Some common deleterious mutations are shared in SARS-CoV-2 genomes from deceased COVID-19 patients across continents

Abstract

AbstractThe identification of deleterious mutations in different variants of SARS-CoV-2 and their roles in the morbidity of COVID-19 patients has yet to be thoroughly investigated. To unravel the spectrum of mutations and their effects within SARS-CoV-2 genomes, we analyzed 5,724 complete genomes from deceased COVID-19 patients sourced from the GISAID database. This analysis was conducted using the Nextstrain platform, applying a generalized time-reversible model for evolutionary phylogeny. These genomes were compared to the reference strain (hCoV-19/Wuhan/WIV04/2019) using MAFFT v7.470. Our findings revealed that SARS-CoV-2 genomes from deceased individuals belonged to 21 Nextstrain clades, with clade 20I (Alpha variant) being the most predominant, followed by clade 20H (Beta variant) and clade 20J (Gamma variant). The majority of SARS-CoV-2 genomes from deceased patients (33.4%) were sequenced in North America, while the lowest percentage (0.98%) came from Africa. The ‘G’ clade was dominant in the SARS-CoV-2 genomes of Asian, African, and North American regions, while the ‘GRY’ clade prevailed in Europe. In our analysis, we identified 35,799 nucleotide (NT) mutations throughout the genome, with the highest frequency (11,402 occurrences) found in the spike protein. Notably, we observed 4150 point-specific amino acid (AA) mutations in SARS-CoV-2 genomes, with D614G (20%) and N501Y (14%) identified as the top two deleterious mutations in the spike protein on a global scale. Furthermore, we detected five common deleterious AA mutations, including G18V, W45S, I33T, P30L, and Q418H, which play a key role in defining each clade of SARS-CoV-2. Our novel findings hold potential value for genomic surveillance, enabling the monitoring of the evolving pattern of SARS-CoV-2 infection, its emerging variants, and their impact on the development of effective vaccination and control strategies.