A study conducted by researchers in the UK and Spain suggests that viral load is the main determinant of transmission risk in cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
The SARS-CoV-2 virus is the agent responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic that continues to threaten global public health and the worldwide economy.
Using data from linked index cases of COVID-19 and their contacts, the team established that the viral load among index cases was the main factor determining whether contacts became infected with SARS-CoV-2.
Increased viral loads among asymptomatic contacts were also strongly associated with a higher risk of developing symptomatic COVID-19. This association was further reflected in the incubation time, which became shorter with increasing viral loads.
Michael Marks from the London School of Hygiene & Tropical Medicine in London and colleagues say that to their knowledge, this is the largest study to date evaluating the relationship between viral load among patients with COVID-19 and the risk of transmission.
Writing in The Lancet Infectious Diseases, the team says: “when a patient with high viral load is identified, the implementation of reinforced contact tracing measures and quarantines might be crucial to reduce onward transmission.”
Data on variables affecting transmission risk are scarce
The availability of data regarding the factors that may enhance SARS-CoV-2 transmission is crucial for designing interventions to help curb the spread of the virus.
Currently, data on transmission risk related to the place and duration of exposure are available, but data on other variables related to the characteristics of index cases and their contacts are scarce, says Marks and colleagues.
The SARS-CoV-2 virus has been identified in respiratory tract samples 1 to 2 days before symptoms begin, and it can persist for as long as several weeks post-symptom-onset.
However, the detection of viral RNA does not necessarily reflect infectiousness, and the precise relationship between viral load among cases and the risk of transmission to contacts is still not clear.
“Although studies have suggested that the viral load of cases might be associated with risk of disease or transmission, no published data so far have directly addressed this question,” say the researchers.
Furthermore, little is known about variables that might influence the incubation period and the risk of COVID-19 symptoms developing.
What did the current study involve?
The team conducted a post-hoc analysis of data collected during a randomized controlled trial (Barcelona Postexposure Prophylaxis Study Against SARS-CoV-2) of COVID-19 cases and their close contacts. The trial took place between March 17th and April 28th, 2020 – during the initial wave of the SARS-CoV-2 outbreak.
All COVID-19 cases were aged 18 years or older, were not hospitalized, and had polymerase chain reaction (PCR) test results available at baseline. They had experienced mild symptoms in the five days prior to enrollment but had no symptoms of SARS-CoV-2 infection reported within their accommodation or workplace in the 14 days before enrollment.
Contacts were also aged 18 years or older, had recently been exposed to index cases as household contacts or healthcare workers, but did not have any COVID-19 symptoms in the 7 days prior to enrollment.
What did the researchers find?
The team identified 314 COVID-19 patients, of whom 282 (90%) had at least one close contact and giving a total of 753 contacts.
The viral load of the index case was the leading factor determining the risk of PCR-confirmed SARS-CoV-2 infection among contacts.
The overall secondary attack rate (proportion of contacts with PCR-positive results) during the study period was 17% (125 of 753 contacts). However, this rate varied from 12% when the viral load of the index case was lower than 1×10⁶ copies per mL, to 24% when it was 1×10¹⁰ copies per mL or higher.
Multivariate analysis showed that for each log10 increase in viral load, the odds of onward transmission increased by 30%.
The team also found that a high viral load among asymptomatic contacts was strongly associated with the risk of developing COVID-19 symptoms. The risk of symptoms developing increased from around 40% when the initial viral load was lower than 1×10⁷ copies per mL, to more than than 66% when it was 1×10¹⁰ copies per mL or higher.
Multivariable analysis revealed no association between sex, age, diabetes, cardiovascular disease, or respiratory disease and the risk of or time to developing symptomatic COVID-19.
Moreover, the initial viral load was significantly associated with incubation time, which increased from 5 days among participants with a high viral load to 7 days among participants with a low viral load.
Viral load may be the predominant driver of transmission
“Taken together, our results indicate that the viral load, rather than symptoms, might be the predominant driver of transmission,” writes Marks and colleagues.
The team says the findings suggest that all cases should be considered potential transmitters, irrespective of their presentation, and support the assessment of viral load in patients with a large number of close contacts.
“Similarly, our results regarding the risk and expected time to developing symptomatic COVID-19 encourage risk stratification of newly diagnosed SARS-CoV-2 infections on the basis of the initial viral load,” concludes the team.
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