SARS-CoV-2 viral-load distribution reveals that viral loads increase with age: a retrospective cross-sectional cohort study

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Abstract

Background

Describing the SARS-CoV-2 viral-load distribution in different patient groups and age categories.

Methods

All results from first nasopharyngeal (NP) and oropharyngeal (OP) swabs from unique patients tested via SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) collected between 1 January and 1 December 2020 predominantly in the Public Health Services regions Kennemerland and Hollands Noorden, province of North Holland, the Netherlands, were included in this study. SARS-CoV-2 PCR crossing-point (Cp)-values were used to estimate viral loads.

Results

In total, 278 455 unique patients were tested, of whom 9.1% (n = 25.374) were SARS-CoV-2-positive. PCRs performed by Public Health Services (n = 211 914), in which sampling and inclusion were uniform, revealed a clear relation between age and SARS-CoV-2 viral load, with especially children aged <12 years showing lower viral loads than adults (β: –0.03, 95% confidence interval: –0.03 to –0.02, p < 0.001), independently of sex and/or symptom duration. Interestingly, the median Cp-values between the >79- and <12-year-old populations differed by more than four PCR cycles, suggesting an ∼16-fold difference in viral load. In addition, the proportion of children aged <12 years with a low load (Cp-value >30) was higher compared with other patients (31.1% vs 17.2%, p-value < 0.001).

Conclusions

In patients tested by Public Health Services, SARS-CoV-2 viral load increases with age. Further studies should elucidate whether the lower viral load in children is indeed related to their suggested limited role in SARS-CoV-2 transmission. Moreover, as rapid antigen tests are less sensitive than PCR, these results suggest that SARS-CoV-2 antigen tests have lower sensitivity in children than in adults.

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  1. SciScore for 10.1101/2021.01.15.21249691: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics Statement: The Medical Ethical Committee of the Amsterdam UMC approved this study on January 19th, 2021 (Study number: 2021.0022).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot 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:
    One of the limitations of our study is that there were no data available on symptoms, underlying disease, sampling method, and moment of onset of first symptoms of all patients for whom respiratory samples were included. This is why the analyses of the relation between age and viral load was evaluated in samples from patients tested in the Public Health testing facilities which was considered to be a relatively consistent population with respect to performed sampling procedure and patient characteristics, and for whom time of onset of first symptoms was known (for a large subset of patients). Another limitation was the inclusion of symptomatic patients only, thus not reflecting the spectrum of SARS-CoV-2 infection, especially as asymptomatic presentations are frequently seen in children.19–21 In addition, it should be noted that the samples included in this study were collected before the novel SARS-CoV-2 variant, VOC 202012/01, that was first identified in the UK was likely to have been widespread in the Netherlands.22 To conclude, with this study we have tried to emphasize the usefulness of analyzing SARS-CoV-2 RT-PCR (viral load) data that are derived from a large population made up of a broad range of patient groups and age categories in a single laboratory (using the same SARS-CoV-2 RT-PCR method for all samples). With these data, shifts in tested patients populations and viral load distributions during the course of the COVID-19 pandemic can be closely monitored. This m...

    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. SciScore for 10.1101/2021.01.15.21249691: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementEthics Statement The Institutional Review Board of the Spaarne Gasthuis, Hoofddorp/Haarlem, the Netherlands, approved to conduct the study on November 10th, 2020 (Study number: 2020.0154).Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variablenot 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:

    One of the limitations of our study is that there were no data available on symptomatic status, underlying disease, sampling method, and moment of onset of first symptoms of all patients for whom respiratory samples were included. This is why the analyses of the relation between age and viral load was evaluated in samples from patients tested in the Public Health testing facilities which was considered to be a relatively consistent population with respect to performed sampling procedure and patient characteristics, and for whom time of onset of first symptoms was known (for a large subset of patients). Another limitation was the inclusion of symptomatic patients only, thus not reflecting the spectrum of SARS-CoV-2 infection, especially as asymptomatic presentations are frequently seen in children.16-17 In addition, it should be noted that the samples included in this study were collected before the novel SARS-CoV-2 variant, VOC 202012/01, that was first identified in the UK was likely to have been widespread in the Netherlands.18 To conclude, with this study we have tried to emphasize the usefulness of analyzing SARS-CoV-2 RT-PCR (viral load) data that are derived from a large population made up of a broad range of patient groups and age categories in a single laboratory (using the identical SARS-CoV-2 RT-PCR method for all samples). With these data, shifts in tested patients populations and viral load distributions during the course of the COVID-19 pandemic can be closely mo...


    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.


    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.