The median incubation period for SARS-CoV-2 is 5 days, with a range of 2 to 7 days. Approximately 98% of infected individuals who develop symptoms do so within 12 days. In most patients, viral RNA is detectable in the respiratory tract 2 to 3 days before symptoms appear, peaks at symptom onset, and declines over the following 7 to 8 days.

SARS-CoV-2 appears to be most contagious around the time of symptom onset when viral RNA levels peak. Infectivity rapidly decreases thereafter to near-zero after about 10 days in mild to moderately ill patients and 15 days in severely ill and immunocompromised patients. The longest interval of infectivity that has been observed so far is 20 days from symptom onset.

Early in the pandemic, WHO and CDC recommended obtaining at least two negative RT-PCR tests before removing Covid-19 patients from isolation. This strategy was recommended to safeguard health care workers and prevent transmission to other patients. However, it led to prolonged isolation for many patients who had persistently positive RT-PCR results for weeks to months despite apparent clinical recovery. The duration of PCR positivity was longer when testing lower respiratory tract versus upper respiratory tract samples.

Subsequently, multiple studies have demonstrated that persistently positive SARS-CoV-2 RNA PCRs are due to residual viral subgenomic RNA fragments rather than intact virus that is capable of replication. Patients with persistently positive PCR results are generally not contagious.

 In response to these more recent findings, WHO and CDC have modified their recommendations. On May 27, WHO recommended that symptomatic patients should remain in isolation for 10 days after symptom onset plus at least 3 additional days without symptoms.  Isolation can be discontinued 10 days after a positive PCR result in asymptomatic individuals.

In July and August CDC modified its recommendations based on illness severity and immunocompetence. CDC now recommends 10 days of isolation from symptom onset for mild to moderately ill patients who are not severely immunocompromised. It also recommends at least 10 and up to 20 days for patients with severe disease or severe immunocompromise. For asymptomatic individuals, isolation should be maintained for 10 days from the first positive PCR test or for up to 20 days if severely immunocompromised. CDC does not recommend PCR based clearance except in rare situations.

Studies on the duration of SARS-CoV-2 infectivity have had major implications for public health and infection control. Current guidelines are designed to prevent premature release of patients from isolation and its associated risk of disease transmission while also minimizing unnecessary prolonged isolation. The latter is associated with patient loneliness, consumption of personal protective equipment, scarcity of isolation rooms, delay of procedures and other medical care and delay of discharge.

Reference

Rhee C et al, Duration of SARS-CoV-2 Infectivity: When is it Safe to Discontinue Isolation? Published online August 25, 2020. Clinical Infectious Diseases, ciaa1249, https://doi.org/10.1093/cid/ciaa1249


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