麻豆传媒

SARS-CoV-2 viral load in the upper respiratory tract reached a maximum during the first week of illness based on cycle threshold values, a systematic review and meta-analysis found, though individuals continued to shed viral matter for more than 2 weeks.

But none of the 79 studies in the review found "live" virus beyond 9 days, (maximum 83), reported Müge Çevik, MD, of the University of St. Andrews in Scotland, and colleagues.

Interestingly, pooled mean viral shedding was associated with age, but not sex, they wrote online in .

"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," Çevik said in a statement. "We also need to raise public awareness about the range of symptoms linked with the disease, including mild symptoms that may occur earlier on in the course of the infection than those that are more prominent like cough or fever."

The authors added that "in clinical practice, repeat testing might not be indicated to deem patients no longer infectious."

The duration of SARS-CoV-2 RNA detection has not been well characterized, and the study sought to fill that gap, the researchers noted. They examined the literature, including pre-print sites, for studies published from January 1 to June 6.

There were 79 studies, with a total of 5,340 patients, with 58 studies in China, and 73 studies including hospitalized patients only. A total of 61 studies reported median or maximum viral RNA shedding in at least one body fluid.

Of those, 43 studies that examined shedding in the upper respiratory tract reported duration of shedding of 17 days (95% CI 15.5-18.6). Seven studies measured shedding in the lower respiratory tract, which was a mean duration of 14.6 days (95% CI 9.3-20.0) and 13 studies looked at shedding in stool samples, which was a mean duration of 17.2 days (95% CI 14.1-20.1). Only two studies examined this in serum samples (median 16.6 days, 95% CI 3.6-29.7).

However, while viable virus was isolated during up to 4 weeks of illness in stool, fecal-oral transmission was not thought to be a "primary driver of infection," the researchers stated. "The role of [fecal] shedding in viral transmission remains unclear."

The maximum duration of viral shedding was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stool samples, and 60 days in serum samples.

Eight of 13 studies examining viral load in upper respiratory tract samples showed peak viral load within the first week of symptom onset, with the highest viral loads reported "soon or after" symptom onset, or day 3 to 5 of illness.

There were 20 studies examining duration of viral RNA shedding based on disease severity, and not surprisingly, 13 of these studies found longer duration of viral shedding in patients with severe illnesses versus non-severe illnesses.

In the 12 studies reporting on load dynamics or duration in individuals with asymptomatic SARS-CoV-2, two found lower viral loads among asymptomatic patients, while four found "similar" initial viral loads.

But, the authors added, "data on the shedding of infectious virus in asymptomatic individuals are too scarce to quantify their transmission potential in order to inform policy on quarantine duration in the absence of testing."

Importantly, among 11 studies that attempted to isolate live virus, eight that attempted virus isolation in respiratory samples "successfully cultured viable virus within the first week of illness," but no live virus was isolated from respiratory samples after day 8 in three studies or after day 9 in two studies, Çevik and co-authors said.

Limitations to the data, the team noted, included that the patients were on a wide range of treatments, which may have "modified the shedding dynamics," and the substantial heterogeneity in the study populations, follow-up, and management approaches. In addition, "the true clinical window of infectious shedding might not entirely align with viral culture duration," the investigators explained.

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