Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation
Abstract SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after s...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46673-2 |
| _version_ | 1827315937930379264 |
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| author | Farina Karim Catherine Riou Mallory Bernstein Zesuliwe Jule Gila Lustig Strauss van Graan Roanne S. Keeton Janine-Lee Upton Yashica Ganga Khadija Khan Kajal Reedoy Matilda Mazibuko Katya Govender Kershnee Thambu Nokuthula Ngcobo Elizabeth Venter Zanele Makhado Willem Hanekom Anne von Gottberg Monjurul Hoque Quarraisha Abdool Karim Salim S. Abdool Karim Nithendra Manickchund Nombulelo Magula Bernadett I. Gosnell Richard J. Lessells Penny L. Moore Wendy A. Burgers Tulio de Oliveira Mahomed-Yunus S. Moosa Alex Sigal |
| author_facet | Farina Karim Catherine Riou Mallory Bernstein Zesuliwe Jule Gila Lustig Strauss van Graan Roanne S. Keeton Janine-Lee Upton Yashica Ganga Khadija Khan Kajal Reedoy Matilda Mazibuko Katya Govender Kershnee Thambu Nokuthula Ngcobo Elizabeth Venter Zanele Makhado Willem Hanekom Anne von Gottberg Monjurul Hoque Quarraisha Abdool Karim Salim S. Abdool Karim Nithendra Manickchund Nombulelo Magula Bernadett I. Gosnell Richard J. Lessells Penny L. Moore Wendy A. Burgers Tulio de Oliveira Mahomed-Yunus S. Moosa Alex Sigal |
| author_sort | Farina Karim |
| collection | DOAJ |
| description | Abstract SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants. |
| first_indexed | 2024-04-24T23:05:21Z |
| format | Article |
| id | doaj.art-cf97d17abeb74e59ba27f92ef737342a |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T23:05:21Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-cf97d17abeb74e59ba27f92ef737342a2024-03-17T12:32:22ZengNature PortfolioNature Communications2041-17232024-03-0115111610.1038/s41467-024-46673-2Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiationFarina Karim0Catherine Riou1Mallory Bernstein2Zesuliwe Jule3Gila Lustig4Strauss van Graan5Roanne S. Keeton6Janine-Lee Upton7Yashica Ganga8Khadija Khan9Kajal Reedoy10Matilda Mazibuko11Katya Govender12Kershnee Thambu13Nokuthula Ngcobo14Elizabeth Venter15Zanele Makhado16Willem Hanekom17Anne von Gottberg18Monjurul Hoque19Quarraisha Abdool Karim20Salim S. Abdool Karim21Nithendra Manickchund22Nombulelo Magula23Bernadett I. Gosnell24Richard J. Lessells25Penny L. Moore26Wendy A. Burgers27Tulio de Oliveira28Mahomed-Yunus S. Moosa29Alex Sigal30Africa Health Research InstituteInstitute of Infectious Disease and Molecular Medicine, Division of Medical Virology, Department of Pathology, University of Cape TownAfrica Health Research InstituteAfrica Health Research InstituteCentre for the AIDS Programme of Research in South AfricaSAMRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the WitwatersrandInstitute of Infectious Disease and Molecular Medicine, Division of Medical Virology, Department of Pathology, University of Cape TownAfrica Health Research InstituteAfrica Health Research InstituteAfrica Health Research InstituteAfrica Health Research InstituteAfrica Health Research InstituteAfrica Health Research InstituteAfrica Health Research InstituteAfrica Health Research InstituteSAMRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the WitwatersrandSAMRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the WitwatersrandAfrica Health Research InstituteCentre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, a division of the National Health Laboratory ServiceKwaDabeka Community Health CentreCentre for the AIDS Programme of Research in South AfricaCentre for the AIDS Programme of Research in South AfricaDepartment of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, University of KwaZulu-NatalDepartment of Internal Medicine, Nelson R. Mandela School of Medicine, University of Kwa-Zulu NatalDepartment of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, University of KwaZulu-NatalCentre for the AIDS Programme of Research in South AfricaSAMRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the WitwatersrandInstitute of Infectious Disease and Molecular Medicine, Division of Medical Virology, Department of Pathology, University of Cape TownCentre for the AIDS Programme of Research in South AfricaDepartment of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, University of KwaZulu-NatalAfrica Health Research InstituteAbstract SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants.https://doi.org/10.1038/s41467-024-46673-2 |
| spellingShingle | Farina Karim Catherine Riou Mallory Bernstein Zesuliwe Jule Gila Lustig Strauss van Graan Roanne S. Keeton Janine-Lee Upton Yashica Ganga Khadija Khan Kajal Reedoy Matilda Mazibuko Katya Govender Kershnee Thambu Nokuthula Ngcobo Elizabeth Venter Zanele Makhado Willem Hanekom Anne von Gottberg Monjurul Hoque Quarraisha Abdool Karim Salim S. Abdool Karim Nithendra Manickchund Nombulelo Magula Bernadett I. Gosnell Richard J. Lessells Penny L. Moore Wendy A. Burgers Tulio de Oliveira Mahomed-Yunus S. Moosa Alex Sigal Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation Nature Communications |
| title | Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation |
| title_full | Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation |
| title_fullStr | Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation |
| title_full_unstemmed | Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation |
| title_short | Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation |
| title_sort | clearance of persistent sars cov 2 associates with increased neutralizing antibodies in advanced hiv disease post art initiation |
| url | https://doi.org/10.1038/s41467-024-46673-2 |
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