Asymptomatic and presymptomatic transmission of SARS-CoV-2: A systematic review

  1. Christina Savvides
  2. Robert Siegel

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Abstract

Background and Purpose

Many of the statutes comprising the shelter-in-place and phased-reopening orders are centered around minimizing asymptomatic and presymptomatic transmission. Assumptions about the presence and relative importance of asymptomatic and presymptomatic transmission are based on case reports, the failing of quarantine measures aimed at sequestering ill patients, viral dynamic studies suggesting SARS-CoV-2 production peaks before symptoms appear, and modeling evidence that calculates serial interval between successive generations of infection. In aggregate, these data offer compelling evidence of asymptomatic and presymptomatic transmission, but individually these studies have notable shortcomings that undermine their conclusions. The purpose of this review is to discuss the literature of asymptomatic and presymptomatic transmission, highlight limitations of recent studies, and propose experiments that, if conducted, would provide a more definitive analysis of the relative role of asymptomatic and presymptomatic transmission in the ongoing SARS-CoV-2 pandemic.

Methods

We conducted a systematic review of literature on PubMed using search filters that relate to asymptomatic and presymptomatic transmission as well as serial interval and viral dynamics. We focused on studies that provided primary clinical data.

Results

34 studies were eligible for inclusion in this systematic review: 11 case reports pertaining to asymptomatic transmission, 9 viral kinetic studies, 13 serial interval studies, and 1 study with viral kinetics and serial interval.

Conclusion

Different approaches to determining the presence and prevalence of asymptomatic and presymptomatic SARS-CoV-2 transmission have notable shortcomings, which were highlighted in this review and limit our ability to draw definitive conclusions. Conducting high quality studies with the aim of understanding the relative role of asymptomatic and presymptomatic transmission is instrumental to developing the most informed policies on reopening our cities, states, and countries.

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  1. Version published to 10.1101/2020.06.11.20129072v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2020.06.11.20129072: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Articles for this review were extracted from a PubMed search conducted on June 10, 2020.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)

    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:
    Case Studies: While case studies, in aggregate, can offer compelling insight into the existence of asymptomatic and presymptomatic transmission, these reports have many limitations. Even if broad community transmission is not observed, it is still extremely difficult to rule out other sources of infection. Future studies should use viral sequence to more precisely determine sources of infection and transmission chains. Additionally, the temporal variation in what is classified as a symptom of COVID-19, combined with bias and reporting errors, make anecdotal reports of symptom start date unreliable. These factors confound the case reports that highlight asymptomatic or presymptomatic transmission and make it difficult to draw reliable conclusions. Viral Dynamics: The preliminary SARS-CoV-2 viral dynamics studies demonstrate that viral titer peaks at patient presentation. Without more knowledge of the temporal distribution of viral load, presymptomatic transmission cannot be conclusively shown. In interpreting viral dynamic studies, a sharp rise in viral load, as would be observed if viral load followed a lognormal or gamma distribution, may link infectiousness with the start of symptom onset. On the other hand, a normal or Weibull distribution in viral load supports the possibility of presymptomatic transmission. It is important that the viral dynamics data be validated with culture data on infectivity. As Wolfel and colleagues demonstrated, while viral load is a proxy for inf...

    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

    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.

  3. Version published to 10.1101/2020.06.11.20129072v1 on medRxiv