Comparing viral load and infectivity in different virus variants
An NRP 78 research team compared viral load and infectivity in wildtype, Delta and Omicron virus variants and in vaccinated and unvaccinated infected individuals.
The University of Geneva research team led by Olha Puhach, Benjamin Meyer and Isabella Eckerle investigated the role of viral load as a factor in the transmission of different SARS-CoV-2 variants. In addition, the effect of vaccination on viral load and thus infectivity of a vaccinated compared to an unvaccinated person was determined. The rapid spread of the Alpha and Delta variants of the virus was attributed, at least in part, to a higher viral load. Therefore, a deeper understanding of viral load is critical, especially for breakthrough infections. Because RNA viral load is only a weak indicator of infectivity, the researchers conducted a study using cell culture isolation to determine the amount of infectious virus.
The study covered a total of 384 patients: 118 unvaccinated individuals infected with SARS-CoV-2 (original virus) and 127 infected with the delta variant, as well as 121 individuals with vaccine breakthrough infections from the Delta variant and another 18 with breakthrough infections from the Omicron variant.
Puhach O, Kenneth A, et al. Infectious viral load in unvaccinated and vaccinated patients infected with SARS-CoV-2 WT, Delta and Omicron. medRxiv 2022 01.10.22269010
Figure 1: Genome copies (B) and infectious viral loads (C) measured in vaccinated and unvaccinated Delta-infected patients at different points in time. The solid lines represent the adjusted curve calculated using the Local Estimated Scatterplot Smoothing (LOESS) method.
Using nasopharyngeal swabs from the 384 Covid-19 patients, the researchers compared infectious virus concentrations (infectious virus titers IVT) with overall virus isolation success and RNA genome copies. They observed the development of infectious viral titers during the first 5 symptomatic days.
The correlation between the number of RNA genome copies and infectious virus titers was low in all groups. Also, no correlation was found between infectious viruses and age or sex. Thus, RNA viral load does not tell us very much about infectivity. Furthermore, the researchers observed a higher number of RNA genome copies in the wildtype SARS-CoV-2 than in the Delta variant, but there was a significantly higher infectious viral load in Delta-infected individuals. In addition, viral load was higher in Delta 3-5 days after symptom onset. More and longer infectious viral shedding could explain the higher transmissibility of Delta.
In vaccinated and unvaccinated Delta-infected individuals, RNA genome copies were similar, but vaccinated individuals had significantly less infectious virus and degraded it more rapidly. This means that vaccination also reduces the risk of transmission.
Vaccinated individuals with Omicron infection had comparable numbers of infectious viruses to those with Delta breakthrough infection. This suggests that the high infectivity in Omicron patients is not due to a higher viral load compared to Delta.
The Geneva research team recently published these important findings as a preprint. They have since been the subject of intense discussion, including on Twitter.