The Kinetics of SARS-CoV-2 Antibody Development Is Associated with Clearance of RNAemia
ABSTRACT Persistent SARS-CoV-2 replication and systemic dissemination are linked to increased COVID-19 disease severity and mortality. However, the precise immune profiles that track with enhanced viral clearance, particularly from systemic RNAemia, remain incompletely defined. To define whether ant...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2022-08-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.01577-22 |
| _version_ | 1828342431465078784 |
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| author | Chuangqi Wang Yijia Li Paulina Kaplonek Matteo Gentili Stephanie Fischinger Kathryn A. Bowman Moshe Sade-Feldman Kyle R. Kays James Regan James P. Flynn Marcia B. Goldberg Nir Hacohen Michael R. Filbin Douglas A. Lauffenburger Galit Alter Jonathan Z. Li |
| author_facet | Chuangqi Wang Yijia Li Paulina Kaplonek Matteo Gentili Stephanie Fischinger Kathryn A. Bowman Moshe Sade-Feldman Kyle R. Kays James Regan James P. Flynn Marcia B. Goldberg Nir Hacohen Michael R. Filbin Douglas A. Lauffenburger Galit Alter Jonathan Z. Li |
| author_sort | Chuangqi Wang |
| collection | DOAJ |
| description | ABSTRACT Persistent SARS-CoV-2 replication and systemic dissemination are linked to increased COVID-19 disease severity and mortality. However, the precise immune profiles that track with enhanced viral clearance, particularly from systemic RNAemia, remain incompletely defined. To define whether antibody characteristics, specificities, or functions that emerge during natural infection are linked to accelerated containment of viral replication, we examined the relationship of SARS-CoV-2-specific humoral immune evolution in the setting of SARS-CoV-2 plasma RNAemia, which is tightly associated with disease severity and death. On presentation to the emergency department, S-specific IgG3, IgA1, and Fc-γ-receptor (Fcγ R) binding antibodies were all inversely associated with higher baseline plasma RNAemia. Importantly, the rapid development of spike (S) and its subunit (S1/S2/receptor binding domain)-specific IgG, especially FcγR binding activity, were associated with clearance of RNAemia. These results point to a potentially critical and direct role for SARS-CoV-2-specific humoral immune clearance on viral dissemination, persistence, and disease outcome, providing novel insights for the development of more effective therapeutics to resolve COVID-19. IMPORTANCE We showed that persistent SARS-CoV-2 RNAemia is an independent predictor of severe COVID-19. We observed that SARS-CoV-2-targeted antibody maturation, specifically Fc-effector functions rather than neutralization, was strongly linked with the ability to rapidly clear viremia. This highlights the critical role of key humoral features in preventing viral dissemination or accelerating viremia clearance and provides insights for the design of next-generation monoclonal therapeutics. The main key points will be that (i) persistent SARS-CoV-2 plasma RNAemia independently predicts severe COVID-19 and (ii) specific humoral immune functions play a critical role in halting viral dissemination and controlling COVID-19 disease progression. |
| first_indexed | 2024-04-13T23:28:48Z |
| format | Article |
| id | doaj.art-4fedcf9b53004f06aeb4f5c246c1eec3 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-13T23:28:48Z |
| publishDate | 2022-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-4fedcf9b53004f06aeb4f5c246c1eec32022-12-22T02:24:58ZengAmerican Society for MicrobiologymBio2150-75112022-08-0113410.1128/mbio.01577-22The Kinetics of SARS-CoV-2 Antibody Development Is Associated with Clearance of RNAemiaChuangqi Wang0Yijia Li1Paulina Kaplonek2Matteo Gentili3Stephanie Fischinger4Kathryn A. Bowman5Moshe Sade-Feldman6Kyle R. Kays7James Regan8James P. Flynn9Marcia B. Goldberg10Nir Hacohen11Michael R. Filbin12Douglas A. Lauffenburger13Galit Alter14Jonathan Z. Li15Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USABrigham and Women’s Hospital, Boston, Massachusetts, USARagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USABroad Institute of MIT and