New SARS-CoV-2 Variants - Clinical, Public Health, and Vaccine Implications.
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ABSTRACT:
SUBMITTER: Abdool Karim SS
PROVIDER: S-EPMC8008749 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus 2) has accumulated multiple mutations during its global circulation. Recently, three SARS-CoV-2 lineages, B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (P.1), have emerged in the United Kingdom, South Africa and Brazil, respectively. Here, we have presented global viewpoint on implications of emerging SARS-CoV-2 variants based on structural-function impact of crucial mutations occurring in its spike (S), ORF8 and nucleocapsid (N) proteins. While the N501Y mutation was observed in all three lineages, the 501Y.V1 and P.1 accumulated a different set of mutations in the S protein. The missense mutational effects were predicted through a COVID-19 dedicated resource followed by atomistic molecular dynamics simulations. Current findings indicate that some mutations in the S protein might lead to higher affinity with host receptors and resistance against antibodies, but not all are due to different antibody binding (epitope) regions. Mutations may, however, result in diagnostic tests failures and possible interference with binding of newly identified anti-viral candidates against SARS-CoV-2, likely necessitating roll out of recurring "flu-like shots" annually for tackling COVID-19. The functional relevance of these mutations has been described in terms of modulation of host tropism, antibody resistance, diagnostic sensitivity and therapeutic candidates. Besides global economic losses, post-vaccine reinfections with emerging variants can have significant clinical, therapeutic and public health impacts.
| S-EPMC8000172 | biostudies-literature
Project description:ObjectivesThe four SARS-CoV-2 variants of concern (VOC; Alpha, Beta, Gamma and Delta) identified by May 2021 are highly transmissible, yet little is known about their impact on public health measures. We aimed to synthesise evidence related to public health measures and VOC.DesignA rapid scoping review.Data sourcesOn 11 May 2021, seven databases (MEDLINE, Embase, the Cochrane Database of Systematic Reviews, Central Register of Controlled Trials, Epistemonikos' L-OVE on COVID-19, medRxiv, bioRxiv) were searched for terms related to VOC, public health measures, transmission and health systems. No limit was placed on date of publication.Eligibility criteriaStudies were included if they reported on any of the four VOCs and public health measures, and were available in English. Only studies reporting on data collected after October 2020, when the first VOC was reported, were included.Data extraction and synthesisTitles, abstracts and full-text articles were screened by two independent reviewers. Data extraction was completed by two independent reviewers using a standardised form. Data synthesis and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.ResultsOf the 37 included studies, the majority assessed the impact of Alpha (n=32) and were conducted in Europe (n=12) or the UK (n=9). Most were modelling studies (n=28) and preprints (n=28). The majority of studies reported on infection control measures (n=17), followed by modifying approaches to vaccines (n=13), physical distancing (n=6) and either mask wearing, testing or hand washing (n=2). Findings suggest an accelerated vaccine rollout is needed to mitigate the spread of VOC.ConclusionsThe increased severity of VOC requires proactive public health measures to control their spread. Further research is needed to strengthen the evidence for continued implementation of public health measures in conjunction with vaccine rollout. With no studies reporting on Delta, there is a need for further research on this and other emerging VOC on public health measures.
| S-EPMC8640198 | biostudies-literature
Project description:The sudden rise in COVID-19 cases in 2020 and the incessant emergence of fast-spreading variants have created an alarming situation worldwide. Besides the continuous advancements in the design and development of vaccines to combat this deadly pandemic, new variants are frequently reported, possessing mutations that rapidly outcompeted an existing population of circulating variants. As concerns grow about the effects of mutations on the efficacy of vaccines, increased transmissibility, immune escape, and diagnostic failures are few other apprehensions liable for more deadly waves of COVID-19. Although the phenomenon of antigenic drift in new variants of SARS-CoV-2 is still not validated, it is conceived that the virus is acquiring new mutations as a fitness advantage for rapid transmission or to overcome immunological resistance of the host cell. Considerable evolution of SARS-CoV-2 has been observed since its first appearance in 2019, and despite the progress in sequencing efforts to characterize the mutations, their impacts in many variants have not been analyzed. The present article provides a substantial review of literature explaining the emerging variants of SARS-CoV-2 circulating globally, key mutations in viral genome, and the possible impacts of these new mutations on prevention and therapeutic strategies currently administered to combat this pandemic. Rising infections, mortalities, and hospitalizations can possibly be tackled through mass vaccination, social distancing, better management of available healthcare infrastructure, and by prioritizing genome sequencing for better serosurveillance studies and community tracking.
