Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets

Dhiraj Kumar Singh; Bindu Singh; Shashank R. Ganatra; Michal Gazi; Journey Cole; Rajesh Thippeshappa; Kendra J. Alfson; Elizabeth Clemmons; Olga Gonzalez; Ruby Escobedo; Tae Hyung Lee; Ayan Chatterjee; Yenny Goez-Gazi; Riti Sharan; Maya Gough; Cynthia Alvarez; Alyssa Blakley; Justin Ferdin; Carmen Bartley; Hilary Staples; Laura Parodi; Jessica Callery; Amanda Mannino; Benjamin Klaffke; Priscilla Escareno; Roy N. Platt; Vida Hodara; Julia Scordo; Shalini Gautam; Andreu G. Vilanova; Angelica Olmo-Fontanez; Alyssa Schami; Adelekan Oyejide; Dharani K. Ajithdoss; Richard Copin; Alina Baum; Christos Kyratsous; Xavier Alvarez; Mushtaq Ahmed; Bruce Rosa; Anna Goodroe; John Dutton; Shannan Hall-Ursone; Patrice A. Frost; Andra K. Voges; Corinna N. Ross; Ken Sayers; Christopher Chen; Cory Hallam; Shabaana A. Khader; Makedonka Mitreva; Timothy J.C. Anderson; Luis Martinez-Sobrido; Jean L. Patterson; Joanne Turner; Jordi B. Torrelles; Edward J. Dick; Kathleen Brasky; Larry S. Schlesinger; Luis D. Giavedoni; Ricardo Carrion; Deepak Kaushal

doi:10.1038/s41564-020-00841-4

Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets

Dhiraj Kumar Singh, Bindu Singh, Shashank R. Ganatra, Michal Gazi, Journey Cole, Rajesh Thippeshappa, Kendra J. Alfson, Elizabeth Clemmons, Olga Gonzalez, Ruby Escobedo, Tae Hyung Lee, Ayan Chatterjee, Yenny Goez-Gazi, Riti Sharan, Maya Gough, Cynthia Alvarez, Alyssa Blakley, Justin Ferdin, Carmen Bartley, Hilary StaplesLaura Parodi, Jessica Callery, Amanda Mannino, Benjamin Klaffke, Priscilla Escareno, Roy N. Platt, Vida Hodara, Julia Scordo, Shalini Gautam, Andreu G. Vilanova, Angelica Olmo-Fontanez, Alyssa Schami, Adelekan Oyejide, Dharani K. Ajithdoss, Richard Copin, Alina Baum, Christos Kyratsous, Xavier Alvarez, Mushtaq Ahmed, Bruce Rosa, Anna Goodroe, John Dutton, Shannan Hall-Ursone, Patrice A. Frost, Andra K. Voges, Corinna N. Ross, Ken Sayers, Christopher Chen, Cory Hallam, Shabaana A. Khader, Makedonka Mitreva, Timothy J.C. Anderson, Luis Martinez-Sobrido, Jean L. Patterson, Joanne Turner, Jordi B. Torrelles, Edward J. Dick, Kathleen Brasky, Larry S. Schlesinger, Luis D. Giavedoni, Ricardo Carrion, Deepak Kaushal

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Abstract

Non-human primate models will expedite therapeutics and vaccines for coronavirus disease 2019 (COVID-19) to clinical trials. Here, we compare acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old rhesus macaques, baboons and old marmosets. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies, and both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage was increased in old versus young baboons. Using techniques including computed tomography imaging, immunophenotyping, and alveolar/peripheral cytokine response and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent type-I interferon response. Macaques developed T-cell memory phenotypes/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young macaques. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.

Original language	English
Pages (from-to)	73-86
Number of pages	14
Journal	Nature microbiology
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s41564-020-00841-4
State	Published - Jan 2021

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Singh, D. K., Singh, B., Ganatra, S. R., Gazi, M., Cole, J., Thippeshappa, R., Alfson, K. J., Clemmons, E., Gonzalez, O., Escobedo, R., Lee, T. H., Chatterjee, A., Goez-Gazi, Y., Sharan, R., Gough, M., Alvarez, C., Blakley, A., Ferdin, J., Bartley, C., ... Kaushal, D. (2021). Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets. Nature microbiology, 6(1), 73-86. https://doi.org/10.1038/s41564-020-00841-4

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title = "Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets",

abstract = "Non-human primate models will expedite therapeutics and vaccines for coronavirus disease 2019 (COVID-19) to clinical trials. Here, we compare acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old rhesus macaques, baboons and old marmosets. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies, and both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage was increased in old versus young baboons. Using techniques including computed tomography imaging, immunophenotyping, and alveolar/peripheral cytokine response and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent type-I interferon response. Macaques developed T-cell memory phenotypes/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young macaques. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.",

