Novel coronavirus infection: from pathogenesis to therapy

Ezhov M.V.; Popova M.D.; Alekseeva I.A.; Pokrovsky N.S.; Paleyev F.N.

doi:https://doi.org/10.17116/Cardiobulletin20211601110

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Abstract:

Novel coronavirus infection pandemic (COVID-19, COronaVIrus Disease 2019), is a rapidly spreading global threat. SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2) is a highly contagious agent causing severe viral pneumonia with acute respiratory distress syndrome (ARDS), acute respiratory and multiple organ failure and mortality. COVID-19-associated case-fatality rate (CFR) is 2.3—4.2%. However, this value may be up to 49% in extremely severe cases. According to modern concepts, severe course of disease and mortality are most likely due to development of a «cytokine storm» induced by SARS-CoV-2. At least 10% of patients with severe COVID-19 will be eventually presented with lung injury, ARDS and multiple organ failure within 8—14 days after manifestation of disease. Excessive release of proinflammatory cytokines results ARDS and damage to various organs and tissues. Target therapy for cytokine storm and pathogenetic therapeutic approaches can improve course of disease and reduce morbidity and mortality.

Keywords:

novel coronavirus infection

COVID-19

ARDS

SARS-CoV-2

cytokine storm

interleukine-6

Authors:

Ezhov M.V.

National Medical Research Center of Cardiology

Popova M.D.

Lomonosov Moscow State University

Alekseeva I.A.

National Medical Research Center of Cardiology

Pokrovsky N.S.

National Medical Research Center of Cardiology

Paleyev F.N.

Chazov National Medical Research Center of Cardiology

ORCID: 0000-0001-9481-9639

Received:

05.02.2021

Accepted:

06.02.2021

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References:

