COVID-19 patients most infectious in 1st week of symptom onset

People infected with SARS-CoV-2 appear to be highly infectious within the first week following symptom onset, with the highest viral load and live virus detected during this period, according to a systematic review and meta-analysis of three human coronaviruses.

The study also shows that although viral shedding (based on detection of viral RNA) in respiratory or stool samples might be prolonged for weeks, no viable virus could be isolated beyond 9 days of symptom onset.

Understanding when infected people are most likely infectious is critical to guide public health measures to contain the spread of SARS-CoV-2, the researchers highlighted.

“Our findings are in line with contact tracing studies which suggest the majority of viral transmission events occur very early, and especially within the first 5 days after symptom onset, indicating the importance of self-isolation immediately after symptoms start,” said lead author Dr Muge Cevik from the University of St Andrews, UK.

“These findings [also] suggest that in clinical practice, repeat PCR testing may not be needed to deem that a patient is no longer infectious, as this could remain positive for much longer and does not necessarily indicate they could pass on the virus to others. In patients with non-severe symptoms, their period of infectiousness could instead be counted as 10 days from symptom onset,” suggested Cevik.

For the analysis, 98 studies — of which 79 were on SARS-CoV-2 (n=5,340), eight were on SARS-CoV (n=1,858), and 11 were on MERS-CoV (n=799) — were included. Three measures being looked at in the study included: viral load, viral RNA shedding and isolation of viable virus. [Lancet Microbe 2020;doi:10.1016/S2666-5247(20)30172-5]

The researchers found that the viral load of SARS-CoV-2 in the upper respiratory tract peaked early on in the disease course —within 5 days of symptom onset. By comparison, the viral loads were highest during 10–14 days and 7–10 days from symptom onset for SARS-CoV and MERS-CoV, respectively.

This finding may explain why COVID-19 spreads more rapidly than the SARS and MERS outbreak, which according to the authors, “emphasize the importance of immediate isolation with symptom onset early in the course of illness.”

For SARS-CoV-2, viral RNA shedding occurred for a mean duration of 17 days into the upper respiratory tract, 14.6 days into the lower respiratory tract, and 17.2 days 16.6 days in stool and serum samples, respectively. Moreover, viral shedding could persist up to 83, 59, 126, and 60 days, respectively, in the samples.

In addition, analysis by age showed that the duration of viral shedding was prolonged with increasing age (p=0.0016).

Nonetheless, detection of viral RNA does not necessarily mean the virus was viable and the person is infectious. 

There were eight studies which had successfully cultured viable virus using respiratory samples collected during the first week of illness. None of the studies in the systematic review were able to isolate viable virus from any types of samples, beyond 9 days of symptom onset — despite persistently high viral loads.   

“Therefore, RNA detection cannot be used to infer infectiousness,” the researchers noted. “[Nonetheless, there was] an association between viral load and viability of virus, with no successful culture from samples below a certain viral load threshold.”

In addition, twelve of the studies also included data on infected individuals who were asymptomatic.

“Although viral RNA loads appear to be largely similar between those with and without symptoms, a few studies suggest that asymptomatic individuals might clear the viral material from their bodies faster,” observed Cevik. “[This suggests] that those without symptoms may be as infectious as those with symptoms at the beginning of infection, but may be infectious for a shorter period.”

However, there were insufficient data on infectivity of asymptomatic individuals to inform any changes in policy on quarantine duration at the moment, he added.