Duration of isolation Flashcards
14 days and still PCR positive
Recommendations on the duration of isolation for patients with Covid-19 continue to evolve with increased understanding of SARS-CoV-2 transmission dynamics. Early in the Covid-19 pandemic, recommendations from the Centers for Disease Control and Prevention (CDC) included discontinuing isolation when there was clinical improvement and a negative molecular SARS-CoV-2 test. This recommendation was replaced by a time-based approach (rather than a test-based one) when it became apparent that shedding of nonviable SARS-CoV-2 RNA in the upper respiratory tract can continue for days to weeks after recovery from illness.1 Early, albeit small studies showed that SARS-CoV-2 detected by PCR in respiratory specimens beyond day 10 after the onset of symptoms did not grow in cell culture and was probably not transmissible.2,3 Large population-based studies conducted by CDC South Korea indicate that the infectious potential of SARS-CoV-2 declines after the first week following symptom onset, irrespective of resolution of symptoms.4
However, a few studies have recently challenged this concept. One study showed viable virus by in vitro growth in cell culture in 14% of patients (4 of 29) with persistent positive SARS-CoV-2 PCR tests from upper respiratory specimens obtained after the first week following the initial positive PCR test; one patient was never hospitalized, and one had been hospitalized with mild symptoms.5 Complete viral genome sequencing indicated that these cases represented the same infection rather than reinfection. Age, immunocompromised status, and severe illness have been associated with prolonged SARS-CoV-2 RNA shedding1; however, data are insufficient regarding factors associated with prolonged shedding of viable SARS-CoV-2. One recent study showed that some patients with immunosuppression after treatment for cancer could shed viable SARS-CoV-2 for at least 2 months.6 A study of 129 severe cases of Covid-19 showed that the probability of detecting viable virus beyond day 15 after symptom onset was 5% or less.7 The CDC currently recommends isolation precautions for 10 days after symptom onset (with fever resolution lasting at least 24 hours without the use of fever-reducing medications), with extension to 20 days for immunocompromised patients or those with severe illness. The patient described in the clinical vignette had severe infection according to the World Health Organization severity scale and CDC criteria; thus, continuing isolation for a total of 20 days seems reasonable and in accordance with current evidence. No studies to date have reported person-to-person transmission occurring from the observed late shedding of viable SAR-CoV-2; thus, it may be reasonable to customize decisions regarding duration of isolation on the basis of individual circumstances. In the current case, a household member is a kidney transplant recipient, a condition in which Covid-19 infection is associated with high morbidity and mortality, which further justifies a 20-day isolation period.
Repeat SARS-CoV-2 PCR testing to determine the duration of isolation should not be recommended for this patient because, as noted, a positive PCR test does not mean that she is infectious, and viral tissue culture is not available to assess for viable virus in clinical laboratories. Repeat PCR testing can result in unnecessarily prolonged isolation and anxiety for patients and medical teams. Public awareness of the shortcomings of Covid-19 diagnostic tests and the distinction between shedding of viral RNA and viable virus is essential to ensure that patients and health care workers are comfortable with our current approach to isolation precautions for patients with Covid-19.
Answer 2 from Wenzel
The scenario in the vignette focuses on the question of how long after symptom onset a patient with Covid-19 can transmit the virus, SARS-CoV-2. Behind that question are additional questions that highlight current shortcomings in testing. First, is a reverse-transcriptase PCR test result a valid surrogate for the presence of transmissible virus? Second, does in vitro growth of virus from respiratory specimens predict transmissibility to people?
I’ll argue that the answer to the first question is “no” and to the latter “probably,” though we don’t know the infecting dose for transmission.
Fourteen days after the onset of symptoms, a 24-year-old woman with no underlying coexisting conditions is undergoing discharge planning. Though she spent several days in the ICU, her course was moderate, not severe: she was persistently afebrile, was never intubated, and had only moderate changes on chest radiography.
Some reports suggest that patients with Covid-19 who are older, male, or obese, who are immunosuppressed, or who have severe disease have longer-than-average periods of shedding virus. This patient has none of the above characteristics and would not be expected to have prolonged viral shedding.
In a retrospective, cross-sectional study of 90 patients with confirmed Covid-19 (severity not described), the investigators placed respiratory specimens on African green monkey (Vero) cell lines. In vitro infectivity was observed in 29%, and the odds ratio for viral growth decreased by 37% for each additional day after the onset of symptoms. No growth was detected in samples collected more than 8 days after the onset of symptoms.8
A detailed virologic analysis of nine cases of mild Covid-19 in young and middle-aged professionals showed no virus isolation in serial samples of blood, urine, or stool. Viral growth was found from oral–pharyngeal or nasopharyngeal swabs in all the patients from days 1 through 5 after symptom onset. Although viral RNA was detected in 40% of the patients after day 5, and was even detected up to 28 days, viral growth was not detected after day 8.2
Cheng and colleagues prospectively enrolled 100 patients with confirmed Covid-19 and 2761 contacts. The attack rate for 1818 contacts who were exposed within 5 days after symptom onset in the primary pool of patients was 1% (95% confidence interval [CI], 0.6 to 1.6), yet the attack rate among 852 contacts exposed later was 0% (95% CI, 0.0 to 0.4).9
A systematic review and meta-analysis of SARS-CoV-2 case series, cohort studies, and randomized trials showed RNA shedding for 17 days after symptom onset (95% CI, 15.5 to 18.6) in upper respiratory samples among a total of 3229 participants in 43 studies and for 14.6 days (95% CI, 14.4 to 20.1) in lower respiratory tract samples among a total of 260 participants in 7 studies. Although RNA could be detected up to 83 days and 59 days in upper and lower respiratory samples, respectively, no study detected live virus beyond day 9 of illness.1
In February 2021, the CDC, citing their own unpublished data and those from other sources, stated that in patients with mild or moderate Covid-19, replication-competent virus hasn’t been recovered after 10 days following symptom onset. Even in severe illness (the vast of majority of patients admitted to the ICU had been intubated), the probability of virus isolation after 15 days was 5%.10
In summary, a 24-year-old woman with moderate Covid-19 infection and no markers for extended viral shedding has positive RNA detection yet probably has no replication-competent virus. She has little probability of transmitting SARS-CoV-2 to an immunosuppressed family member at home.
