Autoantibodies to protein S may explain rare cases of coagulopathy following COVID-19 vaccination

Sci Rep. 2024 Oct 18;14(1):24512. doi: 10.1038/s41598-024-75514-x.

Abstract

While Coronavirus disease 2019 (COVID-19) vaccines have proven to be both effective and generally safe, rare but severe adverse events following immunization (AEFIs) are described. Autoantibodies to platelet factor-4 are associated with catastrophic thrombotic AEFIs, but comprehensive investigations of other autoantibodies are lacking. We aimed to detect and describe autoantibodies targeting coagulation-related proteins in a population-wide cohort (SWEDEGENE) including AEFIs attributed to COVID-19 vaccines in Sweden. Subjects were recruited from December 2020 to October 2022 and were stratified based on diagnosis and COVID-19 exposure. Screening was carried out in two phases, with a multiplex bead-based assay in the first subset (until September 2021) and with targeted assays for the second (until October 2022). Positivity was defined based on absolute, relative, and biological/technical thresholds. Patients with coagulation-related AEFIs were older and the Vaxzevria vaccine was overrepresented in this group. Two cases had antiphospholipid antibodies but none had PF4 antibodies. We identified six positives for protein S autoantibodies. Protein S concentrations were negatively correlated with autoantibody response in patients with immunoreactivity and functional analysis revealed low protein S activity in three subjects. Our population-wide analysis reveals cases with autoantibodies against protein S which possibly underlie coagulopathic AEFIs.

Keywords: Autoantibodies; Blood coagulation disorders; COVID-19; Protein S; Vaccines/adverse effects.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies* / blood
  • Autoantibodies* / immunology
  • Blood Coagulation Disorders / etiology
  • Blood Coagulation Disorders / immunology
  • COVID-19 Vaccines* / adverse effects
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Factor 4 / immunology
  • Protein S* / immunology
  • SARS-CoV-2* / immunology
  • Sweden
  • Vaccination / adverse effects

Substances

  • Autoantibodies
  • COVID-19 Vaccines
  • Protein S
  • Platelet Factor 4