Is 10 days self-isolation enough for those with symptoms of COVID-19?

In a change to the current NHS advice, the Chief Medical Officers for the four nations of the UK have agreed that the period of self-isolation should increase from seven to ten days.1

The new advice is for people who are either symptomatic or who have had a positive test for COVID-19. This brings the UK in line with advice from both the US and the World Health Organization (WHO). For example, in the US, the centres for disease control advice is that for most people with COVID-19, isolation can be discontinued 10 days after symptom onset.2 On 27 May, the WHO updated its own guidance on self-isolation, The WHO advice defines the criteria for discharging patients from isolation, which for symptomatic patients is “10 days after symptom onset, plus at least 3 additional days without symptoms” and for asymptomatic cases “10 days after positive test for SARS-CoV-2.”3

But where have these figures come from and how robust is the evidence? The basis for these recommendations comes from a series of studies and while some indicate that viral shedding is no longer detectable after 10 days (see reference 2 for details), other data suggest that shedding can continue for longer than 30 days.4 In a more recent review exploring the detection pattern and viral load of COVID-19, researchers identified 113 studies conducted in 17 countries.5 Their analysis revealed that viral RNA becomes undetectable from upper respiratory tract specimens after about 2 weeks of symptom onset, with a median of 14.5 days though for patients with more severe disease and lower respiratory tract infections, it seems that this period may increase to 15.5 days.

Nonetheless, the connection between viral load and infectivity is still not completely understood and a further concern is the potential for the virus to be transmitted prior to the onset of symptoms which in theory should prolong the self-isolation period even further. The pre-symptomatic transmission of COVID-19 was identified in some early work from China6 and also acknowledged as being the most likely cause of infection in a study from Singapore. In this latter study which included 243 infected cases, the authors identified seven clusters of pre-symptomatic transmission.7 For example, in four of these clusters, pre-symptomatic transmission occurred 1-3 days before the onset of symptoms. However, a criticism of the study is that it was not possible to determine whether a single source was responsible for the initiation of all cases. Despite this limitation, in a secondary analysis of published data, Casey et al8 found that the proportion of pre-symptomatic transmission ranged from 42.8% to 80.6%, although the pooled estimate was 56.4%.

In a further review of the duration of infectivity of COVID-19,9 the authors highlighted the difficulty of inferring infectiousness given the heterogeneity of the available evidence. They concluded based on what is currently known, that the median infectious period for asymptomatic individuals is 6.5 – 9.5 days and that the infectious period for pre-symptomatic infection was between 1 and 4 days. They calculated that the mean time from symptom onset to having two negative COVID-19 tests was 13.4 days with a range of 10.9 to 15.8 days. The study including modelling work which implied that patients with more severe infection could be infectious for approximately 4 days longer.

Finally, Byrne et al9 concluded that the highest infectivity (86%) occurred within the first 5 days of symptom onset, but that this could continue for up to 30 days. A further consideration is the evidence that the virus can be detected in faecal swabs of COVID-19 positive patients up to 18 days after the onset of symptoms.10 While this indicates the possibility of oro-faecal transmission of the virus, to date infection through this route has not been reported and thus the significance of this finding remains uncertain.

In summary, the change of government advice on self-isolation is now aligned with guidance from both the US and WHO. While this change is to be welcomed, due to the current uncertainty in the duration of post-symptomatic infectivity, clinicians and patients need to remain cautious to the continued presence of infectivity. Though it seems reasonable to assume that most individuals will much less infective after 10 days there is still uncertainty in this estimate. Furthermore, the current lack of comparative data indicating differences in the period of infectivity between asymptomatic and symptomatic individuals or even if symptom severity prolongs the duration of infectivity, leaves both health professionals and patients with a high degree of uncertainty as to when it might be safe to exit self-isolation. Further research is urgently needed to answer these important, yet unresolved, questions.

References

1. Statement from the UK Chief Medical Officers on extension of self-isolation period: 30 July 2020.
   www.gov.uk/government/news/statement-from-the-uk-chief-medical-officers-on-extension-of-self-isolation-period-30-july-2020
2. CDC. Duration of isolation & precautions for adults. hwww.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html
3. World Health Organization. www.who.int/news-room/commentaries/detail/criteria-for-releasing-covid-19-patients-from-isolation
4. Li N, Wang, X, Lv T. Prolonged SARS-CoV-2 RNA shedding: not a rare phenomena. J Med Virol 2020; Apr 29. doi: 10.1002/jmv.25952.
5. Walsh KA et al. SARS-CoV-2 detection, viral load and infectivity over the course of an infection. J Infect 2020 June 29 doi: 10.1016/j.jinf.2020.06.067.
6. Cheng H et al. Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset. JAMA Intern Med. Published online May 01, 2020. doi:10.1001/jamainternmed.2020.2020
7. Wei W, Li Z, Chiew CJ, Yong SE, et al. In four of these. MMWR Morb Mortal Wkly Rep 2020;69:411–415. DOI: http://dx.doi.org/10.15585/mmwr.mm6914e1
8. Casey M et al. Pre-symptomatic transmission of SARS-CoV-2 infection: a secondary analysis using published data. medRxiv 2020. doi:10.1101/2020.05.08.20094870.
9. Byrne A et al. Inferred duration of infectious period of 1 SARS-CoV-2: rapid review and analysis of available evidence for asymptomatic and symptomatic COVID-19 cases. medRxiv. 2020. doi:10.1101/2020.04.25.20079889.
10. Parasa S et al. Prevalence of Gastrointestinal Symptoms and Fecal Viral Shedding in Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020;3(6):e2011335. doi:10.1001/jamanetworkopen.2020.11335