Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant

  1. Baisheng Li
  2. Aiping Deng
  3. Kuibiao Li
  4. Yao Hu
  5. Zhencui Li
  6. Yaling Shi
  7. Qianling Xiong
  8. Zhe Liu
  9. Qianfang Guo
  10. Lirong Zou
  11. Huan Zhang
  12. Meng Zhang
  13. Fangzhu Ouyang
  14. Juan Su
  15. Wenzhe Su
  16. Jing Xu
  17. Huifang Lin
  18. Jing Sun
  19. Jinju Peng
  20. Huiming Jiang
  21. Pingping Zhou
  22. Ting Hu
  23. Min Luo
  24. Yingtao Zhang
  25. Huanying Zheng
  26. Jianpeng Xiao
  27. Tao Liu
  28. Mingkai Tan
  29. Rongfei Che
  30. Hanri Zeng
  31. Zhonghua Zheng
  32. Yushi Huang
  33. Jianxiang Yu
  34. Lina Yi
  35. Jie Wu
  36. Jingdiao Chen
  37. Haojie Zhong
  38. Xiaoling Deng
  39. Min Kang
  40. Oliver G. Pybus
  41. Matthew Hall
  42. Katrina A. Lythgoe
  43. Yan Li
  44. Jun Yuan
  45. Jianfeng He
  46. Jing Lu

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Abstract

The SARS-CoV-2 Delta variant has spread rapidly worldwide. To provide data on its virological profile, we here report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. However, the transmission of minor iSNVs resulted in at least 3 of the 34 substitutions that were identified in the outbreak, highlighting the contribution of intra-host variants to population-level viral diversity during rapid spread.

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  1. Version published to 10.1038/s41467-022-28089-y
  2. NCRC

    Our take

    This case series, available as a preprint and thus not yet peer-reviewed, attributed 167 SARS-CoV-2 Delta variant cases to one index case between May 21 and June 18, 2021 in Guangdong, China. Although selection criteria for SARS-CoV-2 cases from early 2020 for comparison are not specified, the authors found that among transmission events outside of the same family, there was a median of 4 days from Delta variant exposure to PCR test positivity vs. 6 days in 2020 (pre-Delta) suggesting the potential for rapid and pre-symptomatic transmission with the Delta variant.

    Study design

    case-series

    Study population and setting

    This case series follows SARS-CoV-2 infections in Guangdong, China directly attributed to the first local Delta variant SARS-CoV-2 infection in the region on May 21, 2021. From May 21 to June 18, 2021, researchers performed contact tracing to determine exposure information for positive cases and their close contacts, which included frequent PCR testing following exposure. Transmission pairs included a recipient that was a close contact and had a clear and direct epidemiologic link with the donor and did not have any contacts with other cases. Viral genomes were sequenced to further ascribe linkage between cases and outbreak parameters in a subset of cases, such as the time between exposure and first detectable viral load and viral load measurements on the day of SARS-CoV-2 detection, which were compared to the SARS-CoV-2 outbreak in the same region in early 2020.

    Summary of main findings

    The study found 167 cases epidemiologically or genetically attributed to the index case from May 21 to June 18, 2021. After removing cases that occurred within family-transmission pairs, they found that the time from the exposure to the first positive PCR test for Delta variant cases (n = 34, median 4 days, interquartile range [IQR] 3-5 days) was shorter than during the 2020 pandemic (n = 29, median 6 days, IQR 5-8 days). Among a subset of individuals (n = 62 for the Delta variant, n = 63 for early 2020), they also found higher relative viral loads as measured by PCR cycle threshold (Ct) on the first day of a positive SARS-CoV-2 test (24 with an IQR of 19-29 for Delta cases versus 34 with and IQR of 31-36 for early 2020 cases).

    Study strengths

    Through extensive contact tracing and viral genetic analysis, this study presents essential information on how quickly the SARS-CoV-2 Delta variant can spread in a community.

    Limitations

    The authors do not describe how they selected early 2020 SARS-CoV-2 comparison cases, which makes them difficult to interpret. They also report extensive population PCR testing, but do not elaborate on how frequently close contacts were tested for SARS-CoV-2 or how similar those protocols were during the comparison period. If, for example, they did more frequent testing during their study period, they may find a shorter interval between exposure and PCR-positivity due to more frequent testing. Furthermore, they do not clarify whether or not PCR Ct values were run on the same or different machines, or whether they normalized Ct values to positive controls to account for variability that occurs across PCR runs, further limiting comparisons both within and across SARS-CoV-2 transmission periods.

    Value added

    This study provides evidence of how rapidly the SARS-CoV-2 Delta variant can spread through a community.

  3. Version published to 10.21203/rs.3.rs-738164/v1 on Research Square
  4. Version published to 10.1101/2021.07.07.21260122v2 on medRxiv
  5. ScreenIT

    SciScore for 10.1101/2021.07.07.21260122: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics: This study was approved by the institutional ethics committee of the Guangdong Provincial Center for Disease Control and Prevention (GDCDC).
    Consent: Written consent was obtained from patients or their guardian(s) when samples were collected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    For sequence data from Miniseq, the raw data were first quality controlled (QC) using fastp18 to trim artificial sequences (adapters), to cut low-quality bases (quality scores < 20).
    Miniseq
    suggested: None
    The mapping of cleaned reads was performed against the genome of the first index case (5137_GZ_2021/5/21) using BWA 0.7.1721.
    BWA
    suggested: (BWA, RRID:SCR_010910)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  6. Version published to 10.1101/2021.07.07.21260122v1 on medRxiv