A rare condition has suddenly appeared among a previously uninfected population during the COVID-19 pandemic, killing nine patients, researchers say.
This condition is a type of autoimmune reaction that involves the body's immune system mistakenly attacking itself. Interestingly, the system that is being attacked usually acts as a sentinel or security guard to detect invading viruses.
The disease was seen mainly in East Asian women and girls and was extremely rare in the UK, but researchers from the University of Leeds and Leeds Teaching Hospitals NHS Trust, investigating data on MDA5 autoimmunity in Yorkshire during the pandemic, noticed an unprecedented 60 reported cases, mainly among white men and women.
Researchers investigating the rise in cases believe exposure to the COVID-19 virus may have triggered the condition, which causes a distinctive skin rash, pneumonia and interstitial lung disease (a rapidly progressive lung inflammation with often fatal damage).
Lead researcher Denis McGonagle, professor of research rheumatology at Leeds University Medical School and Leeds Teaching Hospitals NHS Trust, said: “This disease is very rare in the UK but this latest surge in cases is entirely new and highly unusual.
“It's important that doctors understand the symptoms and patients are referred for treatment quickly to maximise the chances of a rapid and full recovery. It could undoubtedly save lives, but research is badly needed to slow or stop the rapid pulmonary progression that occurs in some patients.”
This research paper is published in The Lancet eBioMedicine.
Viruses and autoimmune responses
The immune system contains a protein called MDA5 that helps it detect RNA viruses like COVID-19. Normally, this protein triggers an immune response in the body, which causes more proteins to be produced to fight the virus. But sometimes the immune system mistakenly releases antibodies that attack this protein, leading to MDA5 autoimmune diseases like the rare disorder described in this study. The exact cause is not well understood, but scientists think the virus itself may trigger the response.
Autoimmune diseases seen after viral infections have similar characteristics, including fatigue, painful and swollen joints, skin rashes, and digestive problems. During the COVID-19 pandemic, doctors have seen a rare condition in children called multisystem inflammatory syndrome in children (MIS-C) that lacks evidence of an active viral infection in the lungs.
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Subscribe for freeThis MIS-C syndrome affected several organs of the body, including the heart, kidneys, brain, skin, eyes and digestive tract, but the lungs are not usually affected.The illness identified in Yorkshire was named MIP-C (pronounced “mi-ps-ee”) because it was similar to MIS-C in that it occurred during a pandemic but did not usually show active infection.
The 60 patients in the study went to their primary care doctor or the emergency room with a variety of symptoms, including shortness of breath, muscle pain, rashes and reduced blood flow to the fingers, known as Raynaud's disease, which are associated with the autoimmune condition.
The patients were referred to a rheumatologist for further testing, and all were diagnosed with the disease. Of the 60 patients, 35 had received the COVID-19 vaccination and 15 had previously tested positive for COVID-19. However, the patients were not systematically tested for COVID-19, and some may have been infected but asymptomatic at the time. In these cases, an overreaction of the immune system to minimal exposure to the virus may have led to the development of MDA5 disease.
Twenty-five of the 60 patients (41.7%) developed interstitial lung disease, eight of whom died despite treatment with immunosuppressants. The ninth patient, who did not have interstitial lung disease, died of sepsis.
To understand the rise in cases of this rare disease, the researchers collected data on the number of tests, data on COVID-19 infections and vaccinations, and information on each patient's symptoms from January 2018 to December 2022. The analysis found that only six cases of the rare disease were diagnosed between 2018 and 2019. However, in the three years since, when 60 new cases emerged, eight cases were diagnosed in 2020, 35 in 2021, and 17 in 2022. Very few cases have occurred since then.
Patient Demographics
The patients' ages ranged from 43 to 71 years, and 36 were women.
People:
White: 32, South Asian: 3, Black Caribbean: 2, Black African: 1, other ethnicity: 4, Asian (non-Chinese): 4. Ethnicity data were not available for 14 patients.
The researchers noted that there was a large overlap between vaccination rates in Yorkshire and the surge in MDA5 disease cases in 2021. However, this peak also occurred shortly after a community wave of coronavirus infections in late 2021. A smaller overlap was found between confirmed COVID-19 infections and MDA5. However, it is interesting to note that almost half (42%) of the patients were not recorded to have been vaccinated against COVID-19 before testing positive for MDA5. Four children who tested positive for MDA5 had not been vaccinated. This points to the idea of ​​an overactive immune response after exposure to the virus.
Exposure to the virus
Professor McGonagle said: “We know that vaccines can cause an immune hyperresponse, but given that not all of these patients had been vaccinated against COVID-19 and the increase in cases occurred at a time when there was high levels of the COVID-19 virus circulating, the evidence strongly suggests that the increase in cases of this rare disease is linked to exposure to the virus.”
The data was produced by Dr Paula David and Dr Gabriel DeMarco from the University of Leeds Medical School and Leeds Teaching Hospitals NHS Trust, along with their Trust colleague Dr Khizar Iqbal, in collaboration with Dr Pradipta Ghosh and his team at the University of California, San Diego, and showed that the MDA5 protein was found to be more prevalent in patients with COVID-19 and in patients with other diseases in which MDA5 is involved.
The researchers found that this increase is associated with an abnormal immune response that slows the growth and spread of the virus. Additionally, they found that elevated levels of the MDA5 protein are associated with increased levels of interleukin-15, a protein that activates T cells, or immune cells. This interaction may contribute to the autoimmune response.
The researchers say doctors should be aware of their findings so they can diagnose and treat patients more quickly, potentially reducing lung damage and saving lives. This is especially true for patients who are suspected of having pneumonia but whose symptoms do not improve with treatment and who do not show a rash, muscle problems or other signs of the disease.
Dr Paula David, first author of the paper, said: “We believe this large and unprecedented outbreak of MDA5 disease in Yorkshire will help advance the field in better understanding the role of viruses and autoimmunity.”
Dr Saptarshi Sinha, co-first author of the paper and interim director of PreCSN, added: “Here at PreCSN, we have the advantage of being able to help researchers like the McGonagle group dive into big data and quickly and accurately find patterns that connect the dots. In this case, we are pleased to have found a molecular level link with the clinical manifestations of autoimmune disease against the backdrop of COVID-19.”
Reference: David P, Sinha S, Iqbal K, et al. “MDA5 autoimmunity and interstitial lung inflammation (MIP-C) during the COVID-19 pandemic.” eBioMed. 2024;104. doi: 10.1016/j.ebiom.2024.105136
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