Severe reactions to infection with SARS-CoV-2 are characterized by excessive inflammation in the lower airways, which has been linked to a pathological response of the immune system. Researchers at the Karolinska Institutet in Sweden have been investigating this severe response to identify the mechanisms that may be involved and found that a type of T cell – mucosa-associated invariant T (MAIT) cells – may play a role in the development of severe COVID-19 cases.
MAIT cells are T cells that target microbes and act as innate-like sensors, capable of sensing bacterial metabolites. MAIT cells only make up around 10% of T cell populations in the blood but play an important role in the response to bacterial infections. MAIT cells readily travel to specific tissues in the body in response to infection, for instance, they are often found in relatively high numbers in the lungs and liver. Recent evidence suggests MAIT cells, in addition to targeting microbes, also play a role in the antiviral response and also act as sensors for viral infections.
The Swedish researchers investigated the role that MAIT cells may play in the response to SARS-CoV-2 infection by examining blood samples from 24 patients admitted to hospital with severe COVID-19 and comparing them with blood samples taken from 14 healthy patients and 45 patients who had recovered from COVID-19.
The researchers found that in patients with moderate to severe COVID-19, the number of MAIT cells in the blood decreased, and those that were present were highly activated, indicating they were involved in an immune response to SARS-CoV-2. While other types of T cells reduced in number and were activated, the pattern was most pronounced in the MAIT cells. The MAIT cells that were pro-inflammatory also accumulated in the lungs of patients to a much higher degree than they did in healthy patients.
The reduction in MAIT cells in the blood is consistent with their migration to the lower airways where the virus is present. Once the infection has been tackled they return to the blood, which the analyses of MAIT cells in patients who had recovered from COVID-19 showed.
The researchers’ transcriptomic analyses indicated significant MAIT cell enrichment and pro-inflammatory IL-17A bias in the airways. Unsupervised analysis identified MAIT cell CD69high and CXCR3low immunotypes were associated with poor clinical outcomes. The four patients who died in hospital from COVID-19 had far higher CD69 expression by MAIT cells than patients who survived, suggesting MAIT cells may play a role in COVID-19 immunopathogenesis.
You can read more about the study in the paper – MAIT cell activation and dynamics associated with COVID-19 disease severity – which was recently published in the journal Science Immunology. DOI: 10.1126/sciimmunol.abe1670