Molecular characterization of SARS-CoV-2 detected in Tokyo, Japan during five waves: Identification of the amino acid substitutions associated with transmissibility and severity

Abstract

Many variants of SARS-CoV-2 have emerged around the world. It is therefore important to understand its global viral evolution and the corresponding mutations associated with transmissibility and severity. In this study, we analyzed 112 whole genome sequences of SARS-CoV-2 collected from patients at Juntendo University Hospital in Tokyo and the genome data from entire Japan deposited in Global Initiative on Sharing Avian Influenza Data (GISAID) to examine the relationship of amino acid changes with the transmissibility and the severity of each strain/lineage. We identified 12 lineages, including B.1.1.284, B.1.1.214, R.1, AY.29, and AY.29.1, which were prevalent specifically in Japan. B.1.1.284 was most frequently detected in the second wave, but B.1.1.214 became the predominant lineage in the third wave, indicating that B.1.1.214 has a higher transmissibility than B.1.1.284. The most prevalent lineage during the fourth and fifth wave was B.1.1.7 and AY.29, respectively. In regard to the severity of identified lineages, B.1.1.214 was significantly lower than the reference lineage, B.1.1.284. Analysis of the genome sequence and other traits of each lineage/strain revealed the mutations in S, N, and NSPs that increase the transmissibility and/or severity. These mutations include S: M153T, N: P151L, NSP3: S543P, NSP5: P108S, and NSP12: A423V in B.1.1.284; S: W152L and E484K in R.1; S: H69del, V70del, and N501Y in the Alpha strain; S: L452R, T478K, and P681R in the Delta strain. Furthermore, it is suggested that the transmissibility of B.1.1.214 could be enhanced by the mutations N: M234I, NSP14: P43L, and NSP16: R287I. To address the issue of the virus evolution, it is necessary to continuously monitor the genomes of SARS-CoV-2 and analyze the effects of mutations for developing vaccines and antiviral drugs effective against SARS-CoV-2 variants.

SARS-CoV-2 evolution among patients with immunosuppression in a nosocomial cluster of a Japanese medical center during the Delta (AY.29 sublineage) surge

“…The complete SARS-CoV-2 genomes showed the signatures of the Delta variant (AY.29 sublineage), which was the clade primarily circulating in Tokyo’s metropolitan area ( Tani-Sassa et al, 2021 ; Tsuchiya et al, 2022 ). Phylogenetic tree analysis included 20 samples from the studied cluster, wild type SARS-CoV-2 and AY.29 (hCoV-19/Japan/TKYK15779/2021) as references.…”

Coronavirus disease 2019 in a patient with pulmonary fibrosis and emphysema: An autopsy report

“…Thus, the virus was likely of the same genotype in our case. Disease severity may differ by genotype [ 16 ], and molecular characterization should be encouraged to accumulate the necessary information.…”

Clustering analysis for the evolutionary relationships of SARS-CoV-2 strains

“…Outside the Spike protein, the B.1.1.214 strain exhibits specific mutations: N: M234I, NSP14:P43L, and NSP16: R287I. It is speculated that these amino acid substitutions enhance the efficiency of the viral RNA replication, contributing to the widespread transmission of SARS-CoV-2 coronavirus 27 .…”

“…However, this additional mutation does not impact their pathogenicity, immune evasion, or transmissibility, suggesting similar infectivity between the two strains 30 , 31 . The L452R mutation, situated in the receptor-binding domain (RBD), increases the virus’s infectivity and has been associated with evading neutralizing antibodies 27 .…”