| S-EPMC8669229 | biostudies-literature
Project description:The emergence of antigenically distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility is a public health threat. Some of these variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies, which principally target the receptor binding domain (RBD) on the virus spike glycoprotein. Here, we describe 2C08, a SARS-CoV-2 mRNA vaccine-induced germinal center B cell-derived human monoclonal antibody that binds to the receptor binding motif within the RBD. 2C08 broadly neutralizes SARS-CoV-2 variants with remarkable potency and reduces lung inflammation, viral load, and morbidity in hamsters challenged with either an ancestral SARS-CoV-2 strain or a recent variant of concern. Clonal analysis identified 2C08-like public clonotypes among B cell clones responding to SARS-CoV-2 infection or vaccination in at least 20 out of 78 individuals. Thus, 2C08-like antibodies can be readily induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern.One sentence summaryProtection against SARS-CoV-2 variants by a potently neutralizing vaccine-induced human monoclonal antibody.
| S-EPMC8010723 | biostudies-literature
Project description:Targeted public health interventions for an emerging epidemic are essential for preventing pandemics. During 2020-2022, China invested significant efforts in strict zero-COVID measures to contain outbreaks of varying scales caused by different SARS-CoV-2 variants. Based on a multi-year empirical dataset containing 131 outbreaks observed in China from April 2020 to May 2022 and simulated scenarios, we ranked the relative intervention effectiveness by their reduction in instantaneous reproduction number. We found that, overall, social distancing measures (38% reduction, 95% prediction interval 31-45%), face masks (30%, 17-42%) and close contact tracing (28%, 24-31%) were most effective. Contact tracing was crucial in containing outbreaks during the initial phases, while social distancing measures became increasingly prominent as the spread persisted. In addition, infections with higher transmissibility and a shorter latent period posed more challenges for these measures. Our findings provide quantitative evidence on the effects of public-health measures for zeroing out emerging contagions in different contexts.
| S-EPMC10465600 | biostudies-literature
Project description:The recent global surge in COVID-19 infections has been fueled by new SARS-CoV-2 variants, namely Alpha, Beta, Gamma, Delta, etc. The molecular mechanism underlying such surge is elusive due to 4,653 non-degenerate mutations on the spike protein, which is the target of most COVID-19 vaccines. The understanding of the molecular mechanism of transmission and evolution is a prerequisite to foresee the trend of emerging vaccine-breakthrough variants and the design of mutation-proof vaccines and monoclonal antibodies. We integrate the genotyping of 1,489,884 SARS-CoV-2 genomes isolates, 130 human antibodies, tens of thousands of mutational data points, topological data analysis, and deep learning to reveal SARS-CoV-2 evolution mechanism and forecast emerging vaccine-escape variants. We show that infectivity-strengthening and antibody-disruptive co-mutations on the S protein RBD can quantitatively explain the infectivity and virulence of all prevailing variants. We demonstrate that Lambda is as infectious as Delta but is more vaccine-resistant. We analyze emerging vaccine-breakthrough co-mutations in 20 countries, including the United Kingdom, the United States, Denmark, Brazil, and Germany, etc. We envision that natural selection through infectivity will continue to be the main mechanism for viral evolution among unvaccinated populations, while antibody disruptive co-mutations will fuel the future growth of vaccine-breakthrough variants among fully vaccinated populations. Finally, we have identified the co-mutations that have the great likelihood of becoming dominant: [A411S, L452R, T478K], [L452R, T478K, N501Y], [V401L, L452R, T478K], [K417N, L452R, T478K], [L452R, T478K, E484K, N501Y], and [P384L, K417N, E484K, N501Y]. We predict they, particularly the last four, will break through existing vaccines. We foresee an urgent need to develop new vaccines that target these co-mutations.
