Thread by @vipintukur

A new study finds that people with #LongCOVID have distinct patterns of inflammation detectable in the blood, which could potentially be targeted with immune therapies. The findings confirm that LongCOVID leads to ongoing inflammation which can be detected in the blood. 1/

In an analysis of >650 people who had been hospitalised with severe COVID, patients with prolonged symptoms showed evidence of immune system activation.
The exact pattern of this activation varied depending on the sort of symptoms they predominantly had 2/

The researchers took samples of blood plasma and measured a total of 368 proteins known to be involved in inflammation and immune system modulation. 3/

They found that, relative to patients who had fully recovered, those with LongCOVID showed a pattern of immune system activation.
This indicated inflammation of myeloid cells and activation of a family of immune system proteins called the complement system. 4/

The complement system consists of a cascade of linked proteins that are activated in response to infection or tissue damage.
Notably, overactivation of the complement system is known to be associated with many autoimmune and inflammatory conditions. 5/

Their findings indicate that complement activation and myeloid inflammation could be a common feature of longCOVID after hospitalisation, regardless of symptom type. 6/

It is unusual to find evidence of ongoing complement activation several months after acute infection has resolved, suggesting that long COVID symptoms are a result of active inflammation. 7/

They found certain groups of symptoms appeared to be associated with specific proteins.
For example, people with gastrointestinal symptoms had increased levels of a marker called SCG3, which has previously been linked to impaired communication between the gut and the brain. 8/

The study finds that older women were more likely to experience #LongCovid as estrogen can influence immunological responses. 9/

Women have been reported to have stronger innate immune responses to infection and to be at greater risk of autoimmunity, possibly explaining why some women in the ≥50 years group had higher inflammatory proteins than men the same group. 10/

Overall, there were five overlapping subtypes of Long COVID with different immune signatures, despite some commonalities, namely:
•fatigue
•cognitive impairment
•anxiety and depression
•cardiorespiratory
•gastrointestinal. 11/

These #LongCOVID subtypes seem to represent clear biological mechanisms of disease and highlight that different symptoms may have different underlying causes. 12/

The researchers suggest that existing drugs which modulate the body’s immune system could be helpful in treating Long COVID and should be investigated in future clinical trials. 13/

One such treatment could include drugs called IL-1 antagonists, such as anakinra, which is commonly used to treat rheumatoid arthritis.

As well as another drug class called JAK inhibitors, used to treat some types of cancers and severe forms of rheumatoid arthritis. 14/

Overall, the researchers found markers of myeloid inflammation and complement activation in cohort of patients with #LongCovid, in addition to distinct inflammatory patterns in patients with cognitive impairment or gastrointestinal symptoms. 15/

These findings show the need to consider subphenotypes in managing patients w/ LongCovid & support the use of antiviral or immunomodulatory agents in controlled therapeutic trials. 16/16

nature.com/articles/s4159…