"Multisystem Inflammatory Syndrome in Children"-Like Disease after COVID-19 Vaccination (MIS-V) with Potential Significance of Functional Active Autoantibodies Targeting G-Protein-Coupled Receptors (GPCR-fAAb) for Pathophysiology and Therapy

Marius Schmidt; Steven Hébert; Gerd Wallukat; Rolf Ponader; Tobias Krickau; Matthias Galiano; Heiko Reutter; Joachim Woelfle; Abbas Agaimy; Christian Mardin; André Hoerning; Bettina Hohberger

doi:10.3390/children10121836

"Multisystem Inflammatory Syndrome in Children"-Like Disease after COVID-19 Vaccination (MIS-V) with Potential Significance of Functional Active Autoantibodies Targeting G-Protein-Coupled Receptors (GPCR-fAAb) for Pathophysiology and Therapy

Children (Basel). 2023 Nov 22;10(12):1836. doi: 10.3390/children10121836.

Authors

Affiliations

¹ Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany.
² Berlin Cures GmbH, 13125 Berlin, Germany.
³ Department of Pediatrics and Adolescent Medicine, 95032 Hof, Germany.
⁴ Division of Neonatology and Pediatric Intensive Care, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, 91054 Erlangen, Germany.
⁵ Department of Pathology, University Hospital Erlangen, 91054 Erlangen, Germany.
⁶ Department of Ophthalmology, University Hospital Erlangen, 90766 Erlangen, Germany.
⁷ German Center for Immunotherapy, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany.

Abstract

Background: An infection with SARS-CoV-2 can trigger a systemic disorder by pathological autoimmune processes. A certain type of this dysregulation is known as Multisystemic inflammatory syndrome in children (MIS-C). However, similar symptoms may occur and have been described as Multisystemic inflammatory syndrome after SARS-CoV-2 Vaccination (MIS-V) following vaccination against SARS-CoV-2. We report the case of a 12-year-old boy who was identified with MIS-C symptoms without previous SARS-CoV-2 infection after receiving two doses of the Pfizer-BioNTech COVID-19 vaccine approximately one month prior to the onset of symptoms. He showed polyserositis, severe gastrointestinal symptoms and, consequently, a manifestation of a multiorgan failure. IgG antibodies against spike proteins of SARS-CoV-2 were detected, indicating a successful vaccination, while SARS-CoV-2 Nucleocapsid protein antibodies and SARS-CoV-2 PCR were not detected. Several functional, active autoantibodies against G-protein-coupled receptors (GPCR-fAAb), previously associated with Long COVID disease, were detected in a cardiomyocyte bioassay. Immunosuppression with steroids was initiated. Due to side effects, treatment with steroids and later interleukin 1 receptor antagonists had to be terminated. Instead, immunoadsorption was performed and continued with tacrolimus and mycophenolic acid therapy, leading to improvement and discharge after 79 days. GPCR-fAAb decreased during therapy and remained negative after clinical curing and under continued immunosuppressive therapy with tacrolimus and mycophenolic acid. Follow-up of the patient showed him in good condition after one year.

Conclusions: Infection with SARS-CoV-2 shows a broad and severe variety of symptoms, partly due to autoimmune dysregulation, which, in some instances, can lead to multiorgan failure. Despite its rarity, post-vaccine MIS-C-like disease may develop into a serious condition triggered by autoimmune dysregulation. The evidence of circulating GPCR-fAAb and their disappearance after therapy suggests a link of GPCR-fAAb to the clinical manifestations. Thus, we hypothesize a potential role of GPCR-fAAb in pathophysiology and their potential importance for the therapy of MIS-C or MIS-V. However, this observation needs further investigation to prove a causative correlation.

Keywords: COVID-19; GPCR-fAAb; MIS-C; MIS-V; PIMS; SARS-CoV-2.

Publication types

Case Reports

Grants and funding

We acknowledge financial support by the Deutsche Forschungsgemeinschaft and Friedrich Alexander Universität Erlangen-Nürnberg within the funding programme “Open Access Publication Funding”.