Although SARS-CoV-2 genetic material can be detected in respiratory or stool samples for several weeks, a systematic examination and meta-analysis of three human coronaviruses published in The Lancet Microbe has not found no live virus (that can cause infection) in any sample collected more than nine days after the onset of symptoms.
According to the research results, people infected with COVID-19 are more likely to be highly infectious from the onset of symptoms and the following five days. “Our findings are consistent with contact tracing studies that suggest that most viral transmission events occur very early, and especially within first five days after the onset of symptoms, which indicates the importance of self-isolation immediately after the onset of symptoms ”, explains study leader Muge Cevik, from the University of St. Andrews (UK).
The study analyzed infected people, especially those that were hospitalized, so the results are only relevant to the self-isolation period of people with confirmed COVID-19. Understanding when patients are most likely to be infectious is essential to implement effective public health measures designed to control the spread of the virus. Therefore, the work collects the key factors involved in transmission: viral load, shedding of viral RNA and isolation of the live virus.
The researchers included 98 studies with five or more participants. Of these, 79 focused on SARS-CoV-2, 73 of which included only hospitalized patients; eight in SARS-CoV and eleven in infection with MERS-CoV. From these studies, the authors calculated the mean duration of viral RNA excretion and examined the changes in viral load and the successful isolation of live virus from different samples collected throughout an infection.
Ten-day infectivity in patients with mild symptoms
Analysis of the results of the SARS-CoV-2 studies showed that the mean duration of viral RNA shedding in the upper respiratory tract, lower respiratory tract, feces and serum it was 17 days, 14.6 days, 17.2 days and 16.6 days, respectively. The longest duration of RNA shedding was 83, 59, 35, and 60 days, respectively. The shedding of viral RNA consists of the time that someone shed viral genetic material (RNA), which does not necessarily indicate that a person is infectious, since they are not necessarily capable of replicating.
Of the eleven studies that attempted to isolate the live virus, the eight that used respiratory samples successfully cultured viable viruses within the first week of illness. Studies that also measured RNA viral load demonstrated a relationship between the success of live virus isolation and viral load levels. For its part, no study was able to successfully isolate the live virus beyond the ninth day of symptoms in any type of sample, despite persistently high viral RNA loads. So far only a few few studies have successfully isolated live virus from stool samples, despite the prolonged loss of RNA, and the role of oral-fecal transmission for SARS-CoV-2 remains unclear.
“These findings suggest that, in clinical practice, repeat PCR tests may not be necessary to consider that a patient is no longer infectiousas this could remain positive for much longer and does not necessarily indicate that they can transmit the virus to others. In patients with non-severe symptoms, their infectious period could instead be counted as 10 days from the onset of symptoms, ”says Cevik.
Higher viral load in the first days
The highest viral load of SARS-CoV-2 RNA was detected early in the course of the disease, in the when symptoms start, or before fifth day of appearance. In contrast, Viral loads 8 and MERS-CoV peaked at 10-14 days and 7-10 days after onset of symptomsrespectively, which explains why the transmission of these viruses can be effectively reduced by the immediate identification, isolation and quarantine of people who show symptoms of the disease. Only twelve studies reported on asymptomatic people infected with SARS-CoV-2, and of those, six also looked at how quickly people cleared viral material from their bodies.
“Although viral RNA loads appear to be very similar between those with and those without symptoms, a few studies suggest that asymptomatic individuals may clear viral material from their bodies more quickly. Several studies have found that individuals with asymptomatic infection are able to clear the virus more quickly, suggesting that those without symptoms can be just as infectious as those with symptoms early in infection, but can be infectious for a shorter period. However, at this stage, limited data on infectious virus clearance in asymptomatic people to report any policy changes on the duration of the quarantine in the absence of evidence, “adds Cevik.
This is the most comprehensive study of these three respiratory coronaviruses to date, but the authors acknowledge some limitations.
“Most of the studies included in our review were conducted in patients who were admitted to hospital. Therefore, our findings can do not apply to people with a milder infectionAlthough these results suggest that those with milder cases can clear the virus more quickly from their body. Furthermore, it is likely that the growing deployment of treatments such as dexamethasone, remdesivir, and other antivirals and immunomodulators in clinical trials influence virus elimination in hospitalized patients. More studies on virus elimination are needed in this context, ”explains lead author Antonia Ho, from the University of Glasgow Center for Virus Research (UK).