Key links in pathogenesis of respiratory failure in COVID-19 and pharmacological correction
DOI:
https://doi.org/10.11603/bmbr.2706-6290.2022.2.13082Keywords:
COVID-19, pathogenesis, lung failure, cytokines, pharmacological correction, antiviral drugs, monoclonal antibodiesAbstract
Summary. COVID-19 pandemic became a game-changer player in the whole world. The severe course of disease manifests with clinical signs of viral pneumonia with an advanced respiratory failure, which can later lead to the development of acute respiratory distress syndrome (ARDS) and fatal consequences. Correct understanding of the key pathophysiological determinants of complications and hypoxemia will contribute to the most rational pharmacotherapy.
The aim of the study – to analyze and systematize data on the pathogenesis of ARDS in coronavirus disease and its pharmacological correction. Understanding the key links will make possible not only to identify certain aspects of the treatment, but also to prevent the development of complications.
Materials and Methods. Publications of foreign and Ukrainian specialists were analyzed, including databases Medscape/PubMed.
Results. An analysis of the key links in the pathogenesis of ARDS, induced by C|OVID-19, the role of the cytokine storm in the progression of the disease and development of arterial hypoxemia and respiratory failure was carried out. An overview of the development and "evolution" of approaches to the treatment of the disease was conducted, starting from attempts to use chloroquine derivatives at the beginning of pandemic to etiotropic treatment with antiviral drugs (such as remdesivir, the combination of lopinavir/ritonavir and paxlovid); biosimilars – monoclonal antibodies and their combinations; prevention and treatment of thrombosis and microthrombosis, which may develop as a result of endothelial dysfunction in such patients, especially in the presence of comorbid pathology (for example, hypertension, diabetes mellitus, obesity). The latest recommendations and American and European protocols for the treatment of coronavirus disease are summarized.
Conclusions. The review of the most popular and available medicines and pharmacotherapy for COVID 19 was performed. It indicates the necessity and rationality of finding new, more efficient and less toxic drugs to fight the infection and its complications.
References
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. jama. 2020;323(13): 1239-42.
Naidoo J, Wang X, Woo KM, Iyriboz T, Halpenny D, Cunningham J, Chaft JE, Segal NH, Callahan MK, Lesokhin AM, Rosenberg J. Pneumonitis in patients treated with anti–programmed death-1/programmed death ligand 1 therapy. Journal of Clinical Oncology. 2017;35(7): 709.
Bernheim A, Mei X, Huang M, Yang Y, Fayad ZA, Zhang N, Diao K, Lin B, Zhu X, Li K, Li S. Chest CT findings in coronavirus disease-19 (COVID-19): relationship to duration of infection. Radiology. 2020: 200463.
Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. COVID-19 does not lead to a “typical” acute respiratory distress syndrome. American journal of respiratory and critical care medicine. 2020;201(10): 1299-300.
Sinha P, Calfee CS. Phenotypes in acute respiratory distress syndrome: moving towards precision medicine. Curr Opin Crit Care. 2019;25(1): 12-20.
Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive care medicine. 2020;46(6): 1099-102.
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8): 727-33.
Cressoni M, Cadringher P, Chiurazzi C, Amini M, Gallazzi E, Marino A, Brioni M, Carlesso E, Chiumello D, Quintel M, Bugedo G. Lung inhomogeneity in patients with acute respiratory distress syndrome. American journal of respiratory and critical care medicine. 2014;189(2): 149-58.
Vaporidi K, Akoumianaki E, Telias I, Goligher EC, Brochard L, Georgopoulos D. Respiratory drive in critically ill patients. Pathophysiology and clinical implications. American journal of respiratory and critical care medicine. 2020;201(1): 20-32.
Wilkerson RG, Adler JD, Shah NG, Brown R. Silent hypoxia: a harbinger of clinical deterioration in patients with COVID-19. Am J Emerg Med. 2020;38(10): 2243-e5.
Dhont S, Derom E, Van Braeckel E, Depuydt P, Lambrecht BN. The pathophysiology of ‘happy’hypoxemia in COVID-19. Respir Res. 2020;21(1): 1-9.
González-Duarte A, Norcliffe-Kaufmann L. Is "happy hypoxia"' in COVID-19 a disorder of autonomic interoception? A hypothesis. Clin Auton Res. 2020;30(4): 331-3.
