Kristin A Sauter, Gabriela M Webb, Lindsay Bader, Craig N Kreklywich, Diana L Takahashi, Cicely Zaro, Casey M McGuire, Anne D Lewis, Lois M A Colgin, Melissa A Kirigiti, Hannah Blomenkamp, Cleiton Pessoa, Matthew Humkey, Jesse Hulahan, Madeleine Sleeman, Robert C Zweig, Sarah Thomas, Archana Thomas, Lina Gao, Alec J Hirsch, Maayan Levy, Sara Cherry, Steven E Kahn, Mark K Slifka, Daniel N Streblow, Jonah B Sacha, Paul Kievit, Charles T Roberts
{"title":"肥胖对非人类灵长类动物对SARS-CoV-2感染的急性反应和COVID-19急性后后遗症的影响","authors":"Kristin A Sauter, Gabriela M Webb, Lindsay Bader, Craig N Kreklywich, Diana L Takahashi, Cicely Zaro, Casey M McGuire, Anne D Lewis, Lois M A Colgin, Melissa A Kirigiti, Hannah Blomenkamp, Cleiton Pessoa, Matthew Humkey, Jesse Hulahan, Madeleine Sleeman, Robert C Zweig, Sarah Thomas, Archana Thomas, Lina Gao, Alec J Hirsch, Maayan Levy, Sara Cherry, Steven E Kahn, Mark K Slifka, Daniel N Streblow, Jonah B Sacha, Paul Kievit, Charles T Roberts","doi":"10.1371/journal.ppat.1012988","DOIUrl":null,"url":null,"abstract":"<p><p>Long-term adverse consequences of SARS-CoV-2 infection, termed \"long COVID\" or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection. We utilized a nonhuman primate model to compare the effects of infection with the SARS-CoV-2 delta variant in lean and obese/insulin-resistant adult male rhesus macaques over a 6-month time course. While some longitudinal responses to SARS-CoV-2 infection, including overall viral dynamics, SARS-CoV-2-specific IgG induction, cytokine profiles, and tissue persistence of viral RNA, did not appreciably differ between lean and obese animals, other responses, including neutralizing Ab dynamics, lung pathology, body weight, degree of insulin sensitivity, adipocytokine profiles, body temperature, and nighttime activity levels were significantly different in lean versus obese animals. Furthermore, several parameters in lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. Notably, persistent changes in multiple parameters were present in most animals, suggesting that PASC may be more prevalent than estimated from self-reported symptoms in human studies.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"21 7","pages":"e1012988"},"PeriodicalIF":4.9000,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates.\",\"authors\":\"Kristin A Sauter, Gabriela M Webb, Lindsay Bader, Craig N Kreklywich, Diana L Takahashi, Cicely Zaro, Casey M McGuire, Anne D Lewis, Lois M A Colgin, Melissa A Kirigiti, Hannah Blomenkamp, Cleiton Pessoa, Matthew Humkey, Jesse Hulahan, Madeleine Sleeman, Robert C Zweig, Sarah Thomas, Archana Thomas, Lina Gao, Alec J Hirsch, Maayan Levy, Sara Cherry, Steven E Kahn, Mark K Slifka, Daniel N Streblow, Jonah B Sacha, Paul Kievit, Charles T Roberts\",\"doi\":\"10.1371/journal.ppat.1012988\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Long-term adverse consequences of SARS-CoV-2 infection, termed \\\"long COVID\\\" or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection. We utilized a nonhuman primate model to compare the effects of infection with the SARS-CoV-2 delta variant in lean and obese/insulin-resistant adult male rhesus macaques over a 6-month time course. While some longitudinal responses to SARS-CoV-2 infection, including overall viral dynamics, SARS-CoV-2-specific IgG induction, cytokine profiles, and tissue persistence of viral RNA, did not appreciably differ between lean and obese animals, other responses, including neutralizing Ab dynamics, lung pathology, body weight, degree of insulin sensitivity, adipocytokine profiles, body temperature, and nighttime activity levels were significantly different in lean versus obese animals. Furthermore, several parameters in lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. 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Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates.
Long-term adverse consequences of SARS-CoV-2 infection, termed "long COVID" or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection. We utilized a nonhuman primate model to compare the effects of infection with the SARS-CoV-2 delta variant in lean and obese/insulin-resistant adult male rhesus macaques over a 6-month time course. While some longitudinal responses to SARS-CoV-2 infection, including overall viral dynamics, SARS-CoV-2-specific IgG induction, cytokine profiles, and tissue persistence of viral RNA, did not appreciably differ between lean and obese animals, other responses, including neutralizing Ab dynamics, lung pathology, body weight, degree of insulin sensitivity, adipocytokine profiles, body temperature, and nighttime activity levels were significantly different in lean versus obese animals. Furthermore, several parameters in lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. Notably, persistent changes in multiple parameters were present in most animals, suggesting that PASC may be more prevalent than estimated from self-reported symptoms in human studies.
期刊介绍:
Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.