Daily infectious SARS-CoV-2 virus shedding varied substantially among 60 newly diagnosed asymptomatic or mildly ill COVID-19 patients early in the pandemic, suggesting that individual differences in viral dynamics may account for “superspreading,” according to a first-of-its-kind modeling study published yesterday in Nature Microbiology.
A superspreader transmits the virus to an exceptionally large number of other people. “Transmission of SARS-CoV-2 by both presymptomatic and asymptomatic individuals has been a major contributor to the explosive spread of this virus,” the researchers wrote.
Led by scientists from the Los Alamos National Laboratory and the University of Illinois, the study tracked daily SARS-CoV-2 viral loads in university staff and students’ saliva and nose starting within 24 hours of diagnosis for up to 14 days early in the pandemic.
The team used rapid antigen COVID-19 tests, polymerase chain reaction (PCR) tests, and viral culture to determine loads of live (infectious) SARS-CoV-2 and noninfectious viral RNA. The researchers used mathematical models to estimate viral replication and clearance rates and overall infectiousness for each participant. Participants had a median age of 28 years and were primarily White; none had been vaccinated against COVID-19, because vaccines weren’t available at that time
Viral dynamics may differ in superspreaders
Some participants shed live SARS-CoV-2 for only a day or two, while others did so for up to 9 days. “Based on that finding, we predict that those people who are shedding virus for more than a week are going to be a much greater risk of transmission than someone who only has live virus detectable for a day or two,” senior author Christopher Brooke, PhD, of the University of Illinois, said in a news release from the Carle Illinois College of Medicine.
Coauthor Pamela Martinez, PhD, also of the University of Illinois, said this finding is key. “People have observed that viral transmission is heterogenous, but most attribute those differences to individual behavior,” she said in the release. “We assume that superspreaders are less cautious or are in contact with more people. This shows that intrinsic infection dynamics also play an important role.”
Viral loads often peaked in saliva days before they did so in nasal swabs, which the researchers said indicates that saliva may be the better sample for early COVID-19 diagnosis. The Alpha variant’s viral loads and clearance dynamics didn’t differ significantly from those of previous strains, which the study authors said suggests that higher viral loads or delayed clearance cannot alone explain Alpha’s higher transmissibility in relation to the wild-type virus.
When the researchers integrated the area under the infectious virus load curve over the course of disease to estimate infectiousness, they found a broad range of individual infectiousness, with a greater than 57-fold difference between the most and least infectious.
Findings may inform surveillance, control strategies
There were no significant links between participants’ symptoms and disease course, a finding that challenges the assumption that those who have more symptoms are always more infectious. But the authors cautioned against reading too much into that conclusion because all participants were asymptomatic or mildly ill, and none required treatment.
They said that previous studies on the dynamics of SARS-CoV-2 shedding over time have been limited by low sampling frequency; failure to capture the early stages of infection, when viral spread is most likely; a lack of individual-level data on infectious virus shedding dynamics; and a bias toward the most severe clinical outcomes.
The researchers said that understanding the factors underlying the differences in individual viral transmission can inform the development of more targeted and effective infection-control methods.
“Viral infection is a highly complex process in which viral replication and shedding dynamics are shaped by the complex interplay between host and viral factors,” they wrote. “In addition to implications for pathogenesis and transmission, defining the contours of viral shedding dynamics is also critical for designing effective surveillance, screening and testing strategies.”