SARS-CoV-2 viral dynamics in non-human primates

• Published in: PLoS computational biology 2021-03, Vol.17 (3), p.e1008785-e1008785
• Main Authors: Gonçalves, Antonio, Maisonnasse, Pauline, Donati, Flora, Albert, Mélanie, Behillil, Sylvie, Contreras, Vanessa, Naninck, Thibaut, Marlin, Romain, Solas, Caroline, Pizzorno, Andres, Lemaitre, Julien, Kahlaoui, Nidhal, Terrier, Olivier, Ho Tsong Fang, Raphael, Enouf, Vincent, Dereuddre-Bosquet, Nathalie, Brisebarre, Angela, Touret, Franck, Chapon, Catherine, Hoen, Bruno, Lina, Bruno, Rosa Calatrava, Manuel, de Lamballerie, Xavier, Mentré, France, Le Grand, Roger, van der Werf, Sylvie, Guedj, Jérémie
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antiviral Agents; Antiviral Agents - pharmacology; Basic Reproduction Number; Biology and Life Sciences; COVID-19; COVID-19 - blood; COVID-19 - prevention & control; COVID-19 - virology; Cytokines; Cytokines - blood; Disease Models, Animal; Disease prevention; Dosage; Dynamic models; Health aspects; Infections; Influenza; Laboratory animals; Life Sciences; Macaca fascicularis; Macaca fascicularis - virology; Macaques; Medicine and Health Sciences; Microbiology and Parasitology; Model testing; Nasopharynx; Nasopharynx - virology; Normal distribution; Parameter estimation; Physiological aspects; Prophylaxis; SARS-CoV-2; SARS-CoV-2 - drug effects; SARS-CoV-2 - physiology; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Standard deviation; Trachea; Trachea - virology; Upper bounds; Viral diseases; Viral Load; Virology; Virus diseases; Virus Replication; Virus Replication - drug effects; Viruses
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/JOURNAL.PCBI.1008785

Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics in 31 cynomolgus macaques for which nasopharyngeal and tracheal viral load were frequently assessed. We identified that infected cells had a large burst size (>104 virus) and a within-host reproductive basic number of approximately 6 and 4 in nasopharyngeal and tracheal compartment, respectively. After peak viral load, infected cells were rapidly lost with a half-life of 9 hours, with no significant association between cytokine elevation and clearance, leading to a median time to viral clearance of 10 days, consistent with observations in mild human infections. Given these parameter estimates, we predict that a prophylactic treatment blocking 90% of viral production or viral infection could prevent viral growth. In conclusion, our results provide estimates of SARS-CoV-2 viral kinetic parameters in an experimental model of mild infection and they provide means to assess the efficacy of future antiviral treatments.