New Australian research is offering a thorough look at the lasting impact of COVID-19 on immune system activity. Tracking a wide variety of biomarkers the research found immune abnormalities persisting at least six months after patients recover from acute disease.
Eighteen months into this global pandemic researchers are increasingly investigating the long-lasting effects of a SARS-CoV-2 infection. Dubbed "long COVID", growing numbers of patients are reporting persistent symptoms lingering for months following the acute disease.
The Australian research is following 69 recovered COVID-19 patients, the majority of whom (47) only suffered from mild disease. Because of Australia’s unique position in the world, having temporarily eliminated the virus from certain regions, the ongoing project can track long-term immune responses to an infection without worrying about re-infection or vaccination status.
This new study, not yet peer-reviewed or published in a journal, outlines the effects of an infection on the peripheral immune system in the six months after initial recovery. Blood samples were taken from each subject at three points in the six-month study.
The researchers investigated levels of around 130 different immune cells, as well as tracking antibody responses and measuring the expression of thousands of different genes relating to immune functions. The findings strikingly show persistent inflammatory responses and immune dysregulation up to six months after recovery.
“The study found substantial dysregulation of immune cell numbers that was strongest at 12-weeks post infection but was still evident in most cases for up to six months and potentially even longer,” explains David Lynn, one of the lead investigators on the project.
A number of genes linked to inflammation were found to be upregulated six months after infection. This indicates these dysfunctional immune mechanisms could be part of the long COVID mystery, however, Lynn is clear further research is needed to verify this hypothesis.
“One could logically infer that this dysregulation is linked to the physical symptoms of long COVID, however, further research is needed to prove this,” adds Lynn.
The new research is part of a growing body of evidence implicating immune system abnormalities in the pathology of long COVID. A UK study published in April detected persistent immune alterations in hospitalized COVID-19 patients six months after discharge.
This Australian research, however, focused on a variety of COVID-19 cases, ranging from mild to severe. And one of the biggest surprises in the new findings was the lack of any correlation between acute disease severity and the degree of post-infection immune dysfunction.
“We’ve seen a very broad spectrum in the rate of recovery and we still don’t understand why some people are recovering so much quicker than others,” says Lynn. “The level of disease severity doesn’t translate directly to the level of immune dysregulation and we haven’t been able to find any patterns indicating that an individual’s age or sex is a differentiating factor governing differences in recovery.”
One limitation in the Australian research is there is no data tracking long COVID symptoms in the cohort, so these findings cannot be directly linked with long COVID cases. But the immune dysfunction/long COVID hypothesis is becoming increasingly plausible.
Danny Altmann, an immunologist from Imperial College London, is part of a larger ongoing UK project investigating long COVID. He says there is precedent for viral infections triggering long-term chronic health conditions, glandular fever being a perfect example. And those chronic conditions can be linked to lingering immune dysfunction following an acute infection.
“I describe it as a bit like somebody throwing a hand grenade into our immune system, that all the populations [of immune cells] are completely topsy turvy and unsettled for years,” Altmann explained in a recent interview. “And, that's a guess, but we've got the technology to look at that in quite a lot of detail.”
Branka Grubor-Bauk, an Australian researcher working on the new study, suggests there is an urgent need for a better understanding of long COVID, particularly as it looks like the virus is not going away.
“At present there are no treatments for long COVID sufferers and as the world slowly transitions to living with COVID, we will need to find answers and better solutions to prevent and treat long COVID in the years to come” says Grubor-Bauk.
The new research is yet to be peer-reviewed or published but it has been posted on medRxiv.
Source: University of Adelaide
