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

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-ß2 glycoprotein I (anti-ß2GPI), 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-ß2GPI (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-ß2GPI 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.

Differences in SARS-CoV-2-Specific Antibody Responses After the First, Second, and Third Doses of BNT162b2 in Naïve and Previously Infected Individuals: A 1-Year Observational Study in Healthcare Professionals.

Background: Safe and effective vaccines against COVID-19 are critical for preventing the spread of SARS-CoV-2, but little is known about the humoral immune response more than 9 months after vaccination. We aimed to assess the humoral immune response after the first, second, and third (booster) doses of BNT162b2 vaccine in SARS-CoV-2 naïve and previously infected healthcare professionals (HCP) and the humoral immune response after infection in vaccinated HCP. Methods: We measured anti-spike (anti-S) and anti-nucleocapsid antibodies at different time points up to 12 months in the sera of 300 HCP who had received two or three doses of BNT162b2 vaccine. Mixed-model analyses were used to assess anti-S antibody dynamics and to determine their predictors (age, sex, BMI, and previous infection). Results: Naïve individuals had statistically lower anti-S antibody concentrations after the first dose (median 253 BAU/ml) than previously infected individuals (median 3648 BAU/ml). After the second dose, anti-S antibody concentrations increased in naïve individuals (median 3216 BAU/ml), whereas the second dose did not significantly increase concentrations in previously infected individuals (median 4503 BAU/ml). The third dose resulted in an additional increase in concentrations (median 4844 BAU/ml in naïve and median 5845 BAU/ml in previously infected individuals). Anti-S antibody concentrations steadily decreased after the second dose and after the third dose in naïve and previously infected individuals. In addition, we found that age had an effect on the humoral immune response. Younger individuals had higher anti-S antibody concentrations after the first and second doses. After infection with the new variant Omicron, a further increase in anti-S antibody concentrations to a median value of 4794 BAU/ml was observed in three times vaccinated HCP whose anti-S antibody concentrations were relatively high before infection (median 2141 BAU/ml). Our study also showed that individuals with systemic adverse events achieved higher anti-S antibody concentrations. Conclusion: In this study, significant differences in humoral immune responses to BNT162b2 vaccine were observed between naïve and previously infected individuals, with age playing an important role, suggesting that a modified vaccination schedule should be practiced in previously infected individuals. In addition, we showed that the high anti-S antibodies were not protective against new variants of SARS-CoV-2.

COVID-19 in Association With Development, Course, and Treatment of Systemic Autoimmune Rheumatic Diseases.

Autoimmune diseases and infections are often closely intertwined. Patients with autoimmune diseases are more susceptible to infections due to either active autoimmune disease or the medications used to treat them. Based on infections as environmental triggers of autoimmunity, an autoimmune response would also be expected in COVID-19. Although some studies have shown the occurance of autoantibodies and the possible development of autoimmune diseases after SARS-CoV-2 infection, current data suggest that the levels of autoantibodies following SARS-CoV-2 infection is comparable to that of some other known infections and that the autoantibodies might only be transient. The risk of SARS-CoV-2 infection in patients with a systemic autoimmune rheumatic disease (SARD) appears slightly higher compared to the general population and the course of COVID-19 disease does not seem to be very different, however, specific therapies such as glucocorticoids and anti-TNF might modulate the risk of hospitalization/death. Cytokine release syndrome is a severe complication in COVID-19. Many drugs used for the treatment of SARD are directly or indirectly targeting cytokines involved in the cytokine release syndrome, therefore it has been suggested that they could also be effective in COVID-19, but more evidence on the use of these medications for the treatment of COVID-19 is currently being collected.