Initial Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load Is Associated With Disease Severity: A Retrospective Cohort Study

  1. Dennis Souverein
  2. Karlijn van Stralen
  3. Steven van Lelyveld
  4. Claudia van Gemeren
  5. Milly Haverkort
  6. Dominic Snijders
  7. Robin Soetekouw
  8. Erik Kapteijns
  9. Evelien de Jong
  10. Gonneke Hermanides
  11. Sem Aronson
  12. Bjorn Herpers
  13. Jeroen den Boer
  14. Alex Wagemakers
  15. Sjoerd Euser

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Abstract

Background

We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and hospital admission, intensive care unit (ICU) admission, and in-hospital mortality.

Methods

All SARS-CoV-2–positive persons with a combined nasopharyngeal and oropharyngeal swab that was collected between 17 March 2020 and 31 March 2021 in public health testing facilities were included.

Results

From 20 207 SARS-CoV-2–positive persons, 310 (1.5%) were hospitalized within 30 days. High viral loads (crossing point [Cp] <25) were associated with an increased risk of hospitalization as compared to low viral loads (Cp >30), adjusted for age and sex (adjusted odds ratio [aOR], 1.57 [95% confidence interval {CI}, 1.11–2.26]). The same association was seen for ICU admission (aOR, 7.06 [95% CI, 2.15–43.57]). The median [interquartile range] Cp value of the 17 patients who died in hospital was significantly lower compared to the 226 survivors (22.7 [3.4] vs 25.0 [5.2]).

Conclusions

Higher initial SARS-CoV-2 viral load is associated with an increased risk of hospital admission, ICU admission, and in-hospital mortality. Our findings emphasize the added value of reporting SARS-CoV-2 viral load or cycle threshold/Cp values to identify persons who are at the highest risk of adverse outcomes such as hospital or ICU admission and who therefore may benefit from more intensive monitoring or early initiation of antiviral therapy.

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  1. Version published to 10.1093/ofid/ofac223
  2. ScreenIT

    SciScore for 10.1101/2021.10.01.21264412: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics Statement: The Medical Ethical Committee of the Amsterdam UMC approved this study on January 19th, 2021 (Study number:2021.0170).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    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:
    Our study has a few notable limitations. Although this is one of the first studies to connect viral load with increased risk of mortality, the number of in-hospital deaths in our study population was low, and larger studies are needed to assess the role of viral load in the outpatient setting and after adjustments for potential confounding factors. The data on hospital (and ICU) admission of our study population were collected from the two large teaching hospitals our region that largely cover the adherence area of the Regional Public Health Laboratory Kennemerland (where the tests were performed). It can however not be excluded that (ICU)hospitalization data of some of the included patients were missed when they were admitted to other hospitals in adjacent regions. However, we do not think that this will have influenced our main results as the chance of admission to a hospital in another region is not likely to be related to the initial SARS-CoV-2 viral load of a particular patient and would only have resulted in nondifferential misclassification of our outcome measurement. And finally, including only patients who were able to have themselves tested at Public Health Service testing facilities may have resulted in a healthy selection of all SARS-CoV-2 positive patients, as patients were able to make an appointment and go to the public health care facility. Even though this generally took place after a mean of 2 days, patients who got very ill, or needed to be admitted to the ...

    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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2021.10.01.21264412v1 on medRxiv