Antirheumatic drugs for COVID-19 treatment based on the phases of the disease: Current concept

Main Article Content

Marco Valentini
Hassan Zmerly

Keywords

COVID-19, phases, treatment, antirheumatic drugs

Abstract

COVID-19 disease is the most recent pandemic, since it has affected more than four and a half million people and caused more than 300,000 deaths. It is a very complex systemic disease in terms of pathogenesis, treatment, and prognosis. Pharmacological treatment may include antiviral and antimalarial drugs, antibiotics, monoclonal antibodies, corticosteroids as well as low-molecular-weight heparins to prevent the evolution of the disease from reaching the severe inflammatory phase that can lead to respiratory complications, multiple organ failure, disseminated intravascular coagulation (DIC), and finally death. Therefore, pending the development of the much sought-after vaccine, there needs to be a multidisciplinary approach to tackling this disease, and it is essential to use different medical treatments at the correct pathogenic moment. The aim of this article is to evaluate the rationale and reason behind the use of antirheumatic drugs, by expert point of view, in the various phases of the disease. Another important aspect in the management of the disease is to identify patients at high risk, both to change their lifestyle and to correct the state of their health through non-pharmacological measures for improving their immuno-balance. Our literature review reveals the important role and the therapeutic potential of antirheumatic agents in preventing the progression of the disease and aiding recovery from the disease. However, there is a lack of clinical evidence to support the use of these agents, indicating that further randomized controlled studies are required.

Abstract 1195 | PDF Downloads 365 HTML Downloads 49 XML Downloads 0

References

1. Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically III patients with COVID-19 in Washington state. JAMA. 2020; 323(16):1612–14.  https://doi.org/10.1001/jama. 2020.4326

2. Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China [published online ahead of print, 2020 Mar 13]. JAMA Intern Med. 2020;e200994. https://doi.org/10.1001/jamainternmed.2020.0994

3. Xu Z, Shi L, Wang Y, et al. Pathological findings of  COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020
Apr;8(4):420–2. https://doi.org/10.1016/S2213-2600 (20)30076-X

4. Horisberger A, Moi L, Ribi C, Comte D. Impact of COVID-19 pandemic on SLE: Beyond the risk of infection. Lupus Sci Med. 2020 May;7(1):pii: e000408. https://doi.org/10.1136/ lupus-2020-000408

5. Ding Y, Wang H, Shen H, et al. The clinical pathology of severe acute respiratory syndrome (SARS): A report from China. J Pathol. 2003;200(3):282–9.https://doi.org/10.1002/ path.1440

6. Michael D. Covid-19: Identifying and isolating asymptomatic people helped eliminate virus in Italian village. BMJ. 2020;368:m1165. https://doi. org/10.1136/bmj.m1165

7. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplantation 2020;39(5):405–407. doi:10.1016/ j. healun.2020.03.012

8. Gralinski LE, Bankhead A 3rd, Jeng S, et al. Mechanisms of severe acute respiratory syndrome coronavirus-induced acute lung injury. mBio. 2013;4(4):e00271–13. https://doi.org/10.1128/mBio. 00271-13

9. Spyropoulos AC, Lipardi C, Xu J, et al. Modified IMPROVE VTE risk score and elevated D-dimer identify a high venous thromboembolism risk in acutely III medical population for extended thromboprophylaxis. TH Open. 2020 Mar 13;4(1): e59–e65. https://doi.org/10.1055/s-0040-1705137

10. Zhang C, Wu Z, Li JW, Zhao H, Wang G-Q. The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality. Int J Antimicrob Agents. 2020;55(5):105954. https://doi.org/10.1016/j.ijantimicag.2020.105954

11. McGonagle D, Sharif K, O’Regan A, Bridgewood C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020;19(6):102537. https://doi.org/10.1016/j. autrev.2020.102537

12. Levi M, Scully M. How I treat disseminated intravascular coagulation. Blood. 2018 Feb 22;131(8):845–54.https://doi.org/10.1182/ blood-2017-10-804096

13. Conti P, Younes A. Coronavirus COV-19/SARS-CoV-2 affects women less than men: Clinical response to viral infection. J Biol Regul Homeost Agents. 2020;34(2). doi: 10.23812/Editorial-Conti-3.

