omicron (20.38%) VOCs with wide distribution in all health regions of the Rondônia state. Regarding the vaccination profile, there was a higher percentage of unvaccinated and partially vaccinated individuals, with more representatives by the Gamma variant. A total of 1412 sequences were suitable for mutation analysis in the S gene region. The Omicron VOC showed 38 mutations, with the Delta and Gamma variants with 16 and 17, respectively. The VOC Omicron and Gamma shared 4 mutations E484K, H655Y, N501Y, and N679K with high frequency, and Delta and Omicron 2 mutations (T478K and T95I). Regarding the comparison between the frequency of mutations for each variant concerning the vaccination groups, there were no changes in mutations for each group. In conclusion, the study showed a temporal increase in mutations and subvariants for characterized strains. Furthermore, the vaccination profile did not impact significant changes in the mutational profile yet remains a determining factor for severe disease.
Project description:The emergence of SARS-CoV-2 variants complicates efforts to control the COVID-19 pandemic. Increasing genomic surveillance of SARS-CoV-2 is imperative for early detection of emerging variants, to trace the movement of variants, and to monitor effectiveness of countermeasures. Additionally, determining the amount of viable virus present in clinical samples is helpful to better understand the impact these variants have on viral shedding. In this study, we analyzed nasal swab samples collected between March 2020 and early November 2021 from a cohort of United States (U.S.) military personnel and healthcare system beneficiaries stationed worldwide as a part of the Defense Health Agency's (DHA) Global Emerging Infections Surveillance (GEIS) program. SARS-CoV-2 quantitative real time reverse-transcription PCR (qRT-PCR) positive samples were characterized by next-generation sequencing and a subset was analyzed for isolation and quantification of viable virus. Not surprisingly, we found that the Delta variant is the predominant strain circulating among U.S. military personnel beginning in July 2021 and primarily represents cases of vaccine breakthrough infections (VBIs). Among VBIs, we found a 50-fold increase in viable virus in nasal swab samples from Delta variant cases when compared to cases involving other variants. Notably, we found a 40-fold increase in viable virus in nasal swab samples from VBIs involving Delta as compared to unvaccinated personnel infected with other variants prior to the availability of approved vaccines. This study provides important insight about the genomic and virological characterization of SARS-CoV-2 isolates from a unique study population with a global presence.