Long COVID patients show abnormal immune activity 8 months post infection
A comprehensive new study published in the journal Nature Immunology has reported immune dysregulation persists in long COVID patients up to eight months after initial infection. The Australian research found long COVID is characterized by elevated levels of specific immune biomarkers, offering the strongest objective evidence to date of this emerging chronic disease. However, researchers indicate it is still unclear what impact vaccination or the Omicron variant will have on long COVID.
The study systematically followed 147 people for eight months following an acute SARS-CoV-2 infection. About 20 percent of the cohort experienced symptoms of long COVID at four months past initial infection.
Blood samples were taken from all subjects at several points over the study. The researchers were interested in how each patient’s immune system was responding in the months following COVID-19.
“In conducting this research, we were looking for proteins in the serum,” said co-lead author on the new study, Chansavath Phetsouphanh. “These proteins, or biomarkers, are evidence of an abnormal process caused by a disease. We analyzed 31 different biomarkers that we suspected could be ‘triggered’ by COVID-19, and we identified a small subset that were associated with long COVID syndrome.”
Compared to a control group composed of uninfected subjects, or subjects infected with other coronaviruses, six specific immune biomarkers were notably elevated in COVID-19 patients. There was little difference in these biomarker levels between long COVID cases and COVID cases with no persistent symptoms up to four months after infection. But from four months these elevated immune biomarkers began to drop in non-long-COVID subjects while remaining high in long COVID patients.
In particular, the research noted two types of immune cells known as interferons remained significantly high in the long COVID cohort at the eight-month mark compared to all other controls. This pattern of immune dysfunction was so apparent that the researchers could effectively identify a long COVID patient with 80 percent accuracy just by studying immune biomarkers in a blood sample.
“… we found persistently elevated levels of Type I and Type III interferons – types of protein that cells make in response to the presence of a virus,” explained Phetsouphanh. “These interferons generally disappear after an infection clears, but in patients with long COVID we found they were present for an extended period.”
Phetsouphanh also pointed out these ongoing immunological changes were not linked to the severity of the initial infection. While long COVID has been reported in high rates for those hospitalized with the acute disease, anywhere from 10 to 30 percent of mild cases are showing signs of long COVID.
This new research was conducted in a cohort of unvaccinated subjects initially infected in 2020. So it is unclear at this stage whether new variants such as Omicron, or two- to three-dose vaccination schedules, significantly affect these immunological long COVID characteristics.
“From some early international data, we are very hopeful that with a milder variant and with high vaccination rates we may see less long COVID, but we will need further immunological data before we can say this for certain,” added co-lead author David Darley. “We are currently looking at some data from the Delta wave to understand whether vaccination may reduce the possibility of long COVID.”
A similar recent study from researchers at Cedars-Sinai homed in on another immune biomarker that is persistently elevated in long COVID patients up to six months past initial infection. Deepti Gurdasani, a researcher from Queen Mary University of London who did not work on this new study, says it is unclear what this kind of lingering immune dysregulation means, but she calls it concerning nonetheless.
“Whether this is because of persistence of virus, or virus antigen, or auto-immunity post-infection isn't known yet,” Gurdasani said on Twitter. “It could be one of these, or even a combination – but all possibilities should concern us.”
In a recent interview, Eric Topol, founder of the Scripps Research Translational Institute, discussed the uncertainty surrounding Omicron, vaccination and long COVID. He said because of Omicron's immune evasiveness it is possible long COVID could be highly prevalent with this variant. And, Topol pointed out, even if vaccination reduces a person's chances of developing long COVID by half, we still may be facing a huge problem by letting the virus sweep through a community.
"Right now we should plan for the worst about long COVID," said Topol. "This whole idea of having millions of infections per day basically ignores the long COVID concern."
“There is reason why we think #LongCovid could be worse with #omicron.. 1st is most cases of Long Covid occur after mild infection.. 2nd is due to omicron’s immune evasiveness, which may make it harder to clear”— charlos (@loscharlos) January 14, 2022
Excellent convo w/ @EricTopol & @Bob_Wachter pic.twitter.com/pjg8aczH8Y
Speaking to the Sydney Morning Herald, co-author on the new study Greg Dore said the coming months will be key in understanding what kind of long COVID burden is leveled by the Omicron variant. Dore suggested Omicron’s massive transmissibility could lead to considerable levels of long COVID.
“With an enormous wave of Omicron cases, even with a variant that is less severe, a small proportion of those with long COVID could translate to considerable disease burden,” said Dore. “We will know more about Omicron’s impact on long in COVID in the next three months.”
The new study was published in Nature Immunology.