Impact of variants of concern on SARS-CoV-2 viral dynamics in non-human primates

Author summarySARS-CoV-2 has been characterized by the successive emergence of Variants of Concern (VoC) that have caused large epidemic rebounds. However, as VoC emerged in very different contexts of pre-existing immunity, the comparison of their intrinsic effect of viral dynamics and infectiousness remains poorly understood. Here we analysed data from 78 non-human primates infected by different VoC (Beta, Delta, Gamma and Omicron BA.1) and we used a mathematical model to quantity the impact of VoCs on viral load and infectivity. Compared with the historical variant, Omicron and Delta variants were associated with a longer and larger excretion of infectious particles, which was attributed in the model to an enhanced capability to escape the immune response. While Delta variant was associated with a larger peak viral load than the historical variant, no such effect was observed for Omicron variant. This suggests that the increased transmissibility of Omicron variant does not stem from higher viral load levels but rather from its ability to maintain high levels of infectious particles over time. Altogether, these results illustrate the importance of quantifying both viral load and infectiousness to better understand some differences observed in the patterns of viral transmission of VoCs. The impact of variants of concern (VoC) on SARS-CoV-2 viral dynamics remains poorly understood and essentially relies on observational studies subject to various sorts of biases. In contrast, experimental models of infection constitute a powerful model to perform controlled comparisons of the viral dynamics observed with VoC and better quantify how VoC escape from the immune response. Here we used molecular and infectious viral load of 78 cynomolgus macaques to characterize in detail the effects of VoC on viral dynamics. We first developed a mathematical model that recapitulate the observed dynamics, and we found that the best model describing the data assumed a rapid antigen-dependent stimulation of the immune response leading to a rapid reduction of viral infectivity. When compared with the historical variant, all VoC except beta were associated with an escape from this immune response, and this effect was particularly sensitive for delta and omicron variant (p<10(-6) for both). Interestingly, delta variant was associated with a 1.8-fold increased viral production rate (p = 0.046), while conversely omicron variant was associated with a 14-fold reduction in viral production rate (p<10(-6)). During a natural infection, our models predict that delta variant is associated with a higher peak viral RNA than omicron variant (7.6 log(10) copies/mL 95% CI 6.8-8 for delta; 5.6 log(10) copies/mL 95% CI 4.8-6.3 for omicron) while having similar peak infectious titers (3.7 log(10) PFU/mL 95% CI 2.4-4.6 for delta; 2.8 log(10) PFU/mL 95% CI 1.9-3.8 for omicron). These results provide a detailed picture of the effects of VoC on total and infectious viral load and may help understand some differences observed in the patterns of viral transmission of these viruses.

Automated summary

By analyzing data from 78 non-human primates infected by different Variants of Concern (VoC), the researchers found that Omicron and Delta variants were associated with a longer and larger excretion of infectious particles, attributed to their enhanced capability to escape the immune response. While the Delta variant had a higher peak viral load, the Omicron variant did not show a similar effect. This suggests that the increased transmissibility of the Omicron variant is not due to higher viral load levels, but rather its ability to maintain high levels of infectious particles over time. These results highlight the importance of quantifying viral load and infectiousness to better understand the differences observed in the transmission patterns of VoCs.