Scientists may be closer to unraveling the mysteries of long covid. New research this week has found several potentially key differences in the blood of people diagnosed with the chronic ailment compared to those who were not. These differences could help scientists develop accurate diagnostic tests for the condition and provide important clues to understanding how and why long covid happens.
In the simplest of terms, people with long covid are thought to have a variety of lingering symptoms caused by their initial infection with the coronavirus. But there are still many unanswered questions about the condition, including its precise definition. Currently, long covid is a diagnosis of exclusion, meaning that it’s diagnosed after other plausible explanations for a person’s illness have been ruled out. There are commonly shared symptoms of long covid, such as chronic fatigue and “brain fog,” but there is still no simple test for identifying someone with it.
Some studies have shown measurable abnormalities in a proportion of people diagnosed with long covid. But a good test for long covid would require the discovery of biomarkers widely and easily seen in patients that wouldn’t otherwise be spotted in healthy people. In this new study, published Monday in Nature, a large team of researchers working with these patients believe that they might have found these biomarkers, or at least a good place to start looking for them.
The study involved over 270 people, who were divided into three groups: People diagnosed with long covid (here defined as having symptoms for at least four months or more after a confirmed infection); people with no confirmed prior infection, and people who had a confirmed infection but recovered fully. The latter two groups served as a control and were matched to the long covid patients in terms of age and other factors. The scientists then compared the blood samples of each group.
Overall, they managed to find consistent immune and hormonal differences between people with and without long covid. Those with long covid tended to have an “exaggerated” humoral immune response to the coronavirus, for example (humoral immunity being the part of our immune system guided by antibodies). The researchers also used machine learning that took their findings into account to develop a potential diagnostic algorithm. This algorithm was then able to differentiate between long covid patients and controls in the study with 96% accuracy.
“This work is so exciting because it is one of the first to show us clear, measurable differences in blood biomarkers of people with long covid compared with people who recovered fully from an acute infection and a group of people who have never been infected with SARS-CoV-2,” said study author David Putrino, a rehabilitation specialist and researchers at Mount Sinai Health System who has worked with long covid patients for several years, in a statement from Mount Sinai. “This is a decisive step forward in the development of valid and reliable blood testing protocols for long covid.”
Their research will have to be confirmed by larger studies and ideally replicated by other scientists before we can expect to see a diagnostic test based on it. But assuming their work does pay off, it may also help scientists better understand long covid as well. The team found that long covid patients tended to have lower levels of cortisol (the so-called stress hormone), for instance, which could possibly be one reason why patients often experience fatigue.
At the same time, many scientists believe that there are several subsets of long covid patients whose symptoms might be caused by different mechanisms, so it’s likely that we’ll need to find more than one way to help people afflicted by it.
“Complex illnesses require complex treatment solutions and we need more rapid research to better understand long covid and discover new and promising therapies,” Putrino said.