Long COVID abnormalities appear to resolve over time

In January 2022, researchers at UNSW’s Kirby Institute revealed that long COVID clinical symptoms were consistent with biomarkers showing a sustained inflammatory response at eight months following infection, providing a clear biological basis for the syndrome of long COVID. Now the researchers have shown that these biomarkers had largely resolved by 24 months post-infection, providing hope for long COVID patients.

The ADAPT study followed people who contracted COVID-19 during Australia’s first wave, as well as a matched control group, for up to two years. Jointly led by the Kirby Institute and St Vincent’s Hospital Sydney, it combined systematic self-reported health information collected from patients with detailed analysis of bloods specimens in the laboratory.

Almost one and a half years after identifying the sustained inflammatory response, the researchers found significant improvements in the blood markers of the original group of long COVID patients, as published in the journal Nature Communications. As noted by Dr Chansavath Phetsouphanh, first author on the paper and a Senior Lecturer at the Kirby Institute, “For the majority of samples we analysed in the laboratory, the biomarkers previously indicating abnormal immune function have resolved.”

While the exact scale of the immunological improvements is difficult to quantify, as immune function varies significantly from person to person, by 24 months there were no observable differences between the group with long COVID and the control group — whereas at eight months the two groups had marked differences. This trend in the laboratory data was also visible in the patients’ self-reported data, with 62% reporting improvements in health-related quality of life.

“While this is very encouraging and a reason for optimism, there are still around one-third of patients who identify some ongoing impact on their quality of life,” said the Kirby Institute’s Professor Gail Matthews, lead investigator of ADAPT and Head of Infectious Diseases at St Vincent’s Hospital.

“This is likely explained by the reality that patients may have a range of underlying causes for their long COVID symptoms, not all of which are driven by immunological abnormalities and some of which are likely to persist even when the immunological environment has largely returned to normal.”

ADAPT is one of only a handful of studies that measure clinical data, patient self-reported information and intense biological sampling consistently within the same cohort of people, over a prolonged period of time. But while the study findings are encouraging, Kirby Institute Director Professor Anthony Kelleher said they relate to just one cohort who experienced an early strain of COVID-19, where the initial COVID-19 infection was generally considered mild or moderate.

“Immunology is a complex science, and it is impossible to say for certain that outcomes in our unvaccinated clinical cohort will be true for vaccinated people or for people who may have been infected with a different strain of COVID-19,” Kelleher said.

“What we do know is that for most people with long COVID, both their symptoms and their biomarkers improve significantly over time, and this is a cause for optimism.

“Importantly, we will continue to undertake research to understand more about why some people don’t improve, and what can be done for those people.”

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