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Review
. 2023 Mar 9:14:1129459.
doi: 10.3389/fimmu.2023.1129459. eCollection 2023.

Therapeutic trials for long COVID-19: A call to action from the interventions taskforce of the RECOVER initiative

Hector Bonilla  1 , Michael J Peluso  2 , Kathleen Rodgers  3 , Judith A Aberg  4 , Thomas F Patterson  5 , Robert Tamburro  6 , Lawrence Baizer  7 , Jason D Goldman  8   9 , Nadine Rouphael  10 , Amelia Deitchman  11 , Jeffrey Fine  12 , Paul Fontelo  13 , Arthur Y Kim  14 , Gwendolyn Shaw  15 , Jeran Stratford  15 , Patricia Ceger  15 , Maged M Costantine  16 , Liza Fisher  17 , Lisa O'Brien  18 , Christine Maughan  18 , John G Quigley  19 , Vilma Gabbay  20 , Sindhu Mohandas  21 , David Williams  22 , Grace A McComsey  23
Affiliations
Review

Therapeutic trials for long COVID-19: A call to action from the interventions taskforce of the RECOVER initiative

Hector Bonilla et al. Front Immunol. .

Abstract

Although most individuals recover from acute SARS-CoV-2 infection, a significant number continue to suffer from Post-Acute Sequelae of SARS-CoV-2 (PASC), including the unexplained symptoms that are frequently referred to as long COVID, which could last for weeks, months, or even years after the acute phase of illness. The National Institutes of Health is currently funding large multi-center research programs as part of its Researching COVID to Enhance Recover (RECOVER) initiative to understand why some individuals do not recover fully from COVID-19. Several ongoing pathobiology studies have provided clues to potential mechanisms contributing to this condition. These include persistence of SARS-CoV-2 antigen and/or genetic material, immune dysregulation, reactivation of other latent viral infections, microvascular dysfunction, and gut dysbiosis, among others. Although our understanding of the causes of long COVID remains incomplete, these early pathophysiologic studies suggest biological pathways that could be targeted in therapeutic trials that aim to ameliorate symptoms. Repurposed medicines and novel therapeutics deserve formal testing in clinical trial settings prior to adoption. While we endorse clinical trials, especially those that prioritize inclusion of the diverse populations most affected by COVID-19 and long COVID, we discourage off-label experimentation in uncontrolled and/or unsupervised settings. Here, we review ongoing, planned, and potential future therapeutic interventions for long COVID based on the current understanding of the pathobiological processes underlying this condition. We focus on clinical, pharmacological, and feasibility data, with the goal of informing future interventional research studies.

Keywords: SARS- CoV-2; clinical trials; long COVID; long haulers; post-acute sequela of SARS-CoV-2 (PASC); recover; treatment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Most common symptoms reported in long COVID population.
See this image and copyright information in PMC

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