Marco Maria Santi, Eleonora Genovese, Thor Mertz Schou, Matheus da Silva, Sophie Erhardt, Lilly Schwieler, Jacob Ahlberg Weidenfors, Giorgia Marino, Søren Riis Paludan, Samia Joca, Gregers Wegener, Line Reinert, Cecilie Bay-Richter
{"title":"SARS-CoV-2感染急性后神经精神和认知后遗症——来自K18-hACE C57BL/6 J小鼠的证据","authors":"Marco Maria Santi, Eleonora Genovese, Thor Mertz Schou, Matheus da Silva, Sophie Erhardt, Lilly Schwieler, Jacob Ahlberg Weidenfors, Giorgia Marino, Søren Riis Paludan, Samia Joca, Gregers Wegener, Line Reinert, Cecilie Bay-Richter","doi":"10.1093/ijnp/pyaf072","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Survivors of COVID-19 frequently report psychiatric and cognitive sequelae. The origin of such sequelae has not been determined, as it has been a challenge to resolve whether these symptoms have a viral origin or are related to the contextual stressors associated with the pandemic. In the current study, we used a mouse model of post-acute sequelae of SARS-CoV-2 infection (PASC) to evaluate the neurobiological nature of the sequelae without the interference of the contextual effects on behavior following SARS-CoV-2 infection.</p><p><strong>Results: </strong>SARS-CoV-2 infection resulted in behavioral deficits related to cognition but not anxiety- or depression-like behavior. The cognitive deficits were affected by the severity of the acute disease. Cytokine and chemokine levels as well as kynurenine pathway metabolites were significantly altered in the brains of infected mice. Both cytokine/chemokine levels and kynurenine pathway metabolites correlated with the severity of the acute disease. Microbiome taxonomic profiling revealed significant differences between groups, suggesting that specific bacterial species may be associated with the development of PASC.</p><p><strong>Conclusions: </strong>These results suggest that SARS-CoV-2 infection leads to cognitive deficits in PASC, influenced by the severity of the acute disease. In contrast, PASC anxiety- and depression-like behavior was not related to the viral infection itself. This could indicate that PASC anxiety and depression is more linked to contextual stressors related to the pandemic, rather than the viral infection per se. Additionally, our results points to a role of cytokines and in particular metabolites of the kynurenine pathway in PASC, suggesting their potential as biomarkers and targets for pharmacological treatment.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Neuropsychiatric- and cognitive post-acute sequelae of SARS-CoV-2 infection - evidence from K18-hACE C57BL/6 J mice.\",\"authors\":\"Marco Maria Santi, Eleonora Genovese, Thor Mertz Schou, Matheus da Silva, Sophie Erhardt, Lilly Schwieler, Jacob Ahlberg Weidenfors, Giorgia Marino, Søren Riis Paludan, Samia Joca, Gregers Wegener, Line Reinert, Cecilie Bay-Richter\",\"doi\":\"10.1093/ijnp/pyaf072\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Survivors of COVID-19 frequently report psychiatric and cognitive sequelae. The origin of such sequelae has not been determined, as it has been a challenge to resolve whether these symptoms have a viral origin or are related to the contextual stressors associated with the pandemic. In the current study, we used a mouse model of post-acute sequelae of SARS-CoV-2 infection (PASC) to evaluate the neurobiological nature of the sequelae without the interference of the contextual effects on behavior following SARS-CoV-2 infection.</p><p><strong>Results: </strong>SARS-CoV-2 infection resulted in behavioral deficits related to cognition but not anxiety- or depression-like behavior. The cognitive deficits were affected by the severity of the acute disease. Cytokine and chemokine levels as well as kynurenine pathway metabolites were significantly altered in the brains of infected mice. Both cytokine/chemokine levels and kynurenine pathway metabolites correlated with the severity of the acute disease. Microbiome taxonomic profiling revealed significant differences between groups, suggesting that specific bacterial species may be associated with the development of PASC.</p><p><strong>Conclusions: </strong>These results suggest that SARS-CoV-2 infection leads to cognitive deficits in PASC, influenced by the severity of the acute disease. In contrast, PASC anxiety- and depression-like behavior was not related to the viral infection itself. This could indicate that PASC anxiety and depression is more linked to contextual stressors related to the pandemic, rather than the viral infection per se. Additionally, our results points to a role of cytokines and in particular metabolites of the kynurenine pathway in PASC, suggesting their potential as biomarkers and targets for pharmacological treatment.</p>\",\"PeriodicalId\":14134,\"journal\":{\"name\":\"International Journal of Neuropsychopharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Neuropsychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ijnp/pyaf072\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Neuropsychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ijnp/pyaf072","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Neuropsychiatric- and cognitive post-acute sequelae of SARS-CoV-2 infection - evidence from K18-hACE C57BL/6 J mice.
Background: Survivors of COVID-19 frequently report psychiatric and cognitive sequelae. The origin of such sequelae has not been determined, as it has been a challenge to resolve whether these symptoms have a viral origin or are related to the contextual stressors associated with the pandemic. In the current study, we used a mouse model of post-acute sequelae of SARS-CoV-2 infection (PASC) to evaluate the neurobiological nature of the sequelae without the interference of the contextual effects on behavior following SARS-CoV-2 infection.
Results: SARS-CoV-2 infection resulted in behavioral deficits related to cognition but not anxiety- or depression-like behavior. The cognitive deficits were affected by the severity of the acute disease. Cytokine and chemokine levels as well as kynurenine pathway metabolites were significantly altered in the brains of infected mice. Both cytokine/chemokine levels and kynurenine pathway metabolites correlated with the severity of the acute disease. Microbiome taxonomic profiling revealed significant differences between groups, suggesting that specific bacterial species may be associated with the development of PASC.
Conclusions: These results suggest that SARS-CoV-2 infection leads to cognitive deficits in PASC, influenced by the severity of the acute disease. In contrast, PASC anxiety- and depression-like behavior was not related to the viral infection itself. This could indicate that PASC anxiety and depression is more linked to contextual stressors related to the pandemic, rather than the viral infection per se. Additionally, our results points to a role of cytokines and in particular metabolites of the kynurenine pathway in PASC, suggesting their potential as biomarkers and targets for pharmacological treatment.
期刊介绍:
The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.