Variation of SARS-CoV-2 viral loads by sample type, disease severity and time: a systematic review

  1. Thomas Edwards
  2. Victor S. Santos
  3. Anne L. Wilson
  4. Ana I. Cubas-Atienzar
  5. Konstantina Kontogianni
  6. Christopher T. Williams
  7. Emily R. Adams
  8. Luis E. Cuevas

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Abstract

Background

To describe whether SARS-CoV-2 viral loads (VLs) and cycle thresholds (CTs) vary by sample type, disease severity and symptoms duration.

Methods

Systematic searches were conducted in MEDLINE, EMBASE, BioRxiv and MedRxiv. Studies reporting individual SARS-CoV-2 VLs and/or CT values from biological samples. Paired reviewers independently screened potentially eligible articles. CT values and VLs distributions were described by sample type, disease severity and time from symptom onset. Differences between groups were examined using Kruskal-Wallis and Dunn ‘s tests (post-hoc test). The risk of bias was assessed using the Joanna Briggs Critical Appraisal Tools.

Results

14 studies reported CT values, 8 VLs and 2 CTs and VLs, resulting in 432 VL and 873 CT data points. VLs were higher in saliva and sputum (medians 4.7×108 and 6.5×104 genomes per ml, respectively) than in nasopharyngeal and oropharyngeal swabs (medians 1.7×102 and 4.8×103). Combined naso/oropharyngeal swabs had lower CT values (i.e. higher VLs) than single site samples (p=<0.0001). CT values were also lower in asymptomatic individuals and patients with severe COVID-19 (median CT 30 for both) than among patients with moderate and mild symptoms (31.4 and 31.3, respectively). Stool samples were reported positive for a longer period than other specimens.

Conclusion

VLs are higher in saliva and sputum and in individuals who are asymptomatic of with severe COVID-19. Diagnostic testing strategies should consider that VLs vary by sample type, disease severity and time since symptoms onset.

Summary

This systematic review found a higher viral load in saliva and sputum than in nasopharyngeal swabs, in asymptomatic individuals and patients with severe COVID-19. Diagnostic testing strategies should consider the type of sample, disease severity and the time since symptoms onset.

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  1. ScreenIT

    SciScore for 10.1101/2020.09.16.20195982: (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
    Data were analysed using GraphPad Prism Version 5 (GraphPad Software, Inc.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: Thank you for sharing your code.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our data has several limitations that need to be considered to interpret the data. Most studies were case reports or case series and therefore testing was initiated by clinical need or patient management. It is thus possible that data was collected from patients with unusual conditions and does not represent the whole spectrum of disease. Data also represents early reports during the pandemic, when diagnostic capacity was limited, and testing was prioritised for patients with the greatest need. Therefore, VLs may have over-represented patients with symptomatic infections and their contacts and further studies are needed to further document VLs in asymptomatic and mild cases through community surveillance. Other potential limitations include the use of the disease severity classifications of the authors, which were not standardised until later in the epidemic. Moreover, we included pre-prints that had not been peer-reviewed, with potentially varying quality. Despite these limitations, few studies had a significant risk of bias and the main issues noted were data aggregation and a lack of timelines to describe the patient clinical progression. In conclusion, we have demonstrated that SARS-CoV-2 CTs and VLs vary between sample type, time point, and disease severity. This information will be useful for the selection of specimens for SARS-CoV-2 confirmation, the development of new diagnostic assays and a better understanding of the patterns of VLs over time to be expected among th...

    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.

  2. Version published to 10.1101/2020.09.16.20195982v1 on medRxiv