Document Type : Research articles

Authors

1 1Department of Allergy and Clinical Immunology, Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

2 Department of Allergy and Clinical Immunology, Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

3 2Radiology Department, Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

4 3Medical Intern, Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

Abstract

Background: Post-acute COVID-19 syndrome involves the persistence of the patients symptoms due to the residual inflammation of the acute phase.
Objectives: In the current study, we aimed to evaluate medication intervention to accelerate the improvement of prolonged respiratory symptoms in this phase.
Methods: Thirty-four patients, aged 20-50 years, in the recovery phase of COVID-19, were enrolled, who still suffered from respiratory problems even two weeks after being discharged from Rasool Akram Hospital, Tehran, Iran. They were divided into three groups based on the type of treatment for eliminating the remaining symptoms: hydroxychloroquine (HCQ, 200 mg twice daily for four weeks), clarithromycin (500 mg twice daily for four weeks), and control (receiving a placebo similar to the last two groups). At the beginning and end of the treatment, patients dyspnea and cough were assessed using Medical Research Council and visual analog scale (VAS), respectively, their laboratory tests were checked, and they took a 6-min walk test.
Results: At the end of the treatment, the VAS of cough was 0.74 in the HCQ group, which was higher than that in the clarithromycin group. In addition, dyspnea decreased in the HCQ and clarithromycin groups by 64% and 40%, respectively, compared to the control group. Furthermore, there was a significant relationship between residual dyspnea at the end of the treatment and the severity of initial lung involvement in the acute phase.
Conclusion: Based on these findings, it can be concluded that HCQ was more effective in reducing dyspnea, compared to clarithromycin, in the recovery phase, especially in patients with milder lung involvement in the acute phase. Additionally, clarithromycin was found to be more effective in improving coughs.

