Research Article

Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2)

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Science  16 Mar 2020:
eabb3221
DOI: 10.1126/science.abb3221

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  • Travel restrictions are effective to control SARS-CoV2. 
    • Yezhao Wang, Zhejiang Province Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, 315211, China.

    Dear editor:
    The recent coronavirus pneumonia that emerged in Wuhan (SARS-CoV2) at the end of 2019 quickly spread to all Chinese provinces, as of 27 Mar 2020, confirmed cases was reported has reached 600000 worldwide according to statistical data, which attracted global attention (https://www.who.int/) (1).
    Therefore, I read the recent article by Li et al with interest (1). As the authors have made a strong comment as “We estimate 86% of all infections were undocumented (95% CI: [82%–90%]) prior to 23 January 2020 travel restrictions ” (1). However, it was reported that “initial testing was focused mainly on travelers from Wuhan, potentially biasing estimates of travel related infections upwards ” recently (2).
    In their manuscript, the authors stated that “Efforts to contain the virus are ongoing; however, given the many uncertainties regarding pathogen transmissibility and virulence, the effectiveness of these efforts is unknown” (1). However, China has almost contained the spread of SARS-CoV2 through controlling the source of infection, cutting off the route of transmission, and protecting vulnerable groups including quarantining Wuhan City on January 23 (2, 3). It was also reported that “The combination of interventions implemented in China were clearly successful in mitigating spread and reducing local transmission of COVID-19”(2).
    There are lots of overstatements in this manuscript (1). For exa...

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    Competing Interests: None declared.
  • RE: Some thoughts on the analysis of the novel coronavirus epidemics by a dynamic model of infectious disease
    • Zuiyuan Guo, Military surgeon, Center for Disease Control and Prevention in Northern Theater Command
    • Other Contributors:
      • Shuang Xu, Military surgeon, Center for Disease Control and Prevention in Northern Theater Command
      • Dan Xiao, associate professor, Beijing Tiantan Hospital

    Undocumented patients can spread the novel coronavirus. However, the exact number cannot be directly counted. Therefore, a mathematical model is needed to estimate the number and assess the impact of these patients on the epidemic. A paper published in Science titled “Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2)” used a dynamic model to provide a methodological reference for solving this problem.
    In this study, the authors estimated that the median basic reproductive number (R0) at the beginning of the epidemic was 2.38. I questioned this number for three reasons.
    First, the authors presumed that the epidemic emerged on November 1, 2019, and that the cumulative infections reached approximately 2000 on January 10, 2020. On this basis, the authors estimated that the initial undocumented infections (I0u) that plays a key role in the research results were randomly selected from 0 to seedmax (2000). However, the authors did not provide strict evidence or reasons for the above hypothesis.
    Second, the hypothesis that every patient in I0u is sick and has a full infection period is also flawed. The actual situation is that some patients just get sick, while others will get better; therefore the period during which they are infecting other people is shorter than that proposed by the author. This will cause the average number of susceptible persons infected by a patient in I0u to be less than the assumption....

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    Competing Interests: None declared.
  • What’s the value of these findings in controlling the outbreak of SARS-CoV2?
    • Yezhao Wang, M.B.B.S, Department of Biochemistry and Molecular Biology, Ningbo University School of Medicine, Ningbo, 315211, China.

    Dear Théo Valette,
    Please understand that there were about 10 million people in Wuhan and Wuhan had a floating population of nearly 5 million before 23 January 2020, a full grasp of dissemination of Wuhan before 23 January 2020 was impossible and further it is more important to contain spread than to know if every person has the condition. When you know there were 86% of all infections were undocumented (95% CI: [82%–90%]) prior to 23 January 2020 travel restrictions, could you find them in 10 million people? The indiscriminate testing without medical expert advice on whether an individual should be tested would only cause panic and not contain the spread. In a word, China will control the spread of SARS-CoV2 completely in the near future!

    Yezhao Wang, 1,2*
    1Zhejiang Province Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, 315211, China.
    2Department of Biochemistry and Molecular Biology, Ningbo University School of Medicine, Ningbo, 315211, China.

