Study co-authored by UMass Chan researchers finds big differences in SARS-CoV-2 infectivity

A wide variation in the amount or infectivity of SARS-CoV-2 among people in the early stages of COVID-19 may be an explanation for the phenomenon of “super spreaders”, according to a study by researchers at the UMass Chan and collaborators from several institutions which was recently published in Natural microbiology .

Laura Gibson, MD

The research provides an in-depth view of SARS-CoV-2 infection through serial viral testing by multiple methods: PCR test, antigen test, and viral culture to measure viral growth.

Nasal and saliva samples were obtained from late 2020 to early 2021 from 60 individuals at the University of Illinois at Urbana-Champaign who were asymptomatic or mildly symptomatic with COVID-19. The participants had either received a new positive PCR result within the previous 24 hours or had been exposed to someone with COVID-19 within the previous five days. The study was supported by the National Institutes of Health’s Rapid Acceleration of Diagnostics (RADx) initiative.

The term super spreader refers to an infected person who contributes a disproportionately large share of SARS-CoV-2 transmission.

“Until this study, the reason why some people seem to transmit the virus to others more widely than others has not been well explained,” said co-author Laura L. Gibson, MD, professor Associate of Medicine at UMass Chan. Dr. Gibson was previously co-lead of the RADx Clinical Studies Core with David D. McManus, MD, the Richard M. Haidack Professor of Medicine and President and Professor of Medicine.

Based on the study results, Gibson said, COVID-19 appears to be like most other infectious diseases in which some people get sick and others don’t from the same infection. This clinical variability depends on many factors, including differences between pathogens, individual differences in immune responses or even the location of the virus in the oral or nasal cavities.

The current study was performed on individuals with no known immunity to SARS-CoV-2. They had not been infected before, and because the study took place before the vaccine was widely available, none had received a COVID-19 vaccine.

The researchers measured the dynamics of the SARS-CoV-2 virus in several ways through daily sampling of participants for up to 14 days.

First, they tested nasal swabs using the sample from one nostril for a PCR test, which detects viral genetic material whether the virus is dead or alive, and from the other nostril for an antigen test. , which detects viral proteins. The PCR nasal sample was also tested in viral culture, a laboratory test that detects virus that is alive and replicating and therefore could spread to the next person.

Gibson explained, “The unique aspect of this approach was to use multiple testing modalities on samples obtained on the same day and to repeat these measurements daily throughout the SARS-CoV-2 infection.”

To analyze the data from these samples, the researchers used mathematical models to map the longitudinal dynamics of viral shedding based on data from PCR tests and viral culture performed during infection. The models not only described viral expansion and clearance, but also viral shedding, which generally indicates infectious activity when the virus is released from the body.

“Daily sampling of participants provided robust granular data for this modeling,” Gibson said. “We found that individuals differ significantly in terms of viral infectivity, and that such heterogeneity likely depends on human and viral factors and supports the idea of ​​super spreaders.”

The researchers also compared PCR test results in saliva and nasal samples and found surprising differences between the two anatomical locations, even though they are connected at the back of the throat. “We found virus in saliva at least a day before nasal swabs in approximately 85% of participants,” Gibson said.

The authors of the paper did not suggest that saliva testing was better than nasal testing, “But it supports the argument that if you want to catch infected people earlier, you might be better off testing the saliva – with a PCR test authorized for this use – rather than nasal swabs.But there are many caveats with this approach, and people should only use diagnostic tests with the specific type of sample for which they are designed.

Although the study took place when the alpha and previous variants were circulating, Gibson said the general conclusions would likely still apply to other variants because the researchers did not see differences in viral dynamics depending on the variants assessed in this study.

Additionally, the study found differences between participants that were not fully explained by virus test results, Gibson said. “The general conclusion was that people vary in the amount or duration of virus in samples, regardless of how the virus is tested, and not all of this variation has been explained by virus measurements. Human factors – for example the level of anti-SARS-CoV-2 antibodies in the nose – are likely important and could be measured as a clinical tool.

Other UMass Chan Medical School researchers who authored the paper along with researchers from the University of Illinois at Urbana-Champaign, Johns Hopkins School of Medicine, and the National Institute of Biomedical Imaging and bioengineering were: Alyssa N. Owens, PhD, research coordinator; John P. Broach, MD, MPH, MBA, assistant professor of emergency medicine; Bruce A. Barton, PhD, Professor of Population and Quantitative Health Sciences; Peter Lazar, Application Database Developer; and Dr. McManus.

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