Study reveals new insight into Long COVID

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PORTLAND – Initial findings from a study of nearly 10,000 Americans, including those in Maine, indicate that certain symptoms of long COVID occur together and that long COVID was more common and severe in study participants infected before the 2021 Omicron variant. The study is funded by the National Institutes of Health (NIH), and has been published in JAMA, the Journal of the American Medical Association. It was co-authored by Ivette Emery, PhD, a translation scientist at the MaineHealth Institute for Research (MHIR).

These findings come from the NIH’s Researching COVID to Enhance Recovery (RECOVER) initiative, a nationwide effort dedicated to understanding why some people develop long-term symptoms following COVID-19, and most importantly, how to detect, treat and prevent long COVID. The goal is to eventually find potential treatments for long COVID. Clinical symptoms can vary and include fatigue, brain fog and dizziness, and last for months or years after a person has had COVID-19.

“Americans living with long COVID want to understand what is happening with their bodies,” Adm. Rachel L. Levine said, MD, Assistant Secretary for Health for the U.S. Department of Health and Human Services. “RECOVER, as part of a broader government response, in collaboration with academia, industry, public health institutions, advocacy organizations and patients, is making great strides toward improving our understanding of long COVID and its associated conditions.”

Researchers examined data from 9,764 adults, including 119 people who participated through MHIR. Of the study participants, 8,646 had COVID-19 and 1,118 did not. They assessed more than 30 symptoms across multiple body areas and organs and applied statistical analyses that identified 12 symptoms that most set apart those with and without long COVID: post-exertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, heart palpitations, issues with sexual desire or capacity, loss of smell or taste, thirst, chronic cough, chest pain and abnormal movements.

They then established a scoring system based on patient-reported symptoms. By assigning points to each of the 12 symptoms, the team gave each patient a score based on symptom combinations. With these scores in hand, researchers identified a meaningful threshold for identifying participants with long COVID. They also found that certain symptoms occurred together, and defined four subgroups or “clusters” with a range of impacts on health.

“We see through this study that long COVID can take many forms and impacts all parts of the body,” Dr. Emery said, co-Investigator for the MaineHealth RECOVER site. “We are incredibly grateful to our study participants, many of whom continue to suffer with few answers, for helping us take this first step toward understanding this condition.”

Based on a subset of 2,231 patients in this analysis who had a first COVID-19 infection on or after Dec. 1, 2021, when the Omicron variant was circulating, about 10 percent experienced long-term symptoms or long COVID after six months. The researchers found that participants who were unvaccinated, had COVID-19 for the first time before the 2021 Omicron strain, or who had reinfections were more likely to have long COVID and more severe cases of long COVID.

The results are based on a survey of a highly diverse set of patients and are not final. Survey results will next be compared for accuracy against an array of lab tests and imaging.

“Studying the underlying biological mechanisms of long COVID is central to our being able to identify effective treatment strategies in the future,” Cliff Rosen said, MD, Principal Investigator of the Clinical and Translational Research grant at MHIR and the MaineHealth RECOVER site. “Patients need and deserve interventions that will help them get their lives back.”

The ongoing RECOVER research serves as the foundation for planned clinical trials, which would contain interventions rooted in many of the symptoms outlined in this study. RECOVER clinical trials are expected to begin enrolling patient participants later this year. In addition to Drs. Emery and Rosen, the team conducting research at MHIR includes Nurse Practitioner Theresa Roelke and research coordinators Abigail Arruda and Lauren Moore.

“Researching better ways to provide care is a central piece of MaineHealth’s mission,” Elizabeth Jacobs said, MD, MaineHealth Vice President of Research. “Through RECOVER, our team at MHIR is proud to contribute to the science of long COVID and give Maine people access to clinical trials that may lead to treatments or cures.”

To date, more than 100 million Americans have been infected with SARS-CoV-2, the virus that causes COVID-19. As of April, the federal government’s Household Pulse survey estimates that about 6 percent of those infected with the virus continue to experience and suffer from the many symptoms termed together as long COVID. Patients and researchers have identified more than 200 symptoms associated with long COVID.

For more information on RECOVER, visit

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