SARS-CoV-2, SARS-CoV-1 and MERS-CoV viral load dynamics, duration of viral shedding and infectiousness – a living systematic review and meta-analysis

Abstract

Background Viral load kinetics and the duration of viral shedding are important determinants for disease transmission. We aim i) to characterise viral load dynamics, duration of viral RNA, and viable virus shedding of SARS-CoV-2 in various body fluids and ii) to compare SARS-CoV-2 viral dynamics with SARS-CoV-1 and MERS-CoV. Methods: Medline, EMBASE, Europe PMC, preprint servers and grey literature were searched to retrieve all articles reporting viral dynamics and duration of SARS-CoV-2, SARS-CoV-1 and MERS-CoV shedding. We excluded case reports and case series with < 5 patients, or studies that did not report shedding duration from symptom onset. PROSPERO registration: CRD42020181914. Findings: Seventy-nine studies on SARS-CoV-2, 8 on SARS-CoV-1, and 11 on MERS-CoV were included. Mean SARS-CoV-2 RNA shedding duration in upper respiratory tract, lower respiratory tract, stool and serum were 17.0, 14.6, 17.2 and 16.6 days, respectively. Maximum duration of SARS-CoV-2 RNA shedding reported in URT, LRT, stool and serum was 83, 59, 35 and 60 days, respectively. Pooled mean duration of SARS-CoV-2 RNA shedding was positively associated with age (p=0.002), but not gender (p = 0.277). No study to date has detected live virus beyond day nine of illness despite persistently high viral loads. SARS-CoV-2 viral load in the upper respiratory tract appears to peak in the first week of illness, while SARS-CoV-1 and MERS-CoV peak later. Conclusion: Although SARS-CoV-2 RNA shedding in respiratory and stool can be prolonged, duration of viable virus is relatively short-lived. Thus, detection of viral RNA cannot be used to infer infectiousness. High SARS-CoV-2 titres are detectable in the first week of illness with an early peak observed at symptom onset to day 5 of illness. This review underscores the importance of early case finding and isolation, as well as public education on the spectrum of illness. However, given potential delays in the isolation of patients, effective containment of SARS-CoV-2 may be challenging even with an early detection and isolation strategy. Funding: No funding was received.

Test sensitivity is secondary to frequency and turnaround time for COVID-19 screening

“…Viral loads appear to become undetectable by PCR within 3 weeks of symptom onset (45,48,50), but detectability and timing may differ, depending on the degree or presence of symptoms (50,51). The majority of studies reviewed by Cevik et al (18) found initial viral loads to be similar between symptomatic and asymptomatic infections (1,(24)(25)(26), but viral clearance was significantly and substantially faster among asymptomatic infections (24,(26)(27)(28)(29). Last, we note that the general understanding of viral kinetics may vary depending on the mode of sampling, as demonstrated via a comparison between sputum and swab samples (12).…”

“…For qPCR, this corresponds to the time required during viral growth to go from Ct values of 40 to ∼34. While this time window for SARS-CoV- 2 is not yet rigorously defined (18), for other respiratory viruses such as influenza, and in ferret models of SARS-CoV-2 transmission, it is on the order of a day (19,20). Last, high-sensitivity screening tests, when applied during the viral decline accompanying recovery, are unlikely to substantially affect transmission because such individuals detected have low, if any, infectiousness (14).…”

“…Last, high-sensitivity screening tests, when applied during the viral decline accompanying recovery, are unlikely to substantially affect transmission because such individuals detected have low, if any, infectiousness (14). A recent review by Cevik et al (18) notes that no study to date has successfully cultured live virus more than 9 days after the onset of symptoms.…”

Determining the level of social distancing necessary to avoid a second COVID-19 epidemic wave: a modelling study for North East London

“…Firstly, in absence of data to suggest otherwise, the infectious period is treated as equal for both symptomatic and asymptomatic cases and as a population average of all cases. A recent literature review suggested that COVID-19 infectiousness peaks in the rst 5 days following symptom onset, while no live virus has been cultured after 9 days following symptom onset [20]. Based on this, and taking in consideration that the single population average parameter for infectiousness period is likely to be shortened by self-isolation of a signi cant proportion of symptomatic patients, we simulated three scenarios for the infectiousness periods of 1, 3 and 5 days.…”

Determining the level of social distancing necessary to avoid a second COVID-19 epidemic wave: a modelling study for North East London 

“…The rst case of COVID-19 in the region was reported on February 19, 2020, and the rst COVID-19 associated death was documented on March 06, 2020 [3,4]. Since then the local epidemic has spread rapidly with 7,205 con rmed cases (up to August 03, 2020) and 1,732 deaths (registered by August 01, 2020) associated with COVID-19 across NEL [3,4]. The boroughs of Newham (144.3) and Hackney (127.4) have the highest and third highest age-standardised mortality rate per 100,000 people in the country [5], while Havering, Tower Hamlets and Waltham Forest all have death rates signi cantly higher than the rest of London [5].…”