An umbrella review on treatments and therapeutic options for COVID-19

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Abstract

Introduction. As the COVID-19 pandemic continues to pose a significant challenge to global health, effective therapeutic options for preventing and treating the disease have become increasingly important. We aimed to provide an update on current treatments and therapeutic options for COVID-19 patients. Materials and methods. The purpose of this umbrella review is to explore the current treatments and therapeutic options for COVID-19 patients. Keywords and their combinations were searched across online databases in Embase, PubMed/MEDLINE, Web of Science, and Scopus spanning from July 1, 2020, through March 3, 2023. Publications were selected for data extraction in two steps based on the study inclusion/exclusion criteria. The study adheres to the PRISMA checklist as well as NIH bias risk and quality assessment tool. Results. In this review, 28 relevant articles were selected for the final qualitative synthesis. The majority of included studies had reported on the efficacy of Lopinavir/Ritonavir (n = 4), Ivermectin (n = 3), Baricitinib (n = 2), Tocilizumab (n = 2), Remdesivir (n = 2), ACEI/ARB (n = 2), Vitamin D (n = 2), Molnupiravir (n = 2), Traditional Chinese medicine (TCM) (n = 2), Convalescent plasma transfusion (CPT) (n = 2) and hydroxychloroquine (n = 2) in treating COVID-19. It appeared that Baricitinib, Remdesivir, ACEI/ARB, TCM, and CPT may have beneficial effects on reducing mortality, hospitalization duration, and disease severity in COVID-19 patients. Other interventions, such as Lopinavir/Ritonavir, Ivermectin, Vitamin D, and Hydroxychloroquine did not show clear benefits or had inconclusive results. Conclusion. This umbrella review provides a comprehensive overview of the current evidence on the effectiveness and safety of various pharmacological and non-pharmacological interventions for COVID-19. These results provide an updated overview of the current landscape for COVID-19 treatments, highlighting potential avenues for further research and clinical practice. It is crucial to continue monitoring emerging evidence and conducting rigorous studies to guide the development and optimization of therapeutic strategies against COVID-19.

About the authors

SeyedAhmad SeyedAlinaghi

Iranian Research Center for HIV/AIDS (IRCHA), Tehran University of Medical Sciences

Email: s_a_alinaghi@yahoo.com

MD, MPhil, PhD, Clinical Epidemiologist, Associate Professor, Research Deputy 

Iran, Islamic Republic of, Tehran

Amir M. Afsahi

University of California

Email: amir.masoud.afsahi@gmail.com

MD, PhD, Department of Radiology, School of Medicine

United States, San Diego

Ayoob Molla

Bushehr University of Medical Sciences

Email: Ayoob.dpt87@gmail.com

MD Student, School of Medicine

Iran, Islamic Republic of, Bushehr

Pegah Mirzapour

Iranian Research Center for HIV/AIDS (IRCHA), Tehran University of Medical Sciences

Email: pegah.mirzapour@yahoo.com

Iranian Research Center for HIV/AIDS (IRCHA)

Iran, Islamic Republic of, Tehran

Ramin Shahidi

Bushehr University of Medical Sciences

Email: dr.raminshahidi1@gmail.com

MD, School of Medicine

Iran, Islamic Republic of, Bushehr

Haleh Siami

Islamic Azad University

Email: Haleh.siami@gmail.com

MD student, School of Medicine

Iran, Islamic Republic of, Tehran

Farid F. Rad

Tehran University of Medical Sciences

Email: farid.f.rad@gmail.com

MD student, School of Medicine

Iran, Islamic Republic of, Tehran

Faeze Abbaspour

Tehran University of Medical Sciences

Email: absprfaeze@gmail.com

School of Medicine

Iran, Islamic Republic of, Tehran

Navid Mozafari

Bushehr University of Medical Sciences

Email: navidmozaffari97@gmail.com

School of Medicine

Iran, Islamic Republic of, Bushehr

Kamal Fakhredini

Behavioral Diseases Research Center, Health Institute, Kermanshah University of Medical Sciences