World Health Organisation. Pneumonia of unknown cause — China. Disease outbreak news. 5 January 2020. https://www.who.int/csr/don/05-january-2020-pneumonia-of-unkown-cause-china/en/
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W. China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. The New England Journal of Medicine. 2020;382(8):727-733. https://doi.org/10.1056/NEJMoa2001017
WHO Timeline - COVID-19. Accessed March 05, 2021. (In Russ.). https://www.who.int/ru/news-room/detail/27-04-2020-who-timeline-covid-19
World Health Organization. (2020). Coronavirus disease 2019 (COVID-19): situation report, 68. World Health Organization. https://apps.who.int/iris/handle/10665/331614
COVID-19, MERS & SARS. NIH: National Institute of Allergy and Infectious Diseases. (n.d.). Accessed February 28, 2020. https://www.niaid.nih.gov/diseases-conditions/covid-19).
World Health Organization. (2020). Coronavirus disease 2019 (COVID-19): Weekly epidemiological update — 29 December 2020. https://www.who.int/publications/m/item/weekly-epidemiological-update-29-december-2020
Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. Journal of Medical Virology. 2020;92(4):418-423. https://doi.org/10.1002/jmv.25681
Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerging Microbes and Infections. 2020;9(1):221-236. https://doi.org/10.1080/22221751.2020.1719902
Tahir Ul Qamar M, Alqahtani SM, Alamri MA, Chen L-L. Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants. Journal of Pharmaceutical Analysis. 2020;10:313-319. https://doi.org/10.1016/j.jpha.2020.03.009
Chan-Yeung M, Xu RH. SARS: epidemiology. Respirology. 2003;8 (suppl 1):9-14. https://doi.org/10.1046/j.1440-1843.2003.00518.x
Middle East Respiratory Syndrome Coronavirus. Accessed February 20, 2020. https://www.who.int/emergencies/mers-cov/en/
Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. The Journal of Hospital Infection. 2020;104(3):246-251. https://doi.org/10.1016/j.jhin.2020.01.022
Wax RS, Christian MD. Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients. Canadian Journal of Anaesthesia. 2020;67(5):568-576. https://doi.org/10.1007/s12630-020-01591-x
Guo ZD, Wang ZY, Zhang SF, Li X, Li L, Li C, Cui Y, Fu RB, Dong YZ, Chi XY, Zhang MY, Liu K, Cao C, Liu B, Zhang K, Gao YW, Lu B, Chen W. Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020. Emerging Infectious Diseases. 2020;26(7):1583-1591. https://doi.org/10.3201/eid2607.200885
Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, Azman AS, Reich NG, Lessler J. The Incubation Period of Coronavirus Disease 2019 (COVID-19) from Publicly Reported Confirmed Cases: Estimation and Application. Annals of Internal Medicine. 2020;172(9):577-582. https://doi.org/10.7326/M20-0504
Millet JK, Whittaker GR. Host cell proteases: critical determinants of coronavirus tropism and pathogenesis. Virus Research. 2015;202:120-134. https://doi.org/10.1016/j.virusres.2014.11.021
Astuti I, Ysrafil. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response. Diabetes and Metabolic Syndrome. 2020;14(4):407-412. https://doi.org/10.1016/j.dsx.2020.04.020
Lamas-Barreiro JM, Alonso-Suárez M, Fernández-Martín JJ, Saavedra-Alonso JA. Angiotensin II suppression in SARS-CoV-2 infection: a therapeutic approach. Nefrologia. 2020;40(3):213-216. https://doi.org/10.1016/j.nefroe.2020.06.014
Vremennyye metodicheskiye rekomendatsii Minzdrava Rossii. Profilaktika, diagnostika i lecheniye noviy koronavirusnoy infektsii (COVID-19), versiya 9 (26.10.2020). M.: Minzdrav RF; 2020. (In Russ).
Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, Tan KSen, Wang DY, Yan Y. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak — an update on the status. Military Medical Research. 2020;7(1):11. https://doi.org/10.1186/s40779-020-00240-0
Nishiga M, Wang DW, Han Y, Lewis DB, Wu JC. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nature Reviews. Cardiology. 2020;17(9):543-558. https://doi.org/10.1038/s41569-020-0413-9
Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pacific Journal of Allergy and Immunology. 2020;38(1):1-9. https://doi.org/10.12932/AP-200220-0772
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. https://doi.org/10.1016/S0140-6736(20)30183-5
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):1239-1242. https://doi.org/10.1001/jama.2020.2648
Wilson N, Kvalsvig A, Barnard LT, Baker MG. Case-Fatality Risk Estimates for COVID-19 Calculated by Using a Lag Time for Fatality. Emerging Infectious Diseases. 2020;26(6):1339-1441. https://doi.org/10.3201/eid2606.200320
Song F, Shi N, Shan F, Zhang Z, Shen J, Lu H, Ling Y, Jiang Y, Shi Y. Emerging 2019 Novel Coronavirus (2019-nCoV) Pneumonia. Radiology. 2020;295:210-217. https://doi.org/10.1148/radiol.2020200274
Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, Fan Y, Zheng C. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. The Lancet. Infectious Diseases. 2020;20(4):425-434. https://doi.org/10.1016/S1473-3099(20)30086-4
