Long-Term Evaluation of Antiphospholipid Antibodies in Patients with COVID-19

Background: The role of antiphospholipid antibodies (aPL) in COVID-19 coagulopathy remains controversial; moreover, follow-up data after >12 weeks are lacking. Methods: In this prospective single-centre study, we determined ‘criteria’ (IgG, IgM) and ‘non-criteria’ (IgA) anti–β2-glycoprotein I (anti-β2-GPI), and anti-cardiolipin (aCL) antibodies, as well as lupus anticoagulant (LAC) in 157 consecutive adult inpatients with COVID-19. Repeat testing was offered after >12 weeks to all patients with initially positive results. Findings: Patients had a median age of 69 years, and 38·9% were admitted to the intensive care unit (ICU). LAC was present in 35·6%, aCL in 12·5%, and anti-β2-GPI in 15·6% of the patients, respectively. The most commonly detected isotype was IgA (17·1%), followed by IgM (5·9%), and IgG (2·6%). Occurrence of LAC and/or aPL was observed in 73 (48·7%) patients and was associated with ICU treatment and higher C-reactive protein (p=0·009, and p=0·019 respectively), but not with thromboembolic events (p=0·130) when compared to the aPL-negative population. Patients with IgA double-positivity showed an increased 30-days mortality (75·0% vs 95·1%; p=0·001). Of the 73 patients with positivity for LAC and/or aPL, 38 (52·1%) patients were available for follow-up after >12 weeks. The median LAC ratio decreased from 1·30 (1·22-1·37) at first timepoint to 1·15 (1·10-1·25) (p=0·001) at follow-up, while aPL positivity remained unchanged. Interpretation: aPL are a transient phenomenon in COVID-19 most likely related to ‘non-criteria’ antibodies and inflammation and are associated with disease severity, but not with macrothrombotic events. Patients with double positivity for IgA aPL have an inferior survival probability. Funding Statement: Laboratory testing was supported in parts by Axonlab and Thermo Fisher Scientific. Declaration of Interests: Dr. Gerber reports non-financial support and funding for accredited continuing medical education program from Axonlab, and from Thermo Fisher Scientific, during the conduct of the study; personal fees and funding for accredited continuing medical education program from Alnylam, grants, personal fees and funding for accredited continuing medical education program from Pfizer, funding for accredited continuing medical education program from Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Takeda, Octapharma, SOBI, Janssen, Novo Nordisk, Mitsubishi Tanabe Pharma, outside the submitted work; Dr. Rossi reports unrestricted research grant, consultancy, travel from Jannsen, Abbvie, and AstraZeneca, outside the submitted work; Dr. Bernasconis institution received fees for his participation to advisory boards, travel grants from Gilead Sciences, ViiV Healthcare, Merck Sharp and Dohme, Pfizer, Abbvie, Sandoz AG, outside the submitted work; All other authors have nothing to disclose. Ethics Approval Statement: Clinical data were extracted from the electronic medical records. The study was approved by the Ethical Committee Ticino, Switzerland (2020-00838 RIF.CE 3621), and the need for a written informed consent was waived due to the non-interventional design of the trial with use of pre-existing biological material and health care data.