In:
PLOS Computational Biology, Public Library of Science (PLoS), Vol. 19, No. 8 ( 2023-8-9), p. e1010721-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1553-7358
DOI:
10.1371/journal.pcbi.1010721
DOI:
10.1371/journal.pcbi.1010721.g001
DOI:
10.1371/journal.pcbi.1010721.g002
DOI:
10.1371/journal.pcbi.1010721.g003
DOI:
10.1371/journal.pcbi.1010721.g004
DOI:
10.1371/journal.pcbi.1010721.g005
DOI:
10.1371/journal.pcbi.1010721.t001
DOI:
10.1371/journal.pcbi.1010721.s001
DOI:
10.1371/journal.pcbi.1010721.s002
DOI:
10.1371/journal.pcbi.1010721.s003
DOI:
10.1371/journal.pcbi.1010721.s004
DOI:
10.1371/journal.pcbi.1010721.s005
DOI:
10.1371/journal.pcbi.1010721.s006
DOI:
10.1371/journal.pcbi.1010721.s007
DOI:
10.1371/journal.pcbi.1010721.s008
DOI:
10.1371/journal.pcbi.1010721.s009
DOI:
10.1371/journal.pcbi.1010721.s010
DOI:
10.1371/journal.pcbi.1010721.s011
DOI:
10.1371/journal.pcbi.1010721.s012
DOI:
10.1371/journal.pcbi.1010721.r001
DOI:
10.1371/journal.pcbi.1010721.r002
DOI:
10.1371/journal.pcbi.1010721.r003
DOI:
10.1371/journal.pcbi.1010721.r004
DOI:
10.1371/journal.pcbi.1010721.r005
DOI:
10.1371/journal.pcbi.1010721.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2193340-6