Email: fakhredini1@gmail.com

PhD, MD student

Iran, Islamic Republic of, Kermanshah

Esmaeil Mehraeen

Khalkhal University of Medical Sciences

Author for correspondence.
Email: es.mehraeen@gmail.com

PhD, Assistant Professor, Department of Health Information Technology

Iran, Islamic Republic of, Khalkhal

Omid Dadras

University of Bergen

Email: omiddadras@yahoo.com

MD, Dr.PH, Bergen Addiction Research, Department of Addiction Medicine

Norway, Bergen

References

  1. Albuquerque A.M., Eckert I., Tramujas L., Butler-Laporte G., McDonald E.G., Brophy J.M., Lee T.C. Effect of tocilizumab, sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: a systematic review and meta-analysis. Clin. Microbiol. Infect. 2023, vol. 29, no. 1, pp. 13–21. doi: 10.1016/j.cmi.2022.07.008
  2. Amstutz A., Speich B., Mentré F., Rueegg C.S., Belhadi D., Assoumou L., Burdet C., Murthy S., Dodd L.E., Wang Y., Tikkinen K.A.O., Ader F., Hites M., Bouscambert M., Trabaud M.A., Fralick M., Lee T.C., Pinto R., Barratt-Due A., Lund-Johansen F., Müller F., Nevalainen O.P.O., Cao B., Bonnett T., Griessbach A., Taji Heravi A., Schönenberger C., Janiaud P., Werlen L., Aghlmandi S., Schandelmaier S., Yazdanpanah Y., Costagliola D., Olsen I.C., Briel M. Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials. Lancet Respir. Med., 2023, vol. 11, no. 5, pp. 453–464. doi: 10.1016/S2213-2600(22)00528-8
  3. Ansems K., Grundeis F., Dahms K., Mikolajewska A., Thieme V., Piechotta V., Metzendorf M.I., Stegemann M., Benstoem C., Fichtner F. Remdesivir for the treatment of COVID-19. Cochrane Database Syst. Rev., 2021, vol. 8, no. 8: CD014962. doi: 10.1002/14651858.CD014962
  4. Areri H., Marshall A., Harvey G. Factors influencing self-management of adults living with HIV on antiretroviral therapy in Northwest Ethiopia: a cross-sectional study. BMC Infect. Dis., 2020, vol. 20, no. 1: 879. doi: 10.1186/s12879-020-05618-y
  5. Celotto S., Veronese N., Barbagallo M., Ometto F., Smith L., Pardhan S., Barnett Y., Ilie P.C., Soysal P., Lagolio E., Kurotschka P.K., Tonelli R., Demurtas J. An umbrella review of systematic reviews with meta-analyses evaluating positive and negative outcomes of Hydroxychloroquine and chloroquine therapy. Int. J. Infect. Dis., 2021, vol. 103, pp. 599–606. doi: 10.1016/j.ijid.2020.12.018
  6. Cheema H.A., Sohail A., Fatima A., Shahid A., Shahzil M., Ur Rehman M.E., Awan R.U., Chinnam S., Nashwan A.J. Quercetin for the treatment of COVID-19 patients: a systematic review and meta-analysis. Rev. Med. Virol., 2023, vol. 33, no. 2: e2427. doi: 10.1002/rmv.2427
  7. Chinta S., Rodriguez-Guerra M., Shaban M., Pandey N., Jaquez-Duran M., Vittorio T.J. COVID-19 therapy and vaccination: a clinical narrative review. Drugs Context, 2023, vol. 12: 2022-7-2. doi: 10.7573/dic.2022-7-2
  8. Dahms K., Mikolajewska A., Ansems K., Metzendorf M.I., Benstoem C., Stegemann M. Anakinra for the treatment of COVID-19 patients: a systematic review and meta-analysis. Eur. J. Med. Res., 2023, vol. 28, no. 1: 100. doi: 10.1186/s40001-023-01072-z
  9. Deng J., Rayner D., Ramaraju H.B., Abbas U., Garcia C., Heybati K., Zhou F., Huang E., Park Y.J., Moskalyk M. Efficacy and safety of selective serotonin reuptake inhibitors in COVID-19 management: a systematic review and meta-analysis. Clin. Microbiol. Infect., 2023, vol. 29, no. 5, pp. 578–586. doi: 10.1016/j.cmi.2023.01.010
  10. Dhawan M., Priyanka, Parmar M., Angural S., Choudhary O.P. Convalescent plasma therapy against the emerging SARS-CoV-2 variants: delineation of the potentialities and risks. Int. J. Surg., 2022, vol. 97: 106204. doi: 10.1016/j.ijsu.2021.106204