14. El Ghoch M, Valerio A. Let food be the medicine, but no not for coronavirus. Nutrition and food science telling myths from facts. JPTCP. 2020;27(SP1):e1–4. doi: https://doi.org/10.15586/ jptcp.v27iSP1.682

15. Isaia G, Giorgino R, Rini GB, et al. Prevalence of hypovitaminosis D in elderly women in Italy: Clinical consequences and risk factors. Osteoporos Int. 2003;14:577–82. https://doi.org/10.1007/ s00198-003-1390-7

16. Van der Wielen RPJ, De Groot MLCPGM, Van Staveren WA, et al. Serum vitamin D concentrations among elderly people in Europe. Lancet. 1995;346(8969):207–10. https://doi.org/10.1016/ S0140-6736(95)91266-5

17. Favalli EG, Ingegnoli F, De Lucia O, et al. COVID-19 infection and rheumatoid arthritis: Faraway, so close! Autoimmun Rev. 2020;19(5): 102523. https://doi.org/10.1016/j.autrev.2020. 102523

18. Georgiev T. Coronavirus disease 2019 (COVID-19) and anti-rheumatic drugs. Rheumatol Int. 2020;40(5):825–6. https://doi.org/10.1007/s00296-020-04570-z

19. Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: Implications for rheumatology. Nat Rev Rheumatol. 2000;16:155–66. https://doi.org/ 10.1038/s41584-020-0372-x

20. Collins KP, Jackson KM, Gustafson DL. Hydroxychloroquine: A physiologically- based pharmacokinetic model in the context of cancer-related autophagy modulation. J Pharmacol Exp Ther. 2018;365:447–59. https://doi.org/10.1124/ jpet.117.245639

21. Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020;57:279–83.https:// doi.org/10.1016/j.jcrc.2020.03.005

22. Gautret P, Lagier JC, Parola P, et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Med Infect  Dis. 2020 Apr 11;34:101663. https://doi. org/10.1016/j.tmaid.2020.101663

23. Mitra RL, Greenstein SA, Epstein LM. An algorithm for managing QT prolongation in coronavirus disease 2019 (COVID-19) patients treated with either chloroquine or hydroxychloroquine in conjunction with azithromycin: Possible benefits of intravenous lidocaine. Heart Rhythm Case Rep. 2020;6(5):244–8. https://doi.org/10.1016/j. hrcr.2020.03.016.

24. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [published online ahead of print, 2020 Mar 20]. Int J Antimicrob Agents. 2020;105949. https://doi.org/10.1016/j. ijantimicag.2020.105949

25. Gao J, Tian Z, Yang Xu. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72–73.https://doi.org/10.5582/ bst.2020.01047

26. Wengliu W, Hualan L. COVID-19: Attacks the 1-beta chain of hemoglobin and captures the porphyrin to inhibit human heme metabolism. ChemRxiv. Preprint. doi: 10.26434/chemrxiv. 11938173.v7. https://doi.org/10.26434/chemrxiv. 11938173.v7

27. Russell B, Moss C, George G, et al. Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence. Ecancermedicalscience. 2020;14:1022.https://doi.org/10.3332/ecancer. 2020.1022

28. Fontana F, Alfano G, Mori G, et al. Covid-19 pneumonia in a kidney transplant recipient successfully treated with Tocilizumab and Hydroxychloroquine. Am J Transplant. 2020 Apr 23. doi: 10.1111/ajt.15935. https://doi.org/10.1111/ ajt.15935

29. Shanmugaraj B, Siriwattananon K, Wangkanont K, Phoolcharoen W. Perspectives on monoclonal antibody therapy as potential therapeutic intervention for coronavirus disease-19 (COVID-19). Asian Pac J Allergy Immunol. 2020 Mar;38(1): 10–18. doi: 10.12932/AP-200220-0773

30. Efficacy and safety of emapalumab and anakinra in reducing hyperinflammation and respiratory distress in patients with COVID-19 infection. https://clinicaltrials.gov/ct2/show/NCT04324021

31. Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential treatment for 2019-nCov acute respiratory disease. Lancet. 2020;395(10223): PE30–1. https://doi.org/10.1016/S0140-6736(20) 30304-4

32. Zhang W, Zhao Y, Zhang F, Wang Q. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The perspectives of clinical immunologists from China. Clin Immunol Clin Immunol. 2020 May;214:108393. https://doi. org/10.1016/j.clim.2020.108393

33. Han JE, Jones JL, Tangpricha V, et al. High dose vitamin D administration in ventilated intensive care unit patients: A pilot double blind randomized controlled trial. J Clin Transl Endocrinol. 2016 Jun;4:59–65. https://doi.org/10.1016/j.jcte. 2016.04.004

34. Borella E, Nesher G, Israeli E, Shoenfeld Y. Vitamin D: A new anti-infective agent? Ann N Y Acad Sci. 2014 May;1317:76–83. https://doi. org/10.1111/nyas.12321

