Respiratory disease in rhesus macaques inoculated with SARS-CoV-2
Open accessPublished version of a preprint
Abstract
An outbreak of coronavirus disease 2019 (COVID-19), which is caused by a novel coronavirus (named SARS-CoV-2) and has a case fatality rate of approximately 2%, started in Wuhan (China) in December 2019 1,2. Following an unprecedented global spread 3, the World Health Organization declared COVID-19 a pandemic on 11 March 2020. Although data on COVID-19 in humans are emerging at a steady pace, some aspects of the pathogenesis of SARS-CoV-2 can be studied in detail only in animal models, in which repeated sampling and tissue collection is possible. Here we show that SARS-CoV-2 causes a respiratory disease in rhesus macaques that lasts between 8 and 16 days. Pulmonary infiltrates, which are a hallmark of COVID-19 in humans, were visible in lung radiographs. We detected high viral loads in swabs from the nose and throat of all of the macaques, as well as in bronchoalveolar lavages; in one macaque, we observed prolonged rectal shedding. Together, the rhesus macaque recapitulates the moderate disease that has been observed in the majority of human cases of COVID-19. The establishment of the rhesus macaque as a model of COVID-19 will increase our understanding of the pathogenesis of this disease, and aid in the development and testing of medical countermeasures.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Inoculation with BBIBP-CorV does not result in side effects on serum biochemical parameters in rhesus macaques.
“Because a recent study showed that SARS-CoV-2 infection does not affect host blood chemistry (Munster et al., 2020), this result suggests that inoculation with BBIBP-CorV does not result in side effects on serum biochemical parameters.”
From Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2 (2020) · cites this paper as Munster et al., 2020
The NHP model exhibits upper and lower airway infection and pathology similar to clinical presentations of mild COVID-19 in humans.
“This model exhibits upper and lower airway infection and pathology similar to clinical presentations of mild COVID-19 in humans (14).”
From Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates (2021) · cites this paper as [14]
In a non-human primate model of COVID-19, nasal infection did not lead to identifiable CoV-2 antigens in brain.
“Additionally, two recent studies in mouse models expressing human ACE2 have found CoV-2 in the brain after intranasal inoculation (67, 68), although neither specifically queried the OB; this work stands in contrast to results in a non-human primate model of COVID-19, in which nasal infection did not lead to the presence of identifiable CoV-2 antigens in the brain (83).”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [83]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Clinical characteristics of coronavirus disease 2019 in China
Guan, W.-J., Ni, Z.-Y., Hu, Y., Liang, W.-H., Ou, C.-Q., He, J.-X., Liu, L., Shan, H., Lei, C.-L., Hui, D. S. C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2002032 · Cited by 30,246 · see citing works
A novel coronavirus from patients with pneumonia in China, 2019
Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2001017 · Cited by 28,244 · see citing works
Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., Xiang, J., Wang, Y., Song, B., Gu, X., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30566-3 · Cited by 27,263 · see citing works
Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., Wang, B., Xiang, H., Cheng, Z., Xiong, Y., et al. (2020) · JAMA · doi:10.1001/jama.2020.1585 · Cited by 20,148 · see citing works
La certeza de lo impredecible: Cultura Educación y Sociedad en tiempos de COVID19
Martínez González, M. (2020) · DSPACE System - Metalibrary (University of the Coast) · Cited by 18,463 · see citing works
A new coronavirus associated with human respiratory disease in China
Wu, F., Zhao, S., Yu, B., Chen, Y.-M., Wang, W., Song, Z.-G., Hu, Y., Tao, Z.-W., Tian, J.-H., Pei, Y.-Y., et al. (2020) · Nature · doi:10.1038/s41586-020-2008-3 · Cited by 11,688 · see citing works
Yang, X., Yu, Y., Xu, J., Shu, H., Xia, J., Liu, H., Wu, Y., Zhang, L., Yu, Z., Fang, M., et al. (2020) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(20)30079-5 · Cited by 10,066 · see citing works