| S-EPMC8437313 | biostudies-literature
Project description:Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of clinical concern. In a cohort of 417 persons who had received the second dose of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine at least 2 weeks previously, we identified 2 women with vaccine breakthrough infection. Despite evidence of vaccine efficacy in both women, symptoms of coronavirus disease 2019 developed, and they tested positive for SARS-CoV-2 by polymerase-chain-reaction testing. Viral sequencing revealed variants of likely clinical importance, including E484K in 1 woman and three mutations (T95I, del142-144, and D614G) in both. These observations indicate a potential risk of illness after successful vaccination and subsequent infection with variant virus, and they provide support for continued efforts to prevent and diagnose infection and to characterize variants in vaccinated persons. (Funded by the National Institutes of Health and others.).
| S-EPMC8117968 | biostudies-literature
Project description:Background: This study aimed to characterize sources of knowledge on the means of prevention of SARS-CoV-2 infections as well as to assess the methods of preventing SARS-CoV-2 infection among police employees in Poland and their potential impact on the risk of SARS-CoV-2 infection.Methods: The study consisted of two phases: questionnaire and laboratory tests for SARS-CoV-2 infection. The questionnaire included 30 questions related to risk factors, knowledge about SARS-CoV-2, and methods of infection prevention.Results: Data were obtained from 5082 police employees. The most common source of knowledge for a daily update on SARS-CoV-2 infection prevention was the Internet (42.6%), television (40.3%), and radio (39.7%). The most commonly used methods of SARS-CoV-2 infection included washing one's hands for at least 20 seconds (95.8%), wearing facemasks (82.9%), and physical distancing (74.9%). Results of IgG tests were lower in police units where the overall compliance with the preventive measures was higher (p < 0.01). Women were more likely to exercise SARS-CoV-2 infection prevention behaviors compared to men. Compliance with the recommended protective measures increased with age.Conclusions: Lower anti-SARS-CoV-2 IgG seropositivity rates were observed in police units with better overall compliance with the preventive measures, suggesting the key importance of group rather than individual behaviors.
| S-EPMC7731213 | biostudies-literature
Project description:Coronavirus 19 Disease (COVID-19) originating in the province of Wuhan, China in 2019, is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), whose infection in humans causes mild or severe clinical manifestations that mainly affect the respiratory system. So far, the COVID-19 has caused more than 2 million deaths worldwide. SARS-CoV-2 contains the Spike (S) glycoprotein on its surface, which is the main target for current vaccine development because antibodies directed against this protein can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. However, the emergence of new SARS-CoV-2 variants could affect the effectiveness of vaccines. Here, we review the different types of vaccines designed and developed against SARS-CoV-2, placing emphasis on whether they are based on the complete S glycoprotein, its antigenic domains such as the receptor-binding domain (RBD) or short epitopes within the S glycoprotein. We also review and discuss the possible effectiveness of these vaccines against emerging SARS-CoV-2 variants.
| S-EPMC8311925 | biostudies-literature
Project description:A new coronavirus (CoV) called SARS-CoV-2 emerged in Wuhan, China in December 2019 as the etiological agent of a viral pneumonia called COVID-19. The global spread of SARS-CoV-2 has been so extensive that the WHO declared COVID-19 a pandemic on March 11, 2020. Below, we discuss the emergence of SARS-CoV-2 and provide the historical context, which strongly suggests emerging CoVs provide an immediate threat to global public health and will continue to do so in the future.
| S-EPMC7269927 | biostudies-literature