Infectious viral load in unvaccinated and vaccinated patients infected with SARS-CoV-2 WT, Delta and Omicron

Abstract

Background Viral load (VL) is one determinant of secondary transmission of SARS-CoV-2. Emergence of variants of concerns (VOC) Alpha and Delta was ascribed, at least partly, to higher VL. Furthermore, with parts of the population vaccinated, knowledge on VL in vaccine breakthrough infections is crucial. As RNA VL is only a weak proxy for infectiousness, studies on infectious virus presence by cell culture isolation are of importance. Methods We assessed nasopharyngeal swabs of COVID-19 patients for quantitative infectious viral titres (IVT) by focus-forming assay and compared to overall virus isolation success and RNA genome copies. We assessed infectious viral titres during the first 5 symptomatic days in a total of 384 patients: unvaccinated individuals infected with pre-VOC SARS-CoV-2 (n= 118) or Delta (n= 127) and vaccine breakthrough infections with Delta (n= 121) or Omicron (n=18). Findings Correlation between RNA copy number and IVT was low for all groups. No correlation between IVTs and age or sex was seen. We observed higher RNA genome copies in pre-VOC SARS-CoV-2 compared to Delta, but significantly higher IVTs in Delta infected individuals. In vaccinated vs. unvaccinated Delta infected individuals, RNA genome copies were comparable but vaccinated individuals have significantly lower IVTs, and cleared virus faster. Vaccinated individuals with Omicron infection had comparable IVTs to Delta breakthrough infections. Interpretation Quantitative IVTs can give detailed insights into virus shedding kinetics. Vaccination was associated with lower infectious titres and faster clearance for Delta, showing that vaccination would also lower transmission risk. Omicron vaccine breakthrough infections did not show elevated IVTs compared to Delta, suggesting that other mechanisms than increase VL contribute to the high infectiousness of Omicron. Funding This work was supported by the Swiss National Science Foundation 196644, 196383, NRP (National Research Program) 78 Covid-19 Grant 198412, the Fondation Ancrage Bienfaisance du Groupe Pictet and the Fondation Privée des Hôpitaux Universitaires de Genève.

Quantifying the impact of immune history and variant on SARS-CoV-2 viral kinetics and infection rebound: a retrospective cohort study

“…Based on the similarity of viral dynamics between Omicron and Delta found here, these data do not support increased viral load, as measured by RT-PCR, as an explanation for why Omicron exhibits such high infectivity nor its potentially earlier onset of infectiousness 6,7,17,22 . This is consistent with recent findings of poor correlation between RNA genome copies and infectious viral titers 23 , suggesting that factors other than viral RNA load are needed to explain differences between the Omicron and Delta infectivity profile. These data also suggest that the less severe disease demonstrated by Omicron infection is not obviously accounted for by decreased viral loads in the nasopharynx or oropharynx 2 .…”

Early introduction and rise of the Omicron SARS-CoV-2 variant in highly vaccinated university populations

“…Over an 8-13 day period, variant proportions converted from > 90% Delta to > 90% Omicron. Importantly, the rapid increase in Omicron case counts was identified in highly vaccinated populations in which Omicron's viral load, as inferred from anterior nares diagnostic Ct, was comparable to or lower than that of Delta, consistent with other reports 33,34 . This highlights that Omicron's fitness is neither driven by a higher viral load nor reliant on an immunologically naive population.…”

Mucosal Vaccines, Sterilizing Immunity, and the Future of SARS-CoV-2 Virulence

“…The paucity of IgA after non-mucosal vaccination suggests that systemically vaccinated patients, while mildly symptomatic or asymptomatic, could still become infected with SARS-CoV-2. There is no conclusive evidence yet as to whether asymptomatically infected vaccinees are infectious since theoretically the virions could be immune-complexed and not infectious [51][52][53][54], but the similar viral load seen in NPS from infected vaccinees versus infected naives suggests there is a serious risk of transmission. However, vaccinated individuals who develop symptomatic (e.g., breakthrough) infections are contagious for SARS-CoV-2 [55].…”