  11. Feiner Solís Á., Avedillo Salas A., Luesma Bartolomé M.J., Santander Ballestín S. The effects of Vitamin D supplementation in COVID-19 patients: a systematic review. Int. J. Mol. Sci., 2022, vol. 23, no. 20: 12424. doi: 10.3390/ijms232012424
  12. Giles G., Varghese S., Shymko G., Nguyen T., Waters F. Clozapine therapy and COVID-19: a systematic review of the prevalence rates, health outcomes, hematological markers, and patient perspectives. Schizophr Bull., 2023, vol. 49, no. 1, pp. 53–67. doi: 10.1093/schbul/sbac148
  13. Greene C., Wilson J., Griffin H., Tingle A., Cooper T., Semple M.G., Enoch D., Lee A., Loveday H. The role of pandemic planning in the management of COVID-19 in England from an infection prevention and control perspective: results of a national survey. Public Health., 2023, vol. 217, pp. 89–94. doi: 10.1016/j.puhe.2023.01.028
  14. Hayden M.K., Hanson K.E., Englund J.A., Lee F., Lee M.J., Loeb M., Morgan D.J., Patel R., El Alayli A., El Mikati I.K., Sultan S., Falck-Ytter Y., Mansour R., Amarin J.Z., Morgan R.L., Murad M.H., Patel P., Bhimraj A., Mustafa R.A. The Infectious Diseases Society of America Guidelines on the diagnosis of COVID-19: antigen testing. Clin. Infect. Dis., 2023: ciad032. doi: 10.1093/cid/ciad032
  15. Huang N.X., Yuan Q., Fang F., Yan B.P., Sanderson J.E. Systematic review and meta-analysis of the clinical outcomes of ACEI/ARB in East-Asian patients with COVID-19. PLoS One, 2023, vol. 18, no. 1: e0280280. doi: 10.1371/journal.pone.0280280
  16. Kramer A., Prinz C., Fichtner F., Fischer A.L., Thieme V., Grundeis F., Spagl M., Seeber C., Piechotta V., Metzendorf M.I., Golinski M., Moerer O., Stephani C., Mikolajewska A., Kluge S., Stegemann M., Laudi S., Skoetz N. Janus kinase inhibitors for the treatment of COVID-19. Cochrane Database Syst. Rev., 2022, vol. 6, no. 6: CD015209. doi: 10.1002/14651858.CD015209
  17. Kurniawati D.R., Subagjo A., Djuari L. Efficacy and safety of prophylactic-dose anticoagulation therapy with intermediate-therapeutic doses in COVID-19 patients. Indian Journal of Forensic Medicine & Toxicology, 2023, vol. 17, no. 1, pp. 97–101, doi: 10.37506/ijfmt.v17i1.18902
  18. Li Y., Qin Y., Chen N., Ge L., Wang Q., Aboudou T., Han J., Hou L., Cao L., Li R., Li M., Mi N., Xie P., Wu S., Hu L., Li X., Song Z., Ji J., Zhang Z., Yang K. Use of traditional Chinese medicine for the treatment and prevention of COVID-19 and rehabilitation of COVID-19 patients: an evidence mapping study. Front. Pharmacol., 2023, vol. 14: 1069879. doi: 10.3389/fphar.2023.1069879
  19. Liang W., Liang H., Ou L., Chen B., Chen A., Li C., Li Y., Guan W., Sang L., Lu J., Xu Y., Chen G., Guo H., Guo J., Chen Z., Zhao Y., Li S., Zhang N., Zhong N., He J. China Medical Treatment Expert Group for COVID-19. Development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19. JAMA Intern. Med., 2020, vol. 180, no. 8, pp. 1081–1089. doi: 10.1001/jamainternmed.2020.2033
  20. Liu Q., Fu W., Zhu C.J., Ding Z.H., Dong B.B., Sun B.Q., Chen R.C. Effect of continuing the use of renin-angiotensin system inhibitors on mortality in patients hospitalized for coronavirus disease 2019: a systematic review, meta-analysis, and meta-regression analysis. BMC Infect. Dis., 2023, vol. 23, no. 1: 53. doi: 10.1186/s12879-023-07994-7
  21. Luo X., Zhang Y., Li H., Ren M., Liu Y., Liu Y., Zhang Y., Kuang Z., Cai Y., Chen Y., Ni X. Clinical evidence on the use of Chinese herbal medicine for acute infectious diseases: an overview of systematic reviews. Front. Pharmacol., 2022, vol. 13: 752978. doi: 10.3389/fphar.2022.752978
