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

• Main Authors: Yong, Shin Jie *, Halim, Alice, Halim, Michael, Long, Chiau Ming *, Goh, Khang Wen, Alfaresi, Mubarak, Alsalem, Zainab, Alwashmi, Ameen S S, Khamis, Faryal, Al Kaabi, Nawal A, Albayat, Amal, Alsheheri, Ahmed, Garout, Mohammed, Alsalman, Jameela, Alfaraj, Amal H, Alhajri, Mashael, Dhama, Kuldeep, Alburaiky, Lamees M, Alsanad, Ahlam H, AlShurbaji, Abdelmunim T, Rabaan, Ali A
• Format: Article
• Published: 2023
• Subjects: RA Public aspects of medicine; RM Therapeutics. Pharmacology; RS Pharmacy and materia medica
• Online Access: http://eprints.sunway.edu.my/2766/; https://doi.org/10.1080/13543784.2023.2242773

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.