author = "Singh, {Dhiraj Kumar} and Bindu Singh and Ganatra, {Shashank R.} and Michal Gazi and Journey Cole and Rajesh Thippeshappa and Alfson, {Kendra J.} and Elizabeth Clemmons and Olga Gonzalez and Ruby Escobedo and Lee, {Tae Hyung} and Ayan Chatterjee and Yenny Goez-Gazi and Riti Sharan and Maya Gough and Cynthia Alvarez and Alyssa Blakley and Justin Ferdin and Carmen Bartley and Hilary Staples and Laura Parodi and Jessica Callery and Amanda Mannino and Benjamin Klaffke and Priscilla Escareno and Platt, {Roy N.} and Vida Hodara and Julia Scordo and Shalini Gautam and Vilanova, {Andreu G.} and Angelica Olmo-Fontanez and Alyssa Schami and Adelekan Oyejide and Ajithdoss, {Dharani K.} and Richard Copin and Alina Baum and Christos Kyratsous and Xavier Alvarez and Mushtaq Ahmed and Bruce Rosa and Anna Goodroe and John Dutton and Shannan Hall-Ursone and Frost, {Patrice A.} and Voges, {Andra K.} and Ross, {Corinna N.} and Ken Sayers and Christopher Chen and Cory Hallam and Khader, {Shabaana A.} and Makedonka Mitreva and Anderson, {Timothy J.C.} and Luis Martinez-Sobrido and Patterson, {Jean L.} and Joanne Turner and Torrelles, {Jordi B.} and Dick, {Edward J.} and Kathleen Brasky and Schlesinger, {Larry S.} and Giavedoni, {Luis D.} and Ricardo Carrion and Deepak Kaushal",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = jan,

doi = "10.1038/s41564-020-00841-4",

language = "English",

volume = "6",

pages = "73--86",

journal = "Nature microbiology",

issn = "2058-5276",

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Singh, DK, Singh, B, Ganatra, SR, Gazi, M, Cole, J, Thippeshappa, R, Alfson, KJ, Clemmons, E, Gonzalez, O, Escobedo, R, Lee, TH, Chatterjee, A, Goez-Gazi, Y, Sharan, R, Gough, M, Alvarez, C, Blakley, A, Ferdin, J, Bartley, C, Staples, H, Parodi, L, Callery, J, Mannino, A, Klaffke, B, Escareno, P, Platt, RN, Hodara, V, Scordo, J, Gautam, S, Vilanova, AG, Olmo-Fontanez, A, Schami, A, Oyejide, A, Ajithdoss, DK, Copin, R, Baum, A, Kyratsous, C, Alvarez, X, Ahmed, M, Rosa, B, Goodroe, A, Dutton, J, Hall-Ursone, S, Frost, PA, Voges, AK, Ross, CN, Sayers, K, Chen, C, Hallam, C, Khader, SA, Mitreva, M, Anderson, TJC, Martinez-Sobrido, L, Patterson, JL, Turner, J, Torrelles, JB, Dick, EJ, Brasky, K, Schlesinger, LS, Giavedoni, LD, Carrion, R & Kaushal, D 2021, 'Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets', Nature microbiology, vol. 6, no. 1, pp. 73-86. https://doi.org/10.1038/s41564-020-00841-4

TY - JOUR

T1 - Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets

AU - Singh, Dhiraj Kumar

AU - Singh, Bindu

AU - Ganatra, Shashank R.

AU - Gazi, Michal

AU - Cole, Journey

AU - Thippeshappa, Rajesh

AU - Alfson, Kendra J.

AU - Clemmons, Elizabeth

AU - Gonzalez, Olga

AU - Escobedo, Ruby

AU - Lee, Tae Hyung

AU - Chatterjee, Ayan

AU - Goez-Gazi, Yenny

AU - Sharan, Riti

AU - Gough, Maya

AU - Alvarez, Cynthia

AU - Blakley, Alyssa

AU - Ferdin, Justin

AU - Bartley, Carmen

AU - Staples, Hilary

AU - Parodi, Laura

AU - Callery, Jessica

AU - Mannino, Amanda

AU - Klaffke, Benjamin

AU - Escareno, Priscilla

AU - Platt, Roy N.

AU - Hodara, Vida

AU - Scordo, Julia

AU - Gautam, Shalini

AU - Vilanova, Andreu G.

AU - Olmo-Fontanez, Angelica

AU - Schami, Alyssa

AU - Oyejide, Adelekan

AU - Ajithdoss, Dharani K.

AU - Copin, Richard

AU - Baum, Alina

AU - Kyratsous, Christos

AU - Alvarez, Xavier

AU - Ahmed, Mushtaq

AU - Rosa, Bruce

AU - Goodroe, Anna

AU - Dutton, John

AU - Hall-Ursone, Shannan

AU - Frost, Patrice A.

AU - Voges, Andra K.

AU - Ross, Corinna N.

AU - Sayers, Ken

AU - Chen, Christopher

AU - Hallam, Cory

AU - Khader, Shabaana A.

AU - Mitreva, Makedonka

AU - Anderson, Timothy J.C.

AU - Martinez-Sobrido, Luis

AU - Patterson, Jean L.

AU - Turner, Joanne

AU - Torrelles, Jordi B.

AU - Dick, Edward J.

AU - Brasky, Kathleen

AU - Schlesinger, Larry S.

AU - Giavedoni, Luis D.

AU - Carrion, Ricardo

AU - Kaushal, Deepak

PY - 2021/1

Y1 - 2021/1

N2 - Non-human primate models will expedite therapeutics and vaccines for coronavirus disease 2019 (COVID-19) to clinical trials. Here, we compare acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old rhesus macaques, baboons and old marmosets. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies, and both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage was increased in old versus young baboons. Using techniques including computed tomography imaging, immunophenotyping, and alveolar/peripheral cytokine response and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent type-I interferon response. Macaques developed T-cell memory phenotypes/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young macaques. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.

AB - Non-human primate models will expedite therapeutics and vaccines for coronavirus disease 2019 (COVID-19) to clinical trials. Here, we compare acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old rhesus macaques, baboons and old marmosets. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies, and both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage was increased in old versus young baboons. Using techniques including computed tomography imaging, immunophenotyping, and alveolar/peripheral cytokine response and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent type-I interferon response. Macaques developed T-cell memory phenotypes/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young macaques. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.

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JO - Nature microbiology

JF - Nature microbiology

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ER -

Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets

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