Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5

Kimura, Izumi; Yamasoba, Daichi; Tamura, Tomokazu; Nao, Naganori; Oda, Yoshitaka; Mitoma, Shuya; Ito, Jumpei; Nasser, Hesham; Zahradník, Jiří; Uriu, Keiya; Fujita, Shigeru; Kosugi, Yusuke; Wang, Lei; Tsuda, Masumi; Kishimoto, Mai; Ito, Hayato; Suzuki, Rigel; Shimizu, Ryo; Begum, MST Monira; Yoshimatsu, Kumiko; Sasaki, Jiei; Sasaki-Tabata, Kaori; Yamamoto, Yuki; Nagamoto, Tetsuharu; Kanamune, Jun; Kobiyama, Kouji; Asakura, Hiroyuki; Nagashima, Mami; Sadamasu, Kenji; Yoshimura, Kazuhisa; Kuramochi, Jin; Schreiber, Gideon; Ishii, Ken J.; Hanabusa, Takao; Ikeda, Terumasa; Saito, Akatsuki; Fukuhara, Takasuke; Tanaka, Shinya; Matsuno, Keita; Sato, Kei

doi:10.1101/2022.05.26.493539

Cited by 64 publications

(172 citation statements)

References 58 publications

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“…In our study, individuals infected with BA.4/BA.5 lineages did not have increased clinical severity compared to individuals infected with BA.1. Recent data from a study conducted in hamsters showed that BA.4/BA.5 was more pathogenic than BA.2 14 . However, in our study, this increased pathogenicity did not translate into clinical severity.…”

Section: Discussionmentioning

confidence: 99%

Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages in South Africa

Wolter

Jassat²,

Walaza

et al. 2022

Preprint

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Omicron lineages BA.4 and BA.5 drove a fifth wave of COVID-19 cases in South Africa. We assessed the severity of BA.4/BA.5 infections using the presence/absence of the S-gene target for infections diagnosed using the TaqPath PCR assay between 1 October 2021 and 26 April 2022. We linked national COVID-19 individual-level data including case, laboratory test and hospitalisation data. We assessed severity using multivariable logistic regression comparing the risk of hospitalisation and risk of severe disease, once hospitalised, for Delta, BA.1, BA.2 and BA.4/BA.5 infections. After controlling for factors associated with hospitalisation and severe outcome respectively, BA.4/BA.5-infected individuals had a similar odds of hospitalisation (aOR1.24, 95% CI 0.98–1.55) and severe outcome (aOR 0.71, 95%CI 0.41–1.25) compared to BA.1-infected individuals. Newly emerged Omicron lineages BA.4/BA.5 continue to show reduced clinical severity compared to previous variants, as observed for Omicron BA.1.

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Section: Discussionmentioning

confidence: 99%

Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages in South Africa

Wolter

Jassat²,

Walaza

et al. 2022

Preprint

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“…A previous study demonstrated that the L452R mutation enhances the infectivity of a pseudovirus carrying the BA.1 S protein in K18-hACE2 transgenic mice 11 . Notably, a recent paper (Kimura et al 5 ) reported that a recombinant chimeric virus possessing the BA.4 or BA.5 S gene in the background of a BA.2 strain is more pathogenic than the parental recombinant BA.2 virus in hamsters, suggesting that the S sequence differences between BA.2 and BA.4 or BA.5 are responsible for the difference in pathogenicity between these chimeric viruses; based on these data, Kimura et al concluded that BA.4 and BA.5 are more pathogenic than BA.2. However, in authentic viruses isolated from patients, the genomes of BA.2, BA.4, and BA.5 differ at locations other than the S gene.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that the L452R mutation increases the fusogenicity and infectivity of SARS-CoV-2 variants including Omicron 10,11 . Notably, a recent study reported that a recombinant chimeric virus possessing the BA.4/BA.5 S gene in the background of a BA.2 strain is more pathogenic than the parental recombinant BA.2 virus 5 . This nding suggests that the infectivity and pathogenicity of BA.4 and BA.5 may be higher than those of BA.1 and BA.2.…”

