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. 2022 Jul;54(7):467-477.
doi: 10.1080/23744235.2022.2043560. Epub 2022 Mar 14.

Registered clinical trials investigating treatment of long COVID: a scoping review and recommendations for research

Felicia Ceban  1   2 , Alexia Leber  1 , Muhammad Youshay Jawad  1 , Mathew Yu  1 , Leanna M W Lui  1 , Mehala Subramaniapillai  1   2 , Joshua D Di Vincenzo  1   3 , Hartej Gill  1 , Nelson B Rodrigues  1 , Bing Cao  4 , Yena Lee  1   2 , Kangguang Lin  5   6 , Rodrigo B Mansur  1   7 , Roger Ho  8   9 , Matthew J Burke  7   10   11 , Joshua D Rosenblat  1   7 , Roger S McIntyre  1   2   3   7
Affiliations

Registered clinical trials investigating treatment of long COVID: a scoping review and recommendations for research

Felicia Ceban et al. Infect Dis (Lond). 2022 Jul.

Abstract

Background: A considerable proportion of individuals report persistent, debilitating and disparate symptoms despite resolution of acute COVID-19 infection (i.e. long COVID). Numerous registered clinical trials investigating treatment of long COVID are expected to be completed in 2021-2022. The aim of this review is to provide a scope of the candidate treatments for long COVID. A synthesis of ongoing long COVID clinical trials can inform methodologic approaches for future studies and identify key research vistas.

Methods: Scoping searches were conducted on multiple national and international clinical trial registries. Interventional trials testing treatments for long COVID were selected. The search timeline was from database inception to 28 July 2021.

Results: This scoping review included 59 clinical trial registration records from 22 countries with a total projected enrolment of 6718. Considerable heterogeneity was exhibited amongst component records with respect to the characterization of long COVID (i.e. name, symptoms- including frequency, intensity, trajectory and duration- mode of ascertainment, and definition of acute phase). In addition, the majority of proposed interventions were non-pharmacological and either targeted multiple long COVID symptoms simultaneously, or focussed on treatment of respiratory/pulmonary sequelae. Multiple interventions targeted inflammation, as well as tissue oxygenation and cellular recovery, and several interventions were repurposed from analogous conditions.

Conclusions: The results of this scoping review investigating ongoing clinical trials testing candidate treatments for long COVID suggest that a greater degree of definitional stringency and homogeneity is needed insofar as the characterization of long COVID and inclusion/exclusion criteria.

Keywords: Long COVID; dyspnoea; fatigue; post-COVID-19 condition; rehabilitation; treatment.

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Conflict of interest statement

FC and RSM conceptualized and designed study. FC and AL performed study search and selection. FC, AL, MYJ and MY performed data extraction. FC and AL performed data synthesis. FC performed data analyses and drafted the manuscript. All authors revised and approved the final version of the manuscript.

RSM has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie. RSM is a CEO of Braxia Scientific Corp. JDR is the medical director of Braxia Health (formally known as the Canadian Rapid Treatment Centre of Excellence and is a fully owned subsidiary of Braxia Scientific Corp) which provides ketamine and esketamine treatment for depression; he has received research grant support from the American Psychiatric Association, the American Society of Psychopharmacology, the Canadian Cancer Society, the Canadian Psychiatric Association, the Joseph M. West Family Memorial Fund, the Timeposters Fellowship, the University Health Network Centre for Mental Health, and the University of Toronto and speaking, consultation, or research fees from Allergan, COMPASS, Janssen, Lundbeck and Sunovion. YL has received personal fees from Braxia Scientific Corp. LMWL has received personal fees from Braxia Scientific Corp and honoraria Medscape. All other authors declare no conflicts of interest or financial disclosures.

Figures

Figure 1.
Figure 1.
Flow diagram of registration record selection.
Figure 2.
Figure 2.
Global distribution of included trials (n = 59).
Figure 3.
Figure 3.
(A) Proportions of types of interventions. Intervention categories are mutually exclusive (n = 59 trials). (B) Proportions of long COVID symptoms under investigation. Symptom categories are mutually exclusive (n = 59 trials).
See this image and copyright information in PMC

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