Daily Rapid Antigen Testing in a University Setting to Inform COVID-19 Isolation Duration Policy

  1. Rebecca Earnest
  2. Christine Chen
  3. Chrispin Chaguza
  4. Nathan D. Grubaugh
  5. Madeline S. Wilson
  6. the Yale COVID-19 Resulting and Isolation Team

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Abstract

Importance

The suitability of the currently recommended 5-day COVID-19 isolation period remains unclear in an Omicron-dominant landscape. Early data suggest high positivity via rapid antigen test beyond day 5, but evidence gaps remain regarding optimal isolation duration and the best use of limited RATs to exit isolation.

Objective

To determine the percentage of SARS-CoV-2 infected persons who remain positive via RAT on isolation day 5+ and assess possible factors associated with isolation duration.

Design

We evaluated daily rapid antigen test case series data from 324 persons in a managed isolation program who initially tested positive between January 1 and February 11, 2022, an Omicron-dominant period. Arrival tests and twice-weekly screening were mandated. Positive persons isolated and began mandatory daily self-testing on day 5 until testing negative. Trained staff proctored exit testing.

Setting

A mid-sized university in the United States.

Participants

University students in isolation.

Main Outcomes and Measures

The percentage of persons remaining positive on isolation day 5 and each subsequent day. The association between possible prognostic factors and isolation duration as measured by event-time-ratios (ETR).

Results

We found 47% twice-weekly screeners and 26-28% less frequent screeners remained positive on day 5, with the percentage approximately halving each additional day. Having a negative test ≥ 10 days before diagnosis (ETR 0.85 (95% CI 0.75-0.96)) and prior infection > 90 days (ETR 0.50 (95% CI 0.33-0.76)) were significantly associated with shorter isolation. Symptoms before or at diagnosis (ETR 1.13 (95% CI 1.02-1.25)) and receipt of 3 vaccine doses (ETR 1.20 (95% CI 1.04-1.39)) were significantly associated with prolonged isolation. However, these factors were associated with duration of isolation, not infection, and could reflect how early infections were detected.

Conclusions and Relevance

A high percentage of university students during an Omicron-dominant period remained positive after the currently recommended 5-day isolation, highlighting possible onward transmission risk. Persons diagnosed early in their infections or using symptom onset as their isolation start may particularly require longer isolations. Significant factors associated with isolation duration should be further explored to determine relationships with infection duration.

Key Points

Question

What percentage of SARS-CoV-2 infected persons remain positive via rapid antigen test on days 5+ of isolation?

Findings

In this case series of 324 university students, 47% of twice-weekly screeners and 26-28% of less frequent screeners remained positive via rapid antigen on isolation day 5, with the percent still positive approximately halving with each subsequent day.

Meaning

While isolation duration decisions are complex, our study adds to growing evidence that a 5-day isolation may be 1-2 days too short to sufficiently reduce the onward transmission risk, particularly for those in dense settings or among vulnerable populations.

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  1. ScreenIT

    SciScore for 10.1101/2022.03.11.22272264: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We used RStudio v1.4.1106 for our analyses.
    RStudio
    suggested: (RStudio, RRID:SCR_000432)
    We checked the assumption that the ratio of survival times (i.e. the event-time-ratio) is constant for all fixed probabilities of S(t), the survival function, by a visual inspection of QQ plots generated for each covariate level comparison using the R package AFTtools v0.2.1.20
    AFTtools
    suggested: None

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations: Symptom status only captures self-reported symptoms before or at diagnosis and may not always be related to the subsequent SARS-CoV-2 diagnosis. Three persons reported a symptom onset > 10 days before diagnosis. Some asymptomatic persons may have later become symptomatic. Prior infections > 90 days only included confirmed infections reported in the medical records. There likely are missed prior infections that occurred during breaks or before routine screening was implemented at the university in Fall 2021. The PCR CT value was only measured at diagnosis. Some CT values were missing due to external tests or RAT. Our study population, primarily 18-22 year old students, may not be representative of the general population due to their youth and likely lower rate of comorbidities. However, it is unlikely that older age groups or those with higher comorbidity rates would experience shorter isolation durations. We do not have a full medical history for our study population, and it is possible that some persons may experience longer isolations due to medical conditions. There could be changes in staff accuracy over time in reading RAT results, which are qualitative in nature, although their training procedures render this less likely. We do not have RAT data for days 1-4 and accounted for this interval-censoring in our analysis. RATs have a lower sensitivity than PCR, reducing the risk that a non-infectious person would remain in isolation but increasing the risk of a f...

    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.

  2. Version published to 10.1101/2022.03.11.22272264v1 on medRxiv