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
The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (<i>Macaca mulatta</i>) and cynomolgus macaques (<i>Macaca fascicularis</i>). During the acute phase of infection, SARS-CoV-2 was shed via the nose and throat, and viral RNA was occasionally detected in f...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/8/1673 |
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doaj-f07ae1b8ce4d430cb2e9428534484966 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Kinga P. Böszörményi Marieke A. Stammes Zahra C. Fagrouch Gwendoline Kiemenyi-Kayere Henk Niphuis Daniella Mortier Nikki van Driel Ivonne Nieuwenhuis Richard A. W. Vervenne Tom Haaksma Boudewijn Ouwerling Deborah Adema Roja Fidel Acar Ella Zuiderwijk-Sick Lisette Meijer Petra Mooij Ed J. Remarque Herman Oostermeijer Gerrit Koopman Alexis C. R. Hoste Patricia Sastre Bart L. Haagmans Ronald E. Bontrop Jan A. M. Langermans Willy M. Bogers Ivanela Kondova Ernst J. Verschoor Babs E. Verstrepen |
| spellingShingle |
Kinga P. Böszörményi Marieke A. Stammes Zahra C. Fagrouch Gwendoline Kiemenyi-Kayere Henk Niphuis Daniella Mortier Nikki van Driel Ivonne Nieuwenhuis Richard A. W. Vervenne Tom Haaksma Boudewijn Ouwerling Deborah Adema Roja Fidel Acar Ella Zuiderwijk-Sick Lisette Meijer Petra Mooij Ed J. Remarque Herman Oostermeijer Gerrit Koopman Alexis C. R. Hoste Patricia Sastre Bart L. Haagmans Ronald E. Bontrop Jan A. M. Langermans Willy M. Bogers Ivanela Kondova Ernst J. Verschoor Babs E. Verstrepen 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 Viruses SARS-CoV-2 COVID-19 non-human primates animal models NHPs |
| author_facet |
Kinga P. Böszörményi Marieke A. Stammes Zahra C. Fagrouch Gwendoline Kiemenyi-Kayere Henk Niphuis Daniella Mortier Nikki van Driel Ivonne Nieuwenhuis Richard A. W. Vervenne Tom Haaksma Boudewijn Ouwerling Deborah Adema Roja Fidel Acar Ella Zuiderwijk-Sick Lisette Meijer Petra Mooij Ed J. Remarque Herman Oostermeijer Gerrit Koopman Alexis C. R. Hoste Patricia Sastre Bart L. Haagmans Ronald E. Bontrop Jan A. M. Langermans Willy M. Bogers Ivanela Kondova Ernst J. Verschoor Babs E. Verstrepen |
| author_sort |
Kinga P. Böszörményi |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| publisher |
MDPI AG |
| series |
Viruses |
| issn |
1999-4915 |
| publishDate |
2021-08-01 |
| description |
The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (<i>Macaca mulatta</i>) and cynomolgus macaques (<i>Macaca fascicularis</i>). 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. |
| topic |
SARS-CoV-2 COVID-19 non-human primates animal models NHPs |
| url |
https://www.mdpi.com/1999-4915/13/8/1673 |
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1721189427844218880 |
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doaj-f07ae1b8ce4d430cb2e94285344849662021-08-26T14:27:18ZengMDPI AGViruses1999-49152021-08-01131673167310.3390/v13081673The 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 TissuesKinga P. Böszörményi0Marieke A. Stammes1Zahra C. Fagrouch2Gwendoline Kiemenyi-Kayere3Henk Niphuis4Daniella Mortier5Nikki van Driel6Ivonne Nieuwenhuis7Richard A. W. Vervenne8Tom Haaksma9Boudewijn Ouwerling10Deborah Adema11Roja Fidel Acar12Ella Zuiderwijk-Sick13Lisette Meijer14Petra Mooij15Ed J. Remarque16Herman Oostermeijer17Gerrit Koopman18Alexis C. R. Hoste19Patricia Sastre20Bart L. Haagmans21Ronald E. Bontrop22Jan A. M. Langermans23Willy M. Bogers24Ivanela Kondova25Ernst J. Verschoor26Babs E. Verstrepen27Biomedical Primate Research Centre (BPRC), Department of Virology, 2288 GJ Rijswijk, The NetherlandsDepartment of Parasitology, BPRC, 2288 GJ Rijswijk, The NetherlandsBiomedical Primate Research Centre (BPRC), Department of Virology, 2288 GJ Rijswijk, The NetherlandsBiomedical Primate Research Centre (BPRC), Department of Virology, 2288 GJ Rijswijk, The NetherlandsBiomedical Primate Research Centre (BPRC), Department of Virology, 2288 GJ Rijswijk, The NetherlandsBiomedical Primate Research Centre (BPRC), Department of Virology, 2288 GJ Rijswijk, The NetherlandsAnimal Science Department, BPRC, 2288 GJ Rijswijk, The NetherlandsDepartment of Parasitology, BPRC, 2288 GJ Rijswijk, The NetherlandsDepartment of Parasitology, BPRC, 2288 GJ Rijswijk, The NetherlandsAnimal Science Department, BPRC, 2288 GJ Rijswijk, The NetherlandsAnimal Science Department, BPRC, 2288 GJ Rijswijk, The NetherlandsAnimal Science Department, BPRC, 2288 GJ Rijswijk, The NetherlandsBiomedical Primate Research Centre (BPRC), Department of Virology, 2288 GJ Rijswijk, The NetherlandsAlternatives Unit, BPRC, 2288 GJ Rijswijk, The NetherlandsDepartment of Parasitology, BPRC, 2288 GJ Rijswijk, The NetherlandsBiomedical Primate Research Centre (BPRC), Department of Virology, 2288 GJ Rijswijk, The NetherlandsBiomedical Primate Research Centre (BPRC), Department of Virology, 2288 GJ Rijswijk, The NetherlandsBiomedical Primate Research Centre (BPRC), Department of Virology, 2288 GJ Rijswijk, The NetherlandsBiomedical Primate Research Centre (BPRC), Department of Virology, 2288 GJ Rijswijk, The NetherlandsEurofins-Inmunología y Genética Aplicada (Eurofins-INGENASA), 28037 Madrid, SpainEurofins-Inmunología y Genética Aplicada (Eurofins-INGENASA), 28037 Madrid, SpainDepartment of Viroscience, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Comparative Genetics and Refinement, BPRC, 2288 GJ Rijswijk, The NetherlandsAnimal Science Department, BPRC, 2288 GJ Rijswijk, The NetherlandsBiomedical Primate Research Centre (BPRC), Department of Virology, 2288 GJ Rijswijk, The NetherlandsAnimal Science Department, BPRC, 2288 GJ Rijswijk, The NetherlandsBiomedical Primate Research Centre (BPRC), Department of Virology, 2288 GJ Rijswijk, The NetherlandsBiomedical Primate Research Centre (BPRC), Department of Virology, 2288 GJ Rijswijk, The NetherlandsThe post-acute phase of SARS-CoV-2 infection was investigated in rhesus (<i>Macaca mulatta</i>) and cynomolgus macaques (<i>Macaca fascicularis</i>). 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.https://www.mdpi.com/1999-4915/13/8/1673SARS-CoV-2COVID-19non-human primatesanimal modelsNHPs |