Pak AI, Shevchuk OO, Palii SM, Selskyi BP, Korda MM. Endothelial dysfunction at COVID-19 (Literature review). Ukr med chasop. 2021;3(143)V/VI: 1-7. Ukrainian.
D'Alonzo GE, Dantzker DR. Respiratory failure, mechanisms of abnormal gas exchange, and oxygen delivery. Med Clin North Am. 1983;67(3): 557-71.
Meng L, Qiu H, Wan L, Ai Y, Xue Z, Guo Q, Deshpande R, Zhang L, Meng J, Tong C, Liu H, Xiong L. Intubation and Ventilation amid the COVID-19 Outbreak: Wuhan's Experience. Anesthesiology. 2020 Jun;132(6):1317-32.
Tobin MJ, Jubran A, Laghi F. Respiratory drive measurements do not signify conjectural patient self-inflicted lung injury. Am J Respir Crit Care Med. 2021;203(1): 142-3
Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18): 1301-8.
Evora PR, Alves Junior L, Ferreira CA, Menardi AC, Bassetto S, Rodrigues AJ, Scorzoni Filho A, Vicente WV. Twenty years of vasoplegic syndrome treatment in heart surgery. Methylene blue revised. Rev Bras Cir Cardiovasc. 2015;30(1): 84-92.
Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2): 120-8
Wang Z, Zhang D, Wang S, Jin Y, Huan J, Wu Y, Xia C, Li Z, Qi X, Zhang D, Han X, Zhu X, Qu Y, Wang Q. A Retrospective study from 2 centers in China on the effects of continued use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with hypertension and COVID-19. Med Sci Monit. 2020;26: e926651.
Li J, Wang X, Chen J, Zhang H, Deng A. Association of renin-angiotensin system inhibitors with severity or risk of death in patients with hypertension hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China. JAMA Cardiol. 2020;5(7): 825-30.
Ishiguro T, Matsuo K, Fujii S, Takayanagi N. Acute thrombotic vascular events complicating influenza-associated pneumonia. Respir Med Case Rep. 2019;28: 100884.
Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, Clark C, Iba T. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020;18(5): 1023-26.
Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta. 2020;506: 145-8.
Han H, Yang L, Liu R, Liu F, Wu KL, Li J, Liu XH, Zhu CL. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020;58(7): 1116-20.
Sinha P, Matthay MA, Calfee CS. Is a “cytokine storm” relevant to COVID-19?. JAMA internal medicine. 2020;180(9): 1152-4.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. 2020;395(10229): 1033-4.
Wan S, Yi Q, Fan S, Lv J, Zhang X, Guo L, Lang C, Xiao Q, Xiao K, Yi Z, Qiang M, Xiang J, Zhang B, Chen Y, Gao C. Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID-19) infected patients. Br J Haematol. 2020;189(3): 428-37.
Xu B, Fan CY, Wang AL, Zou YL, Yu YH, He C, Xia WG, Zhang JX, Miao Q. Suppressed T cell-mediated immunity in patients with COVID-19: A clinical retrospective study in Wuhan, China. J Infect. 2020;81(1): e51-e60
Buszko M, Park JH, Verthelyi D, Sen R, Young HA, Rosenberg AS. The dynamic changes in cytokine responses in COVID-19: a snapshot of the current state of knowledge. The dynamic changes in cytokine responses in COVID-19: A snapshot of the current state of knowledge. Nat. Immunol. 2020,21: 1146-51.
Kox M, Waalders NJ, Kooistra EJ, Gerretsen J, Pickkers P. Cytokine levels in critically ill patients with COVID-19 and other conditions. Jama. 2020;324(15): 1565-7.
Mangalmurti N, Hunter CA. Cytokine storms: understanding COVID-19. Immunity. 2020;53(1): 19-25.
Severin R, Arena R, Lavie CJ, Bond S, Phillips SA. Respiratory muscle performance screening for infectious disease management following COVID-19: a highly pressurized situation. Am J Med. 2020;133(9): 1025-32.
Сarfì A, Bernabei R, Landi F. Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324 (6): 603-5.
Adamson CS , Chibale K , Goss RJM , Jaspars M , Newman DJ , Dorrington RA. Antiviral drug discovery: preparing for the next pandemic. Chem Soc Rev. 2021;50(6): 3647-55
Benlloch JM, Cortés JC, Martínez-Rodríguez D, Julián RS, Villanueva RJ. Effect of the early use of antivirals on the COVID-19 pandemic. A computational network modeling approach. Chaos Solitons Fractals. 2020;140: 110168.