Keywords

  1. Al-Saud B, Hazzazi KM, Mohammed R, Al Najjar A, Al Hazmi T, Monies D, et al. SARS-CoV-2–related acute respiratory distress syndrome uncovers a patient with severe combined immunodeficiency disease. J Clin Immunol. 2021;41(7):1507-10. doi: 10.1007/s10875-021-01063-x. [PubMed: 34173127].
  2. Phua J, Weng L, Ling L, Egi M, Lim CM, Divatia JV, et al. Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations. Lancet Respir Med. 2020;8(5):506-17. doi: 10.1016/S2213-2600(20)30161-2. [PubMed: 32272080].
  3. Li X, Zeng W, Li X, Chen H, Shi L, Li X, et al. CT imaging changes of corona virus disease 2019 (COVID-19): a multi-center study in Southwest China. J Transl Med. 2020;18(1):1-8. doi: 10.1186/s12967-020-02324-w. [PubMed: 32252784].
  4. Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020;7(1):1-23. doi: 10.1186/s40779-020-0233-6. [PubMed: 32029004].
  5. Yang LL, Yang T. Pulmonary rehabilitation for patients with coronavirus disease 2019 (COVID-19). Chronic Dis Transl Med. 2020;6(2):79-86. doi: 10.1016/j.cdtm.2020.05.002. [PubMed: 32411496].
  6. Halpin SJ, McIvor C, Whyatt G, Adams A, Harvey O, McLean L, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID‐19 infection: A cross‐sectional evaluation. J Med Virol. 2021;93(2):1013-22. doi: 10.1002/jmv.26368. [PubMed: 32729939].
  7. Garg P, Arora U, Kumar A, Wig N. The"post-COVID" syndrome: How deep is the damage?. J Med Virol. 2020;93(2):673-4. doi: 10.1002/jmv.26465. [PubMed: 32852801].
  8. Greenhalgh T, Knight M, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020;370:m3026. doi: 10.1136/bmj.m3026. [PubMed: 32784198].
  9. Gemelli Against COVID-19 Post-Acute Care Study Group. Post-COVID-19 global health strategies: the need for an interdisciplinary approach. Aging Clin Exp Res. 2020;32(8):1613-20. doi: 10.1007/s40520-020-01616-x. [PubMed: 32529595].
  10. Moreno-Perez O, Merino E, Leon-Ramirez JM, Andres M, Ramos JM, Arenas-Jimenez J, et al. Post-acute COVID-19 syndrome. Incidence and risk factors: A Mediterranean cohort study. J Infect. 2021;82(3):378-83. doi: 10.1016/j.jinf.2021.01.004. [PubMed: 33450302].
  11. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420-2. doi: 10.1016/S2213-2600(20)30076-X. [PubMed: 32085846].
  12. Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary pathology of early-phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J Thorac Oncol. 2020;15(5):700-4.
  13. Yang R, Li X, Liu H, Zhen Y, Zhang X, Xiong Q, et al. Chest CT severity score: an imaging tool for assessing severe COVID-19. Radiol Cardiothorac Imaging. 2020;2(2):e200047. doi: 10.1148/ryct.2020200047. [PubMed: 33778560].
  14. Chopra V, Flanders SA, O’Malley M, Malani AN, Prescott HC. Sixty-day outcomes among patients hospitalized with COVID-19. Ann Intern Med. 2021;174(4):576-8. doi: 10.7326/M20-5661. [PubMed: 33175566].
  15. Michielsen HJ, De Vries J, Van Heck GL. Psychometric qualities of a brief self-rated fatigue measure: the fatigue assessment scale. J Psychosom Res. 2003;54(4):345-52. doi: 10.1016/s0022-3999(02)00392-6. [PubMed: 12670612].
  16. Carfì A, Bernabei R, Landi F. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324(6):603-5. doi: 10.1001/jama.2020.12603. [PubMed: 32644129].
  17. Yaghoubi M, Salimi M, Meskarpour-Amiri M, Hosseini_shokouh SM. COVID-19-related absenteeism and presenteeism among healthcare workers. Iran Red Crescent Med J. 2022:10-.
  18. Zhao YM, Shang YM, Song WB, Li QQ, Xie H, Xu QF, et al. Follow-up study of the pulmonary function and related
  19. physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine. 2020;25:100463. doi: 10.1016/j.eclinm.2020.100463. [PubMed: 32838236].
  20. Balachandar V, Mahalaxmi I, Subramaniam M, Kaavya J, Kumar NS, Laldinmawii G, et al. Follow-up studies in COVID-19 recovered patients-is it mandatory?. Sci Total Environ. 2020;729:139021. doi: 10.1016/j.scitotenv.2020.139021. [PubMed: 32360909].
  21. McDonald LT. Healing after COVID-19: are survivors at risk
