During the COVID-19 pandemic, there has been a significant increase in a rare condition that has impacted groups of people who were not previously affected. This condition has resulted in the deaths of nine patients and is believed to be a type of autoimmune response. This means that the body’s immune system is mistakenly attacking itself. Interestingly, the body’s immune system, which is normally responsible for detecting invading viruses, is the target of the attack. This condition was previously uncommon in the UK and was mainly seen in East Asian women and girls. However, researchers studying data on MDA5 autoimmunity in Yorkshire during the pandemic observed an unprecedented 60 cases, primarily affecting white men and women. Researchers are investigating this surge in cases and its potential link to the COVID-19 pandemic.
Researchers have observed a surge in a rare condition among people who were previously unaffected during the COVID-19 pandemic, resulting in the deaths of nine patients.
Experts believe that exposure to the COVID-19 virus may be the cause of the increase in cases of the condition, which is characterized by distinctive skin rashes, pneumonia, and interstitial lung disease. This type of lung disease involves rapidly progressing inflammation and damage to the lungs, and is often fatal. The condition is thought to be a result of an autoimmune response, where the body’s immune system mistakenly attacks itself. Interestingly, the system being attacked normally functions as a sentinel
The MDA5 protein acts as a guard against invading viruses, and is more commonly found in East Asian women and girls. However, there has been an unusual increase in cases among mainly white men and women in the UK, with 60 reported cases during the pandemic. Researchers at the University of Leeds and Leeds Teaching Hospitals NHS trust were studying MDA5 autoimmunity in Yorkshire and found a link to exposure to the COVID-19 virus. This condition can cause distinct skin rashes, pneumonia, and interstitial lung disease, which is a rapidly progressing and often fatal lung inflammation with damage.Lead Researcher Dennis McGonagle, a Professor of Investigative Rheumatology at the University of Leeds’ School of Medicine and Leeds Teaching Hospitals NHS Trust, remarked, “While we rarely encounter this illness in the UK, this sudden increase in cases was entirely unprecedented and unique.
“It’s crucial for doctors to recognize the symptoms so that patients can be promptly referred for treatment and have the best chance of a swift and complete recovery. Without a doubt, lives could be saved, but there is a pressing need for research to address the rapid progression of lung issues in some patients.”
The research paper is published in The Lancet eBioMedicine, a study on MDA5 autoimmune diseases related to viruses.
MDA5, a protein in the immune system, is responsible for detecting RNA viruses such as COVID-19. Normally, it triggers an immune response by producing more of the protein to combat the virus. However, in some cases, the immune system produces antibodies that mistakenly attack MDA5, leading to autoimmune diseases. The specific cause of this response is not fully understood, but it is believed that the virus itself may be a trigger.
Autoimmune diseases that can occur after viral infections have similar symptoms, such as fatigue, joint pain, swelling, skin rashes, and digestive issues. During the COVID-19 pandemic, doctors observed a rare condition in children known as multisystem inflammatory syndrome in children (MIS-C), where there was no evidence of an active viral infection in the lungs. This MIS-C syndrome affected multiple systems in the body, including the heart, kidneys, brain, skin, eyes, and digestive organs, but usually did not affect the lungs. The disease seen in Yorkshire was called MIP-C (pronounced “mipsy”) because it was similar to MIS-C in how it occurred.The study focused on patients who developed symptoms similar to autoimmune disease during the pandemic, even though active infection was not usually present. The 60 patients sought medical help for various symptoms such as shortness of breath, muscle pain, rashes, and reduced blood flow to the fingers, which is known as Raynaud’s disease. These symptoms are commonly linked to autoimmune disease.
The patients were referred to rheumatology specialists for further evaluation and all were diagnosed with the condition. Out of the 60 patients, 35 had received COVID-19 vaccinations, and 15 had previously tested positive for COVID-19. However, COVID-19 testing was not consistently performed on these patients.
Some individuals may have been infected with the virus without showing any symptoms at the time. These individuals may have developed MDA5 disease due to an excessive immune system response to minimal exposure to the virus.
Out of the 60 patients, 25 of them (41.7%) developed interstitial lung disease. Despite receiving treatment with immunosuppressant medication, eight of these patients passed away. The ninth patient, who did not have interstitial lung disease, died from sepsis.
To better understand the increase in cases of this rare condition, researchers gathered data on the number of tests conducted between January 2018 and December 2022, as well as data on COVID-19 infections.The analysis revealed that there were only six cases of the rare condition diagnosed from 2018 to 2019, but there was a significant increase in new cases in the 3 following years. In 2020, eight cases were diagnosed, followed by 35 cases in 2021 and 17 cases in 2022. Since then, there have been very few cases.
Patient demographics showed that the affected individuals were between the ages of 43 and 71, with 36 of them being female.
Regarding ethnicity, the breakdown is as follows:
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- White: 32
- South Asian: 3
- Black Caribbean: 2
- Black African: 1
- White: 29
- Black: 7
- Hispanic: 4
- Any other ethnic group: 4
- Asian (not Chinese): 4
- There was no ethnicity data for 14 patients.
In 2021, researchers observed a strong correlation between vaccination rates in Yorkshire and the increase in MDA5 disease cases. This peak coincided with a community-wide outbreak of coronavirus infection in late 2021. A smaller correlation was found between confirmed COVID-19 infection and MDA5. It is notable that almost 42% of patients who tested positive for MDA5 did not have documented COVID-19 vaccination. Additionally, four children who were not vaccinated against COVID-19 before testing positive for MDA5.The individuals who tested positive for MDA5 did not receive the COVID-19 vaccine, indicating that their immune system may have overreacted after being exposed to the virus.
Professor McGonagle explained: “We understand that vaccines can cause an exaggerated immune response, but since not all of these patients were vaccinated against COVID-19, and the rise in cases coincided with a significant spread of the COVID-19 virus, the evidence strongly suggests that the increase in cases of this rare disease is connected to exposure to the virus.”
The findings came from Dr. Paula David and Dr. Gabriele DeMarco of the University of Leeds’ School of Medicine and the Leeds Teaching Hospitals NHS Trust.The research was conducted by the team at King’s College London and Guy’s and St Thomas’ NHS Trust, in partnership with Dr. Khizer Iqbal. Their work involved collaborating with Dr. Pradipta Ghosh and her team at the University of California, San Diego. They found that patients with COVID-19 and other diseases related to MDA5 had higher levels of the MDA5 protein. This increase in protein was linked to an abnormal immune response that hindered the virus’s ability to replicate and spread. In addition, they observed that higher MDA5 protein levels were associated with increased Interleukin-15 levels, a protein that activates immune T-cells.
According to the researchers, contributing to the autoimmune response could be a factor.
They recommend that doctors take note of their findings in order to speed up diagnosis and treatment for patients, potentially reducing lung damage and saving lives. This is particularly important for individuals with suspected pneumonia that isn’t improving with therapy, and who don’t exhibit rashes, muscle involvement, or other disease features.
Dr. Paula David, the paper’s lead author, stated: “We believe that this significant outbreak of MDA5 disease in Yorkshire will contribute to a better understanding of the relationship between viruses and autoimmunity.”
Dr Saptarshi Sinha, who co-authored the paper and is currently serving as the interim director of PreCSN, emphasized the team’s ability to assist researchers like the McGonagle group in analyzing large sets of data and identifying patterns quickly and accurately. He expressed satisfaction in being able to establish a connection between the clinical manifestation of autoimmune disease in the context of COVID-19 at a molecular level.
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