The Covid-19 pandemic has caused a surge in a rare health condition


A rare condition has surged in groups of previously unaffected people during the Covid-19 pandemic and led to the deaths of 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 normally acts as a sentinel or protector, tasked with detecting invading viruses.

It is mainly seen in East Asian women and girls and was very uncommon in the U.K. But researchers from the University of Leeds and Leeds Teaching Hospitals NHS Trust, who were examining data on MDA5 autoimmunity in Yorkshire during the pandemic, noted an unprecedented 60 cases in mainly white men and women.

Researchers investigating the rise in cases believe the condition may be triggered by exposure to the COVID-19 virus, which causes distinctive skin rashes, pneumonia and interstitial lung disease, a rapidly progressing lung inflammation that is often fatal.

Principal investigator Denis McGonagle, Professor of Investigative Rheumatology at Leeds School of Medicine and Leeds Teaching Hospitals NHS Trust, said: “Although we see this disease occasionally in the UK, this surge in cases is completely new and very different.

“It's vital that clinicians understand the symptoms so patients can be referred for treatment quickly and have the best chance of a quick and full recovery. Lives can undoubtedly be saved but research is vitally needed to slow or prevent the rapid progression of lung disease that occurs in some patients.”

This research paper has been published in The Lancet eBioMedicine.

Viruses and autoimmune response

The immune system has a protein called MDA5, which helps detect RNA viruses like COVID-19. Normally, this protein helps trigger an immune response in the body, where more proteins are produced to help fight the virus. However, sometimes the immune system releases antibodies that mistakenly attack this protein, leading to MDA5 autoimmune diseases like the rare disease described in this study. The exact cause is not well understood, but scientists believe the virus itself may trigger the response.

Autoimmune diseases seen after viral infections have similar features such as fatigue, joint pain and swelling, skin rashes and digestive problems. During the COVID-19 pandemic, doctors observed a rare condition called Multisystem Inflammatory Syndrome in Children (MIS-C) in children with no evidence of active viral infection in the lungs.

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This MIS-C syndrome affected many systems in the body, including the heart, kidneys, brain, skin, eyes, and digestive organs, but the lungs were usually spared. The disease seen in Yorkshire was named MIP-C (pronounced “mipsy”) because it resembled MIS-C, as it occurred around the time of the epidemic, but where active infection was usually absent.

The 60 patients in the study visited their GP or A&E with a range of symptoms, including shortness of breath, muscle pain, rashes and reduced blood flow to the fingers, known as Raynaud's disease. These symptoms are linked to the autoimmune disease.

The patients were referred to rheumatology specialists for further investigation and all were diagnosed with the disease. Of the 60 patients, 35 had received Covid-19 vaccines 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 had no symptoms at the time. Such cases may develop MDA5 disease due to an excessive response of their immune system due to minimal exposure to the virus.

Twenty-five of the 60 patients (41.7%) developed interstitial lung disease, and despite treatment with immunosuppressant medication, eight of them died. The ninth patient, who did not have interstitial lung disease, died of sepsis.

To understand the rise in cases of this rare condition, the researchers collected data on the number of these tests between January 2018 and December 2022, as well as data on COVID-19 infection and vaccination and information about each patient's symptoms. The analysis showed that only six cases of the rare condition were diagnosed between 2018 and 2019. However, in the 3 years after 60 new cases were reported, eight cases were diagnosed in 2020; 35 cases were diagnosed in 2021 and 17 cases were diagnosed in 2022. Very few cases have been reported since then.

Patient demographics

The patients ranged in age from 43 to 71 years, of which 36 were women.

CASTEISMAND:

  • White: 32
  • South Asian: 3
  • Black Caribbean: 2
  • Black Africans: 1
  • Any other ethnic group: 4
  • Asian (not Chinese): 4
  • No ethnic data were available for 14 patients.

The researchers found that there was a strong overlap between vaccination rates and the surge in MDA5 disease cases in Yorkshire in 2021. However, this peak also occurred shortly after the community wave of coronavirus infections in late 2021. A small overlap was observed between confirmed COVID-19 infections and MDA5. However, it was interesting to note that almost half (42%) of the patients were not documented to have been vaccinated against COVID-19 before testing positive for MDA5. Four of the children who tested positive for MDA5 were not vaccinated, pointing to the idea of ​​an exaggerated immune response after exposure to the virus.

Viral Exposure

Professor McGonagle said: “We know that vaccines can boost the immune response, but given that not all of these patients were vaccinated against COVID-19, and the increase in cases occurred when the COVID-19 virus was circulating in significant numbers, the evidence strongly suggests that the increase in cases of this rare disease is linked to exposure to the virus.”

The data was developed by Dr Paula David and Dr Gabriele DeMarco from the University of Leeds School of Medicine and Leeds Teaching Hospitals NHS Trust, along with their Trust colleague Dr Khizar Iqbal. The work was carried out in collaboration with Dr Pradipta Ghose and her team at the University of California, San Diego, who showed that MDA5 protein was found to be higher in patients with Covid-19 and in patients with other MDA5-related diseases.

They found that this increase was associated with an abnormal immune response that slows the virus's ability to multiply and spread. Additionally, they found that high levels of the MDA5 protein were 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 investigators say doctors should be aware of their findings so that patients can be diagnosed more quickly and referred for treatment, which could help reduce lung damage and save lives. This is particularly true in subjects with suspected pneumonia who are not responding to treatment and in whom rashes, muscle involvement, and other disease symptoms are absent.

Dr Paula David, first author of the paper, said: “We believe this large, unprecedented outbreak of MDA5 disease in Yorkshire will help advance the field in better understanding the role between the virus and autoimmunity.”

Dr. Saptarshi Sinha, co-first author of the paper and interim director of PreCSN, said: “At PreCSN, we enjoy the ability to help researchers like the McGonagle group dive into big data and find patterns quickly with a precision that allows us to connect the dots. In this case, we are pleased that we were able to find a connection between the clinical presentation of autoimmune disease in the background of COVID-19 at the molecular level.”

Reference: David P, Sinha S, Iqbal K, et al. MDA5-autoimmunity and interstitial pneumonitis contemporary with the COVID-19 pandemic (MIP-C). ebiomed2024;104. doi: 10.1016/j.ebiom.2024.105136

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