Advertisement

Detection of the Omicron BA.2.75 subvariant in Japan

Published:September 07, 2022DOI:https://doi.org/10.1016/j.jinf.2022.08.038

      Highlights

      • New emergent Omicron BA.2.75 subvariant was detected in Japan.
      • Familial transmission occurred and family members had no history of overseas travel.
      • Phylogenetic analysis likely showed the community-acquired infection of BA.2.75.

      Abbreviations:

      SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), Ct (threshold cycle), ORF (open reading frame)
      Letter to the Editor
      In this journal, we previously reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2 replaces BA.1.1.
      • Hirotsu Y.
      • Maejima M.
      • Shibusawa M.
      • Natori Y.
      • Nagakubo Y.
      • Hosaka K.
      • et al.
      SARS-CoV-2 Omicron sublineage BA.2 replaces BA.1.1: genomic surveillance in Japan from September 2021 to March 2022.
      After the successive emergence and predominance of SARS-CoV-2 subvariants Omicron BA.1, BA.1.1 and BA.2, several other subvariants, e.g., BA.2.12.1, BA.4, and BA.5, emerged,
      • Tegally H.
      • Moir M.
      • Everatt J.
      • Giovanetti M.
      • Scheepers C.
      • Wilkinson E.
      • et al.
      Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa.
      ,
      • Qasmieh S.A.
      • Robertson M.M.
      • Teasdale C.A.
      • Kulkarni S.G.
      • Jones H.
      • Larsen D.A.
      • et al.
      The prevalence of SARS-CoV-2 infection and other public health outcomes during the BA.2/BA.2.12.1 surge, New York City, April-May 2022.
      among which BA.5 became predominant. There is now concern that incidences of the newly emerged Omicron BA.2.75 subvariant may increase in the future. BA.2.75 has nine new mutations (K147E, W152R, F157L, I210V, G257S, G339H, G446S, N460K, and R493Q [a reversion mutation towards the ancestral variant]) compared with BA.2, which may be related to immune escape and resistance to antibody therapies.
      • Yamasoba D.
      • Kimura I.
      • Kosugi Y.
      • Uriu K.
      • Fujita S.
      • Ito J.
      • et al.
      Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies.
      The World Health Organization (WHO) has designated BA.2.75 as a variant under monitoring.
      World Health Organization
      Tracking SARS-CoV-2 variants.
      BA.2.75 was first identified in a specimen from India collected on January 7, 2022 (EPI_ISL_13804325); its detection frequency gradually increased near the end of May, after which detection of this variant expanded to other countries.
      • Hodcroft E.
      covariants: SARS-CoV-2 mutations and variants of interest. 2021.
      As of August 2, 870 entries containing sequencing data for BA.2.75 from 27 countries had been loaded in GISAID (Supplemental materials).
      • Shu Y.
      • McCauley J.
      GISAID: global initiative on sharing all influenza data - from vision to reality.
      By country, the most entries were from India (n = 614), followed by the United States of America (n = 51), Singapore (n = 42), Canada (n = 29), the United Kingdom (n = 27), and Japan (n = 20) (Table 1). The number of BA.2.75 detections has remarkably increased in India (Fig. 1A) and began rising in Singapore after the first BA.2.75 identification on July 18, 2022 (Fig. 1B).
      Table 1Number of BA.2.75-positive samples reported in each country.
      NoCountryTotal number of BA.2.75
      1India614
      2USA51
      3Singapore42
      4Canada29
      5United Kingdom27
      6Japan20
      7Nepal16
      8Australia15
      9Denmark12
      10Indonesia8
      11Germany6
      12Israel5
      13Luxembourg4
      14New Zealand4
      15South Korea3
      16France2
      17Thailand2
      18Austria1
      19Cambodia1
      20China1
      21Italy1
      22Martinique1
      23Netherlands1
      24Peru1
      25Slovakia1
      26Slovenia1
      27Turkey1
      Fig 1
