Longitudinal Analysis of Antiphospholipid Antibody Dynamics after Infection with SARS-CoV-2 or Vaccination with BNT162b2

Abstract

Antiphospholipid antibodies (aPL) comprise a group of autoantibodies that reflect prothrombotic risk in antiphospholipid syndrome (APS) but may also be present in a small proportion of healthy individuals. They are often transiently elevated in infections, including SARS-CoV-2, and may also be associated with vaccine-induced autoimmunity. Therefore, we aimed to investigate the dynamics of aPL in COVID-19 patients and in individuals (healthcare professionals—HCPs) after receiving BNT162b2 vaccine and to compare aPL levels and positivity with those found in APS patients. We measured solid-phase identifiable aPL, including anticardiolipin (aCL), anti-β2 glycoprotein I (anti-β2GPI), and anti-prothrombin/phosphatidylserine (aPS/PT) antibodies in 58 HCPs before and after vaccination (at 3 weeks, 3, 6, and 9 months after the second dose, and 3 weeks after the third booster dose), in 45 COVID-19 patients hospitalized in the ICU, in 89 COVID-19 patients hospitalized in the non-ICU (at admission, at hospital discharge, and at follow-up), and in 52 patients with APS. The most frequently induced aPL in COVID-19 patients (hospitalized in non-ICU) were aCL (50.6% of patients had positive levels at at least one time point), followed by anti-β2GPI (21.3% of patients had positive levels at at least one time point). In 9/89 COVID-19 patients, positive aPL levels persisted for three months. One HCP developed aCL IgG after vaccination but the persistence could not be confirmed, and two HCPs developed persistent anti-β2GPI IgG after vaccination with no increase during a 1-year follow-up period. Solid-phase aPL were detected in 84.6% of APS patients, in 49.4% of COVID-19 patients hospitalized in the non-ICU, in 33.3% of COVID-19 patients hospitalized in the ICU, and in only 17.2% of vaccinated HCPs. aPL levels and multiple positivity were significantly lower in both infected groups and in vaccinated individuals compared with APS patients. In conclusion, BNT162b2 mRNA vaccine may have induced aPL in a few individuals, whereas SARS-CoV-2 infection itself results in a higher percentage of aPL induction, but the levels, persistence, and multiple positivity of aPL do not follow the pattern observed in APS.

Antiphospholipid antibody-related hepatic vasculitis in a juvenile after non-severe COVID-19: a case report and literature review

“…Thrombosis and corresponding organ infarctions (80%) were the most common manifestation, followed by thrombocytopenia (30%). There were 12 patients mentioned in four cohort studies who also fulfilled the inclusion criteria but were not included due to the lack of individualized information (50, 64,67,[77][78][79][80][81]85). In addition to newly diagnosed APS, five cases have reported relapses of completely remitted APS following COVID-19 infections (Table 2), reiterating SARS-CoV-2 as a potential trigger for pathogenic effects of aPL and exacerbation of APS in some patients.…”

SARS‐CoV‐2 vaccination appears to be safe in antiphospholipid antibody syndrome: Comment on evaluation of patients with antiphospholipid syndrome subsequently COVID‐19 vaccinations

“…Overall, very few people developed APLs after vaccination and no increased thrombotic risk was noted in such individuals. [9][10][11][12] The titers of APLs (IgM, IgG, or IgA anticardiolipin antibodies), IgG, IgM, or IgA anti-β2GP1, IgM or IgG anti-PS/PT, and antinuclear antibody were similar before and 4 weeks after completing the course of vaccination. New-onset of anti-platelet factor 4 antibodies was noted in 7/406 individuals after vaccination.…”

“…The identified studies are summarized in Table 1. 1,[4][5][6][7][8][9][10][11][12] Six studies assessed the safety of COVID-19 vaccination in more than 1300 patients with APS. Most of these studies did not report any thrombotic events or any increase in the titers or prevalence of APLs in APS patients following COVID-19 vaccination.…”

Antiphospholipid Antibodies and Vascular Thrombosis in Patients with Severe Forms of COVID-19

“…anti-β2GPI were measured by in-house ELISA [28] and evaluated by the European Forum for aPL [29]. aPS/PT were measured with in-house ELISA first described in 2011 [24] and later repeatedly evaluated [6,30,31]. Values above the 99th percentile of the healthy control population were regarded as positive, i.e., for aCL ≥ 11AU, for anti-β2GPI ≥ 2 AU, and for aPS/PT ≥ 5 AU.…”