Beta‐2‐Glycoprotein‐I Deficiency Could Precipitate an Antiphospholipid Syndrome‐like Prothrombotic Situation in Patients With Coronavirus Disease 2019

Abstract

Objective Patients with coronavirus disease 2019 (COVID‐19) present coagulation abnormalities and thromboembolic events that resemble antiphospholipid syndrome (APS). This work has aimed to study the prevalence of APS‐related antigens, antibodies, and immune complexes in patients with COVID‐19 and their association with clinical events. Methods A prospective study was conducted on 474 adults with severe acute respiratory syndrome coronavirus 2 infection hospitalized in two Spanish university hospitals. Patients were evaluated for classic and extra‐criteria antiphospholipid antibodies (aPLs), immunoglobulin G (IgG)/immunoglobulin M (IgM) anticardiolipin, IgG/IgM/immunoglobulin A (IgA) anti‐β2‐glicoprotein‐I (aβ2GPI), IgG/IgM antiphosphatidylserine/prothrombin (aPS/PT), the immune complex of IgA aβ2GPI (IgA‐aβ2GPI), bounded to β2‐glicoprotein‐1 (β2GPI) and β2GPI levels soon after COVID‐19 diagnosis and were followed‐up until medical discharge or death. Results Prevalence of aPLs in patients with COVID‐19 was as follows: classic aPLs, 5.8%; aPS/PT, 4.6%; IgA‐aβ2GPI, 15%; and any aPL, 21%. When patients were compared with individuals of a control group of a similar age, the only significant difference found was the higher prevalence of IgA‐aβ2GPI (odds ratio: 2.31; 95% confidence interval: 1.16‐4.09). No significant differences were observed in survival, thrombosis, or ventilatory failure in aPL‐positive versus aPL‐negative patients. β2GPI median levels were much lower in patients with COVID‐19 (15.9 mg/l) than in blood donors (168.8 mg/l; P < 0.001). Only 3.5% of patients with COVID‐19 had normal levels of β2GPI (>85 mg/l). Low levels of β2GPI were significantly associated with ventilatory failure (P = 0.026). Conclusion β2GPI levels were much lower in patients with COVID‐19 than in healthy people. Low β2GPI‐levels were associated with ventilatory failure. No differences were observed in the COVID‐19 evolution between aPL‐positive and aPL‐negative patients. Functional β2GPI deficiency could trigger a clinical process similar to that seen in APS but in the absence of aPLs.

Systematic Review of Antiphospholipid Antibodies in COVID-19 Patients: Culprits or Bystanders?

“…Ferrari et al found a similar prevalence for LA, aβ 2 -GPI and aCL in severe and non-severe COVID-19 patients [ 43 ], and other authors did not find more aPL (aCL or aβ 2 -GPI) between patients with COVID-19 related acute respiratory disease syndrome and patients with pneumonia-associated acute respiratory disease syndrome in ICU [ 19 , 53 ]. One study did not find more LA in COVID-19 non-survivors than in survivors [ 32 ], likewise other studies did not find any association between overall aPL positivity and in-hospital mortality [ 50 , 55 ].…”

Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID-19 Complications?

“…A higher prevalence of autoantibodies IgA anti-β2-glycoprotein-I was confirmed in a larger cohort of COVID-19 patients with the additional finding of significantly lower levels of β2-glycoprotein-I in COVID-19 patients than in healthy controls, with an inverse correlation with ventilation failure [ 57 ]. More recently, several studies have informed an elevated incidence of lupus anticoagulant presence in COVID-19 patients, by coagulometric tests [ 47 , 58 , 59 ].…”

Anti-Phosphatidylserine/Prothrombin Antibodies in Healthy Women with Unexplained Recurrent Pregnancy Loss

“…The QUANTA Lite ELISA (INOVA DIAGNOSTICS, San Diego, CA, USA) was used to evaluate aPS/PT IgG & IgM. We had previously described our calculated aPS/PT for our local population based on the 99th percentile, which resulted in 30 U/mL for IgG and 40 U/mL for IgM [ 21 ].…”