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COVID-19 Severity, Delayed Admission Tied to Longer Viral Shedding
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IAS COVID-19 Conference, July 10-11, 2020.
Mark Mascolini
More severe COVID-19 and delayed hospital admission predicted longer SARS-CoV-2 shedding, according to a 480-person single-center study in Italy [1]. Each additional comorbidity at hospital admission cut chances of viral clearance 10%.
Researchers at Rome’s National Institute for Infectious Diseases Lazzaro Spallanzani noted that viral dynamics of SARS-CoV-2 infection remain poorly understood. Although several studies indicate a median viral shedding time of 12 to 21 days, anecdotal reports suggest shedding may persist up to 63 days, even after symptoms resolve and seroconversion occurs. Small studies link several factors to longer viral shedding: COVID-19 severity, male gender, delayed hospital admission after symptoms begin, and longer hospital stay.
To shed more light on these issues, these researchers conducted an observational retrospective study of their large cohort. They aimed to (1) estimate time to SARS-CoV-2 clearance from the upper respiratory tract, (2) identify predictors of both clearance and prolonged shedding, and (3) explore associations between viral clearance and clinical outcomes.
The researchers defined clearance as consecutive negative PCRs for SARS-CoV-2. Prolonged viral shedding meant a positive PCR for SARS-CoV-2 for more than 17 days. And clinical recovery meant weaning from oxygen or hospital discharge, whichever came first.
This single-center analysis involved all consecutive patients admitted to the cohort with a PCR-confirmed diagnosis of COVID-19 between March 1 and May 10, 2020. The table shows methods used to assess study outcomes:
The analysis included 480 adults, 64.6% of them men, 24.6% with 1 comorbidity, and 36.6% with 2 or more comorbidities. Median age stood at 61 years (interquartile range [IQR] 50 to 74), while median time from symptom onset to hospital admission measured 7 days (IQR 4 to 11). Almost half of the group, 45.8%, had respiratory failure at admission. While 40.2% received 1 drug (hydroxychloroquine or a boosted protease inhibitor), 44.6% received both of those drugs. One in five received immunomodulatory therapy.
During a median follow-up of 12 days (IQR 8 to 20), 72.7% of patients needed oxygen therapy. While 11.3% of patients died, the rest were discharged from the hospital. Two thirds of participants, 66%, achieved viral clearance, and median shedding time from symptom onset to clearance stood at 17 days (IQR 11 to 24). Kaplan-Meier analysis estimated that 69.9% of participants achieved viral clearance in 20 days and 87.3% in 30 days.
Poisson regression tied two factors to a lower probability of viral clearance: PaO2/FiO2 ratio* below 200 during hospitalization (adjusted incidence rate ratio [aIRR] 0.37, 95% confidence interval [CI] 0.23 to 0.60, P < 0.001) and each additional baseline comorbidity (aIRR 0.90, 95% CI 0.82 to 1.00, P = 0.049). Receiving immunomodulatory therapy boosted chances of viral clearance almost 50% (aIRR 1.47, 95% CI 1.06 to 2.06, P = 0.022).
Three variables raised chances of prolonged viral shedding: each additional baseline comorbidity (aIRR 1.26, 95% CI 1.01 to 1.56, P = 0.040), PaO2/FiO2 ratio* below 200 during hospitalization (aIRR 3.57, 95% CI 1.97 to 6.45, P < 0.001), and each additional day of symptoms before hospital admission (aIRR 1.17, 95% CI 1.11 to 1.23, P < 0.001).
Viral clearance almost doubled chances of clinical recovery (adjusted hazard ratio [aHR] 1.80, 95% CI 1.28 to 2.54, P < 0.001). Viral clearance also appeared to cut chances of mechanical ventilation or death by 75%, but that association did not reach statistical significance (aHR 0.25, 95% CI 0.23 to 1.33, P = 0.184).
The findings underline the value of rapid testing for SARS-CoV-2 in close contacts of already infected people and prompt hospital admission when symptoms arise. Every extra day between symptom appearance and hospital admission hiked the risk of prolonged viral shedding more than 15%.
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*A P/FP Ratio of 300 to 200 indicates mild Acute Respiratory Distress Syndrome (ARDS), 200 to 100 indicates moderate ARDS, and less than 100 indicates severe ARDS [2].
References
1. Mondi A, Castilletti C, Lorenzini P, et al. Risk and predictive factors of prolonged viral shedding in respiratory specimens in patients with COVID-19 admitted in an Italian reference hospital. IAS COVID-19 Conference, July 10-11, 2020. Track B. https://cattendee.abstractsonline.com/meeting/9307/session/619
2. ClinicalTrials.gov. PaO2/FiO2*PEEP (P/FP) Ratio and mortality in acute respiratory distress syndrome. ClinicalTrials.gov identifier NCT03946150.
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