Novel SARS-CoV-2 variants: the pandemics within the pandemic

Boehm, Erik; Kronig, Ilona; Neher, Richard A.; Eckerle, Isabella; Vetter, Pauline; Kaiser, Laurent

BACKGROUND: Many new variants of SARS-CoV-2 have been termed Variants of Concern/Interest (VOC/I) because of their greater risk due to possibly: enhanced transmissibility and/or severity, immune escape, diagnostic and/or treatment failure, and reduced vaccine efficacy. OBJECTIVES: We sought to review current knowledge of emerging SARS-CoV-2 variants, particularly those deemed VOC/Is: B.1.351, B.1.1.7, and P.1. SOURCES: MEDLINE 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. CONTENT: Mutations on the spike protein in particular may affect both affinity for the SARS-CoV-2 cell receptor ACEII or antibody binding. These VOC/Is often share similar mutation sets. The N501Y mutation is shared by the main three 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, favoring reinfections, and decreased in vitro efficacy of some antibody therapies or vaccines. Those mutations may also have phenotypical repercussions of higher 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 adaptation of SARS-CoV-2 to humans in a background of increasing immunity. IMPLICATIONS: These VOC/Is are increasing in frequency globally and pose challenges to any herd immunity approach of 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.