Long COVID not caused by COVID-19 immune inflammatory response, study

Immune activation may persist for months after COVID-19.


Immune disturbances brought on by Coronavirus Disease-19 (COVID-19) may last for a long time, and patients typically continue to have symptoms for months after their condition has improved. Long COVID is a condition that affects 8 to 21% of people who have mild to severe COVID-19.

A recent study investigated the possibility that chronic inflammation and persistent immunological activation could be the root causes of extended Covid. According to the University of Bristol study, COVID-19 does not generate an inflammatory immune response that results in Long Covid.

Researchers used blood samples from 63 people- hospitalized with mild, moderate, or severe COVID-19 at the pandemic’s start and before vaccinations were available- to collect and analyze immunological responses. After that, they retested the patients’ immune responses eight and twelve months after hospital admission. Breathlessness and excessive fatigue were the most prevalent symptoms described by 79% of these patients (82%, 75%, and 86% of mild, moderate, and severe patients, respectively).

The researchers discovered that patients’ immune responses three months after developing severe symptoms showed considerable T-cell profile malfunction, indicating that inflammation may continue for months even after the virus has been treated. Results showed that even in severe cases, inflammation in these patients resolved with time, which was reassuring. Individuals with severe disease had immunological profiles and inflammatory levels at 12 months compared to those with mild and moderate disease.

Patients with severe COVID-19 exhibited more long-lasting COVID symptoms than patients with mild or moderate COVID-19. However, after correcting for age, sex, and disease severity, the team’s further investigation found no evidence of a connection between long-lasting Covid symptoms and immune-inflammatory responses for the markers evaluated in any of the patients.

The immune cells that fight SARS-CoV-2 did not rapidly increase at three months. Still, T-cells that fight the common Cytomegalovirus (CMV), which is typically harmless but can remain dormant in your body for life once infected, did exhibit a small increase. This suggests that the extended T-cell activation seen at three months in individuals with severe disease may not be caused by SARS-CoV-2 but rather be “bystander driven” or caused by cytokines.

Dr. Laura Rivino, Senior Lecturer at Bristol’s School of Cellular and Molecular Medicine and the study’s lead author, explained, “Our findings suggest that prolonged immune activation and long Covid may correlate independently with severe COVID-19. Larger studies should be conducted looking at a larger number of patients, including vaccinated and non-vaccinated COVID-19 patients, and measuring a larger range of markers and cytokines.”

“Understanding whether inflammation and immune activation associated with long Covid would allow us to understand whether targeting these factors may be a useful therapy for this debilitating condition.”

Journal Reference:

  1. Marianna Santopaolo, Michaela Gregorova, Fergus Hamilton, et al. Prolonged T-cell activation and long COVID symptoms independently associate with senahivere COVID-19 at 3 months. eLife. DOI: 10.7554/eLife.85009
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