Inferred duration of infectious period of SARS-CoV-2: rapid scoping review and analysis of available evidence for asymptomatic and symptomatic COVID-19 cases

  1. Andrew William Byrne
  2. David McEvoy
  3. Aine B Collins
  4. Kevin Hunt
  5. Miriam Casey
  6. Ann Barber
  7. Francis Butler
  8. John Griffin
  9. Elizabeth A Lane
  10. Conor McAloon
  11. Kirsty O'Brien
  12. Patrick Wall
  13. Kieran A Walsh
  14. Simon J More

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Abstract

Our objective was to review the literature on the inferred duration of the infectious period of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, and provide an overview of the variation depending on the methodological approach.

Design

Rapid scoping review. Literature review with fixed search terms, up to 1 April 2020. Central tendency and variation of the parameter estimates for infectious period in (A) asymptomatic and (B) symptomatic cases from (1) virological studies (repeated testing), (2) tracing studies and (3) modelling studies were gathered. Narrative review of viral dynamics.

Information sources

Search strategies developed and the following searched: PubMed, Google Scholar, MedRxiv and BioRxiv. Additionally, the Health Information Quality Authority (Ireland) viral load synthesis was used, which screened literature from PubMed, Embase, ScienceDirect, NHS evidence, Cochrane, medRxiv and bioRxiv, and HRB open databases.

Results

There was substantial variation in the estimates, and how infectious period was inferred. One study provided approximate median infectious period for asymptomatic cases of 6.5–9.5 days. Median presymptomatic infectious period across studies varied over <1–4 days. Estimated mean time from symptom onset to two negative RT-PCR tests was 13.4 days (95% CI 10.9 to 15.8) but was shorter when studies included children or less severe cases. Estimated mean duration from symptom onset to hospital discharge or death (potential maximal infectious period) was 18.1 days (95% CI 15.1 to 21.0); time to discharge was on average 4 days shorter than time to death. Viral dynamic data and model infectious parameters were often shorter than repeated diagnostic data.

Conclusions

There are limitations of inferring infectiousness from repeated diagnosis, viral loads and viral replication data alone and also potential patient recall bias relevant to estimating exposure and symptom onset times. Despite this, available data provide a preliminary evidence base to inform models of central tendency for key parameters and variation for exploring parameter space and sensitivity analysis.

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  1. Version published to 10.1136/bmjopen-2020-039856
  2. ScreenIT

    SciScore for 10.1101/2020.04.25.20079889: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Publications on the electronic databases PubMed, Google Scholar, MedRxiv and BioRxiv were searched with the following keywords: “Novel coronavirus” OR “SARS-CoV-2” OR “2019-nCoV” OR “COVID-19” AND “infectious”.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    Briefly, the evidence synthesis process included searching databases from 30th December 2019 to 27th March 2020 (PubMed, Embase, ScienceDirect, NHS evidence, Cochrane, medRxiv and bioRxiv, HRB open), screening, data extraction, critical appraisal and summarizing the evidence.
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Cochrane
    suggested: (Cochrane Library, RRID:SCR_013000)
    bioRxiv
    suggested: (bioRxiv, RRID:SCR_003933)

    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:
    Furthermore, virus was not isolated from blood or urine in that study.[50] Study limitations: Overall, the studies included were of good quality, though due to the rapid need for information from the global research community many papers are pre-prints that have yet to be reviewed (at time of writing). Many papers were limited in terms of sample sizes, with several papers being case studies of one patient or single cluster outbreaks. There was a diversity of methods employed to infer dynamics of infectiousness across studies, and therefore the evidential base was variable. Some issues around nomenclature were noted, including definitions of asymptomatic, infectious period, latent, and incubation period. It is possible the same data may have been used across different studies, especially where publicly available data were used. There was significant heterogeneity across study findings, and this was related to diversity of clinical findings and methods employed. The meta-analysis employed for one parameter (T5) using virological studies, where cross study comparisons could be made, suggested that the heterogeneity was high. Fu et al.[70] cautions against combining studies to give an overall estimate without exploring subgroup or meta-regression analysis, which we have done here. The meta-regression was based on a small number of studies (n=12-13). Cochrane’s handbook suggests 10 studies for each level of a meta-regression, however in practice much lower numbers have been used t...

    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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  3. Version published to 10.1101/2020.04.25.20079889v1 on medRxiv