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Viral dynamics of SARS-CoV-2 infection and the predictive value of repeat testing

Our take —

This prospective longitudinal study among National Basketball Association players, coaches, staff and vendors, available as a preprint and thus not yet peer reviewed, provides the first set of data on the RT-qPCR dynamics of early SARS-CoV-2 infection. Peak viral load appears to occur early during the response and symptomatic individuals appear to shed SARS-CoV-2 for a longer period of time. A second test within 2 days of a positive test may predict if an individual’s viral load is increasing or decreasing which can inform clinical care.

Study design

Prospective Cohort

Study population and setting

Study subjects included the National Basketball Association (NBA) players, staff, and vendors tested for SARS-CoV-2 using real-time quantitative PCR (RT-qPCR) from June 23 to July 9, 2020. Data presented in this article was collected in the teams’ local cities prior to relocation of the study cohort to isolation in Orlando, Florida. Multiple samples (n>5) were taken from each individual and data from individuals that tested positive for SARS-CoV-2 one or more times was analyzed.

Summary of Main Findings

In total, 2,411 serial RT-qPCR threshold cycle (Ct) values from 68 individuals with SARS-CoV-2 infections were analyzed, with a median number of 41 test results per person. Ct values were used to estimate viral load, with a lower Ct value corresponding to a higher viral load. Of the 68 individuals with positive results, 46/68 had active infections and only 13/46 of these individuals reported symptoms. Results demonstrated no significant difference in peak Ct values between symptomatic and asymptomatic individuals [mean Ct 22.2 (95% CI: 19.1, 25.1) vs 22.4 (95% CI: 20.2, 24.5), respectively) implying that there was no difference in viral load between those with and without symptoms. Individuals with symptoms took longer to clear the virus [mean duration 10.5 days (95% CI: 6.5, 14.0)] compared to asymptomatic individuals [mean duration 6.7 days (95% CI: 3.2, 9.2)]. Regardless of symptoms, the mean duration of acute shedding for the 46 individuals with active infection was 10.1 days (95% CI: 6.5, 12.6). The remaining 22/68 individuals were presumed to be infected prior to study implementation and were still clearing virus but did not have a new infection. Probability estimation showed that while Ct values alone could predict if a person was in the acute or persistent viral shedding stage, a positive test followed by a second test with a higher viral RNA concentration within a 48-hour window was strongly associated with an active infection in the proliferation phase.

Study Strengths

The longitudinal design of the study and multiple testing outcomes for each individual provided insight into the kinetics of early SARS-CoV-2 infection using Ct values rather than a binary positive or negative result. Additionally, the data presented pre-dated the “bubble” phase of testing and simulated real-world exposure to the virus.

Limitations

Statistical modeling was used to infer a time frame from onset of infection to peak infection and a time frame from peak infection to the conclusion of viral shedding which may or may not correlate with actual clinical time frames. The study findings may have limited applicability to the general population as the study cohort was composed of predominantly male professional athletes with unrestricted access to health care. No association between Ct values and viral copy number was reported, which limits the applicability of these findings for diagnostic assessments.

Value added

This is the first study to use serial PCR to infer if a person is in the proliferation or recovery (clearance) stage of viral infection, and provides strong evidence that a follow-up test within two days of the initial positive test can determine if an individual’s viral load is increasing or decreasing. Repeated testing can identify individuals carrying SARS-CoV-2 if they are infectious or not and in turn, help to reduce the number of overall infections in a community setting.

This review was posted on: 14 January 2021