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S., & McLellan, J. S. (2020) · Science · doi:10.1126/science.abb2507 · Cited by 8,897 · see citing works
Pathological findings of COVID-19 associated with acute respiratory distress syndrome
Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., Liu, S., Zhao, P., Liu, H., Zhu, L., et al. (2020) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(20)30076-x · Cited by 8,545 · see citing works
Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR
Corman, V. M., Landt, O., Kaiser, M., Molenkamp, R., Meijer, A., Chu, D. K. W., Bleicker, T., Brünink, S., Schneider, J. A., Schmidt, M. L., et al. (2020) · Eurosurveillance · doi:10.2807/1560-7917.es.2020.25.3.2000045 · Cited by 7,266 · see citing works
Virological assessment of hospitalized patients with COVID-2019
Wölfel, R., Corman, V. M., Guggemos, W., Seilmaier, M., Zange, S., Müller, M. A., Niemeyer, D., Jones, T. C., Vollmar, P., Rothe, C., et al. (2020) · Nature · doi:10.1038/s41586-020-2196-x · Cited by 6,661 · see citing works
SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients
Zou, L., Ruan, F., Huang, M.-X., Liang, L.-J., Huang, H., Hong, Z.-S., Yu, J.-X., Kang, M., Song, Y.-C., Xia, J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmc2001737 · Cited by 4,590 · see citing works
Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study
Shi, H., Han, X., Jiang, N., Cao, Y., Alwalid, O., Gu, J., Fan, Y., & Zheng, C. (2020) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(20)30086-4 · Cited by 3,664 · see citing works
SARS and MERS: recent insights into emerging coronaviruses
de Wit, E., van Doremalen, N., Falzarano, D., & Munster, V. J. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.81 · Cited by 3,510 · see citing works
Self-citationAntibody Responses to SARS-CoV-2 in Patients With Novel Coronavirus Disease 2019
Zhao, J., Yuan, Q., Wang, H., Liu, W., Liao, X., Su, Y., Wang, X., Yuan, J., Li, T., Li, J., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa344 · Cited by 2,607 · see citing works
Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State
Arentz, M., Yim, E., Klaff, L., Lokhandwala, S., Riedo, F. X., Chong, M., & Lee, M. (2020) · JAMA · doi:10.1001/jama.2020.4326 · Cited by 2,259 · see citing works
Assiri, A., Al-Tawfiq, J. A., Al-Rabeeah, A. A., Al-Rabiah, F. A., Al-Hajjar, S., Al-Barrak, A., Flemban, H., Al-Nassir, W. N., Balkhy, H. H., Al-Hakeem, R. F., et al. (2013) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(13)70204-4 · Cited by 1,435 · see citing works
Tian, S., Hu, W., Niu, L., Liu, H., Xu, H., & Xiao, S. (2020) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2020.02.010 · Cited by 1,414 · see citing works
Clinical Features and Short-term Outcomes of 144 Patients With SARS in the Greater Toronto Area
Booth, C. M. (2003) · JAMA · doi:10.1001/jama.289.21.joc30885 · Cited by 1,405 · see citing works
Positive RT-PCR test results in patients recovered from COVID-19
Lan, L., Xu, D., Ye, G., Xia, C., Wang, S., Li, Y., & Xu, H. (2020) · JAMA · doi:10.1001/jama.2020.2783 · Cited by 1,251 · see citing works
Lung pathology of fatal severe acute respiratory syndrome
Nicholls, J. M., Poon, L. L., Lee, K. C., Ng, W. F., Lai, S. T., Leung, C. Y., Chu, C. M., Hui, P. K., Mak, K. L., Lim, W., et al. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13413-7 · Cited by 1,076 · see citing works
Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion ConformationPreprint
Wrapp, D., Wang, N., Corbett, K. S., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.02.11.944462 · Cited by 1,010 · see citing works
Yang, W., Cao, Q., Qin, L., Wang, X., Cheng, Z., Pan, A., Dai, J., Sun, Q., Zhao, F., Qu, J., et al. (2020) · Journal of Infection · doi:10.1016/j.jinf.2020.02.016 · Cited by 994 · see citing works
The clinical pathology of severe acute respiratory syndrome (SARS): a report from China
Ding, Y., Wang, H., Shen, H., Li, Z., Geng, J., Han, H.-X., Cai, J., Li, X., Kang, W., Weng, D., et al. (2003) · The Journal of Pathology · doi:10.1002/path.1440 · Cited by 765 · see citing works
Severe Acute Respiratory Syndrome Coronavirus 2 from Patient with Coronavirus Disease, United States
Harcourt, J. L., Tamin, A., Lu, X., Kamili, S., Sakthivel, S. K., Murray, J., Queen, K. J., Tao, Y., Paden, C. R., Zhang, J., et al. (2020) · Emerging infectious diseases · doi:10.3201/eid2606.200516 · Cited by 524 · see citing works
