Production of antiphospholipid antibodies is common after viral infections; however, their clinical significance is still unknown. Some patients may have these antibodies for short period of time, yet in some cases they persist and can contribute to the development of autoimmune diseases . aCL is an antiphospholipid antibody, found at high concentrations in the antiphospholipid syndrome (APS). In fact, the hallmark of APS involves the setting of aCL, at the site of thrombosis. Furthermore, it has been found that antibodies induced by SARS-CoV-2 cross-react with red blood cells, platelets and serum albumin which results in blood thickening. Specifically, SARS‐CoV‐2 spike protein is structurally similar enough to some blood coagulation factors . Several studies investigated the safety of the ChAdOx1 vaccine indicating a shared pathophysiological basis of a syndrome similar to autoimmune heparin-induced thrombocytopenia in some individuals [8, 9].
In the present study, aCL IgG antibodies were evaluated in COVID-19 positive patients and individuals vaccinated with BNT162b2 and ChAdOx1-S. All study groups were compared to COVID-19 negative, non-vaccinated individuals. The highest percentage of subjects positive for aCL IgG antibodies was the COVID-19 positive group (18.2%), significantly different (p = 0.0167) from the control group. This is in line with a recent study, showing severe cases of COVID-19 are more prone to thrombotic events, with patients admitted to ICU presenting high concentration of aCL IgG antibodies [10, 11]. However, none of the COVID-19 positive subjects included in our study required hospitalization.
Interestingly, BNT162b2 vaccinated group had a higher percentage of positivity for aCL, at 11.9%, in comparison with ChAdOx1-S, at 2.7%, which was also found to be significantly different (p = 0.0037). An association between ChAdOx1-S vaccination and thrombosis is reported . Interestingly, individuals vaccinated with ChAdOx1-S had the lowest positivity (2.7%) but also the lowest overall concentration of aCL IgG antibodies following administration of the second dose, even when compared to the non-vaccinated individuals (p = 0.0289) (Fig. 1B). Importantly, literature thus far have not explored the full set of groups included in the present study, therefore there is insufficient knowledge in interpreting the presence of aCL antibodies.
Moreover, a significant difference (p = 0.0391) was observed between concentration levels of aCL IgG antibodies over time in the study groups vaccinated with ChAdOx1-S (Fig. 2A). On the contrary, a significant difference was not observed in the BNT162b2 vaccinated group. Noteworthy, there is a significant difference after the second dose is administrated for both vaccines. For BNT162b2, T2 samples were around 3 weeks after administration of the first dose, whereas for ChAdOx1-S the second dose was given at around 8 to 12 weeks after the first dose. Assuming both doses spike the exact same response regarding the production of aCL IgG antibodies, ChAdOx1-S vaccinated group had more time to lower levels back to baseline in comparison to BNT162b2. This could also explain the higher concentration and degree of positivity in the BNT162b2 vaccinated group. T2 samples could account for the increase of aCL in both doses together. In addition, this could also explain why the ChAdOx1-S vaccinated group had a significantly lower (p = 0.0289) concentration that the control group at the T2 time point. Another important detail that needs to be taken into consideration, is the fact that ChAdOx1-S and BNT162b2 differ in the molecular design delivery system used. In the case of ChAdOx1-S, viral vectors are designed to specifically express antigens of target pathogens. The delivery of the target antigen by viral vectors produces potent antigens consequently mimicking the natural infection which then induces strong T cell responses . The chimpanzee adenovirus vector was used due to the low human prevalence, as humans have low pre-existing immunity to its viral backbone . The BNT16b2 vaccine employs the use of S antigen-encoding mRNA. They need to be delivered to the cytoplasm of host cells for translation to occur . Further studies are required, which may provide clues as to the origins of coagulopathies in COVID‐19 and determine whether is due to the production of aCL IgG antibodies.
Noteworthy, a recent study has concluded that antiphospholipid antibodies produced in APS differ from those seen in SARS-CoV-2 . Despite that, it does not mean that aCL linked to SARS-CoV-2, have no association with thrombosis [13, 14]. Severe cases of COVID-19 infection can still benefit from antiphospholipid antibody tests as they can demonstrate the risk of thrombosis in patients and preventative care can be applied.