Abstract

Identification of SARS-CoV-2 mutations allows tracking across geographic regions to inform public health responses and may elucidate the role of strain variability in COVID-19 clinical syndromes. Identification of SARS-CoV-2 mutations allows tracking across geographic regions to inform public health responses and may elucidate the role of strain variability in COVID-19 clinical syndromes. A striking feature of COVID-19 infection has been the extraordinary array of clinical manifestations of disease, including fever and lymphopenia, pneumonitis, myocarditis, thromboembolism, unusual skin findings, and neurological manifestations, coupled with an intense inflammatory syndrome. The diversity of syndromes suggests that variation in host immune responses and/or viral strain differences account for the observed variability. The identification of SARS-CoV-2 mutations allows construction of clades and the tracking of virus across geographic regions, including to new areas where they pose a public health risk.1Koyama T Platt D Parida L. Variant analysis of SARS-CoV-2 genomes.Bull World Health Organ. 2020; 98 (https://doi.org/10.2471/BLT.20.253591): 495-504Crossref PubMed Scopus (315) Google Scholar, 2Brufsky A. Distinct viral clades of SARS-CoV-2: implications for modeling of viral spread.J Med Virol. 2020; 92 (https://doi.org/10.1002/jmv.25902): 1386-1390Crossref PubMed Scopus (74) Google Scholar, 3Tang X Wu C Li X et al.On the origin and continuing evolution of SARS-CoV-2.Natl Sci Rev. 2020; 7 (https://doi.org/10.1093/nsr/nwaa036): 1012-1023Crossref PubMed Scopus (970) Google Scholar Some significant genetic changes have been identified between isolates from the proposed bat (host) and pangolin (intermediate host) and human strains. Large genetic shifts are likely due to homologous genome recombination. This may account for the acquisition, for example, of the novel 4 amino acid-insertion furin target, a protease that increases proteolytic activation of the virus, viral replication, and resultant cytopathology.4Hoffmann M Kleine-Weber H Pöhlmann S. A Multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells.Mol Cell. 2020; 78 (e5): 779-784Abstract Full Text Full Text PDF PubMed Scopus (973) Google Scholar Tracking of point mutations across many human isolates from multiple regions provides epidemiological clues to viral spread and to the efficacy of preventative strategies.5Bushman D Alroy KA Greene SK et al.Detection and genetic characterization of community-based SARS-CoV-2 infections - New York City, March 2020.MMWR Morb Mortal Wkly Rep. 2020; 69 (https://doi.org/10.15585/mmwr.mm6928a5): 918-922Crossref PubMed Scopus (14) Google Scholar For example, sequence mutations in the viral spike protein, responsible for cell-surface receptor binding and membrane fusion in tissues, reveals differing amino acid residues in predominant isolates from east (A2a) and west (B1) coasts of the United States. Mutations in this highly conserved region could alter viral pathogenicity. Surprisingly, the analysis in MMWR by Bushman et al. reveals that isolates from New York City, presumed to be directly from China, apparently spread to New York through Italy and the rest of Europe.5Bushman D Alroy KA Greene SK et al.Detection and genetic characterization of community-based SARS-CoV-2 infections - New York City, March 2020.MMWR Morb Mortal Wkly Rep. 2020; 69 (https://doi.org/10.15585/mmwr.mm6928a5): 918-922Crossref PubMed Scopus (14) Google Scholar Characterization of the genetic sequences of SARS-CoV-2 isolates may elucidate the role of strain variability in COVID-19 syndromes.

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