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Review 1: "High Rates of Rapid Antigen Test Positive After 5 days of Isolation for COVID-19"

While results were clearly presented, reviewers point out that the manuscript’s conclusions are not backed up by these results, and the discussion should be better supported by literature.

Published onJun 08, 2022
Review 1: "High Rates of Rapid Antigen Test Positive After 5 days of Isolation for COVID-19"
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key-enterThis Pub is a Review of
High Rates of Rapid Antigen Test Positivity After 5 days of Isolation for COVID-19

AbstractBackgroundThe emergence of the highly transmissible COVID-19 variant, omicron, has resulted in high numbers of breakthrough infections, including among healthcare workers (HCW). Recent CDC recommendations now allow healthcare workers to return to work after day 5 if symptoms have improved, without a requirement for a negative rapid antigen test (RAT).MethodsFully vaccinated and non-immunocompromised HCW at a large, urban, academic medical center who tested positive for COVID-19 starting in late December, 2021 (when omicron was the predominant circulating strain) were allowed to return to work early if all symptoms had resolved excepting mild, intermittent cough and/or lingering loss of taste/smell, provided a rapid antigen test was negative upon return. Those with negative tests were allowed to return to work with the stipulations that they wear an N95 at all times and take breaks and eat meals apart from others. Those with positive tests on first attempt could return 24-48 hours later to test again for as many days as needed to achieve a negative result or until they completed 10 days of restriction from work.ResultsBetween January 2, 2022 and January 12, 2022 there were 309 total RAT done on 260 separate HCW on day 5-10 of illness. Overall, 43% (134 of 309) of all RAT were positive between days 5-10. The greatest percent positive RAT was noted among HCW returning for their first test on day 6 (58%). The rate of positivity was greatest (58%) among HCW returning for their first test on day 6. HCW returning on day 8 and 9 were less likely to have a positive test (26%, 19/74). In RAT positive HCW returning for their first test on days 5 or 6 (and for which line intensity was recorded) 49% (25/51) were recorded as having the darkest intensity on their RAT. HCW who test positive on their first test most often remained positive on their second test, with 56% of second tests, aggregated across all days 6-10, remaining positive. Over all first tests performed on days 5-10, boosted HCW were nearly twice as likely to test RAT positive: 53% (75 out of 141) of boosted HCW tested positive.DiscussionMore than 40% of vaccinated HCW who felt well enough to work still had positive RAT tests when presenting for a first test between days 5 and 10. Boosted individuals were nearly 3x as likely to result positive on day 5, their first day eligible for return, and ∼2x as likely to result positive on first RAT overall. New guidance provides clearance to exit isolation after 5 days from symptom onset, without the need for a negative rapid antigen test to exit, as long as symptoms are beginning to resolve. Per CDC, the guidance was driven by prior studies, mostly collected before Omicron and before most people were vaccinated or infected, that reported on symptom onset beginning one or more days after peak virus loads. In such an instance, where isolation based on symptom onset often did not begin until peak virus load was already attained, then release from isolation at 5 days would be appropriate. However, reports showing much earlier onset of symptoms, coupled with our own results here demonstrate that the relationship between symptom onset and peak virus load has changed, and 5 days from symptom onset may no longer be an appropriate window to end isolation without a negative rapid antigen test to support safe exit.ConclusionThese results indicate that a substantial proportion of individuals with COVID-19 are likely still contagious after day 5 of illness regardless of symptom status. Early liberation from isolation should be undertaken only with the understanding that inclusion of individuals on day 6-10 of illness in community or work settings may increase the risk of COVID-19 spread to others which, in turn, may undermine the intended benefits to staffing by resulting in more sick workers.

RR:C19 Evidence Scale rating by reviewer:

  • Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.



Based on the Strength of Evidence Scale, the information in this manuscript is potentially informative. The authors evaluate the positivity rate of rapid antigen diagnostic tests (RDT) of health care workers (HCW) returning to work after a COVID-19 infection. The study is performed during the omicron wave. The authors show that 43% of the RDT performed between day 5 and day 10 after the first positive test - a period when infected persons are allowed to leave isolation according to recent CDC recommendations - were positive. Interestingly, the positivity rate in boosted individuals was higher in boosted individuals compared to not boosted individuals. The results are clearly presented, but the conclusions of the manuscript - the persons tested positively by RDT are still infectious - are not strongly backed up by the results.

The methods are well explained but RDT generally vary strongly in sensitivity and are thus not well suited as correlate for infectiosity.

The limitations of this study are reasonable. Not all health care workers were tested daily, no information was available on the symptom onset. The discussion about the relation between RDT positivity, PCR Ct value and infectiousness is not backed up well by literature - especially at the end of the infection. This interpretation should be backed up better with literature and the conclusions should be phrased more careful. The study would also benefit from a statistical analysis regarding booster status and positivity. The discussion of the fact that positivity rate was higher in boostered individuals does not seem really clear.

Overall, the results of this study are interesting and in this characteristic new. The analysis and especially the interpretation should be revised if this were to be submitted as a journal paper and the data on at least PCR testing (including derived viral loads), but also the viral culture data will allow to assess if the described RDT positivity poses a risk regarding infectiosity at the end of isolation of COVID-19 positive individuals.


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