Frediansyah A, Tiwari R, Sharun K, Dhama K, Harapan H. Antivirals for COVID-19: A critical review. Clin Epidemiol Glob Health. 2021;9: 90-8.
Eastman RT, Roth JS, Brimacombe KR, Simeonov A, Shen M, Patnaik S, Hall MD. Remdesivir: a review of its discovery and development leading to emergency use authorization for treatment of COVID-19. ACS Cent Sci. 2020;6(5): 672-83
Yao TT, Qian JD, Zhu WY, Wang Y, Wang GQ. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-A possible reference for coronavirus disease-19 treatment option. J Med Virol. 2020;92(6): 556-63.
Imran M, Kumar Arora M, Asdaq SMB, Khan SA, Alaqel SI, Alshammari MK, Alshehri MM, Alshrari AS, Mateq Ali A, Al-Shammeri AM, Alhazmi BD, Harshan AA, Alam MT, Abida. Discovery, development, and patent trends on Molnupiravir: a prospective oral treatment for COVID-19. Molecules. 2021;26(19): 5795.
Painter WP, Holman W, Bush JA, Almazedi F, Malik H, Eraut NCJE, Morin MJ, Szewczyk LJ, Painter GR. Human safety, tolerability, and pharmacokinetics of molnupiravir, a novel broad-spectrum oral antiviral agent with activity against SARS-CoV-2. Antimicrob Agents Chemother. 2021;65(5): e02428-20.
Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020;55(4): 105932.
Choudhary R, Sharma AK. Potential use of hydroxychloroquine, ivermectin and azithromycin drugs in fighting COVID-19: trends, scope and relevance. New Microbes New Infect. 2020;35: 100684.
Colson P, Rolain JM, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents. 2020;55(3): 105923.
Jawhara S. Could intravenous immunoglobulin collected from recovered Coronavirus patients protect against COVID-19 and strengthen the immune system of new patients? Int J Mol Sci. 2020;21(7): 2272.
Galeotti C, Kaveri SV, Bayry J. Intravenous immunoglobulin immunotherapy for coronavirus disease-19 (COVID-19). Clin Transl Immunology. 2020;16;9(10): e1198.
Channappanavar R, Fehr AR, Zheng J, Wohlford-Lenane C, Abrahante JE, Mack M, Sompallae R, McCray PB Jr, Meyerholz DK, Perlman S. IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes. J Clin Invest. 2019;129(9): 3625-39.
Sainz B Jr, Mossel EC, Peters CJ, Garry RF. Interferon-beta and interferon-gamma synergistically inhibit the replication of severe acute respiratory syndrome-associated coronavirus (SARS-CoV). Virology. 2004;329(1): 11-7.
Strati P, Ahmed S, Kebriaei P, Nastoupil LJ, Claussen CM, Watson G, Horowitz SB, Brown ART, Do B, Rodriguez MA, Nair R, Shpall EJ, Green MR, Neelapu SS, Westin JR. Clinical efficacy of anakinra to mitigate CAR T-cell therapy-associated toxicity in large B-cell lymphoma. Blood Adv. 2020;4(13): 3123-7.
Navarro-Millán I, Sattui SE, Lakhanpal A, Zisa D, Siegel CH, Crow MK. Use of Anakinra to prevent mechanical ventilation in severe COVID-19: A case series. Arthritis Rheumatol. 2020;72(12): 1990-7.
Liu B, Li M, Zhou Z, Guan X, Xiang Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J Autoimmun. 2020;111: 102452.
Maeda T, Obata R, Rizk DO D, Kuno T. The association of interleukin-6 value, interleukin inhibitors, and outcomes of patients with COVID-19 in New York City. J Med Virol. 2021;93(1): 463-71.
Galván-Román JM, Rodríguez-García SC, Roy-Vallejo E, Marcos-Jiménez A, Sánchez-Alonso S, Fernández-Díaz C, Alcaraz-Serna A, et al.; REINMUN-COVID Group. IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study. J Allergy Clin Immunol. 2021;147(1): 72-80.e8.
Beović B, Doušak M, Ferreira-Coimbra J, Nadrah K, Rubulotta F, Belliato M, Berger-Estilita J, Ayoade F, Rello J, Erdem H. Antibiotic use in patients with COVID-19: a 'snapshot' Infectious Diseases International Research Initiative (ID-IRI) survey. J Antimicrob Chemother. 2020;75(11): 3386-90.
