Role of S protein in thromboembolic complications during COVID19 and activated protein C as a serious therapeutic avenue in severe forms of patients
Article Main
Abstract
COVID-19 (Coronavirus disease 2019) is a public health emergency of international concern. There is a pressing urgency to find treatments based upon currently available scientific knowledge and epidemiological data. In this article, we provide a novel hypothesis describing how the severity of the pathology is mainly resulting from the Antibody responses to SARS-CoV-2 (virus causing COVID-19) and not due to the direct action of the virus. SARS-CoV-2 appears to alter the endothelial cell. The pathophysiological mechanism is not yet elucidated. The damage caused resembles a systemic, multi-organ vasculitis predominantly in the lungs. An increase in thromboembolic complications has been observed in COVID-19 patients. These are manifested by pulmonary embolisms or systemic microembolism manifested by microangiopathy affecting the lungs, brain, liver, kidneys and intestines. Therefore, we hypothesize that an auto-immune acquired Protein S (PS) deficiency may be involved in the pathogenesis of thrombotic events in Covid-19. Auto-antibodies to Protein S may form immune complexes, inducing increased clearance of PS or interfering with the protein C-protein S system. COVID-19 early thromboprophylaxis in infected patients, or even effective anticoagulation, could prevent the progression to severe forms, thus reducing mortality in patients with COVID-19. Activated Protein C (APC), a physiological coagulation inhibitor with cytoprotective properties, could be an interesting avenue for the treatment of severe forms of the disease in intensive care; its administration in hypoxic patients could improve tissue oxygenation. Randomized resuscitation studies in patients with COVID19 are also needed to confirm our hypothesis.
Article Details
Article Details
Activated protein C, Anticoagulation, COVID19, Protein S deficiency, Thromboembolic
Corti, D., Lanzavecchia, A. (2013). Broadly neutralizing antiviral. Annual Review of Immunology, 31: 705-742.
Delmas B, Laude H, (1990). Assembly of coronavirus spike protein into trimers and its role in epitope expression. Journal of Virology, 64 (11): 5367-5375.
Drosten C, Günther S, Preiser W, Van der Werf S, Brodt H, Becker S, Rabenau H, Panning M, Kolesnikova L, Fouchier R, Berger A, Burguière A, Cinatl J, Eickmann M, Escriou N, Grywna K, Kramme S, Manuguerra JC, Müller S, Rickerts V, Stürmer M, Vieth S, Klenk HD, Osterhaus A, Schmitz H, Doerr HW, (2003). Identification of a novel Coronavirus in patients with severe acute respiratory syndrome. The New England Journal of Medicine, 348: 1967-1976.
Godet M, Grosclaude J, Delmas B, Laude H, (1994). Major receptor-binding and neutralization determinants are located within the same domain of the transmissible gastroenteritis virus (coronavirus) spike protein. Journal of Virology, 68(12): 8008-8016.
Gramberg T, Hofmann H, Möller P, Lalor PF, Marzi A, Geier M, Krumbiegel M, Winkler T, Kirchhoff F, Adams DH, Becker S, Münch J, Pöhlmann S, (2005). LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus. Virology, 340(2): 224-236.
Hofmann H, Pöhlmann S, (2004). Cellular entry of the SARS coronavirus. Trends in Microbiology, 12 (10): 466-472.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens T S, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S, ( 2020). SARS-CoV-2 Cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 181:271-280
Hulswit RJ, de Haan CA, Bosch BJ (2016). Chapter Two - Coronavirus spike protein and tropism changes. Advances in Virus Research, 96: 29-57.
Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, Tong S, Urbani C, Comer JA, Lim W, Rollin PE, Dowell SF, Ling AE, Humphrey CD, Shieh WJ, Guarner J, Paddock CD, Rota P, Fields B, DeRisi J, Yang JY, Cox N, Hughes JM, LeDuc JW, Bellini WJ, Anderson LJ; SARS Working Group (2003). A novel Coronavirus associated with severe acute respiratory syndrome. The New England Journal of Medicine, 348: 1953-1966
Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, Nicholls J, Yee WK, Yan WW, Cheung MT, Cheng VC, Chan KH, Tsang DN, Yung RW, Ng TK, Yuen KY; SARS study group (2003). Coronavirus as a possible cause of severe acute respiratory syndrome. The Lancet, 361: 1319-1325.
Rashid Khan,1 Ajaz Yasmeen,1 Anoop Kumar Pandey,2 Khalid Al Saffar,3 and Sunil Roy Narayanan, (2019). Cerebral Venous Thrombosis and Acute Pulmonary Embolism following Varicella Infection. European Journal of Case Reports in Internal Medecine. 6(10):001171.
Sean Wei Xiang Ong, Yian Kim Tan, Po Ying Chiaal, (2020). Air, Surface Environmental, and personal protective equipment contamination by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) from a symptomatic patient. JAMA, 3227.
Takase-Yoden S, Kikuchi T, Siddell SG, Taguchi F. (1991). Localization of major neutralizing epitopes on the S1 polypeptide of the murine coronavirus peplomer glycoprotein. Virus, 18 (2-3): 99-107.
Van de Poel RH, Meijers JC, Bouma BN, (1999). Interaction between protein S and complement C4b-binding protein (C4BP). Affinity studies using chimeras containing c4bp beta-chain short consensus repeats. J Biol Chem. 274(21):15144-50.
Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. (2020). Structure, function, and antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell, 181: 281-292.
Yang Yang, Yao Deng, Bo Wen, Huijuan Wang, Xin Meng, Jiaming Lan, George F. Gao, Wenjie Tan, (2014). The amino acids 736–761 of the MERS-CoV spike protein induce neutralizing antibodies: Implications for the development of vaccines and antiviral Agents. Viral Immunology, 27 (10): 543-550.
Zhiliang Cao, Lifeng Liu, Lanying Du, Chao Zhang, Shibo Jiang, Taisheng Li, YuxianHe, (2010). Potent and persistent antibody responses against the receptor-binding domain of SARS-CoV spike protein in recovered patients. Virology Journal, 7(1): 299.
Zhao J, Yuan Q, Wang H, Liu W2, Liao X, Su Y, Wang X, Yuan J, Li T, Li J, Qian S1, Hong C, Wang F, Liu Y, Wang Z, He Q, Li Z, He B, Zhang T, Fu Y, Ge S, Liu L, Zhang J, Xia N, Zhang Z, (2020). Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019. Clinical infectious diseases, ciaa344.
This work is licensed under Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) © Author (s)