35. Kim HJ, Jang JG, Hong KS, Park JK, Choi EY. Relationship between serum vitamin D concentrations and clinical outcome of community-acquired pneumonia. Int J Tuberc Lung Dis. 2015 Jun;19(6):729–34. https://doi.org/10.5588/ijtld. 14.0696

36. Sabetta JR, DePetrillo P, Cipriani RJ, et al. Serum 25-hydroxyvitamin d and the incidence of acute viral respiratory tract infections in healthy adults. PLoS One. 2010 Jun 14;5(6):e11088. https://doi. org/10.1371/journal.pone.0011088

37. Grant WB, Lahore H, McDonnell SL, et al. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020 Apr 2;12(4):pii: E988. https://doi.org/10.3390/nu12040988

38. Maes K, Serré J, Mathyssen C, Janssens W, Gayan-Ramirez G. Targeting vitamin D deficiency to limit exacerbations in respiratory diseases: Utopia or strategy with potential? Calcif Tissue Int. 2020;106:76–87.https://doi.org/10.1007/ s00223-019-00591-4

39. Martineau AR, Jolliffe DA, Greenberg L, et al. Vitamin D supplementation to prevent acute respiratory infections: Individual participant data meta-analysis. Health Technol Assess. 2019 Jan;23(2):1–44. doi: https://doi.org/10.1136/ bmj.i6583

40. Stebbing J, Phelan A, Griffin I, et al. COVID-19: Combining antiviral and anti-inflammatory treatments. Lancet Infect Dis. 2020 Apr;20(4): 400–2.https://doi.org/10.1016/S1473-3099(20) 30132-8

41. Shang L, Zhao J, Hu Y. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet. 2020 Feb 29;395(10225):683–4. https://doi.org/10.1016/ S0140-6736(20)30361-5

42. Han H, Yang L, Liu R, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020 Mar 16. https://doi.org/10.1515/cclm-2020-0188
43. Hunt BJ. Bleeding and coagulopathies in critical care. N Engl J Med. 2014 Feb 27;370(9):847–59. https://doi.org/10.1056/NEJMra1208626

44. Ozolina A, Sarkele M, Sabelnikovs O, et al. Activation of coagulation and fibrinolysis in acute respiratory distress syndrome: A prospective pilot study. Front Med (Lausanne). 2016;3:64. https:// doi.org/10.3389/fmed.2016.00064

45. Etoom Y, Banihani R, Finkelstein Y. Critical review of: Efficacy of immunoglobulin plus prednisone for prevention of coronary artery prednisolone for prevention of coronary abnormalities in severe Kawasaki disease (RAISE study): A randomized, open-label, blinded-endpoints trial. J Popul Ther Clin Pharmacol. 2013;20(2):e91–4.

46. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844–7. https://doi. org/10.1111/jth.14768

47. Kissler SM, Tedijanto C, Goldstein E, et al. Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period. Science. 2020 Apr;14:eabb5793. https://doi.org/10.1101/ 2020.03.04.20031112

48. Ahn DG, Shin HJ, Kim MH, et al. Current status of epidemiology, diagnosis, therapeutics, and vaccines for novel coronavirus disease 2019 (COVID-19). J Microbiol Biotechnol. 2020 Mar 28;30(3): 313–24. https://doi.org/10.4014/jmb.2003.03011

49. Perricone C, Triggianese P, Bartoloni E. The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19. J Autoimmun. 2020 Apr;17:102468. https://doi.org/10.1016/j.jaut.2020.102468

50. Ferner RE, Aronson JK. Chloroquine and hydroxychloroquine in covid-19. BMJ. 2020 Apr 8;369:m1432. https://doi.org/10.1136/bmj.m1432

51. Saqrane S, El Mhammedi MA. Review on the global epidemiological situation and the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19. New Microbes New Infect. 2020 Apr 14;35:100680. https://doi. org/10.1016/j.nmni.2020.100680

52. Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: What to expect for COVID-19? Int J Antimicrob Agents. 2020;55(5): 105938. https://doi.org/10.1016/j.ijantimicag. 2020.105938

53. Chowdhury MS, Rathod J, Gernsheimer J. A rapid systematic review of clinical trials utilizing chloroquine and hydroxychloroquine as a treatment for COVID-19. Acad Emerg Med. 2020 May 2: https://doi.org/10.1111/acem.14005. [published online ahead of print, 2020 May 2]. PMID: 32359203; PMCID: PMC7267507.

54. Fu B, Xu X, Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med. 2020 Apr 14;18(1):164. https://doi. org/10.1186/s12967-020-02339-3