SARS‐CoV‐2 R.1 lineage variants that prevailed in Tokyo in March 2021

  1. Katsutoshi Nagano
  2. Chihiro Tani‐Sassa
  3. Yumi Iwasaki
  4. Yuna Takatsuki
  5. Sonoka Yuasa
  6. Yuta Takahashi
  7. Jun Nakajima
  8. Kazunari Sonobe
  9. Naoya Ichimura
  10. Yoko Nukui
  11. Hiroaki Takeuchi
  12. Kousuke Tanimoto
  13. Yukie Tanaka
  14. Akinori Kimura
  15. Shuji Tohda

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Abstract

The spread of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants, such as B.1.1.7 and B.1.351, has become a crucial issue worldwide. Therefore, we began testing all patients with COVID‐19 for the N501Y and E484K mutations by using polymerase chain reaction (PCR)‐based methods. Nasopharyngeal swab samples from 108 patients who visited our hospital between February and April 2021 were analyzed. The samples were analyzed using reverse transcription‐PCR with melting curve analysis to detect the N501Y and E484K mutations. A part of the samples was also subjected to whole‐genome sequencing (WGS). Clinical parameters such as mortality and admission to the intensive care unit were analyzed to examine the association between increased disease severity and the E484K mutation. The ratio of cases showing the 501N + 484K mutation rapidly increased from 8% in February to 46% in March. WGS revealed that the viruses with 501N + 484K mutation are R.1 lineage variants. Evidence of increased disease severity related to the R.1 variants was not found. We found that the R.1 lineage variants rapidly prevailed in Tokyo in March 2021, which suggests the increased transmissibility of R.1 variants, while they showed no increased severity.

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  1. Version published to 10.1002/jmv.27240
  2. ScreenIT

    SciScore for 10.1101/2021.05.11.21257004: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: This study was approved by Medical Research Ethics Committee of Tokyo Medical and Dental University (approval number: M2020-004) and was conducted in accordance with the ethical standards of the 1964 Helsinki declaration. 3.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Using a part of the samples that showed 501N+484E, 501N+484K, and 501Y+484E, whole genome sequencing (WGS) was performed using a nextgeneration sequencer to specify the lineages.
    WGS
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The limitation of our study is that the subjects were limited to the patients who visited our hospital. However, we believe this finding also applies to Tokyo as a whole because the prevalence of R.1 variants in March was not only seen in our hospital, but also in a random sampling survey of patients in Tokyo recently performed by the Tokyo Metropolitan Institute of Public Health.6 Regarding the transmissibility of the R.1 variants, the fact that they rapidly replaced the B.1.1.214 variants (Japan lineage) in March suggests increased transmissibility. Because there were already many patients with COVID-19 in Tokyo in February, the founder effect of the R.1 variants seems unlikely. In a retrospective sampling analysis by WGS of 42 samples collected from November 2020 to January 2021, the R.1 variants were first detected in three samples collected in early January （data not shown）. Furthermore, R.1 variants were rapidly replaced by B.1.1.7 variants in April. This suggests that the B.1.1.7 variants have stronger infectivity, as previously reported.1 Interestingly, our study also revealed that there was no significant difference in copy numbers between the 501Y samples (UK lineage) and 501N samples (Japan lineage and R.1 lineage) as shown in Figure 1(B). Regarding the severity of R.1 variants, there was no significant difference in mortality, ICU admission, and length of hospitalization between R.1 and B.1.1.214 cases, although the number of cases was small to be concluded. Our r...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2021.05.11.21257004v2 on medRxiv
  4. Version published to 10.1101/2021.05.11.21257004v1 on medRxiv