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

• Authors: Hector Bonilla, Stanford University; Michael J. Peluso, University of California San Francisco; Kathleen Rodgers, University of Arizona; Judith A. Aberg, Icahn School of Medicine at Mount Sinai; Thomas F. Patterson, University of Texas San Antonio; Robert Tamburro, National Institutes of Health; Lawrence Baizer, National Institutes of Health; Jason D. Goldman, Swedish Medical Center; Nadine Rouphael, Emory University; Amelia Deitchman, University of California San Francisco; Jeffrey Fine, New York University; Paul Fontelo, National Institutes of Health; Arthur Y. Kim, Harvard Medical School; Gwendolyn Shaw, Research Triangle Institute; Jeran Stratford, Research Triangle Institute; Patricia Ceger, Research Triangle Institute; Maged M. Costantine, Ohio State University; Liza Fisher, Long COVID Families; Lisa O'Brien, Utah Covid 19 Long Haulers; Christine Maughan, Utah Covid 19 Long Haulers; John G. Quigley, University of Illinois; Vilma Gabbay, Albert Einstein College of Medicine; Sindhu Mohandas, University of Southern California; David Williams, University of Michigan; Grace A. McComsey, Case Western Reserve University
• Journal Title: FRONTIERS IN IMMUNOLOGY
• Volume: Volume 14
• Publisher: FRONTIERS MEDIA SA | 2023-03-09, Pages 1129459-1129459
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3389/fimmu.2023.1129459
• Subjects: Health Sciences, Immunology; Biology, Cell; Biology, Virology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; post-acute sequela of SARS-CoV-2 (PASC); long COVID; SARS- CoV-2; long haulers; treatment; clinical trials; recover; INDUCED MICROGLIAL ACTIVATION; IMMUNE ACTIVATION; T-CELLS; ARIPIPRAZOLE; VALGANCICLOVIR; INFECTION; SYMPTOMS; EBV

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.