  22. Maideen N.M.P., Balasubramanian R., Manavalan G., Balasubramanian K., Subramanian N., Murugesan T., Solaimalai V.K. An insight of clinical evidence of ayurveda interventions in the management of COVID-19 patients. Infect. Disord. Drug Targets, 2022, vol. 22, no. 6: e210322202491. doi: 10.2174/1871526522666220321152504
  23. Mali K.R., Eerike M., Raj G.M., Bisoi D., Priyadarshini R., Ravi G., Chaliserry L.F., Janti S.S. Efficacy and safety of Molnupiravir in COVID-19 patients: a systematic review. Ir. J. Med. Sci., 2023, vol. 192, no. 4, pp. 1665–1678. doi: 10.1007/s11845-022-03139-y
  24. Mehraeen E., Najafi Z., Hayati B., Javaherian M., Rahimi S., Dadras O., SeyedAlinaghi S., Ghadimi M., Sabatier J.M. Current treatments and therapeutic options for COVID-19 patients: a systematic review. Infect. Disord. Drug Targets, 2022, vol. 22, no. 1: e260721194968. doi: 10.2174/1871526521666210726150435
  25. Mehraeen E., Oliaei S., SeyedAlinaghi S., Karimi A., Mirzapour P., Afsahi A.M., Barzegary A., Vahedi F., Soleymanzadeh M., Behnezhad F., Javaherian M., Zargari G., Mirghaderi S.P., Noori T., Sabatier J.M. COVID-19 in pediatrics: a systematic review of current knowledge and practice. Infect. Disord. Drug Targets, 2022, vol. 22, no. 5: e290921196908. doi: 10.2174/1871526521666210929121705
  26. Migliorini F., Vaishya R., Eschweiler J., Oliva F., Hildebrand F., Maffulli N. Vitamins C and D and COVID-19 susceptibility, severity and progression: an evidence based systematic review. Medicina (Kaunas), 2022, vol. 58, no. 7: 941. doi: 10.3390/medicina58070941
  27. Mohseni M., Ameri H., Arab-Zozani M. Potential limitations in systematic review studies assessing the effect of the main intervention for treatment/therapy of COVID-19 patients: an overview. Front. Med. (Lausanne), 2022, vol. 9: 966632. doi: 10.3389/fmed.2022.966632
  28. Morishita M., Hojo M. Treatment options for patients with severe COVID-19. Glob. Health Med., 2023, vol. 5, no. 2, pp. 99–105. doi: 10.35772/ghm.2023.01024
  29. Mousavi S., Zare S., Mirzaei M., Feizi A. Novel drug design for treatment of COVID-19: a systematic review of preclinical studies. Can. J. Infect. Dis. Med. Microbiol., 2022, vol. 2022: 2044282. doi: 10.1155/2022/2044282
  30. Niranjan A.K., Patel S.K., Channabasappa N.K., Rana J., Agrawal A., Kumar R., Pandey M.K., Tiwari S.P., Singh D.R. Resurgence of cholera in the COVID-19 era: a global health concern. Ann. Med. Surg. (Lond.), 2023, vol. 85, no. 4, pp. 1321–1322. doi: 10.1097/MS9.0000000000000415
  31. Pahari K.P., Vyas S., Aman S., Singh U., Singh P.K., Tiwari R., Dhanawat M., Therapeutic options for the treatment of 2019-novel Coronavirus in India: a review. Coronaviruses, 2022, vol. 3, no. 2: e041220188720. doi: 10.2174/2666796701999201204115545
  32. Pantsari T., Ali M.M., Ghouri M.H., Alharbi A.M., Alfahemi H. Role of antiviral drugs in management of mild and moderate Coronavirus disease-19: a systematic review. Adv. Life Sci. 2022, vol. 9, no. 3, pp. 270–276
  33. Paraskevas T., Kantanis A., Karalis I., Michailides C., Karamouzos V., Koniari I., Pierrakos C., Velissaris D. N-acetylcysteine efficacy in patients hospitalized with COVID-19 pneumonia: a systematic review and meta-analysis. Rom. J. Intern. Med., 2023, vol. 61, no. 1, pp. 41–52. doi: 10.2478/rjim-2023-0001
  34. Pashaei Z., SeyedAlinaghi S., Qaderi K., Barzegary A., Karimi A., Mirghaderi S.P., Mirzapour P., Tantuoyir M.M., Dadras O., Ali Z., Voltarelli F., Mehraeen E. Prenatal and neonatal complications of COVID-19: a systematic review. Health Sci. Rep., 2022, vol. 5, no. 2: e510. doi: 10.1002/hsr2.510
