A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19?

Pulmonary Therapy - 2020
Natella Maglakelidze1, Kristen Manto1, Timothy J. Craig2
1Penn State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA
2Department of Medicine and Pediatrics, Penn State University, 500 University Drive, Hershey, PA, 17033, USA

Tóm tắt

Abstract Introduction COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. Methods We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. Results Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. Summary Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.

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Tài liệu tham khảo

Li G, et al. Coronavirus infections and immune responses. J Med Virol. 2020;92:424–32. https://doi.org/10.1002/jmv.25685.

Gralinski LE, et al. Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. mBio. 2018. https://doi.org/10.1128/mBio.01753-18.

Janeway CA Jr, Travers P, Walport M, Shlomchik MJ. Immunobiology: the immune system in health and disease. New York: Garland Science; 2001.

Human Coronavirus Types. Centers for disease control and prevention. 2020. https://www.cdc.gov/coronavirus/types.html.

Ip WK, et al. Mannose-binding lectin in severe acute respiratory syndrome coronavirus infection. J Infect Dis. 2005;191:1697–704. https://doi.org/10.1086/429631.

Yuan FF, et al. Influence of FcgammaRIIA and MBL polymorphisms on severe acute respiratory syndrome. Tissue Antigens. 2005;66:291–6. https://doi.org/10.1111/j.1399-0039.2005.00476.x.

Leth-Larsen R, Zhong F, Chow VT, Holmskov U, Lu J. The SARS coronavirus spike glycoprotein is selectively recognized by lung surfactant protein D and activates macrophages. Immunobiology. 2007;212:201–11. https://doi.org/10.1016/j.imbio.2006.12.001.

Jiang Y, et al. Blockade of the C5a–C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV. Emerg Microbes Infect. 2018;7:77. https://doi.org/10.1038/s41426-018-0063-8.

Jiang Y, et al. Complement receptor C5aR1 inhibition reduces pyroptosis in hDPP4-transgenic mice infected with MERS-CoV. Viruses. 2019. https://doi.org/10.3390/v11010039.

Stoermer KA, Morrison TE. Complement and viral pathogenesis. Virology. 2011;411:362–73. https://doi.org/10.1016/j.virol.2010.12.045.

Campbell CM, Kahwash R. Will complement inhibition be the new target in treating COVID-19 related systemic thrombosis? Circulation. 2020. https://doi.org/10.1161/CIRCULATIONAHA.120.047419.

Aronson JK. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers in COVID-19. CEBM. 2020. www.cebm.net/covid-19/angiotensin-converting-enzyme-ace-inhibitors-and-angiotensin-receptor-blockers-in-covid-19/.

Li W, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450–4.

Milewska A, et al. Kallikrein 13: a new player in coronaviral infections. bioRxiv. 2020. https://doi.org/10.1101/2020.03.01.971499.

van de Veerdonk F, et al. Kinins and cytokines in COVID-19: a comprehensive pathophysiological approach. 2020. https://doi.org/10.20944/preprints202004.0023.v1.

Munster VJ, et al. A novel coronavirus emerging in China—key questions for impact assessment. N Engl J Med. 2020;382:692–4. https://doi.org/10.1056/NEJMp2000929.

Rajgor DD, et al. The many estimates of the COVID-19 case fatality rate. Lancet Infect Dis. 2020. https://doi.org/10.1016/S1473-3099(20)30244-9.

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