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More Than One Quarter of People Feel No COVID Symptoms Before Shedding Virus
  IAS COVID-19 Conference: Prevention, February 2, 2021
Mark Mascolini
More than one quarter of people newly infected with SARS-CoV-2 in a prospective US study did not report COVID-19 symptoms before they began shedding virus [1]. Almost half of the study group continued to shed virus 5 or more days after infection. "The use of symptoms to guide SARS-CoV-2 diagnostic laboratory testing underestimates SARS-CoV-2 infection between close contacts," warned researchers from the University of Washington, Seattle, and collaborators from other centers.
Researchers studying hydroxychloroquine in a randomized controlled trial noted that the natural history of early presymptomatic and asymptomatic SARS-CoV-2 infection remains poorly understood because only scant data correlate viral shedding with symptoms. To address these issues, they assessed SARS-CoV-2 levels and symptoms in trial participants who collected midnasal swabs and kept symptom diaries after exposure to SARS-CoV-2 via close contacts.
The analysis involved 829 household members and healthcare workers exposed to lab-confirmed SARS-CoV-2 in the preceding 96 hours between March and August 2020, all of them enrolled in a randomized trial of hydroxychloroquine as COVID-19 postexposure prophylaxis (PEP) [2]. Trial participants collected midnasal swabs and recorded symptoms for 14 days. Among trial participants negative for SARS-CoV-2 on day 1, the researchers used quantitative PCR to track the level and duration of SARS-CoV-2 shedding in relation to COVID-19 symptoms. They used Kaplan-Meier methods to estimate time from viral shedding onset to peak shedding.
Of the 772 people with SARS-CoV-2 results, 83 (11%) tested positive for SARS-CoV-2 at their first test, 591 (76.5%) tested negative for SARS-CoV-2 throughout the study, and 98 (13%) tested negative at their first visit then tested positive during 14 days of follow-up. Median age of the newly infected group stood at 38 years, and 56% were women. A little over half of these newly infected people, 54%, identified themselves as white, 18% as Asian, 10% as black, 2% as Native American, and 30% as Hispanic. Hydroxychloroquine had not the slightest impact on viral shedding duration (hazard ratio 1.0, 95% confidence interval 0.6 to 1.8). And the trial found no evidence that hydroxychloroquine works as PEP to prevent SARS-CoV-2 infection [2].
SARS-CoV-2 shedding lasted for a median of 2 days, and the interquartile range was wide: 1 to 11 days. While 44% of newly infected people shed virus for only 1 day (median peak viral load cycle threshold value [Ct] 38.5), 10% shed for 2 to 4 days (median peak Ct 37.8), 20% for 5 to 13 days (median peak Ct 26.5), and the remaining 25% continued to shed SARS-CoV-2 through the end of follow-up.
Among newly infected participants who shed SARS-CoV-2 for 1 day, 23% were asymptomatic, compared with 50% of those who shed for 2 to 4 days, 15% of those who shed for 5 to 13 days, and 24% who shed through the end of follow-up. Overall, 71% of participants reported symptoms before they started shedding virus, and 29% did not. In other words, more than one quarter of SARS-CoV-2 shedders had no symptoms before shedding began, so these people and their contacts might have no clue that they carried transmissible SARS-CoV-2. Moreover, people primarily reported moderate and severe symptoms after SARS-CoV-2 shedding began.
Besides stressing the danger of relying on symptoms to guide diagnostic lab testing (because it underestimates infection incidence), the researchers emphasized the wide between-person variation in SARS-CoV-2 shedding. They stressed that shedding peaks rapidly after viral detection and that peak load correlates with how long shedding lasts.
1. Stankiewicz Karita H, Dong T, et al. SARS-CoV-2 viral shedding and COVID-19 symptoms in a prospective population-based cohort of newly-infected household members and healthcare workers. IAS COVID-19 Conference: Prevention, February 2, 2021. Abstract 126.
2. Barnabas RV, Brown ER, Bershteyn A, et al., on behalf of the Hydroxychloroquine COVID-19 PEP Study Team. Hydroxychloroquine as postexposure prophylaxis to prevent severe acute respiratory syndrome coronavirus 2 infection: a randomized trial. Ann Intern Med. 2020 Dec 8;M20-6519. doi: 10.7326/M20-6519. Online ahead of print. https://www.acpjournals.org/doi/10.7326/M20-6519