Harvard, Cambridge, Massachusetts, USARagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USABrigham and Women’s Hospital, Boston, Massachusetts, USABroad Institute of MIT and Harvard, Cambridge, Massachusetts, USAMassachusetts General Hospital, Boston, Massachusetts, USABrigham and Women’s Hospital, Boston, Massachusetts, USABrigham and Women’s Hospital, Boston, Massachusetts, USAMassachusetts General Hospital, Boston, Massachusetts, USABroad Institute of MIT and Harvard, Cambridge, Massachusetts, USABrigham and Women’s Hospital, Boston, Massachusetts, USADepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USAMassachusetts General Hospital, Boston, Massachusetts, USABrigham and Women’s Hospital, Boston, Massachusetts, USAABSTRACT Persistent SARS-CoV-2 replication and systemic dissemination are linked to increased COVID-19 disease severity and mortality. However, the precise immune profiles that track with enhanced viral clearance, particularly from systemic RNAemia, remain incompletely defined. To define whether antibody characteristics, specificities, or functions that emerge during natural infection are linked to accelerated containment of viral replication, we examined the relationship of SARS-CoV-2-specific humoral immune evolution in the setting of SARS-CoV-2 plasma RNAemia, which is tightly associated with disease severity and death. On presentation to the emergency department, S-specific IgG3, IgA1, and Fc-γ-receptor (Fcγ R) binding antibodies were all inversely associated with higher baseline plasma RNAemia. Importantly, the rapid development of spike (S) and its subunit (S1/S2/receptor binding domain)-specific IgG, especially FcγR binding activity, were associated with clearance of RNAemia. These results point to a potentially critical and direct role for SARS-CoV-2-specific humoral immune clearance on viral dissemination, persistence, and disease outcome, providing novel insights for the development of more effective therapeutics to resolve COVID-19. IMPORTANCE We showed that persistent SARS-CoV-2 RNAemia is an independent predictor of severe COVID-19. We observed that SARS-CoV-2-targeted antibody maturation, specifically Fc-effector functions rather than neutralization, was strongly linked with the ability to rapidly clear viremia. This highlights the critical role of key humoral features in preventing viral dissemination or accelerating viremia clearance and provides insights for the design of next-generation monoclonal therapeutics. The main key points will be that (i) persistent SARS-CoV-2 plasma RNAemia independently predicts severe COVID-19 and (ii) specific humoral immune functions play a critical role in halting viral dissemination and controlling COVID-19 disease progression.https://journals.asm.org/doi/10.1128/mbio.01577-22longitudinal data modelingpersistent SARS-CoV-2 plasma viremiasystem serologyviremiahumoral immune response |
| spellingShingle | Chuangqi Wang Yijia Li Paulina Kaplonek Matteo Gentili Stephanie Fischinger Kathryn A. Bowman Moshe Sade-Feldman Kyle R. Kays James Regan James P. Flynn Marcia B. Goldberg Nir Hacohen Michael R. Filbin Douglas A. Lauffenburger Galit Alter Jonathan Z. Li The Kinetics of SARS-CoV-2 Antibody Development Is Associated with Clearance of RNAemia mBio longitudinal data modeling persistent SARS-CoV-2 plasma viremia system serology viremia humoral immune response |
| title | The Kinetics of SARS-CoV-2 Antibody Development Is Associated with Clearance of RNAemia |
| title_full | The Kinetics of SARS-CoV-2 Antibody Development Is Associated with Clearance of RNAemia |
| title_fullStr | The Kinetics of SARS-CoV-2 Antibody Development Is Associated with Clearance of RNAemia |
| title_full_unstemmed | The Kinetics of SARS-CoV-2 Antibody Development Is Associated with Clearance of RNAemia |
| title_short | The Kinetics of SARS-CoV-2 Antibody Development Is Associated with Clearance of RNAemia |
| title_sort | kinetics of sars cov 2 antibody development is associated with clearance of rnaemia |
| topic | longitudinal data modeling persistent SARS-CoV-2 plasma viremia system serology viremia humoral immune response |
| url | https://journals.asm.org/doi/10.1128/mbio.01577-22 |
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