National patient study identifies four categories of long COVID, and found potential target for future COVID-19 therapies
Roughly a quarter of U.S. adults who’ve tested positive for COVID-19 report having experienced, or are currently experiencing, three or more months of COVID symptoms, such as dizziness, headache, brain fog, and/or other symptoms, according to October 2023 data from the Center for Disease Control and Prevention’s (CDC) Household Pulse Survey. The condition is known as Post-acute sequelae of SARS-CoV-2 or “long COVID.” And among hospitalized COVID-19 patients, that number increases to roughly half.
Many hospitalized COVID-19 patients report a range of symptoms – fatigue, cough, trouble breathing and more. Now a new study from researchers at Drexel University’s College of Medicine, and additional colleagues from the NationalInstitute of Allergy and Infectious Diseases (NIAID)-funded national “IMmunoPhenotyping Assessment in a COVID-19 Cohort” (IMPACC), gives clinical providers insights to help patients anticipate what they may or may not experience down the road with the disease. It also gives providers more confidence when they set out a care plan for hospitalized patients aimed to help prevent long COVID, such as determining which patients need antivirals early after disease onset.
In the study, researchers surveyed 590 adult COVID patients from 20 hospitals and followed them with quarterly surveys through one year after patients left the hospital. The questionnaire asked participants’ vaccination status, swabbed patients for the amount of virus in their body, took blood samples to measure antibodies and inflammation markers, and assed whether patients were experiencing any upper respiratory, cardiopulmonary, neurologic, or gastrointestinal symptoms, as wells as systemic symptoms like fever, chills, fatigue or muscle aches. Then they followed up with those patients to figure out if those symptoms and attributes of their case in the hospital correlated with symptoms they were experiencing as much as a year later.
As seen in previous studies, more than half of the participants reported long COVID symptoms three months or later after they left the hospital. The authors separated the long COVID outcomes into four categories – minimal, defined as non-impactful symptoms; physical, defined as symptoms that impact vital organ functions; mental or cognitive symptoms; and multidomain, defined as both physical and mental impacts.
The research team found that female gender, those with chronic heart disease and/or neurological diseases, and those who stayed longer in the hospital were at greater risk for long COVID. They also identified a unique group of long COVID patients with only mental and cognitive impact from the disease. The findings were published this month in the journal Nature Communications.
“The effects of long COVID are real in a significant number of patients after hospitalization,” said study co-author Charles Cairns, MD, the Walter H. and Leonore Annenberg dean and senior vice president of medical affairs at Drexel’s College of Medicine. “We’re documenting immunological characteristics that identify which disease course that long COVID patients will have, including manifestations that are mainly physical versus a distinctive group of patients that have predominantly mental and cognitive disorders.”
Authors also found a molecule known as FGF21 that was present in long COVID patients experiencing brain fog and those experiencing multiple symptoms, suggesting that FGF21 may be a target for future drugs against COVID-19. The Drexel authors were surprised to see a group of long COVID patients with cognitive deficits that were not associated with a high viral load or poor antibody response while the patients were still in the hospital (and early in the disease course), suggesting that the responses to infection associated with mental and brain deficits in long COVID may be different from the responses associated with other functional deficits in long COVID.
“This paper is evidence that long COVID is not one thing,” said co-author Elias El-Haddad, PhD, a professor in the College of Medicine. “Long COVID is a heterogenous disease combining mental and physical problems whose cause is different for each patient.”
U.S. Congress has passed more than $1 billion in funding for long COVID studies. Long COVID can follow after cases of mild or more serious illness, and as much as four out of 10 people with the disease are out of the labor force and more than half work fewer hours than they did before their diagnosis. The COVID-19 pandemic’s impact on the U.S. economy is estimated to be $14 trillion through 2023.
Since the early days of the COVID-19 pandemic, IMPACC has led research into the immune responses of COVID-19 patients. Across 15 research institutions, the massive undertaking aims to find out how immunological markers predict the severity of COVID-19 and reveal insights into care and treatments.
This paper marks the research group’s first look into long COVID. In August 2022, the group published insights in The Lancet’s eBioMedicine into characteristics that are linked with more severe COVID cases, as discussed in a 2022 Drexel News Blog post. Additional IMPACC studies have looked at the specific biological characteristics of the immunological response to COVID-19 in Cell Medicine Reports and this study in Nature Communications. For more on Drexel’s role in the IMPACC trial, check out this story on the College of Medicine website.
The IMPACC team is currently working on a series of analyses to integrate immunological features across key areas of biomedical science, including genomic, proteomic, metabolic and immunologic approaches to further define characteristic signatures of disease severity and duration. The authors caution that the findings in this study are correlations, so their next steps in the research will look at predictive modeling, and a group to validate the data.
Reporters interested in talking to Cairns and Haddad should contact Greg Richter, assistant director, news and media relations, at 215-895-2614 or gdr33@drexel.edu.