      Fig. 1Trends in the number of cases of Omicron BA.2.75 infection and evolutionary phylogenetic tree. (A, B) Cumulative number of detected cases of infection with SARS-CoV-2 Omicron BA.2.75 subvariant in each country, according to information registered in GISAID. (A) Cumulative number of cases of infected individuals in the top six countries with the highest number of reported cases (India,  the United States of America, Singapore, the United Kingdom, Canada, and Japan). (B) Cumulative numbers displayed by expanding the data from (A) for countries other than India. (C) Phylogenetic analysis of the Omicron BA.2.75 subvariant conducted by UShER. Mutations noted in the branches of the phylogenetic tree indicate newly acquired mutations. The data shown in red in the right panel are derived from two samples identified in Yamanashi Prefecture, Japan. Abbreviations: ORF, open reading frame; S, spike.
      As of August 2, 2022, two cases of BA.2.75 (Accession ID: EPI_ISL_13762812, EPI_ISL_13762799) had been confirmed in Yamanashi Prefecture, Japan (one each on July 1 and July 7, 2022). The two affected individuals were non-vaccinated six- and three-year-old children. Their parents also tested positive for SARS-CoV-2, indicating that familial transmission occurred in both cases. The family member had no history of overseas travel.
      These children presented to the outpatient fever clinic and were diagnosed as SARS-CoV-2 positive by PCR and quantitative antigen testing.
      • Hirotsu Y.
      • Maejima M.
      • Shibusawa M.
      • Natori Y.
      • Nagakubo Y.
      • Hosaka K.
      • et al.
      Direct comparison of Xpert Xpress, filmarray respiratory panel, lumipulse antigen test, and RT-qPCR in 165 nasopharyngeal swabs.
      In the 6-year-old child, the nasopharyngeal swab viral load and antigen level were 3.2 log10 copies/ml (Ct = 27) and 13.4 pg/ml, respectively. Their symptoms included fever (39 °C), cough, sputum, and fatigue, but not sore throat, nausea, vomiting, or taste disorder. The infection route was unknown, as the patient had not been out of the prefecture or traveled abroad in recent months. Six days later, a 3-year-old child presented to the outpatient clinic with fever (38.6 °C), diarrhea, and fatigue. Their viral load was 5.9 log10 copies/ml (Ct = 19), and their antigen level was 3732 pg/ml.
      Using nucleic acids extracted from the nasopharyngeal swab specimens, we performed SARS-CoV-2 classification by TaqMan Assay.
      • Hirotsu Y.
      • Maejima M.
      • Shibusawa M.
      • Natori Y.
      • Nagakubo Y.
      • Hosaka K.
      • et al.
      Classification of Omicron BA.1, BA.1.1, and BA.2 sublineages by TaqMan assay consistent with whole genome analysis data.
      The presence of Spike mutations Q493R (found in the BA.2 subvariant) and Δ69–70 (found in the BA.4 and BA.5 subvariants) were assessed by TaqMan Assay, but they were not detected in these isolates, suggesting that these viruses were a subvariant other than BA.2, BA.4, or BA.5. We then performed a whole genome sequencing analysis and identified them as BA.2.75.
      To search for the origin of these BA.2.75 isolates, an evolutionary phylogenetic tree including BA.2.75 identified in Japan was created using Ultrafast Sample placement on Existing tRees (UShER).
      • Turakhia Y.
      • Thornlow B.
      • Hinrichs A.S.
      • De Maio N.
      • Gozashti L.
      • Lanfear R.
      • et al.
      Ultrafast sample placement on existing tRees (UShER) enables real-time phylogenetics for the SARS-CoV-2 pandemic.
      It revealed that our identified viruses were genetically close to an ancestral virus (Accession ID: EPI_ISL_13950041) detected from a person who had traveled history to Nepal on June 23, 2022 at the airport quarantine station in Japan (Fig. 1C). Compared with this ancestral virus, two new mutations, ORF1ab D1532N and Spike S408R, were present in our isolates. Therefore, a BA.2.75 influx from overseas may have been infecting people via unknown infection routes. Future work should closely monitor the spread of BA.2.75 infection in Japan.

