The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues
Böszörményi, Kinga; Stammes, Marieke; Fagrouch, Zahra C.; Kiemenyi-Kayere, Gwendoline; Niphuis, Henk; Mortier, Daniella; Driel, Nikki van; Nieuwenhuis, Ivonne; Vervenne, Richard A. W.; Haaksma, Tom; Ouwerling, Boudewijn; Adema, Deborah; Acar, Roja Fidel; Zuiderwijk-Sick, Ella; Meijer, Lisette; Mooij, Petra; Remarque, Ed J.; Oostermeijer, Herman; Hoste, Alexis C. R.; Sastre, Patricia; Haagmans, Bart; Bontrop, Ronald E.; Langermans, Jan; Bogers, Willy; Kondova, Ivanela; Verschoor, Ernst; Verstrepen, Babs E
(2021) Viruses, volume 13, issue 8, pp. 1 - 22
(Article)
Abstract
The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis). During the acute phase of infection, SARS-CoV-2 was shed via the nose and throat, and viral RNA was occasionally detected in feces. This phase coincided with a transient change in systemic immune activation.
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Even after the alleged resolution of the infection, computed tomography (CT) and positron emission tomography (PET)-CT revealed pulmonary lesions and activated tracheobronchial lymph nodes in all animals. Post-mortem histological examination of the lung tissue revealed mostly marginal or resolving minimal lesions that were indicative of SARS-CoV-2 infection. Evidence for SARS-CoV-2-induced histopathology was also found in extrapulmonary tissue samples, such as conjunctiva, cervical, and mesenteric lymph nodes. However, 5–6 weeks after SARS-CoV-2 exposure, upon necropsy, viral RNA was still detectable in a wide range of tissue samples in 50% of the macaques and included amongst others the heart, the respiratory tract and surrounding lymph nodes, salivary gland, and conjunctiva. Subgenomic messenger RNA was detected in the lungs and tracheobronchial lymph nodes, indicative of ongoing virus replication during the post-acute phase. These results could be relevant for understanding the long-term consequences of COVID-19 in humans.
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Keywords: Animal models, COVID-19, NHPs, Non-human primates, SARS-CoV-2, Infectious Diseases, Virology
ISSN: 1999-4915
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
Note: Funding Information: Funding: This study was supported by funding from the Biomedical Primate Research Centre. K.P.B. was supported by the European Union’s Marie Skłodowska-Curie Innovative Training Network HONOURs; grant agreement no. 721367. This publication was also supported by the European Virus Archive GLOBAL (EVA-GLOBAL) project that has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 871029. Funding Information: This study was supported by funding from the Biomedical Primate Research Centre. K.P.B. was supported by the European Union?s Marie Sk?odowska-Curie Innovative Training Network HONOURs; grant agreement no. 721367. This publication was also supported by the European Virus Archive GLOBAL (EVA-GLOBAL) project that has received funding from the European Union?s Horizon 2020 research and innovation program under grant agreement no. 871029. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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