Position Statement from the National Centre for Infectious Diseases and the Chapter of Infectious Disease Physicians, Academy of Medicine, Singapore –
23 May 2020
Compte-rendu de l’expérience singapourienne sur la période de #contagiosité du #sars_cov2
– Les cultures de sars-cov2 n’ont jamais été positives après le 11ieme jour ou lorsque le cycle de seuil (#Ct ; d’autant plus élevé que la charge virale au #PCR est faible) est supérieur ou égal à 30 : les patients pourraient donc être autorisés à sortir de l’hôpital avant la négativité du PCR qui peut prendre plus d’un mois,
– il n’a pas été retrouvé de transmission par des sujets asymptomatiques (à la différence des pré-symptomatiques)
In a study of 77 well characterised infector-infectee pairs in Hong Kong, it was estimated that the serial interval (duration between symptom onset of a primary case to symptom onset of its secondary case) of COVID-19 was 5.8 days (mean), with 7.6% of serial intervals distributed negatively (i.e. the infectee developed symptoms prior to infector), strongly implying pre-symptomatic transmission [He X, Lau EH, Wu P, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nature Med 2020; 26:672-675]. Assuming a median incubation period of 5.2 days (based on other studies), the study estimated that the infectious period of SARS-CoV-2 started 2.3 days before onset of symptoms, peaking at 0.7 days, and declining within 7 days.
Local data, based on an analysis of 766 patients, indicate that by day 15 from onset of illness, 30% of all #COVID-19 patients are PCR-negative by nasopharyngeal swab, this rises to 68% by day 21 and 88% by day 28 and by day 33, 95% of all patients are negative by PCR (NCID data). While the duration of viral shedding1 by PCR may extend to a month and sometimes longer for a small group of patients, and several jurisdictions including Singapore have been using it to guide de-isolation and discharge policies, it is important to note that viral RNA detection by PCR does not equate to infectiousness or viable virus.
A surrogate marker of ‘viral load’ with PCR is the cycle threshold value (Ct). A low Ct value indicates a high viral RNA amount, and vice versa. As noted above, detection of viral RNA does not necessarily mean the presence of infectious or viable virus. In a local study from a multicenter cohort of 73 COVID-19 patients, when the Ct value was 30 or higher (i.e. when viral load is low), no viable virus (based on being able to culture the virus) has been found . In addition, virus could not be isolated or cultured after day 11 of illness . These data corroborate the epidemiologic data and indicate that while viral RNA detection may persist in some patients, such persistent RNA detection represent non-viable virus and such patients are non-infectious.
Robust data are lacking regarding infectiousness of asymptomatic and pre- symptomatic individuals and how much asymptomatic infection drives transmission. However, asymptomatic persons may have similar viral shedding patterns. A Singapore study found pre-symptomatic transmission of SARS-CoV-2 in ~6.4% of 157 locally acquired cases, but no asymptomatic transmission [Wei WE, Li Z, Chiew CJ, et al. Pre-symptomatic transmission of SARS-CoV-2 - Singapore, January 23 - March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020; 69: 411- 415].
Summary and Conclusion
Based on the accumulated data since the start of the COVID-19 pandemic, the infectious period of SARS-CoV-2 in symptomatic individuals may begin around 2 days before the onset of symptoms, and persists for about 7 - 10 days after the onset of symptoms. Active viral replication drops quickly after the first week, and viable virus was not found after the second week of illness despite the persistence of PCR detection of RNA. These findings are supported by epidemiologic, microbiologic and clinical data. These new findings allow for revised discharge criteria based on the data on the time course of infectiousness rather than the absence of RNA detection by PCR testing, taking into consideration both the clinical and public health perspectives, including the individual patient’s physical and mental well-being. In addition, given these findings, resources can focus on testing persons with acute respiratory symptoms and suspected COVID-19 in early presentation, allowing timelier public health intervention and containment.