C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe?
From asymptomatic to severe, SARS-CoV-2, causative agent of COVID-19, elicits varying disease severities. Moreover, understanding innate and adaptive immune responses to SARS-CoV-2 is imperative since variants such as Omicron negatively impact adaptive antibody neutralization. Severe COVID-19 is, in...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Clinical Immunology Communications |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772613422000130 |
| _version_ | 1828348363177721856 |
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| author | Melissa A. Hausburg Jason S. Williams Kaysie L. Banton Charles W. Mains Michael Roshon David Bar-Or |
| author_facet | Melissa A. Hausburg Jason S. Williams Kaysie L. Banton Charles W. Mains Michael Roshon David Bar-Or |
| author_sort | Melissa A. Hausburg |
| collection | DOAJ |
| description | From asymptomatic to severe, SARS-CoV-2, causative agent of COVID-19, elicits varying disease severities. Moreover, understanding innate and adaptive immune responses to SARS-CoV-2 is imperative since variants such as Omicron negatively impact adaptive antibody neutralization. Severe COVID-19 is, in part, associated with aberrant activation of complement and Factor XII (FXIIa), initiator of contact system activation. Paradoxically, a protein that inhibits the three known pathways of complement activation and FXIIa, C1 esterase inhibitor (C1-INH), is increased in COVID-19 patient plasma and is associated with disease severity. Here we review the role of C1-INH in the regulation of innate and adaptive immune responses. Additionally, we contextualize regulation of C1-INH and SERPING1, the gene encoding C1-INH, by other pathogens and SARS viruses and propose that viral proteins bind to C1-INH to inhibit its function in severe COVID-19. Finally, we review the current clinical trials and published results of exogenous C1-INH treatment in COVID-19 patients. |
| first_indexed | 2024-04-14T00:53:53Z |
| format | Article |
| id | doaj.art-b7171331ce51481981fd562c7a611bff |
| institution | Directory Open Access Journal |
| issn | 2772-6134 |
| language | English |
| last_indexed | 2024-04-14T00:53:53Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical Immunology Communications |
| spelling | doaj.art-b7171331ce51481981fd562c7a611bff2022-12-22T02:21:42ZengElsevierClinical Immunology Communications2772-61342022-12-0128390C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe?Melissa A. Hausburg0Jason S. Williams1Kaysie L. Banton2Charles W. Mains3Michael Roshon4David Bar-Or5Department of Trauma Research, Swedish Medical Center, 501 E. Hampden, Englewood, CO 80113, USA; Department of Trauma Research, St. Anthony Hospital, 11600 W 2nd Pl, Lakewood, CO 80228, USA; Department of Trauma Research, Penrose Hospital, 2222 N Nevada Ave, Colorado Springs, CO 80907, USADepartment of Trauma Research, Swedish Medical Center, 501 E. Hampden, Englewood, CO 80113, USA; Department of Trauma Research, St. Anthony Hospital, 11600 W 2nd Pl, Lakewood, CO 80228, USA; Department of Trauma Research, Penrose Hospital, 2222 N Nevada Ave, Colorado Springs, CO 80907, USADepartment of Trauma Research, Swedish Medical Center, 501 E. Hampden, Englewood, CO 80113, USACentura Health Trauma Systems, Centura Health, 9100 E Mineral Circle, Centennial, CO 80112, USACentura Health Trauma Systems, Centura Health, 9100 E Mineral Circle, Centennial, CO 80112, USA; Department of Emergency Services, Penrose Hospital, 2222 N Nevada Ave, Colorado Springs, CO 80907, USADepartment of Trauma Research, Swedish Medical Center, 501 E. Hampden, Englewood, CO 80113, USA; Department of Trauma Research, St. Anthony Hospital, 11600 W 2nd Pl, Lakewood, CO 80228, USA; Department of Trauma Research, Penrose Hospital, 2222 N Nevada Ave, Colorado Springs, CO 80907, USA; Department of Molecular Biology, Rocky Vista University, 8401 S Chambers Rd, Parker, CO 80134, USA; Corresponding author at: 501 E. Hampden Ave, Rm 4-454, Englewood, CO 80113, USA.From asymptomatic to severe, SARS-CoV-2, causative agent of COVID-19, elicits varying disease severities. Moreover, understanding innate and adaptive immune responses to SARS-CoV-2 is imperative since variants such as Omicron negatively impact adaptive antibody neutralization. Severe COVID-19 is, in part, associated with aberrant activation of complement and Factor XII (FXIIa), initiator of contact system activation. Paradoxically, a protein that inhibits the three known pathways of complement activation and FXIIa, C1 esterase inhibitor (C1-INH), is increased in COVID-19 patient plasma and is associated with disease severity. Here we review the role of C1-INH in the regulation of innate and adaptive immune responses. Additionally, we contextualize regulation of C1-INH and SERPING1, the gene encoding C1-INH, by other pathogens and SARS viruses and propose that viral proteins bind to C1-INH to inhibit its function in severe COVID-19. Finally, we review the current clinical trials and published results of exogenous C1-INH treatment in COVID-19 patients.http://www.sciencedirect.com/science/article/pii/S2772613422000130COVID-19C1-INHC1 esterase inhibitorComplementInflammationFXII |
| spellingShingle | Melissa A. Hausburg Jason S. Williams Kaysie L. Banton Charles W. Mains Michael Roshon David Bar-Or C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe? Clinical Immunology Communications COVID-19 C1-INH C1 esterase inhibitor Complement Inflammation FXII |
| title | C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe? |
| title_full | C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe? |
| title_fullStr | C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe? |
| title_full_unstemmed | C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe? |
| title_short | C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe? |
| title_sort | c1 esterase inhibitor mediated immunosuppression in covid 19 friend or foe |
| topic | COVID-19 C1-INH C1 esterase inhibitor Complement Inflammation FXII |
| url | http://www.sciencedirect.com/science/article/pii/S2772613422000130 |
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