Journal Article

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

Sastre, Patricia, van Driel, Nikki, Nieuwenhuis, Ivonne, Niphuis, Henk, Koopman, Gerrit, Fagrouch, Zahra C., Remarque, Ed J., Acar, Roja Fidel, Kiemenyi-Kayere, Gwendoline, Kondova, Ivanela, Hoste, Alexis C. R., Vervenne, Richard A. W., Verstrepen, Babs E., Bogers, Willy M., Stammes, Marieke A., Haaksma, Tom, Mortier, Daniella, Ouwerling, Boudewijn, Bontrop, Ronald E., Adema, Deborah, Zuiderwijk-Sick, Ella, Mooij, Petra, Verschoor, Ernst J., Meijer, Lisette, Langermans, Jan A. M., Haagmans, Bart L., Böszörményi, Kinga P., Oostermeijer, Herman

2021

Overview

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. 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.

• Publisher: MDPI AG,MDPI
• Subject: Animal models / Animals / Antibodies, Viral / Antibodies, Viral/blood / Asymptomatic / Biochemistry / Body temperature / Computed tomography / Conjunctiva / Coronaviruses / COVID-19 / COVID-19 infection / COVID-19 vaccines / COVID-19/immunology / COVID-19/pathology / COVID-19/virology / Cytokines / Cytokines/blood / Disease Models, Animal / feces / heart / Hematology / histology / histopathology / Humans / Immune response / Infections / Infectious Diseases / Laboratory animals / Life sciences / Lung / Lung/pathology / Lung/virology / Lungs / lymph / Lymph Nodes / Lymph Nodes/pathology / Lymph Nodes/physiopathology / Macaca fascicularis / Macaca mulatta / Medical research / messenger RNA / mRNA / Médecine vétérinaire & santé animale / Necropsy / NHPs / non-human primates / nose / Positron emission tomography / Pulmonary lesions / Recovery (Medical) / Replication / Respiratory System / Respiratory System/pathology / Respiratory System/virology / Respiratory tract / RNA, Messenger / RNA, Messenger/analysis / RNA, Viral / RNA, Viral/analysis / Salivary gland / salivary glands / SARS-CoV-2 / SARS-CoV-2/immunology / SARS-CoV-2/physiology / Sciences du vivant / Severe acute respiratory syndrome coronavirus 2 / throat / Veterinary medicine & animal health / Virology / Virus Replication