Section: Introductionmentioning

confidence: 99%

Characterization of SARS-CoV-2 Omicron BA.4 and BA.5 clinical isolates

Kawaoka

Uraki

Halfmann

et al. 2022

Preprint

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The BA.2 sublineage of the SARS-CoV-2 Omicron variant has become dominant in most countries around the world; however, the prevalence of BA.4 and BA.5 is increasing rapidly in several regions. BA.2 is less pathogenic in animal models than previously circulating variants of concern (VOC). Compared with BA.2, however, BA.4 and BA.5 possess additional substitutions in the spike protein, which play a key role in viral infectivity, raising concerns that the infectivity and pathogenicity of BA.4 and BA.5 are higher than those of BA.2. Here, we evaluated the replicative ability and pathogenicity of authentic BA.4 and BA.5 isolates in wild-type Syrian hamsters and human ACE2 (hACE2) transgenic hamsters. In contrast to recent data with a recombinant chimeric virus possessing the spike protein of BA.4/BA.5 in the background of a BA.2 strain, we observed no obvious differences among BA.2, BA.4, and BA.5 isolates in growth ability or pathogenicity in hamsters, and less pathogenicity compared to a previously circulating Delta (B.1.617.2 lineage) isolate. In addition, in vivo competition experiments revealed that BA.5 outcompeted BA.2 in hamsters, whereas BA.4 and BA.2 exhibited similar fitness. These findings suggest that BA.4 and BA.5 have similar pathogenicity to BA.2 in rodents and that BA.5 possesses viral fitness superior to that of BA.2. Our study highlights the importance of using authentic isolates when evaluating virological features.

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“…Others in contrast report that breakthrough infection with VOCs elicits crossreactive antibodies with the ability to neutralize Omicron [49,93,94]. Converging reports indicate that Omicron BA.1 breakthrough infection elicits antibodies with neutralizing activity against Omicron BA.1 and previous VOCs [27,48,[95][96][97] but poorly cross-neutralizing other Omicron sublineages [98]. In unvaccinated individuals, Omicron infections trigger poorly neutralizing antibodies against all VOCs [49,95,96].…”

Section: Introductionmentioning

confidence: 99%

Pre-Omicron vaccine breakthrough infection induces superior cross-neutralization against SARS-CoV-2 Omicron BA.1 than primo infection

Silva

Kohnen

Gilson

et al. 2022

Preprint

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SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here we compared the ability of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and from 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta to neutralize the ancestral B.1 strain, and the Gamma, Delta and Omicron BA.1 variants using live virus. We further determined antibody levels against the Spike protein, the Receptor Binding Domain (RBD) and the N-terminal domain (NTD) of Spike. Convalescent sera featured considerable variability in neutralization of B.1 and in cross-neutralization of different strains, and neutralizing capacity moderately correlated with antibody levels against Spike and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed higher neutralizing ability against all strains than patients with mild or severe forms of disease. Sera from BTI cases fell into one of two categories: half the sera had high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or very low neutralizing activity against all strains. Although antibody levels against Spike and the RBD were lower in BTI cases than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, indicative of cross-neutralization between B.1, Delta and Omicron and suggestive of higher affinity, as confirmed by the IC50:Ab level ratios. Neutralizing activity of BTI sera was strongly correlated with antibodies against Spike and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further suggest that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross neutralizing antibodies against different strains, including Omicron BA.1.

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Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5

Cited by 64 publications

References 58 publications

Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages in South Africa

Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages in South Africa

Characterization of SARS-CoV-2 Omicron BA.4 and BA.5 clinical isolates

Pre-Omicron vaccine breakthrough infection induces superior cross-neutralization against SARS-CoV-2 Omicron BA.1 than primo infection

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