Long-COVID study reveals immunological improvement two years after infection 

Immune abnormalities have largely resolved at 24 months in a cohort of patients with long COVID, providing optimism that long COVID can resolve over time.

Biomarkers for long COVID that were present in patients at eight months have largely resolved by 24 months among a cohort of people who contracted COVID-19 during Australia’s first wave. 

Jointly led by the Kirby Institute at UNSW Sydney and St Vincent’s Hospital Sydney and published today in Nature Communications, the research provides optimistic insights to suggest that long-COVID abnormalities can resolve over time.

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. It combines systematic self-reported health information collected from patients with detailed analysis of blood specimens in the laboratory. 

In January 2022, the Kirby Institute research team were the first globally to show 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.

“Almost one and a half years later, we are pleased to see that among this same group, significant improvements were found in blood markers. For the majority of samples we analysed in the laboratory, the biomarkers previously indicating abnormal immune function have resolved,” says Dr Chansavath Phetsouphanh, first author on the paper and Senior Lecturer at the Kirby Institute.

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.

Importantly, this trend in the laboratory data was also visible in the patients’ self-reported data, with 62 per cent 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,” says Professor Gail Matthews from the Kirby Institute, 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.”

Global first

The ADAPT study is globally important as it 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. 

Professor Anthony Kelleher, Director of the Kirby Institute, says that while the finding is encouraging, it is important to remember that this is just one cohort who experienced an early strain of COVID-19, and it is a group in which 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. 

“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.”