  22. for pulmonary fibrosis?. Am J Physiol Lung Cell Mol Physiol. 2021;320(2):257-65. doi: 10.1152/ajplung.00238.2020. [PubMed: 33355522].
  23. Strieter RM, Mehrad B. New mechanisms of pulmonary fibrosis. Chest. 2009;136(5):1364-70. doi: 10.1378/chest.09-0510. [PubMed: 19892675].
  24. WHO. WHO Director-General's opening remarks at the media briefing on COVID-19-11 March 2020. Geneva, Switzerland; 2020.
  25. Garout MA, Saleh SA, Adly HM, Abdulkhaliq AA, Khafagy AA, Abdeltawab MR, et al. Post‐COVID-19 syndrome: assessment of short-and long-term post-recovery symptoms in recovered cases in Saudi Arabia. Infection. 2022;50(6):1431-9. doi: 10.1007/s15010-022-01788-w. [PubMed: 35294728].
  26. Ichiyama T, Nishikawa M, Yoshitomi T, Hasegawa S, Matsubara T, Hayashi T, et al. Clarithromycin inhibits NF-κB activation in human peripheral blood mononuclear cells and pulmonary epithelial cells. Antimicrob Agents Chemother. 2001;45(1):44-7. doi: 10.1128/AAC.45.1.44-47.2001. [PubMed: 11120942].
  27. Li W, Yang S, Kim SO, Reid G, Challis JR, Bocking AD. Lipopolysaccharide-induced profiles of cytokine, chemokine, and growth factors produced by human decidual cells are altered by Lactobacillus rhamnosus GR-1 supernatant. Reprod Sci. 2014;21(7):939-47.
  28. Marjanović N, Bosnar M, Michielin F, Wille DR, Anić-Milić T, Čulić O, et al. Macrolide antibiotics broadly and distinctively inhibit cytokine and chemokine production by COPD sputum cells in vitro. Pharmacol Res. 2011;63(5):389-97. doi: 10.1016/j.phrs.2011.02.001. [PubMed: 21315154].
  29. Bleyzac N, Goutelle S, Bourguignon L, Tod M. Azithromycin for COVID-19: more than just an antimicrobial?. Clin Drug Investig. 2020;40(8):683-6. doi: 10.1007/s40261-020-00933-3. [PubMed: 32533455].
  30. Cai M, Bonella F, Dai H, Sarria R, Guzman J, Costabel U. Macrolides inhibit cytokine production by alveolar macrophages in bronchiolitis obliterans organizing pneumonia. Immunobiology. 2013;218(6):930-7. doi: 10.1016/j.imbio.2012.10.014. [PubMed: 23199585].
  31. Ferner RE, Aronson JK. Chloroquine and hydroxychloroquine in covid-19. BMJ. 2020;369:m1432. doi: 10.1136/bmj.m1432. [PubMed: 32269046].
  32. Al‐Bari MA. Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases. Pharmacol Res Perspect. 2017;5(1):e00293. doi: 10.1002/prp2.293. [PubMed: 28596841].
  33. Lafyatis R, York M, Marshak‐Rothstein A. Antimalarial agents: closing the gate on toll‐like receptors?. Arthritis Rheum. 2006;54(10):3068-70. doi: 10.1002/art.22157. [PubMed: 17009223].
  34. Nikolaidou P, Charocopos E, Anagnostopoulos G, Lazopoulou D, Kairis M, Lourida A, et al. Cellular interstitial pneumonitis in children: response to hydroxychloroquine treatment in two cases. Pediatr Allergy Immunol. 2003;16(1):45-51.
  35. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. [PubMed: 31986264].
  36. Myall KJ, Mukherjee B, Castanheira AM, Lam JL, Benedetti G, Mak SM, et al. Persistent post–COVID-19 interstitial
  37. lung disease. An observational study of corticosteroid treatment. Ann Am Thorac Soc. 2021;18(5):799-806. doi: 10.1513/AnnalsATS.202008-1002OC. [PubMed: 33433263].
  38. Millan-Oñate J, Millan W, Mendoza LA, Sanchez CG, Fernandez-Suarez H, Bonilla-Aldana DK, et al. Successful recovery of COVID-19 pneumonia in a patient from Colombia after receiving chloroquine and clarithromycin. Ann Clin Microbiol Antimicrob. 2020;19(1):1-9. doi: 10.1186/s12941-020-00358-y.
  39. Mehra MR, Desai SS, Ruschitzka F, Patel AN. RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. 2020;395(10240):1820. doi: 10.1016/S0140-6736(20)31324-6. [PubMed: 32511943].
  40. Machiels JD, Bleeker-Rovers CP, Ter Heine R, Rahamat-Langendoen J, de Mast Q, Ten Oever J, et al. Reply to Gautret et al: hydroxychloroquine sulfate and azithromycin
  41. for COVID-19: what is the evidence and what are the risks?.
  42. Int J Antimicrob Agents. 2020;56(1):106056. doi: 10.1016/j.ijantimicag.2020.106056. [PubMed: 32674929].