A Systematic Review of the Incubation Period of SARS-CoV-2: The Effects of Age, Biological Sex, and Location on Incubation Period

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Abstract

A systematic review of the incubation period of COVID-19 was compiled and analyzed from 21 quantitative studies. We investigated the incubation period of COVID-19 with regard to age, biological sex, location, and severity of the disease. Based on the data extracted, we report an overall mean and median incubation period for SARS-CoV-2 of 5.894 days and 5.598 days, respectively. The incubation period did not statistically vary for biological sex or age, but some studies suggest a longer incubation period in the young and elderly. Cases of COVID-19 in Wuhan and Hubei Province of China may have a shorter incubation period for COVID-19 but the shorter incubation period may be due to an increase in viral load. In studying coronavirus strains such as SARS and MERS, researchers have discovered an inverse relationship between incubation period length and virus severity. Taking into consideration that SARS-CoV-2 is part of the beta-coronavirus family, as well as the study mentioned above, we suggest that people who experience more severe disease due to SARS-CoV-2 may have a shorter incubation period.

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  1. Our take

    This systematic review, available as a preprint and thus not yet peer reviewed, summarized evidence about the link between incubation period of SARS-CoV-2 and age, sex, or location from 21 primary studies conducted before June 15, 2020. The estimated mean and median incubation period of SARS-CoV-2 was 5.9 days and 5.6 days respectively. The findings suggest that longer incubation periods among children and elderly compared to young and middle-aged adults may be possible, but no differences were observed by sex and age-disaggregated data were limited. Living within/travel to the area where the virus was first identified was associated with shorter incubation period, likely reflecting greater infection dose or multiple sources of infections. Caution is needed in interpreting these findings, as they may not necessarily reflect features of emerging variants of the virus or incubation periods in settings outside China, where most included studies took place. Findings of longer incubation among the elderly, a vulnerable population, and children may have implications for additional measures around quarantine and social-distancing measures among these groups, such as quarantine in long-term care facilities and school re-openings. However, more data by age is required before conclusions can be made.

    Study design

    other

    Study population and setting

    This systematic review synthesized evidence from 21 studies to determine if there is a link between incubation period of SARS-CoV-2 and key socio-demographic factors such as age, biological sex, and location. Incubation period—the time between exposure to virus and onset of signs and symptoms—is crucial for determining transmission dynamics and guiding mitigation strategies. For example, the current guideline of a 14-day quarantine period is based on research showing a median incubation period of 5.1 days and that 97.5% of persons who develop symptom do so within 11.5 days, and 99% develop symptoms within 14 days. The primary studies included in this systematic review had to meet the following criteria: have a clearly defined incubation period, use contact tracing to identify incubation period, and have disease confirmed using RT-PCR with nasal/throat swabs or blood specimens. Studies reporting means were used to estimate mean incubation period, while studies reporting medians were used to estimate median incubation period.

    Summary of main findings

    Estimated mean and median incubation period for SARS-CoV-2 were 5.9 days and 5.6 days, respectively. Across six studies reporting on links between age group and incubation period, data suggested possible longer incubation periods among pediatric and geriatric populations, than among young and middle-aged adults. Evidence did not support a link between incubation period and biological sex. With regard to location, taken together, three out of four studies found that living within/travel to Wuhan (area where the virus was discovered) or Hubei province (where Wuhan is located) was associated with shorter incubation period. Some investigators hypothesized that persons who traveled to these areas may have had several sources of infection and thus potentially higher infectious dose.

    Study strengths

    Confirmation of each COVID-19 case across the primary studies was established through real-time polymerase chain reaction (RT-PCR).

    Limitations

    Primary studies included in this review were conducted before June 15, 2020, and were mostly from China. Therefore, findings may not necessarily reflect features of new variants of the virus or associations in broader settings. Furthermore, there was no discussion about the criteria for testing of SARS-CoV-2 in the primary studies. In the absence of universal testing, incubation period of persons recommended for testing may differ in significant ways from those not tested. A key limitation of this analysis was that although 21 studies were included in the review, only a few primary studies examined the association between incubation period and each key demographic factor (e.g., only six studies reported on associations with age group). Thus, determination of trends is heavily influenced by a couple of studies.

    Value added

    This systematic review summarized evidence about the links between incubation period of the SARS-CoV-2 and key demographic factors of age, sex, and location from 21 primary studies conducted within the first seven months of the pandemic.

  2. SciScore for 10.1101/2020.12.23.20248790: (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
    Databases and Search Strategies: Between the dates of June 16th and July 18th 2020, databases including PubMed, Science Direct, and MedRxiv, were searched for primary research articles pertaining to the incubation period of SARS-CoV-2 that had been published since the outbreak of the virus.
    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: 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.

    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.