      Funding

      This study was supported by a Grant-in-Aid for the Genome Research Project from Yamanashi Prefecture (to M.O. and Y.H.), the Japan Society for the Promotion of Science (JSPS) KAKENHI Early-Career Scientists JP18K16292 (to Y.H.), a Grant-in-Aid for Scientific Research (B) 20H03668 (to Y.H.), a Research Grant for Young Scholars (to Y.H.), the YASUDA Medical Foundation (to Y.H.), the Uehara Memorial Foundation (to Y.H.), and Medical Research Grants from the Takeda Science Foundation (to Y.H.).

      Declaration of Competing Interest

      None.

      Acknowledgments

      We thank the researchers who deposited the SARS-CoV-2 sequencing data in the GISAID and all of the medical and ancillary hospital staff (Supplemental materials). We also thank Katie Oakley, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

      Appendix. Supplementary materials

      References

        • Hirotsu Y.
        • Maejima M.
        • Shibusawa M.
        • Natori Y.
        • Nagakubo Y.
        • Hosaka K.
        • et al.
        SARS-CoV-2 Omicron sublineage BA.2 replaces BA.1.1: genomic surveillance in Japan from September 2021 to March 2022.
        J Infect. 2022; 85: 174-211
        • Tegally H.
        • Moir M.
        • Everatt J.
        • Giovanetti M.
        • Scheepers C.
        • Wilkinson E.
        • et al.
        Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa.
        Nat Med. 2022; https://doi.org/10.1038/s41591-022-01911-2
        • Qasmieh S.A.
        • Robertson M.M.
        • Teasdale C.A.
        • Kulkarni S.G.
        • Jones H.
        • Larsen D.A.
        • et al.
        The prevalence of SARS-CoV-2 infection and other public health outcomes during the BA.2/BA.2.12.1 surge, New York City, April-May 2022.
        medRxiv. 2022; https://doi.org/10.1101/2022.05.25.22275603
        • Yamasoba D.
        • Kimura I.
        • Kosugi Y.
        • Uriu K.
        • Fujita S.
        • Ito J.
        • et al.
        Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies.
        bioRxiv. 2022; https://doi.org/10.1101/2022.07.14.500041
        • World Health Organization
        Tracking SARS-CoV-2 variants.
        • Hodcroft E.
        covariants: SARS-CoV-2 mutations and variants of interest. 2021.
        • Shu Y.
        • McCauley J.
        GISAID: global initiative on sharing all influenza data - from vision to reality.
        Eurosurveillance. 2017; 22: 30494
        • Hirotsu Y.
        • Maejima M.
        • Shibusawa M.
        • Natori Y.
        • Nagakubo Y.
        • Hosaka K.
        • et al.
        Direct comparison of Xpert Xpress, filmarray respiratory panel, lumipulse antigen test, and RT-qPCR in 165 nasopharyngeal swabs.
        BMC Infect Dis. 2022; 22: 221
        • Hirotsu Y.
        • Maejima M.
        • Shibusawa M.
        • Natori Y.
        • Nagakubo Y.
        • Hosaka K.
        • et al.
        Classification of Omicron BA.1, BA.1.1, and BA.2 sublineages by TaqMan assay consistent with whole genome analysis data.
        Int J Infect Dis. 2022; 122: 486-491
        • Turakhia Y.
        • Thornlow B.
        • Hinrichs A.S.
        • De Maio N.
        • Gozashti L.
        • Lanfear R.
        • et al.
        Ultrafast sample placement on existing tRees (UShER) enables real-time phylogenetics for the SARS-CoV-2 pandemic.
        Nat Genet. 2021; 53: 809-816