Immune Profile to Distinguish Long COVID

In an exclusive video featured on MedPage Today, Harlan Krumholz, MD, Director of the Center for Outcomes Research and Evaluation, Yale, speaks about a preprint he co-authored still under peer review on the use of immune profiling to differentiate long COVID. Results of the initial study indicate that the syndrome can be explained and indicated through biological methods. The study examines people infected relatively early in the pandemic including a group with persistent symptoms, one with good recoveries, and a healthy control group.

On the patient-reported side of the study, patients who reported long-term COVID symptoms had a particular set of symptoms including brain fog, fatigue, dysautonomia, as well as wide-ranging symptoms that were specific to this group.

Dr. Krumholz points out the many theories that exist about what causes long COVID: viral persistence, autoimmunity, disruption of the microbiome, reactivation of other viruses, and tissue damage starting with the acute infection.  But many doctors even doubt long COVID’s existence,  he indicates in the article–clarifying that he, along with colleagues who have been talking with patients, are convinced that long COVID is real and that people are suffering.

Additionally, he asserts that it is possible that different groups of patients are experiencing symptoms due to unique mechanisms and that there are a lot of people who are affected. “The CDC thinks that maybe one in four people with COVID actually ended up having symptoms that stretched beyond 4 weeks. The estimates of people who have severe symptoms is something like 3-5%, but we still need to learn a lot about this.”

A key finding was the common occurrence of low cortisol levels in those with long COVID. This discovery was associated with disease severity and raised the possibility that this assessment could be used as a screening mechanism.

Krumholz also points out differences, including differences between study participants who had been vaccinated. Additionally, there was  evidence of reactivation of herpes and Epstein-Barr viruses in the long COVID patient group. However, nothing came of taking an extensive look at autoantibodies.

The study needs to be replicated on a larger scale, concludes Dr. Krumholtz, and he states: “Lots of questions remain, but the important thing is that this supports the idea that people who are complaining of long COVID actually have physiologic issues.”

For More Information:

Watch the video of Dr. Harlan Krumholz and read a transcript of his remarks on

Read the study on medRxiv. **Note: This article is a preprint and is in process of being peer-reviewed

Check out LDA’s Lyme & COVID page