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Soon after the emergence and global spread of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron lineage, BA.1 (ref1, 2), another Omicron lineage, BA.2, has initiated outcompeting BA.1. Statistical analysis shows that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralisation experiments show that the vaccine-induced humoral immunity fails to function against BA.2 like BA.1, and notably, the antigenicity of BA.2 is different from BA.1. Cell culture experiments show that BA.2 is more replicative in human nasal epithelial cells and more fusogenic than BA.1. Furthermore, infection experiments using hamsters show that BA.2 is more pathogenic than BA.1. Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1.

After the global spread of SARS-CoV-2 Omicron BA.2 lineage, some BA.2-related variants that acquire mutations in the L452 residue of spike protein, such as BA.2.9.1 and BA.2.13 (L452M), BA.2.12.1 (L452Q), and BA.2.11, BA.4 and BA.5 (L452R), emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these L452R/M/Q-bearing BA.2-related Omicron variants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1 and BA.2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. Furthermore, infection experiments using hamsters indicated that BA.4/5 is more pathogenic than BA.2. Altogether, our multiscale investigations suggest that the risk of L452R/M/Q-bearing BA.2-related Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2.HighlightsSpike L452R/Q/M mutations increase the effective reproduction number of BA.2BA.4/5 is resistant to the immunity induced by BA.1 and BA.2 infectionsBA.2.12.1 and BA.4/5 more efficiently spread in human lung cells than BA.2BA.4/5 is more pathogenic than BA.2 in hamsters

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022.

Background: The number of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Japan are substantially lower in comparison to the US and UK, potentially due to the under-implementation of polymerase chain reaction (PCR) tests. Studies reported that more than half of the SARS-CoV-2 infections are asymptomatic, confirming the importance for conducting seroepidemiological studies. Although the seroepidemiological studies in Japan observed a reported prevalence of 0.10% in Tokyo, 0.17% in Osaka, and 0.03% in Miyagi, sampling bias was not considered. The study objective was to assess the seroprevalence of SARS-CoV-2 in a random sample of households in Utsunomiya City in Tochigi Prefecture, Greater Tokyo, Japan. Methods: We launched the Utsunomiya COVID-19 seROprevalence Neighborhood Association (U-CORONA) Study to assess the seroprevalence of COVID-19 in Utsunomiya City. The survey was conducted between 14 June 2020 and 5 July 2020, in between the first and second wave of the pandemic. Invitations enclosed with a questionnaire were sent to 2,290 people in 1,000 households randomly selected from Utsunomiya basic resident registry. Written informed consent was obtained from all participants. The level of IgG antibodies to SARS-CoV-2 was assessed by chemiluminescence immunoassay analysis. Results: Among 2,290 candidates, 753 returned the questionnaire and 742 received IgG tests (32.4 % participation rate). Of the 742 participants, 86.8% were 18 years or older, 52.6% were women, 71.1% were residing within 10 km from the test clinic, and 89.2% were living with another person. The age and sex distribution, distance to clinic and police district were similar with those of non-participants, while the proportion of single-person households was higher among non-participants than participants (16.2% vs. 10.8%). We confirmed three positive cases through quantitative antibody testing. No positive cases were found among the people who live in the same household as someone with positive. All cases were afebrile. The estimated unweighted and weighted prevalence of SARS-CoV-2 infection were 0.40% (95% confidence interval: 0.08-1.18%) and 1.23% (95% confidence interval: 0.17-2.28%), respectively. Conclusion: This study suggests the importance of detecting all cases using PCR or antigen testing, not only at a hospital, but also in areas where people assemble. Further prospective studies using this cohort are needed to monitor SARS-CoV-2 antibody levels.