A territory-wide study of early COVID-19 outbreak in Hong Kong community: A clinical, epidemiological and phylogenomic investigation

  1. Kenneth Siu-Sing Leung
  2. Timothy Ting-Leung Ng
  3. Alan Ka-Lun Wu
  4. Miranda Chong-Yee Yau
  5. Hiu-Yin Lao
  6. Ming-Pan Choi
  7. Kingsley King-Gee Tam
  8. Lam-Kwong Lee
  9. Barry Kin-Chung Wong
  10. Alex Yat-Man Ho
  11. Kam-Tong Yip
  12. Kwok-Cheung Lung
  13. Raymond Wai-To Liu
  14. Eugene Yuk-Keung Tso
  15. Wai-Shing Leung
  16. Man-Chun Chan
  17. Yuk-Yung Ng
  18. Kit-Man Sin
  19. Kitty Sau-Chun Fung
  20. Sandy Ka-Yee Chau
  21. Wing-Kin To
  22. Tak-Lun Que
  23. David Ho-Keung Shum
  24. Shea Ping Yip
  25. Wing Cheong Yam
  26. Gilman Kit-Hang Siu

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Abstract

Initial cases of COVID-19 reported in Hong Kong were mostly imported from China. However, most cases reported in February 2020 were locally-acquired infections, indicating local community transmissions. We extracted the demographic, clinical and epidemiological data from 50 COVID-19 patients, who accounted for 53.8% of the cases in Hong Kong by February 2020. Whole-genome sequencing of the SARS-CoV-2 were conducted to determine the phylogenetic relatedness and transmission dynamics. Only three (6.0%) patients required ICU admission. Phylogenetic analysis identified six transmission clusters. All locally-acquired cases harboured a common mutation Orf3a G251V and were clustered in two subclades in global phylogeny of SARS-CoV-2. The estimated time to the most recent common ancestor of local COVID-2019 outbreak was December 24, 2019 with an evolutionary rate of 3.04×10 −3 substitutions per site per year. The reproduction number value was 1.84. Social distancing and vigilant epidemiological control are crucial to the containment of COVID-19 transmission.

Article summary lines

A combined epidemiological and phylogenetic analysis of early COVID-19 outbreak in Hong Kong revealed that a SARS-CoV-2 variant with ORF3a G251V mutation accounted for all locally acquired cases, and that asymptomatic carriers could be a huge public health risk for COVID-19 control.

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  1. ScreenIT

    SciScore for 10.1101/2020.03.30.20045740: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the Institutional Review Boards of The Hong Kong Polytechnic University(RSA20021) and the public hospitals involved(HKECREC-20200014;KCC/KEC-20200070;KWC-20200040;NTWC-20200038)
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Consensus genomes were constructed by GATK(v4.1.4.1) based on the VCF file(14).
    GATK(v4.1.4.1
    suggested: None
    Genomic and Phylogenetic analysis: To identify the amino acid change caused by each single-nucleotide polymorphism(SNP), consensus genome of each specimen was BLASTed against the reference NC_045512.2 using BlastX.
    BlastX
    suggested: (BLASTX, RRID:SCR_001653)
    Non-synonymous mutations were identified using custom Python script.
    Python
    suggested: (IPython, RRID:SCR_001658)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are several limitations in our study. Despite 53·8% of the cases reported in Hong Kong up to February 28 were included, another 43 cases including two fatal cases were not analysed in this study. Moreover, incubation period of cases with unknown source might vary widely. Studies have shown that incubation period can vary from 4.5-15.8 days,(24) and can be even longer for patients presenting with mild symptoms. However, as the patient might already be infectious during incubation period, resultant reproductive number in this study could still be underestimated. Moreover, current calculation was solely based on phylodynamic analysis which could be different from those based on epidemiological models. Finally, gap regions were observed in some consensus genomes. This is mainly because WGS was performed on respiratory specimens instead of viral culture. The paucity of viral load in specimens could affect the yield of sequencing libraries. Nevertheless, the uncovered area only accounted for approximately 1-3% of the entire viral genome while the remaining mapped regions had an average coverage of >100X, which should provide sufficient and accurate information for our subsequent analyses. In conclusion, phylogenomic data were consistent with the epidemiological findings that transmission in closed settings especially during family and religious gatherings is a hallmark of COVID-19 outbreak in Hong Kong. Social distancing and vigilant infection control measures, such as rapid ...

    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.

    About SciScore

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  2. Version published to 10.1101/2020.03.30.20045740v2 on medRxiv
  3. Version published to 10.1101/2020.03.30.20045740v1 on medRxiv