Experimental drugs in randomized controlled trials for long-COVID: what's in the pipeline? A systematic and critical review

Yong SJ 1 , Halim A 2 , Halim M 3 , Ming LC 1 , Goh KW 4 , Alfaresi M 5 Show all authors , AlShehail BM 6 , Al Fares MA 7 , Alissa M 8 , Sulaiman T 9 , Alsalem Z 10 , Alwashmi ASS 11 , Khamis F 12 , Al Kaabi NA 13 , Albayat H 14 , Alsheheri A 14 , Garout M 15 , Alsalman J 16 , Alfaraj AH 17 , Alhajri M 18 , Dhama K 19 , Alburaiky LM 20 , Alsanad AH 21 , AlShurbaji AT 22 , Rabaan AA 23

Affiliations 

  • 1 Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Subang Jaya, Malaysia
  • 2 Shanghai Medical College, Fudan University, Shanghai, China
  • 3 Department of Biomedical Science, School of Science, Engineering and Environment, University of Salford, Greater Manchester, UK
  • 4 Faculty of Data Science and Information Technology, INTI International University, Nilai, Malaysia
  • 5 Department of Pathology and Laboratory Medicine, Zayed Military Hospital, Abu Dhabi, United Arab Emirates
  • 6 Pharmacy Practice Department, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
  • 7 Department of Internal Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
  • 8 Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
  • 9 Infectious Diseases Section, Medical Specialties Department, King Fahad Medical City, Riyadh, Saudi Arabia
  • 10 Department of Epidemic Diseases Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
  • 11 Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
  • 12 Infection Diseases Unit, Department of Internal Medicine, Royal Hospital, Muscat, Oman
  • 13 College of Medicine and Health Science, Khalifa University, Abu Dhabi, United Arab Emirates
  • 14 Infectious Disease Department, King Saud Medical City, Riyadh, Saudi Arabia
  • 15 Department of Community Medicine and Health Care for Pilgrims, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
  • 16 Infection Disease Unit, Department of Internal Medicine, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama, Bahrain
  • 17 Pediatric Department, Abqaiq General Hospital, First Eastern Health Cluster, Abqaiq, Saudi Arabia
  • 18 Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
  • 19 Division of Pathology, ICAR-Indian Veterinary Research Institute (IVRI), Bareilly, India
  • 20 Pediatric Department, Safwa General Hospital, Eastern Health Cluster, Dammam, Saudi Arabia
  • 21 Neonatal Intensive Care Unit, Pediatrics Department, Maternity and Children Hospital, Dammam, Saudi Arabia
  • 22 College of Pharmacy, Philadelphia University, Amman, Jordan
  • 23 Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
Expert Opin Investig Drugs, 2023;32(7):655-667.
PMID: 37534972 DOI: 10.1080/13543784.2023.2242773

Abstract

INTRODUCTION: Over three years have passed since the emergence of coronavirus disease 2019 (COVID-19), and yet the treatment for long-COVID, a post-COVID-19 syndrome, remains long overdue. Currently, there is no standardized treatment available for long-COVID, primarily due to the lack of funding for post-acute infection syndromes (PAIS). Nevertheless, the past few years have seen a renewed interest in long-COVID research, with billions of dollars allocated for this purpose. As a result, multiple randomized controlled trials (RCTs) have been funded in the quest to find an effective treatment for long-COVID.

AREAS COVERED: This systematic review identified and evaluated the potential of current drug treatments for long-COVID, examining both completed and ongoing RCTs.

EXPERT OPINION: We identified four completed and 22 ongoing RCTs, investigating 22 unique drugs. However, most drugs were deemed to not have high potential for treating long-COVID, according to three pre-specified domains, a testament to the ordeal of treating long-COVID. Given that long-COVID is highly multifaceted with several proposed subtypes, treatments likely need to be tailored accordingly. Currently, rintatolimod appears to have modest to high potential for treating the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) subtype, LTY-100 and Treamid for pulmonary fibrosis subtype, and metformin for general long-COVID prevention.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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