  35. Patel T.K., Patel P.B., Barvaliya M., Saurabh M.K., Bhalla H.L., Khosla P.P. Efficacy and safety of lopinavir-ritonavir in COVID-19: a systematic review of randomized controlled trials. J. Infect. Public Health, 2021, vol. 14, no. 6, pp. 740–748. doi: 10.1016/j.jiph.2021.03.015
  36. Popp M., Reis S., Schießer S., Hausinger R.I., Stegemann M., Metzendorf M.I., Kranke P., Meybohm P., Skoetz N., Weibel S. Ivermectin for preventing and treating COVID-19. Cochrane Database Syst. Rev., 2022, vol. 6, no. 6: 015017. doi: 10.1002/14651858.CD015017.pub3
  37. RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet, 2020, vol. 396, no. 10259, pp. 1345–1352. doi: 10.1016/S0140-6736(20)32013-4
  38. Reis S., Metzendorf M.I., Kuehn R., Popp M., Gagyor I., Kranke P., Meybohm P., Skoetz N., Weibel S. Nirmatrelvir combined with ritonavir for preventing and treating COVID-19. Cochrane Database Syst. Rev., 2022, vol. 9, no. 9: 015395. doi: 10.1002/14651858.CD015395.pub2
  39. Sanghavi D., Bansal P., Kaur I.P., Mughal M.S., Keshavamurthy C., Cusick A., Schram J., Yarrarapu S.N.S., Giri A.R., Kaur N., Moreno Franco P., Abril A., Aslam F. Impact of colchicine on mortality and morbidity in COVID-19: a systematic review. Ann. Med., 2022, vol. 54, no. 1, pp. 775–789. doi: 10.1080/07853890.2021.1993327
  40. SeyedAlinaghi S., Karimi A., Barzegary A., Mojdeganlou H., Vahedi F., Mirghaderi S.P., Shobeiri P., Ramezani M., Yousefi Konjdar P., Mirzapour P., Tantuoyir M.M., Mehraeen E., Dadras O., Voltarelli F. COVID-19 mortality in patients with immunodeficiency and its predictors: a systematic review. Eur. J. Med. Res., 2022, vol. 27, no. 1: 195. doi: 10.1186/s40001-022-00824-7
  41. Shang W., Zhang B., Ren Y., Wang W., Zhou D., Li Y. Thymosin alpha1 use in adult COVID-19 patients: a systematic review and meta-analysis on clinical outcomes. Int. Immunopharmacol., 2023, vol. 114: 109584. doi: 10.1016/j.intimp.2022.109584
  42. Shibeeb S., Ajaj I., Al-Jighefee H., Abdallah A.M. Effectiveness of convalescent plasma therapy in COVID-19 patients with hematological malignancies: a systematic review. Hematol. Rep., 2022, vol. 14, no. 4, pp. 377–388. doi: 10.3390/hematolrep14040052
  43. Singh A.K., Singh A., Singh R., Misra A. An updated practical guideline on use of molnupiravir and comparison with agents having emergency use authorization for treatment of COVID-19. Diabetes Metab. Syndr., 2022, vol. 16, no. 2: 102396. doi: 10.1016/j.dsx.2022.102396
  44. Singh A.K., Singh A., Singh R., Misra A. Molnupiravir in COVID-19: a systematic review of literature. Diabetes Metab. Syndr., 2021, vol. 15, no. 6: 102329. doi: 10.1016/j.dsx.2021.102329
  45. Van De Laar C.J., Oude Voshaar M.A.H., Fakhouri W.K.H., Zaremba-Pechmann L., De Leonardis F., De La Torre I., Van De Laar M.A.F.J. Cost-effectiveness of a JAK1/JAK2 inhibitor vs a biologic disease-modifying antirheumatic drug (bDMARD) in a treat-to-target strategy for rheumatoid arthritis. Clinicoecon Outcomes Res., 2020, vol. 12, pp. 213–222. doi: 10.2147/CEOR.S231558
  46. Wei Q., Lin H., Wei R.G., Chen N., He F., Zou D.H., Wei J.R. Tocilizumab treatment for COVID-19 patients: a systematic review and meta-analysis. Infect. Dis. Poverty, 2021, vol. 10. no. 1: 71. doi: 10.1186/s40249-021-00857-w
  47. Yang S., Shen S., Hou N. Is Ivermectin effective in treating COVID-19? Front. Pharmacol., 2022, vol. 13: 858693. doi: 10.3389/fphar.2022.858693

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Copyright (c) 2023 SeyedAlinaghi S., Afsahi A.M., Molla A., Mirzapour P., Shahidi R., Siami H., Farahani Rad F., Abbaspour F., Mozafari N., Fakhredini K., Mehraeen E., Dadras O.

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