Detection of Novel Coronavirus by RT-PCR in Stool Specimen from Asymptomatic Child, China
Tang, A., Tong, Z.-D., Wang, H.-L., Dai, Y.-X., Li, K.-F., Liu, J.-N., Wu, W.-J., Yuan, C., Yu, M.-L., Li, P., et al. (2020) · Emerging Infectious Diseases · doi:10.3201/eid2606.200301 · Cited by 516 · see citing works
Virological assessment of hospitalized cases of coronavirus disease 2019Preprint
Wölfel, R., Corman, V. M., Guggemos, W., et al. (2020) · medRxiv · doi:10.1101/2020.03.05.20030502 · Cited by 461 · see citing works
Ng, D. L., Hosani, F. I. A., Keating, M. K., Gerber, S. I., Jones, T. L., Metcalfe, M. G., Tong, S., Tao, Y., Alami, N. N., Haynes, L. M., et al. (2016) · American Journal Of Pathology · doi:10.1016/j.ajpath.2015.10.024 · Cited by 384 · see citing works
Interpreting Stress Responses during Routine Toxicity Studies
Everds, N. E., Snyder, P. W., Bailey, K. L., Bolon, B. N., Creasy, D. M., Foley, G. L., Rosol, T. J., & Sellers, T. S. (2013) · Toxicologic Pathology · doi:10.1177/0192623312466452 · Cited by 338 · see citing works
Viral Load Kinetics of SARS-CoV-2 Infection in First Two Patients in Korea
Kim, J. Y., Ko, J., Kim, Y., Kim, Y., Kim, J., Chung, Y., Kim, H. M., Han, M. G., Kim, S. Y., & Chin, B. S. (2020) · Journal of Korean Medical Science · doi:10.3346/jkms.2020.35.e86 · Cited by 262 · see citing works
First imported case of 2019 novel coronavirus in Canada, presenting as mild pneumonia
Silverstein, W. K., Stroud, L. F., Cleghorn, G., & Leis, J. A. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30370-6 · Cited by 147 · see citing works
High Prevalence of Middle East Respiratory Coronavirus in Young Dromedary Camels in Jordan
van Doremalen, N., Hijazeen, Z. S. K., Holloway, P., et al. (2016) · Vector-Borne and Zoonotic Diseases · doi:10.1089/vbz.2016.2062 · Cited by 54 · see citing works
Clinical and cytogenetic spectrum of duplication 3p
Braga, S., & Schmidt, A. (1982) · European Journal of Pediatrics · doi:10.1007/bf00441155 · Cited by 36 · see citing works
Haley, P. J., Muggenburg, B. A., Rebar, A. H., et al. (1989) · Veterinary Pathology · doi:10.1177/030098588902600312 · Cited by 31 · see citing works
Short-Term and Long-Term Effects of Serial Bronchoalveolar Lavages in a Nonhuman Primate Model
Krombach, F., Fiehl, E., Burkhardt, D., et al. (1994) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.150.1.8025742 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Ziegler, C. G. K., Allon, S. J., Nyquist, S. K., Mbano, I. M., Miao, V. N., Tzouanas, C. N., Cao, Y., Yousif, A. S., Bals, J., Hauser, B. M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.04.035 · Cited by 2,284 · see citing works
SARS-CoV-2 vaccines in development
Krammer, F. (2020) · Nature · doi:10.1038/s41586-020-2798-3 · Cited by 2,098 · see citing works
Brann, D. H., Tsukahara, T., Weinreb, C., Lipovsek, M., Van den Berge, K., Gong, B., Chance, R., Macaulay, I. C., Chou, H.-J., Fletcher, R. B., et al. (2020) · Science Advances · doi:10.1126/sciadv.abc5801 · Cited by 1,198 · see citing works
ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques
van Doremalen, N., Lambe, T., Spencer, A., Belij-Rammerstorfer, S., Purushotham, J. N., Port, J. R., Avanzato, V. A., Bushmaker, T., Flaxman, A., Ulaszewska, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2608-y · Cited by 914 · see citing works
Self-citationImmunological considerations for COVID-19 vaccine strategies
Jeyanathan, M., Afkhami, S., Smaill, F., Miller, M. S., Lichty, B. D., & Xing, Z. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-00434-6 · Cited by 1,015 · see citing works
Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model
Rockx, B., Kuiken, T., Herfst, S., Bestebroer, T., Lamers, M. M., Oude Munnink, B. B., de Meulder, D., van Amerongen, G., van den Brand, J., Okba, N. M. A., et al. (2020) · Science · doi:10.1126/science.abb7314 · Cited by 901 · see citing works
Muñoz-Fontela, C., Dowling, W. E., Funnell, S. G. P., Gsell, P.-S., Riveros-Balta, A. X., Albrecht, R. A., Andersen, H., Baric, R. S., Carroll, M. W., Cavaleri, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2787-6 · Cited by 798 · see citing works
Self-citationWang, H., Zhang, Y., Huang, B., Deng, W., Quan, Y., Wang, W., Xu, W., Zhao, Y., Li, N., Zhang, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.008 · Cited by 748 · see citing works
SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity
Motozono, C., Toyoda, M., Zahradnik, J., Saito, A., Nasser, H., Tan, T. S., Ngare, I., Kimura, I., Uriu, K., Kosugi, Y., et al. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2021.06.006 · Cited by 586 · see citing works
REGN-COV2 antibodies prevent and treat SARS-CoV-2 infection in rhesus macaques and hamsters
Baum, A., Ajithdoss, D., Copin, R., Zhou, A., Lanza, K., Negron, N., Ni, M., Wei, Y., Mohammadi, K., Musser, B., et al. (2020) · Science · doi:10.1126/science.abe2402 · Cited by 517 · see citing works
Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques
Deng, W., Bao, L., Liu, J., Xiao, C., Liu, J., Xue, J., Lv, Q., Qi, F., Gao, H., Yu, P., et al. (2020) · Science · doi:10.1126/science.abc5343 · Cited by 440 · see citing works
Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates
Corbett, K. S., Nason, M. C., Flach, B., Gagne, M., O’Connell, S., Johnston, T. S., Shah, S. N., Edara, V. V., Floyd, K., Lai, L., et al. (2021) · Science · doi:10.1126/science.abj0299 · Cited by 286 · see citing works
Lessons for COVID-19 immunity from other coronavirus infections
Sariol, A., & Perlman, S. (2020) · Immunity · doi:10.1016/j.immuni.2020.07.005 · Cited by 317 · see citing works
Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques
Aid, M., Busman-Sahay, K., Vidal, S. J., Maliga, Z., Bondoc, S., Starke, C., Terry, M., Jacobson, C. A., Wrijil, L., Ducat, S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.005 · Cited by 215 · see citing works
Hoang, T. N., Pino, M., Boddapati, A. K., Viox, E. G., Starke, C. E., Upadhyay, A. A., Gumber, S., Nekorchuk, M., Busman-Sahay, K., Strongin, Z., et al. (2021) · Cell · doi:10.1016/j.cell.2020.11.007 · Cited by 212 · see citing works
Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets
Singh, D. K., Singh, B., Ganatra, S. R., Gazi, M., Cole, J., Thippeshappa, R., Alfson, K. J., Clemmons, E., Gonzalez, O., Escobedo, R., et al. (2020) · Nature Microbiology · doi:10.1038/s41564-020-00841-4 · Cited by 209 · see citing works
Measuring immunity to SARS-CoV-2 infection: comparing assays and animal models
Khoury, D. S., Wheatley, A. K., Ramuta, M. D., Reynaldi, A., Cromer, D., Subbarao, K., O’Connor, D. H., Kent, S. J., & Davenport, M. P. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-00471-1 · Cited by 115 · see citing works
Approaches and Challenges in SARS-CoV-2 Vaccine Development
Dagotto, G., Yu, J., & Barouch, D. H. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.08.002 · Cited by 103 · see citing works
Corbett, K. S., Nason, M. C., Flach, B., Gagne, M., O’ Connell, S., Johnston, T. S., Shah, S. N., Edara, V. V., Floyd, K., Lai, L., et al. (2021) · doi:10.1101/2021.04.20.440647 · Cited by 43 · see citing works
- Authors
- Munster, V. J., Feldmann, F., Williamson, B. N., van Doremalen, N., Pérez-Pérez, L., Schulz, J., Meade-White, K., Okumura, A., Callison, J., Brumbaugh, B., Avanzato, V. A., Rosenke, R., Hanley, P. W., Saturday, G., Scott, D., Fischer, E. R., & de Wit, E.
- Affiliations
- National Institute of Allergy and Infectious Diseases (US)
- ORCID
- Venue
- Nature
- Published
- 2020-05-12
- Volume
- 585
- Issue
- 7824
- Pages
- 268-272
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7486227
- OpenAlex
- W3025271273
- Cited by
- 720
- References
- 35
- Citations by year
- 2026: 13 · 2025: 28 · 2024: 41 · 2023: 61 · 2022: 127 · 2021: 253 · 2020: 197
- FWCI
- 20.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, public-domain)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- PubMed Central (submittedVersion, public-domain)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Vaccine Research Center
- National Institutes of Health (Z99 AI999999)
- Centers for Disease Control and Prevention
- National Institute of General Medical Sciences (T32GM008169)
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, rhesus monkeys, animal models, respiratory diseases, viral pathogenesis, pulmonary infiltrates, viral shedding, bronchoalveolar lavage, nasal and throat swabs
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Animals, Body Fluids, Cough, Disease Models, Animal, Female, Fever, Lung, Macaca mulatta, Male, Pneumonia, Viral, Radiography, Respiration Disorders, Time Factors, Coronavirus Infections, Bronchoalveolar Lavage, Viral Load, Pandemics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
