RECOVER—Researching COVID to Enhance Recovery—is a nationwide initiative dedicated to understanding why some people develop long-term symptoms following COVID-19 infection. Recently, for the first time, the project yielded outcomes that are expected to help standardize the definition of long COVID toward these goals.
The researchers created a scoring system based on the symptoms that most clearly distinguished patients previously infected with COVID-19 from those who had not. Their work was published online May 25 in the Journal of the American Medical Association.
“This initiative is driven by our shared vision to deepen our understanding of one of the most perplexing maladies of our times and to inform recovery and treatment of individuals who grapple with persistent symptoms following COVID-19 infection and learn why they do, so that we can find the most targeted solutions to help patients,” says Alexander Charney, MD, PhD, Associate Professor of Psychiatry, Genetics and Genomic Sciences, Neuroscience, and Neurosurgery, and Director of The Charles Bronfman Institute of Personalized Medicine at the Icahn School of Medicine at Mount Sinai.
Of the 37 symptoms studied, 12 were identified that set those with long COVID apart: post-exertional malaise, fatigue, brain fog, dizziness, gastrointestinal issues, heart palpitations, loss of sexual desire or performance, loss of smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Based on those symptoms, the investigators found that 23 percent of participants with a prior COVID-19 infection crossed the study threshold for long COVID.
“This is the first step of a series of studies that will be published using RECOVER data that will provide critical insights about the incidence, risk factors and pathophysiology of long COVID. This information will be vital for managing the large number of patients afflicted by this emerging condition,” says Juan Wisnivesky, MD, DrPH, Professor of Medicine at Icahn Mount Sinai, a clinical epidemiologist who is one of the primary leads of the RECOVER adult cohort study at the Mount Sinai site. Dr. Wisnivesky is Chief of the Division of General Internal Medicine for the Mount Sinai Health System.
“Our overarching goal for RECOVER is to continue refining the definition of long COVID and to understand the biological causes of the condition. As a major hub for RECOVER enrollment and given the richly diverse communities that we serve—along with our grit—we are uniquely positioned to do just that.” — Alexander Charney, MD, PhD
The results were based on a survey in which 9,764 patients self-reported their symptoms. Next, data from the survey will be compared against lab and imaging results to validate the current findings.
“Until we establish a unifying framework to define it, it’s like we’re flying a plane without navigation,” Dr. Charney says when describing recent developments to come out of the Long COVID RECOVER multi-center study on which Mount Sinai is a co-author. “Defining long COVID in different ways will similarly get us varied answers. Only by creating a clear and uniform definition of long COVID can we accurately diagnose and begin the road to effective treatments. This study brings us closer to that goal of uniformity.”
On the hotly debated vaccination question—in another RECOVER study development—co-author Girish Nadkarni, MD, MPH, noted a preliminary signal in the data showing that being vaccinated was associated with a lower risk of long COVID. Dr. Nadkarni is the Irene and Dr. Arthur M. Fishberg Professor of Medicine, Director of The Charles Bronfman Institute of Personalized Medicine, and Chief, Division of Data Driven and Digital Medicine (D3M), Department of Medicine at Icahn Mount Sinai.
Mount Sinai colleagues in the Department of Psychiatry are leveraging RECOVER biospecimens to gain deeper insights into the cognitive and behavioral manifestations seen in long COVID.
Led by Scott Russo, PhD, Professor of Neuroscience and Director of the Center for Affective Neuroscience and Brain Body Research Center at Icahn Mount Sinai, the research will explore immune-mediated mechanisms underlying the emergence of depression and anxiety observed in this cohort. The work could inform the identification of biomarkers and enhance understanding of psychiatric symptoms associated with the disorder.
Dr. Russo and his team will also use RECOVER MRI data to measure changes in the penetrability of the blood-brain barrier associated with immune alterations and depression in long COVID.
Additional RECOVER brain initiatives, led by a team including Dr. Wisnivesky, Alex D. Federman, MD, MPH, and Jacqueline H. Becker, PhD, will conduct one of the first randomized clinical trials to investigate a potential therapeutic intervention for brain fog, a condition that affects many long COVID patients. Dr. Federman is Professor of Medicine and Director of Research for the Division of General Internal Medicine. Dr. Becker is a neuroscientist and Assistant Professor of Medicine.
Notably, Judith Aberg, MD, FIDA, FACP, the George Baehr Professor of Medicine, Dean of System Operations for Clinical Sciences, and Chief of Infectious Diseases, is a member of the RECOVER Pathobiology and Interventions Task Force. The task force recently published a white paper emphasizing the need for therapeutic interventions for individuals with long COVID. As the Principal Investigator, Dr. Aberg oversees the master contract for upcoming interventional trials sponsored by RECOVER.
“One of the exciting aspects of RECOVER is the collaboration of multi-disciplinary teams across Mount Sinai Health System engaged in interventional trials to improve the quality of life of those with long COVID,” says Dr. Aberg.
Sean Liu, MD, PhD, Medical Director of the COVID-19 Clinical Trials Unit, will lead a study evaluating the use of antivirals to treat long COVID based on the hypothesis that SARS-CoV-2 may persist in certain parts of the body and that a prolonged antiviral course may eliminate these hidden virus reservoirs.
Sarah Humphreys, MD, Assistant Professor of Medicine, will be the local Principal Investigator at Mount Sinai’s Center for Post-COVID Care. Other upcoming trials expected include interventions to improve cognitive function (the RECOVER-NEURO trial) and to address sleep disturbances (the RECOVER-SLEEP trial).
Mariana G. Figueiro, PhD, Professor at the Department of Population Health Science and Policy and Director of the Light and Health Research Center, is one of the Co-Principal Investigators nationally for RECOVER-SLEEP. The upcoming clinical trial will investigate the impact of light, alone and in combination with melatonin, on sleep in long COVID. The Center will serve as the core hub for this research protocol.
“Our overarching goal for RECOVER is to continue refining the definition of long COVID and to understand the biological causes of the condition. As a major hub for RECOVER enrollment and given the richly diverse communities that we serve—along with our grit—we are uniquely positioned to do just that,” says Dr. Charney.