The biological and clinical significance of emerging SARS-CoV-2 variants

Abstract

The past several months have witnessed the emergence of SARS-CoV-2 variants with novel spike protein mutations that are influencing the epidemiological and clinical aspects of the COVID-19 pandemic. These variants can increase rates of virus transmission and/or increase the risk of reinfection and reduce the protection afforded by neutralizing monoclonal antibodies and vaccination. These variants can therefore enable SARS-CoV-2 to continue its spread in the face of rising population immunity while maintaining or increasing its replication fitness. The identification of four rapidly expanding virus lineages since December 2020, designated variants of concern, has ushered in a new stage of the pandemic. The four variants of concern, the Alpha variant (originally identified in the UK), the Beta variant (originally identified in South Africa), the Gamma variant (originally identified in Brazil) and the Delta variant (originally identified in India), share several mutations with one another as well as with an increasing number of other recently identified SARS-CoV-2 variants. Collectively, these SARS-CoV-2 variants complicate the COVID-19 research agenda and necessitate additional avenues of laboratory, epidemiological and clinical research.

Abstract

In this Review, the authors describe our latest understanding of the emergence and properties of SARS-CoV-2 genetic variants, particularly those designated as WHO (World Health Organization) ‘variants of concern’. They focus on the consequences of these variants for antibody-mediated virus neutralization, with important implications for reinfection risk and for vaccine effectiveness.

Key points

• The past several months have witnessed the emergence of four SARS-CoV-2 variants of concern (Alpha, Beta, Gamma and Delta) associated with increased transmissibility, increased risk of reinfection and/or reduced vaccine efficacy.

• Many additional SARS-CoV-2 variants sharing mutations and biological features with these variants are also increasingly being identified.

• The increasing number of SARS-CoV-2 variants share a repertoire of mutations that is enabling the virus to spread despite rising population immunity while maintaining or increasing its replication fitness.

• Whereas most emerging mutations reduce the protective effects of neutralizing antibodies generated by infection and vaccination, several recently identified mutations appear to antagonize the innate immune response to initial infection.

• The emergence of SARS-CoV-2 variants requires an expanded research agenda to improve our understanding of emerging SARS-CoV-2 mutations and the correlates of protective immunity against variants with these mutations.