A post-infection inflammatory response has been a popular hypothesis used to explain long COVID, a condition defined as significant lingering COVID-19 symptoms present weeks and months following the initial infection.
A new UK study, however, suggests that those suffering from severe long COVID symptoms did not have signs of higher cellular immune activation or pro-inflammatory cytokines after adjusting for age, sex, and disease severity. The results are published in the journal eLife.
Previous studies estimate that as many as 8% to 21% of people with mild to severe COVID-19 will have long-COVID symptoms more than 12 weeks after their primary infection, with higher rates among those who required extensive medical treatment, including intensive care unit admission.
In the new study, researchers looked at immune markers in blood samples from 63 patients hospitalized with mild, moderate or severe COVID-19 at the start of the pandemic, before vaccines were available. They analyzed 187 samples collected at 3, 8, and 12 months after hospitalization for myriad immune system markers.
By 12 months, inflammatory markers down
At 3 months post-hospitalization, blood samples of patients with severe COVID-19 showed increased levels of activated CD4+ and CD8+ T-cells and increased plasma levels of T-cell–related cytokines (interleukin [IL]-4, IL-7, IL-17, and tumor necrosis factor-alpha).
Eighty percent of patients reported long COVID at 3 months post-hospitalization, with breathlessness and excessive fatigue being the most common symptoms.
But by 12 months, T-cell activation and cytokine levels decreased and were comparable in patients with mild, moderate, and severe disease. The authors also found no direct association between long-COVID symptoms and immune inflammatory markers.
Our study adds to emerging data suggesting that a prolonged immune activation can be observed following COVID-19 which may not directly associate with long COVID.
"At 12 months post admission T-cell activation was similar and largely undetectable in patients with mild, moderate, and severe disease, suggesting that the differences we observe between patients at 3 months may not be driven by differences in T-cell activation already present in these patients prior to COVID-19," the authors concluded.
"Our study adds to emerging data suggesting that a prolonged immune activation can be observed following COVID-19 which may not directly associate with long COVID."
In a press release on the study from the University of Bristol, senior author Laura Rivino, PhD, said, "Our findings suggest that prolonged immune activation and long Covid may correlate independently with severe COVID-19. Larger studies should be conducted looking at both a larger number of patients, including if possible vaccinated and non-vaccinated COVID-19 patients, and measuring a larger range of markers and cytokines."
