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Abnormal immune system activity may explain long COVID

  • Researchers worldwide are continually updating the scientific knowledge around SARS-CoV-2, the virus that causes COVID-19.
  • In the most recent update, scientists in Australia report that atypical immune activity persists in people with long COVID 8 months after infection with SARS-CoV-2.
  • Their research shows that long COVID features increased levels of specific immune biomarkers in the body.
  • Their findings provide a crucial foundation to enhance our understanding of long COVID, an emerging chronic condition.

Scientists have spent the last few years trying to understand the novel coronavirus, SARS-CoV-2, which is responsible for the COVID-19 pandemic.

As new variants of the SARS-CoV-2 virus emerge, scientists continue to study their effects to find ways of keeping the global population safe.

In line with ongoing scientific efforts, a new study has reported that individuals with long COVID experience dysfunctional immune activity 8 months after the initial COVID-19 illness.

Long COVID, also known as post-acute COVID-19, is a term to describe the effects of COVID-19 that linger for weeks or months beyond the initial illness. The symptoms often involve respiratory and physical distress and, more recently, cardiovascular distress.

The study, led by scientists at The Kirby Institute, University of New South Wales, Australia, appears in the journal Nature Immunology.

“Our observations provide an important foundation for understanding the pathophysiology of this syndrome and [may suggest] potential therapeutic avenues for intervention,” the study authors write.

“Our study indicates an ongoing, sustained inflammatory response following even mild-to-moderate acute COVID-19, which is not found following prevalent common cold coronavirus infection,” Dr. Chansavath Phetsouphanh, a senior research associate and co-lead author of the study, told Medical News Today.

However, he added that “more research from bigger cohorts is required to validate [their] findings.”

Defining the study parameters

The researchers followed 147 individuals for 8 months following a diagnosis of COVID-19.

They were interested in studying the pathophysiological, immunological, and clinical outcomes following infection with SARS-CoV-2.

In the study, the team defined long COVID as the occurrence of one of three major symptoms of fatigue, chest pain, or shortness of breath in the fourth month of infection. A total of 31 out of 147 individuals fitted the description.

The scientists then matched the individuals using gender and age, with 31 asymptomatic controls from the same cohort who did not report symptoms in the fourth month but were symptomatic during the acute phase of COVID-19.

The researchers also recruited a fresh population of individuals who tested negative for SARS-CoV-2 alongside individuals who had contracted other human coronaviruses but not SARS-CoV-2. This group served as the control.

Finally, the experimenters collected blood samples from each group to examine the biomarkers associated with long COVID. In medicine, a biomarker refers to “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”

What the scientists discovered

At first glance, the scientists noted that the long COVID and control groups had significantly higher levels of six immune biomarkers compared with the control group.

However, from the fourth month, they noticed a drop in the elevated biomarker levels in the control group while the long COVID group still maintained high levels of biomarkers.

Specifically, the team noticed that two types of biomarkers — known as interferons — were elevated in the long COVID group 8 months after infection with SARS-CoV-2. Scientists describe interferons as a type of protein that body cells make in response to the presence of viruses.

As well as elevated levels of interferons, Dr. Phetsouphanh and his team discovered that the long COVID group had highly activated immune cells but lacked naive T and B cells. These cells are responsible for helping the immune system respond to novel pathogens that it has not yet encountered.

Taking these findings into consideration, the scientists concluded that:

“SARS-CoV-2 infection exerts unique prolonged residual effects on the innate and adaptive immune systems and that this may be driving the symptomology known as [long COVID],” the study authors write.

Reactions to the study

Dr. Deepti Gurdasani, a senior lecturer at the Queen Mary University of London, who was not involved in the research, responded to the study on Twitter, saying that its results “in practical terms [are] unclear — but concerning nevertheless.”

“Understanding [the meaning of the] immune dysregulation that was clearly present at least at 8 months, and possibly longer will take time,” she wrote, pointing out that “long COVID clearly shows a different immunological profile compared to people who don’t have persistent symptoms.”

She added:

“Whether this is because of [the] persistence of [the] virus, virus antigen, or auto-immunity post-infection isn’t known yet. It could be one of these or even a combination — but all possibilities should concern us.”

Study limitations and conclusion

The study authors report several limitations in their research.

First, because of the timing of ethics approvals and cohort setup, the scientists could not collect samples during the period of acute infection. As a result, they were unable to determine whether elevations in biomarker levels during the recovery period correlated with the levels observed in acute infection.

Additionally, the definition of long COVID in the study was set internally by the researchers, given the lack of international consensus on its definition.

Nevertheless, the scientists note that the inclusion of the most common persisting symptoms of long COVID alongside rigorous research practices helped ensure the validity of their findings.

Needless to say, the research is still largely exploratory, and more studies are necessary to confirm the findings. However, the study results could one day potentially inspire better treatments for people living with long COVID.

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