Scientists have identified a new syndrome linked to COVID-19 that poses a significant threat to lung health. The syndrome, dubbed MIP-C (MDA5-autoimmunity and interstitial pneumonitis contemporaneous with COVID-19), is a rare but severe condition characterized by an immune system malfunction.
This malfunction causes the immune system to inadvertently attack the body, leading to extensive scarring and stiffening in the lungs. In the most severe cases, the lungs become so damaged that the only option for survival is a full organ transplant. However, only two-thirds of MIP-C cases involve lung disease. The remaining patients experience joint aches, muscle inflammation, and skin rashes, mirroring the symptoms of MDA5 dermatomyositis, a known condition predominantly affecting women of Asian descent.
The research team, led by Dr. Patrick McGonagle, a rheumatologist at the University of Leeds, has identified 60 cases of MIP-C to date. Their findings were published in the journal Nature Medicine on May 8. To gain a deeper understanding of the autoimmunity against MDA5, researchers began screening people with autoimmune symptoms for antibodies against the protein. In 2018, they identified three patients who met the criteria, followed by three more cases in 2019 and eight in 2020. However, in 2021, the number of cases surged to 35, prompting further investigation.
Dr. McGonagle and his colleagues collaborated with Dr. Sohini Ghosh, an immunologist at the University of California, San Diego, to analyze the medical data and identify common threads. Their team’s previous work focused on the study of multisystem inflammatory syndrome in children (MIS-C), a condition that can develop in children after COVID-19 infection.
The researchers compared medical records from patients with MIP-C to those with COVID-induced pneumonia and patients with lung scarring unrelated to viruses. They observed increased activity in the gene IFIH1, which provides the blueprint for MDA5, in patients with both pneumonia and autoimmune conditions. Notably, many patients with MIP-C did not have a confirmed history of COVID-19, but it is likely that they were exposed to the virus and had either mild or asymptomatic disease, given the timing of their cases. Over half of the patients had received COVID-19 vaccinations, although the specific vaccine they received was not specified.
The researchers propose that exposure to the coronavirus RNA, either through infection or vaccination, may trigger the production of anti-MDA5 antibodies, leading to the development of MIP-C. Normally, MDA5 activates when it detects viral RNA in cells and triggers the production of antibodies against the virus. However, in people with MIP-C, this immune response goes awry, resulting in the body mistaking the MDA5 protein as foreign and attacking it. Alternatively, the RNA itself may elicit an excessive immune response, causing the body’s proteins, including MDA5, to become targets for attack.
The activation of IFIH1 coincides with a surge in the inflammatory protein interleukin-15 (IL-15), which activates immune cells that can kill infected cells but may also attack the body’s own cells in this case. The researchers emphasize the importance of considering MIP-C in patients who have been exposed to COVID-19 or the vaccine and present with joint pains, rashes, or aches. They recommend examining the lungs in such cases.
The team continues to gather data on MIP-C, and the number of new cases appears to be declining. In 2022, the Yorkshire region reported 17 cases, which is about half the number seen in 2021. Dr. McGonagle speculates that the intense RNA exposure during the widespread COVID-19 waves of 2021, combined with mass vaccination, may have contributed to the spike in cases that year.
Additionally, the study identified a specific genetic sequence within the IFIH1 gene that appears to protect individuals from the runaway IL-15 inflammatory response. Further research is needed to understand why others are vulnerable to this response.
