COVID-19 May Trigger Autoimmune Responses in Children

Katherine Konvinse, MD, PhD

Recently, there have been reports of autoantibodies in individuals who have had COVID-19. Research featured at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2023 Annual Meeting in San Antonio, TX, Katherine Konvinse, MD, PhD, Stanford University, and a team of investigators evaluated the presence of autoantibodies in children after SARS-CoV-2 infection, including those who developed multisystem inflammatory syndrome in children (MIS-C).¹

According to the results of the study, children with current or prior SARS-CoV-2 infection had more autoantibodies than healthy children. IgG autoantibodies against ACE2 and fibrillarin were the most common autoantibodies in the asymptomatic/mild (63%; 19%) and severe COVID-19 groups (22%; 13%) and were also present in children with MIS-C (25%; 14%).

Additionally, anti-interferon, especially anti-IFN-epsilon antibodies, and anti-interleukin antibodies were present in the plasma of children with acute severe COVID-19.

In the study, investigators wrote that the data suggested COVID-19 may trigger the development of autoimmune responses in children. Autoantibodies against ACE2, which is the receptor for SARS-CoV-2, and fibrillarin, a common autoantigen in systemic autoimmune diseases, were found in high levels in children with COVID-19 and MIS-C. This could indicate a potential link between SARS-CoV-2 infection and the development of autoimmunity in children.

The team also identified anti-interferon and anti-interleukin antibodies in the plasma of children with acute severe COVID-19. These cytokines are important for the immune response against viral infections, and their dysregulation may contribute to the severity of COVID-19. The presence of autoantibodies against these cytokines may suggest a potential mechanism for immune dysregulation in severe cases of COVID-19 in children.

The Study Method

Investigators employed a custom 77-plex bead-based protein array to test plasma samples from 95 children aged 0-21 years, representing 3 diagnostic groups including, 27 with asymptomatic/mild SARS-CoV-2 infection, 32 with severe COVID-19, and 36 with MIS-C.

Samples were collected within 0-600 days after infection onset. Investigators also tested for IgG antibodies against classical autoimmune diseases, antiviral antibodies including SARS-CoV-2 nucleocapsid and receptor-binding domain, and anti-cytokine antibodies.

The mean fluorescence intensity (MFI) for each antigen was calculated using samples from healthy children (HC) aged 4-17 years old who have not had COVID-19 or any diagnoses of autoimmune diseases. Antibodies were considered positive if the MFI was >5 standard deviations above the average MFI of HC and >3000 MFI units.

Investigators concluded that these results demonstrated the importance of monitoring for autoimmune responses in children who have been infected with SARS-CoV-2. The high prevalence of autoantibodies in this population suggested the need for further studies to investigate the long-term effects of COVID-19 on the immune system and the potential for the development of autoimmune disorders.

Identifying specific autoantibodies could inform future efforts for surveillance of specific antigens and autoimmune diseases in children who have been infected by SARS-CoV-2, the study concluded.

References:

1. Konvinse K, Bruiners N, Ukey R, Horton D, Gennaro M, Utz P. High prevalence of autoantibodies in children after COVID-19 infection of differing levels of severity. J Allergy Clin Immunol. 2022;149(3 Suppl):AB320. doi: 10.1016/j.jaci.2022.12.794.