Long COVID a over 200 potential symptoms and can affect almost every organ in the body.
With over 65 million people now believed to be living with this often debilitating disease worldwide, and with their numbers increasing daily, there is a desperate need to understand the underlying biology behind it.
There is currently no effective treatment And no test.
To learn more about this long COVID infection – or post-acute sequelae SARS-CoV-2 (PASC), as it’s increasingly being called – researchers at the US National Institute of Health performed extensive tests on 12 people with long COVID and compared those results to a group of healthy volunteers who had not contracted COVID.
The researchers looked for abnormalities in blood samples, cerebrospinal fluid and MRI scans, and they performed a series of tests to detect autonomic nervous system dysfunction.
The long COVID group was mostly made up of middle-aged women who had mild SARS-CoV-2 infections about nine months ago and now suffered from fatigue and cognitive difficulties that severely affected their daily lives.
One of the most apparent disparities between people with long COVID and healthy volunteers was the number of immune cells.
Compared to the control group, participants with long COVID had reduced numbers of immune cells called memory T cells; these cells typically persist for an extended period after infections, retaining the ability to recognize a specific threat and quickly call the rest of the immune system to arms upon further exposure.
The COVID long haulers also had an increased number of immune cells called B cellsB cells secreting antibodies and activated natural killer cellswhich detect and destroy damaged cells.
For those with long COVID, there was also an increase in immune checkpoint molecules like TIGIT and PD-L1 on immune cells, “suggesting the possibility of immune exhaustion”, the researchers writing.
“The persistence of these immune abnormalities several months after mild infection suggests the possibility of either persistent infection or an aberrant immune response to infection,” the authors explain. writing.

The researchers also looked at dysfunction of the autonomic nervous system, which controls heart rate, blood pressure and breathing.
People with long-term COVID often report rapid heartbeat, dizziness, and feeling faint when going from a sitting to a standing position, known as postural orthostatic tachycardia syndrome (JARS).
To measure these effects, the researchers monitored changes in heart rate and blood pressure over the course of the tilt table testwhen a person is moved from a lying position to a standing position, and during Valsalva maneuverwhere a person blows air while keeping their nose and mouth closed, which usually slows the heart rate.
They found that people with long COVID were less able to control their heart rate and blood pressure when these physiological pressures were applied.
The researchers noted that skin temperature was also lower in people with long COVID throughout the tilt table test, suggesting vasoconstriction, where blood vessels constrict and decrease blood flow to the skin.
While previous studies have suggested that the long neurological symptoms of COVID may be due to inflammation of the brainstem and olfactory bulb of the brain, which receives sensory input from the nose, MRI did not identify any structural abnormalities in the brain. one or the other region.
More research is needed to make this all head or tails off, but this research suggests that immunotherapies could be explored as a treatment for long COVID in clinical tests.
“Preliminary findings […] call for further investigation and evaluation of potential immunomodulatory agents in an effort to reduce the enormous public health burden of this syndrome,” the researchers to write.
This article was published in Neurology: Neuroimmunology & Neuroinflammation.