Bhaskar S, Sinha A, Banach M, Mittoo S, Weissert R, Kass JS, Rajagopal S, Pai AR, Kutty S. Cytokine Storm in COVID-19-Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper. Frontiers in Immunology. 2020;11:1648. https://doi.org/10.3389/fimmu.2020.01648
Bernheim A, Mei X, Huang M, Yang Y, Fayad ZA, Zhang N, Diao K, Lin B, Zhu X, Li K, Li S, Shan H, Jacob A, Chung M. Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection. Radiology. 2020;295:685-691. https://doi.org/10.1148/radiol.2020200463
Paranjpe I, Russak AJ, De Freitas JK, Lala A, Miotto R, Vaid A, Johnson KW, Danieletto M, Golden E, Meyer D, Singh M, Somani S, Kapoor A, O’Hagan R, Manna S, Nangia U, Jaladanki SK, O’Reilly P, Huckins LM, Glowe P, Kia A, Timsina P, Freeman RM, Levin MA, Jhang J, Firpo A, Kovatch P, Finkelstein J, Aberg JA, Bagiella E, Horowitz CR, Murphy B, Fayad ZA, Narula J, Nestler EJ, Fuster V, Cordon-Cardo C, Charney D, Reich DL, Just A, Bottinger EP, Charney AW, Glicksberg BS, Nadkarni GN; Mount Sinai COVID Informatics Center (MSCIC). Clinical Characteristics of Hospitalized Covid-19 Patients in New York City. British Medical Journal Open. 2020;10(11):e040736. https://doi.org/10.1136/bmjopen-2020-040736
Zhu J, Zhong Z, Ji P, Li H, Li B, Pang J, Zhang J, Zhao C. Clinico-pathological characteristics of 8697 patients with COVID-19 in China: a meta-analysis. Family Medicine and Community Health. 2020;8(2):e000406. https://doi.org/10.1136/fmch-2020-000406
Perlman S. COVID-19 poses a riddle for the immune system. Nature. 2020;584(7821):345-346. https://doi.org/10.1038/d41586-020-02379-1
Fu L, Wang B, Yuan T, Chen X, Ao Y, Fitzpatrick T, Li P, Zhou Y, Lin Y. fan, Duan Q, Luo G, Fan S, Lu Y, Feng A, Zhan Y, Liang B, Cai W, Zhang L, Du X, Zou H. Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: A systematic review and meta-analysis. The Journal of Infection. 2020;80(6):656-665. https://doi.org/10.1016/j.jinf.2020.03.041
Yin Q, Fu Z, Xie, J, Yang J, Li F, Zhu W, Yu Y, Zhang J. Analysis of Risk Factors of Severe COVID-19 Patients. BMC Infectious Diseases. 2020;1-14. https://doi.org/10.21203/rs.3.rs-23272/v1
Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunologic features in severe and moderate Coronavirus Disease 2019. The Journal of Clinical Investigation. 2020;130(5):2620-2629. https://doi.org/10.1101/2020.02.16.20023903
Picchianti Diamanti A, Rosado MM, Pioli C, Sesti G, Laganà B. Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity. International Journal of Molecular Sciences. 2020;21(9):3330. https://doi.org/10.3390/ijms21093330
Wu D, Yang XO. TH17 responses in cytokine storm of COVID-19: an emerging target of JAK2 inhibitor fedratinib. Journal of Microbiology, Immunology, and Infection. 2020;53(3):368-370. https://doi.org/10.1016/j.jmii.2020.03.005
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-1034. https://doi.org/10.1016/S0140-6736(20)30628-0
Favalli EG, Ingegnoli F, De Lucia O, Cincinelli G, Cimaz R, Caporali R. COVID-19 infection and rheumatoid arthritis: Faraway, so close! Autoimmunity Reviews. 2020;19(5):102523. https://doi.org/10.1016/j.autrev.2020.102523
Ashour HM, Elkhatib WF, Rahman MM, Elshabrawy HA. Insights into the recent 2019 novel coronavirus (SARSCoV-2) in light of past human coronavirus outbreaks. Pathogens. 2020;9(3):186. https://doi.org/10.3390/pathogens9030186
Yang Y, Peng F, Wang R, Yange M, Guan K, Jiang T, Xu G, Sun J, Chang C. The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China. Journal of Autoimmunity. 2020;109:102434. https://doi.org/10.1016/j.jaut.2020.102434
Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, Montgomery SA, Hogg A, Babusis D, Clarke MO, Spahn JE, Bauer L, Sellers S, Porter D, Feng JY, Cihlar T, Jordan R, Denison MR, Baric RS. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nature Communications. 2020;11(1):222. https://doi.org/10.1038/s41467-019-13940-6
COVID-19 treatment guidelines. Antiviral Drugs that are Approved or Under Evaluation for the Treatment of COVID-19. Accessed February 20, 2020. https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy
Qin YY, Zhou YH, Lu YQ, Sun F, Yang S, Harypursat V, Chen YK. Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial. Chinese Medical Journal. 2020;133(9):1080-1086. https://doi.org/10.1097/CM9.0000000000000791
Shakoory B, Carcillo JA, Chatham WW, Amdur RL, Zhao H, Dinarello CA, Cron RQ, Opal SM. Interleukin-1 Receptor Blockade Is Associated with Reduced Mortality in Sepsis Patients with Features of Macrophage Activation Syndrome: Reanalysis of a Prior Phase III Trial. Critical Care Medicine. 2016;44(2):275-281. https://doi.org/10.1097/CCM.0000000000001402
Cavalli G, De Luca G, Campochiaro C, Della-Torre E, Ripa M, Canetti D, Oltolini C, Castiglioni B, Tassan Din C, Boffini N, Tomelleri A, Farina N, Ruggeri A, Rovere-Querini P, Di Lucca G, Martinenghi S, Scotti R, Tresoldi M, Ciceri F, Landoni G, Zangrillo A, Scarpellini P, Dagna L. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. The Lancet. Rheumatology. 2020;2(6):325-331. https://doi.org/10.1016/s2665-9913(20)30127-2
