Anti-phospholipids antibodies and immune complexes in COVID-19 patients: a putative role in disease course for anti-annexin-V antibodies

Abstract

Introduction: Besides distinctive respiratory and digestive hallmarks, COVID-19 has been recently associated with a high prevalence of pro-inflammatory and hypercoagulable states known as “COVID-19 Associated Coagulopathy” (CAC), corresponding to a worsening in patients’ conditions, whose causes are still to be elucidated. A link between anti-phospholipids antibodies (aPLs) and viral infections has long been suggested. APLs are assessed for Anti-phospholipid Syndrome (APS) diagnosis, characterized by thrombocytopenia, thrombosis and coagulopathy. Furthermore, circulating immune complexes (CICs), arisen upon inflammatory responses and related immune dysregulation, can lead to endothelial cells damage and thrombotic complications.Method: We performed an extended panel including IgG/IgM anti-cardiolipin, IgG/IgM anti-β2-glycoprotein-1, coupled with IgG/IgM anti-prothrombin, IgG/IgM anti-annexin-V on two COVID-19 patient groups (early and late infection time) and a negative control group. IgG CICs analysis followed to evaluate inflammatory status, through a possible complement system activation.Results: Our results showed low positive cases percentage in IgG/IgM anti-cardiolipin and IgG/IgM anti-β2-glycoprotein-1 assays (4.54%, 6.25%, 4.55%; in early infection group, late infection group and control group, respectively); few positive cases in IgG/IgM anti-prothrombin and IgG/IgM anti-annexin-V immunoassays; no IgG CICs positivity in any patient.Conclusions: In conclusion, our data show a low aPLs prevalence, likely excluding an involvement in the pathogenesis of CAC.Interestingly, IgG/IgM anti-prothrombin and anti-annexin-V positive cases, detected in late infection group, suggest that aPLs could temporarily increase or could trigger a “COVID-19-induced-APS-like-syndrome” in predisposed patients.Finally, even though aPLs are transient, they may still have a thrombotic potential in genetically predisposed COVID-19 patients.

Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins

“…Indeed, we found that, globally, IgM or IgG levels are increased upon infection with SARS-CoV-2, with 66% of individuals having aPL against �1 antigen (non-infected controls: 15%), 40% against �2 antigens (noninfected controls: 0%), and 21.3% against �3 antigens (non-infected controls: 0%), using a threshold of OD � 50. Thus, the prevalence of aPL was higher in our study than previously reported [13,15,50,51,55], despite not including LA in the measurements, and in spite of omitting IgA aPL. Importantly, we detected significant distributional changes between noninfected controls and SARS-CoV-2-infected individuals for IgM aPL against AnV, β2, and PT using Fisher's exact test (p-values < 0.01), and for β2, and PT using Wilcoxon rank sum test (p-values < 0.01 after Benjamini-Hochberg correction).…”

COVID-19 and Antiphospholipid Antibodies: Time for a Reality Check?

“…Irrespective, as for the case with LA, 11 there was also a large body of publications related to solid-phase aPL. 31 32 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 Although additional relevant papers are likely available in the literature, the captured articles are sufficient for us to critically review the main literature to date. As for LA, 11 there was a wide variety of methods employed to identify solid-phase aPL ( Table 1 ), but sometimes the methodology was not reported.…”

COVID‐19 coagulopathies: Human blood proteins mimic SARS‐CoV‐2 virus, vaccine proteins and bacterial co‐infections inducing autoimmunity

“…Platelet‐activating CIC are found in all severely ill COVID‐19 patients but not mild cases. [ 95 , 96 , 97 ] Notably, neither molecular mimicry theory nor bystander theory predicts the formation of CIC. Complementary antibodies will, in turn, target molecularly complementary host antigens of which many examples exist in Tables 1 and 2 .…”