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

Expert Opin Investig Drugs. 2023 Jul-Dec;32(7):655-667. doi: 10.1080/13543784.2023.2242773. Epub 2023 Aug 4.

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.

Keywords: Long-COVID; drug; post-COVID-19 syndrome; randomized clinical trial; treatment.

Publication types

  • Systematic Review
  • Review

MeSH terms

  • COVID-19*
  • Drugs, Investigational / therapeutic use
  • Fatigue Syndrome, Chronic* / drug therapy
  • Humans
  • Post-Acute COVID-19 Syndrome
  • Randomized Controlled Trials as Topic

Substances

  • N,N'-bis(2-(1H-imidazol-2-yl)ethyl)pentanediamide
  • Drugs, Investigational