Patients with coronavirus disease 2019 (COVID-19) have a high rate of positivity for antiphospholipid (aPL) antibodies that potentially exert clinical effects, according to study results reported in Science Translational Medicine.
Antiphospholipid syndrome is characterized by autoantibodies that target phospholipids and phospholipid-binding proteins, and it is a condition that can promote thrombosis. According to the researchers, features of this syndrome are similar to the coagulopathy sometimes seen with COVID-19, and aPL antibodies have also been reported with COVID-19.
In this study, the researchers aimed to characterize aPL antibodies present in serum samples of hospitalized patients with COVID-19, and to evaluate any clinical features associated with these antibodies. Antibodies that were evaluated included anticardiolipin antibodies (immunoglobulin [Ig] G, IgM, and IgA), anti-b2 glycoprotein I antibodies (IgG, IgM, and IgA), and antiphosphatidylserine/prothrombin (aPS/PT) antibodies (IgG and IgM).
Slightly more than half (52%) of patients’ serum samples showed evidence of aPL antibodies. Nearly a quarter (24%) of patients’ serum samples contained detectable aPS/PT IgG antibodies. Anticardiolipin IgM was found in 23%, and aPS/PT IgM was found in 18%.
Higher neutrophil activation was positively correlated with higher levels of aPL antibodies. Platelet counts were also more elevated in the presence of more aPL antibodies. Estimated glomerular filtration rate and oxygenation efficiency both appeared to be worse in the presence of serum aPL antibodies. Peak plasma D-dimer levels were higher for patients with elevated aPS/PT antibodies, and an elevated peak serum troponin level was also associated with the presence of any aPL antibody.
Enhanced neutrophil activation in patients with COVID-19 was associated with the release of neutrophil extracellular traps (NETs). When IgG was taken from patients with COVID-19 and placed into healthy patients, NETs became released from the healthy individuals’ neutrophils.
Mouse models were also treated with IgG from patients with COVID-19 who had high titers of aPS/PT IgG, which appeared to enhance the rate of venous thrombosis in these models. IgG was injected into mice intravenously, and the mice showed increased thrombus accretion (P =.003), circulating NET remnants (P =.008), and thrombus extension (P =.01) when assessed 24 hours later.
“As we await definitive antiviral and immunological solutions to the current COVID-19 pandemic, we posit that testing for aPL antibodies, including aPS/PT antibodies, may lead to improved risk stratification and personalization of treatment for patients with COVID-19,” concluded the researchers in their report.
Zuo Y, Estes SK, Ali RA, et al. Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19. Sci Transl Med. Published online November 2, 2020. doi:10.1126/scitranslmed.abd3876