Researchers identified four factors that may anticipate if a patient will develop long COVID.
The four factors are preexisting type 2 diabetes, SARS-CoV-2 RNA in the blood, Epstein-Barr virus DNA in the blood, and the presence of certain autoantibodies.
It is estimated that 31% to 69% of COVID-19 patients may experience long COVID, James R. Heath, PhD, professor and president at the Institute for Systems Biology in Seattle, and colleagues wrote in Cell. The CDC defines long COVID as returning or ongoing health problems occurring 4 or more weeks after infection with SARS-CoV-2.
“Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved,” Heath and colleagues wrote.
The researchers enrolled 309 people in a longitudinal multi-omic study of COVID-19 from the time of diagnosis through recovery. They compared a primary cohort of 209 patients with different levels of infection severity with a cohort of 457 healthy controls. They studied the participants at the time of diagnosis, the time of acute disease, and 2 to 3 months after the onset of initial symptoms.
Common symptoms among participants included fatigue (52%), cough (25%), and loss of taste or smell (18%).
Using electronic health records, the researchers found certain correlations between patients with type 2 diabetes and certain long COVID factors. Female patients, those with chronic obstructive pulmonary disease, and those with a higher red blood cell count at diagnosis were more likely to present with three or more long COVID symptoms.
According to the authors, the reactivation of Epstein-Barr virus (EBV) “has been indirectly inferred to correlate with PASC through antibody titer measurements.” They looked for the reactivation of latent viruses and for SARS-CoV-2 RNA in the blood.
They detected EBV viremia in 14% of patients at diagnosis and SARS-CoV-2 RNA in the blood in 25% of patients at the time of diagnosis. An analysis showed that long COVID symptoms were significantly associated with both EBV viremia and SARS-CoV-2 RNA in the blood at diagnosis.
“We found that early blood viral measurements are strongly associated with certain long COVID symptoms that patients will develop months later,” Yapeng Su, a coauthor of the study and research scientist at Institute for Systems Biology, said in a press release.
The researchers conducted autoantibody panels among participants at the time of diagnosis and 2 to 3 months after symptom onset. Between 2 to 3 months after diagnosis, 44% of participants had autoantibodies.
In what they called one of their “major” findings, they discovered that anti-SARS-CoV-2 antibodies and specific autoantibodies were associated with different long COVID symptoms. As autoantibodies increased, protective SARS-CoV-2 antibodies decreased, suggesting that there is a relationship between long COVID, autoantibodies and an elevated risk for reinfection, they said.
“Many patients with high autoantibodies simultaneously have low (protective) antibodies that neutralize SARS-CoV-2, and that’s going to make them more susceptible to breakthrough infections,” Daniel Chen, another coauthor of the study and a lab assistant at the Institute for Systems Biology, said in the press release.
“Identifying these [long COVID] factors is a major step forward for not only understanding long COVID and potentially treating it, but also which patients are at highest risk for the development of chronic conditions,” Heath said the release.
PERSPECTIVE
K
Kathleen Bell
The study published this week is an exciting first cut through the very large swath of potential factors that might impact the occurrence of long COVID.
Some identified factors seem fairly obvious, such as the impact of viral load and the presence of autoantibodies — which are present in other viral syndromes as well.
Intriguing was the role of latent Epstein-Barr virus reactivation anticipating long COVID syndrome, especially in light of the recent evidence for EBV being a factor associated with the development of multiple sclerosis.
The role of co-morbidities, such as type 2 diabetes mellitus, may allow for better early monitoring of patients, especially those with less access to routine medical care.
This is a very preliminary study on a relatively limited, non-diverse population and a relatively short timeline, but starts to give us targets for monitoring and possibly for interventions.
However, this is not pertinent clinically at this time. Autoantibody or EBV testing is not indicated at this time and much larger studies are needed to follow up on these initial indicators.
The other major challenge is formulating a more definitive definition of what constitutes post-acute COVID-19 sequelae or long COVID. There are large population-based studies being funded by both NIH and CDC, which will help to better characterize definite and probable symptomatology and biomarkers.Kathleen Bell, MDKimberly-Clark Distinguished Chair in Mobility Research
University of Texas Southwestern Medical Center
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