    *Correspondence to Yezhao Wang M.B.B.S
    Department of Biochemistry and Molecular Biology, Ningbo University School of Medicine, Ningbo, 315211, China.
    E-mail: wangyezhao666@163.com.

    Competing Interests: None declared.
  • RE: On the article and on some eLetters

    Dear everyone,

    To Mr Hawk,
    Let's not forget that the fraction of reported infections in China is estimated at 0.14 for the period 10/01 - 23/01 and that it rises to 0.65 and 0.69 for the periods 24/01 - 03/02 and 24/01 - 08/02, respectively. So the paper is more about what happens during the time period before travel restrictions, extensive testing and other measures taken to prevent the spread of the virus. This situation probably has already been reproduced in a number of other countries now and it explains in part why the virus spreads so fast before the gouvernments are able to realize it. And this situation, in the future, might reproduce itself if travel restrictions and other measures are lifted too soon.

    To Mr Wang,
    Let's not forget that the paper was written the 15/02 at a time when we didn't know for sure if the measures taken in China would be effective.

    I would also like to signal a minor mistake in the Materials and Methods. Denominator of the last righthand side term of the fourth equation is wrong and so it is on the U12 Poisson distribution but I checked the code and this error whas not reproduced in it so it in no way impacts the results of the paper.

    Competing Interests: None declared.
  • Implication for Lethality
    • Stephen Hawk, Psychiatrist, VHA Veterans Administration, USA

    Given the suggestion from this article that suggests almost 10 fold higher asymptomatic / undocumented COVID-19 infection, the implication for lethality being correspondingly 10x lower is potential reason for hope.

    Further commentary on this aspect would be appreciated.

    Thank you,

    Competing Interests: None declared.
  • The effectiveness of efforts to control SARS-CoV2 is known.
    • Yezhao Wang, Department of Biochemistry and Molecular Biology, Ningbo University School of Medicine, Ningbo, 315211, China.

    Dear editor:
    The recent coronavirus pneumonia that emerged in Wuhan (SARS-CoV2) at the end of 2019 quickly spread to all Chinese provinces, as of 16 Mar 2020, confirmed cases was reported has reached 160000 worldwide according to statistical data, which attracted global attention (https://www.who.int/) (1). Therefore, I read the recent article by Li et al with great interest (1). In their manuscript, the authors stated that “Efforts to contain the virus are ongoing; however, given the many uncertainties regarding pathogen transmissibility and virulence, the effectiveness of these efforts is unknown” (1). However, China has almost contained the spread of SARS-CoV2 through controlling the source of infection, cutting off the route of transmission, and protecting vulnerable groups (2). Can the authors now conclude that “efforts to contain the virus are ongoing; however, given the many uncertainties regarding pathogen transmissibility and virulence, the effectiveness of these efforts is unknown” (1)?
    This work was supported by grants from the National Undergraduate Training Program for Innovation and Entrepreneurship (no. 201811646025), the Student Research and Innovation Program of Ningbo University (no. 2017SRIP1918, no. 2018SRIP2507 and no. 2019SRIP1902 ). The author has nothing to disclose.

    References:

    1. Li R, Pei S, Chen B, et al. Substantial undocumented infection facilitates the rapid dissemination of no...

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    Competing Interests: None declared.
  • RE:
    • F. Brian Boudi, MD, Physician, Associate Professor, University of Arizona College of Medicine

    These findings also suggest unless every person on earth is tested, many times over, a full grasp of dissemination will not be known (asymptomatic carriers) and further it is more important to control spread than to know if every person has the condition. In addition, depending on the test type, one will not know if the person has the condition, developing the condition or had the condition. The indiscriminate testing without medical expert advice on whether an individual should be tested would only cause panic and not improve the spread. There is of course, the false positive and negative issues that it would create. Adhering to social distancing, hand hygiene and common sense will go a long way in stealth asymptomatic transmission.

    Competing Interests: None declared.

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