By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
SYNOPSIS: Patients with COVID-19 were found, by culture, to shed replication-competent virus after an initial PCR test for median durations of four to five days.
SOURCE: Boucau J, Marino C, Regan J, et al. Duration of shedding of culturable virus in SARS-CoV-2 Omicron (BA.1) infection. N Engl J Med 2022;387:275-277.
Boucau et al evaluated the duration of nasopharyngeal shedding after infection with SARS-CoV-2 using two methods: PCR to detect viral RNA and tissue culture to detect viable, presumably transmissible, virus. They enrolled 66 participants from July 2021 through January 2022. Of these, sequencing identified the infection was caused by the delta variant (B.1.61.2) in 34 and by omicron subvariant BA.1 in 32. Approximately one-fourth of each group was unvaccinated, but those with omicron infection were more likely to have received a booster dose. Infections were symptomatic in 65 of 66 patients, but no patients received antiviral therapy.
The time to conversion from an initial positive to a negative PCR was not significantly different between the delta- and omicron-infected cohorts. This also was true for the time from first positive PCR to negative culture, with median intervals of four days (interquartile range, three to five days) and five days (interquartile range, three to nine days) for the delta and omicron groups, respectively. The median intervals from symptom onset to negative culture were somewhat longer at six and eight days. Vaccination status, including boosting, did not significantly affect the results of PCR reversion to negative.
COMMENTARY
A similar study of 29 patients in South Korea performed between February and June 2020 revealed the median time from symptom onset to viral clearance in culture was seven days (although the median time to viral clearance on real-time reverse transcription PCR was an astounding 34 days).1 The current CDC recommendation states: “If you had COVID-19 and had symptoms, isolate for at least five days. To calculate your five-day isolation period, day 0 is your first day of symptoms. Day 1 is the first full day after your symptoms developed. You can leave isolation after five full days. You can end isolation after five full days if you are fever-free for 24 hours without the use of fever-reducing medication and your other symptoms have improved. You should continue to wear a well-fitting mask around others at home and in public for five additional days (day 6 through day 10).”2
However, this study by Boucau et al indicates half of infected individuals continue to shed cultivatable virus after day 4-5, suggesting they may continue to transmit the virus. This makes the admonition for wearing a mask to day 10 all the more important.
The discrepancy between PCR and culture results from the fact PCR detects viral RNA, not necessarily replication-competent virus — which is necessary for transmission of infection. Whether the presence of any amount of cultivatable virus is sufficient for transmission is unknown. Viral culture of SARS-CoV-2 is impractical in the clinical setting. The PCR cycle threshold may provide a clue as to the presence of replication-competent virus. For example, in the South Korean study noted earlier, viral culture was positive only in samples with a cycle threshold value < 28.4. Another proposed correlate of viable transmissible virus is the presence of viral single-strand RNA, which is detected by specific PCR test. SARS-CoV-2 is a single-strand RNA virus that must replicate through a negative strand intermediate, and the detection of this intermediate correlates with the presence of actively replicating virus.
The results reported by Boucau et al should give us some pause in our approach to infected patients. This is especially true of immunocompromised patients, some of whom may shed virus for prolonged periods.
REFERENCES
1. Kim MC, Cui C, Shin KR, et al. Duration of culturable SARS-CoV-2 in hospitalized patients with Covid-19. N Engl J Med 2021;384:671-673.
2. Centers for Disease Control and Prevention. COVID-19. Quarantine and isolation. Updated March 30, 2022.
Patients with COVID-19 were found, by culture, to shed replication-competent virus after an initial PCR test for median durations of four to five days.
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