Chedid M, Waked R, Haddad E, Chetata N, Saliba G, Choucair J. Antibiotics in treatment of COVID-19 complications: a review of frequency, indications, and efficacy. J Infect Public Health. 202114(5): 570-6.
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020;178: 104787.
Wu C, Hou D, Du C, Cai Y, Zheng J, Xu J, Chen X, et al. Corticosteroid therapy for coronavirus disease 2019-related acute respiratory distress syndrome: a cohort study with propensity score analysis. Crit Care. 2020;24(1): 643.
Hasan SS, Capstick T, Ahmed R, Kow CS, Mazhar F, Merchant HA, Zaidi STR. Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis. Expert Rev Respir Med. 2020;14(11): 1149-63.
Ye Z, Wang Y, Colunga-Lozano LE, Prasad M, Tangamornsuksan W, Rochwerg B, Yao L, Motaghi S, et al. Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis. CMAJ. 2020;192(27): E756-E767.
Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, Merdji H, et al.; CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6): 1089-98.
Hao C, Xu H, Yu L, Zhang L. Heparin: An essential drug for modern medicine. Prog Mol Biol Transl Sci. 2019;163: 1-19.
Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18(5): 1094-9.
Camprubí-Rimblas M, Tantinyà N, Guillamat-Prats R, Bringué J, Puig F, Gómez MN, Blanch L, Artigas A. Effects of nebulized antithrombin and heparin on inflammatory and coagulation alterations in an acute lung injury model in rats. J Thromb Haemost. 2020;18(3): 571-83.
Xu X, Han M, Li T, Sun W, Wang D, Fu B, Zhou Y, Zheng X, Yang Y, Li X, Zhang X, Pan A, Wei H. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020;117(20): 10970-5.
Price CC, Altice FL, Shyr Y, Koff A, Pischel L, Goshua G, Azar MM, et al. Tocilizumab Treatment for Cytokine Release Syndrome in Hospitalized Patients With Coronavirus Disease 2019: Survival and Clinical Outcomes. Chest. 2020;158(4): 1397-408.
Karimi Zarchi AA, Faramarzi MA, Gilani K, Ghazi-Khansari M, Ghamami G, Amani A. N-acetylcysteine-loaded PLGA nanoparticles outperform conventional N-acetylcysteine in acute lung injuries in vivo. International Journal of Polymeric Materials and Polymeric Biomaterials. 2017;66(9): 443-54.
Puyo C, Kreig D, Saddi V, Ansari E, Prince O. Case report: use of hydroxychloroquine and N-acetylcysteine for treatment of a COVID-19 positive patient. F1000Research. 2020;9: 491.
Nasi A, McArdle S, Gaudernack G, Westman G, Melief C, Rockberg J, Arens R, Kouretas D, Sjölin J, Mangsbo S. Reactive oxygen species as an initiator of toxic innate immune responses in retort to SARS-CoV-2 in an ageing population, consider N-acetylcysteine as early therapeutic intervention. Toxicol Rep. 2020;7: 768-71.
van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, Tamin A et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020;382(16): 1564-7.
Wu, F., Zhao, S., Yu, B. et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579: 265-9. https://doi.org/10.1038/s41586-020-2008-3.
Ari A. Practical strategies for a safe and effective delivery of aerosolized medications to patients with COVID-19. Respir Med. 2020;167: 105987.
Janowitz T, Gablenz E, Pattinson D, Wang TC, Conigliaro J, Tracey K, Tuveson D. Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series. Gut. 2020;69(9): 1592-7.
Loffredo M, Lucero H, Chen DY, O'Connell A, Bergqvist S, Munawar A, Bandara A, et al. The in-vitro effect of famotidine on sars-cov-2 proteases and virus replication. Sci Rep. 2021;11(1): 5433.
Nehra AK, Alexander JA, Loftus CG, Nehra V. Proton Pump Inhibitors: Review of Emerging Concerns. Mayo Clin Proc. 2018;93(2): 240-6.
Zippi M, Fiorino S, Budriesi R, Micucci M, Corazza I, Pica R, de Biase D, et al. Paradoxical relationship between proton pump inhibitors and COVID-19: A systematic review and meta-analysis. World Journal of Clinical Cases. 2021;9(12): 2763.
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