Huet T, Beaussier H, Voisin O, Jouveshomme S, Dauriat G, Lazareth I, Sacco E, Naccache JM, Bézie Y, Laplanche S, Le Berre A, Le Pavec J, Salmeron S, Emmerich J, Mourad JJ, Chatellier G, Hayem G. Anakinra for severe forms of COVID-19: a cohort study. The Lancet. Rheumatology. 2020;2(7):393-400. https://doi.org/10.1016/S2665-9913(20)30164-8
Ucciferri C, Auricchio A, Di Nicola M, Potere N, Abbate A, Cipollone F, Vecchiet J, Falasca K. Canakinumab in a subgroup of patients with COVID-19. The Lancet. Rheumatology. 2020;2(8):457-458. https://doi.org/10.1016/S2665-9913(20)30167-3
CORIMUNO-19 — Tocilizumab Trial — TOCI (CORIMUNO-TOCI) (CORIMUNO-TOC). Accessed March 05, 2021. https://clinicaltrials.gov
Borku Uysal B, Ikitimur H, Yavuzer S, Ikitimur B, Uysal H, Islamoglu MS, Ozcan E, Aktepe E, Yavuzer H, Cengiz M. Tocilizumab challenge: A series of cytokine storm therapy experiences in hospitalized COVID-19 pneumonia patients. Journal of Medical Virology. 2020;92(11):2648-2656. https://doi.org/10.1002/jmv.26111
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. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(20):10970-10975. https://doi.org/10.1073/pnas.2005615117
Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: A single center experience. Journal of Medical Virology. 2020;92(7):814-818. https://doi.org/10.1002/jmv.25801
Hermine O, Mariette X, Tharaux PL, Resche-Rigon M, Porcher R, Ravaud P; CORIMUNO-19 Collaborative Group. Effect of Tocilizumab vs Usual Care in Adults Hospitalized with COVID-19 and Moderate or Severe Pneumonia: A Randomized Clinical Trial. JAMA Internal Medicine. 2021;181(1):32-40. https://doi.org/10.1001/jamainternmed.2020.6820
Gupta S, Wang W, Hayek SS, Chan L, Mathews KS, Melamed ML, Brenner SK, Leonberg-Yoo A, Schenck EJ, Radbel J, Reiser J, Bansal A, Srivastava A, Zhou Y, Finkel D, Green A, Mallappallil M, Faugno AJ, Zhang J, Velez JCQ, Shaefi S, Parikh CR, Charytan DM, Athavale AM, Friedman AN, Redfern RE, Short SAP, Correa S, Pokharel KK, Admon AJ, Donnelly JP, Gershengorn HB, Douin DJ, Semler MW, Hernán MA, Leaf DE; STOP-COVID Investigators. Association between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. JAMA Internal Medicine. 2021;181(1):41-51. https://doi.org/10.1001/jamainternmed.2020.6252
Richardson P, Griffin I, Tucker C, Smith D, Oechsle O, Phelan A, Rawling M, Savory E, Stebbing J. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet. 2020;395(10223):30-31. https://doi.org/10.1016/S0140-6736(20)30304-4
Goker Bagca B, Biray Avci C. The potential of JAK/STAT pathway inhibition by ruxolitinib in the treatment of COVID-19. Cytokine and Growth Factor Reviews. 2020;54:51-62. https://doi.org/10.1016/j.cytogfr.2020.06.013
Praveen D, Puvvada RC, M VA. Janus kinase inhibitor baricitinib is not an ideal option for management of COVID-19. International Journal of Antimicrobial Agents. 2020;55(5):105967. https://doi.org/10.1016/j.ijantimicag.2020.105967
Cheng LL, Guan WJ, Duan CY, Zhang NF, Lei CL, Hu Y, Chen AL, Li SY, Zhuo C, Deng XL, Cheng FJ, Gao Y, Zhang JH, Xie JX, Peng H, Li YX, Wu XX, Liu W, Peng H, Wang J, Xiao GM, Chen PY, Wang CY, Yang ZF, Zhao JC, Zhong NS. Effect of Recombinant Human Granulocyte Colony-Stimulating Factor for Patients with Coronavirus Disease 2019 (COVID-19) and Lymphopenia: A Randomized Clinical Trial. JAMA Internal Medicine. 2021;181(1):71-78. https://doi.org/10.1001/jamainternmed.2020.5503
Jawhara S. Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients? International Journal of Molecular Sciences. 2020;21(7):2272. https://doi.org/10.3390/ijms21072272
Rajendran K, Krishnasamy N, Rangarajan J, Rathinam J, Natarajan M, Ramachandran A. Convalescent plasma transfusion for the treatment of COVID-19: Systematic review. Journal of Medical Virology. 2020;92(9):1475 1483. https://doi.org/10.1002/jmv.25961
Ma J, Xia P, Zhou Y, Liu Z, Zhou X, Wang J, Li T, Yan X, Chen L, Zhang S, Qin Y, Li X. Potential effect of blood purification therapy in reducing cytokine storm as a late complication of critically ill COVID-19. Clinical Immunology. 2020;214:108408. https://doi.org/10.1016/j.clim.2020.108408
Tabibi S, Tabibi T, Conic RRZ, Banisaeed N, Streiff MB. Therapeutic Plasma Exchange: A potential Management Strategy for Critically Ill COVID-19 Patients. Journal of Intensive Care Medicine. 2020;35(9):827-835. https://doi.org/10.1177/0885066620940259
Sokolov A.A., Sokolov D.V., Pevzner D.V., Popov A.V., Donskikh V.V. Extracorporeal blood purification in the complex treatment of the novel coronavirus infection: the review of opportunities. Messenger of ANESTHESIOLOGY AND RESUSCITATION. 2020;17(4):31-40. (In Russ.) https://doi.org/10.21292/2078-5658-2020-17-4-31-40