Electronic health record study examines how COVID-19 severity impacts risk of autoimmune diseases

In a recent RECOVER study, researchers examined whether the severity of a person’s COVID-19 case impacted their risk for developing a new autoimmune disease. It is estimated that there are nearly 100 different autoimmune diseases that affect millions of Americans. Autoimmune diseases like type 1 diabetes, psoriasis, and rheumatoid arthritis can result from 1 of the following conditions:

• Autoantibodies or immune cells that damage the body instead of protecting against disease.
• Targeted or widespread inflammation (irritation) in the body.
• Organ damage.

The findings from this study, which were recently published in PLOS One, show how COVID can lead to other chronic health conditions.

What did the researchers do?

Researchers analyzed electronic health record (EHR) data from RECOVER research networks that collect medical records from over 100 sites across the country. The study included EHRs in which a patient sought medical attention between April 1, 2020, and April 1, 2021. Researchers collected data about patients’ demographics, doctors’ visits, medical diagnoses, medications, and select lab results. In total, researchers analyzed more than 1.8 million adult EHRs from the National COVID Cohort Collaborative (N3C) and the National Patient-Centered Clinical Research Network (PCORnet®), and over 160,000 pediatric EHRs.

Researchers used several methods to identify EHRs of people who had COVID. They included EHRs with a recorded positive SARS-CoV-2 infection via a COVID-19 test, a COVID-19 diagnosis (noted in the EHR using an ICD-10 code, which doctors use to indicate the illnesses or conditions a patient has), or a treatment for COVID like nirmatrelvir/ritonavir (Paxlovid). Researchers analyzed data from these patients who had COVID to determine whether they developed new autoimmune diseases over a 24-month period.

The study team was also interested in the severity of patients’ COVID-19 cases. They categorized the adult patients’ COVID-19 severity on 4 levels of increasing severity:

• “Outpatient” if there was no evidence of hospitalization or a visit to the emergency department.
• “Emergency department” if there was an emergency department visit only.
• “Hospitalized” if a patient was hospitalized but was not critically ill.
• “Hospitalized with ventilation” if a patient was hospitalized and required intensive care, such as a breathing machine (ventilator) or medications to improve blood pressure and heart function.

Researchers also categorized pediatric COVID-19 severity using 3 levels:

• Mild (symptoms like abdominal pain, fatigue, and nasal congestion).
• Moderate (symptoms like dehydration, pneumonia, and fluid use during an emergency room visit).
• Severe (symptoms like sepsis, which is a life-threatening response to an infection; shock; and respiratory failure).

What did the researchers find?

Results from this study were consistent with previous research, which found that a more severe COVID-19 illness (being hospitalized or put on a ventilator) was associated with increased risk of developing autoimmune diseases. In the largest adult dataset (N3C) and the pediatric dataset, researchers found that as COVID-19 severity increased, so did a person’s risk for developing a new autoimmune disease. In the N3C data, patients were twice as likely to develop a new autoimmune disease if they experienced a severe case of COVID-19 versus those in the outpatient category. Children in the severe category were more than 6 times more likely to develop an autoimmune disease compared to the children with mild COVID-19 cases. The other adult dataset, drawn from PCORnet®, showed no change in autoimmune disease risk among different severity levels.

Adults and children with more severe cases of COVID-19 were reported to have new diagnoses of thyroid disease, psoriasis (chronic skin condition causing red, scaly patches) or psoriatic arthritis, and inflammatory bowel disease. Pediatric patients with more severe cases of COVID-19 received new diagnoses of type 1 diabetes, which have also been reported following other viral infections like mumps, parainfluenza, and human herpesvirus 6 (HHV-6). 

Researchers believe this increased risk for autoimmune disease is due to individuals’ immune system response to the SARS-CoV-2 virus. Although all viral infections prompt an immune response, the body’s reaction to SARS-CoV-2 tends to be more intense. In some cases, this strong immune response does not decrease following the illness and can result in the body’s immune system attacking itself, leading to autoimmune diseases.

Some groups of people were more likely to have a severe COVID-19 case, which may have put them at increased risk of developing an autoimmune disease. These groups included:

• Men.
• People with preexisting autoimmune diseases or other serious preexisting conditions.
• People identifying as non-Hispanic Black, or Hispanic or Latino.

Why is this research important?

The results from this study validate findings from other recent studies that found that more severe COVID-19 illness may be associated with increased autoimmune disease risk after a SARS-CoV-2 infection.

This study extends previous research by including data from pediatric patients to learn more about how COVID impacts children. The study also includes patients with documented preexisting autoimmune disease, who are more susceptible to developing new autoimmune diseases. Data from this study can help inform future studies that examine COVID cases after April 1, 2021. These future studies could help determine whether other COVID variants and COVID vaccinations have an impact on post-COVID autoimmune disease. Additional research should also be done to determine whether the risk of developing autoimmune diseases changes if a person has COVID more than once.

Read the full research study to learn more about the connection between COVID-19 severity and the risk for developing an autoimmune disease.