650-263-7636   contact@endothelix.com             YouTube                                                                       

Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19

Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19

 

Yu Zuo1, Shanea K. Estes1, Ramadan A. Ali1, Alex A. Gandhi1, Srilakshmi Yalavarthi1, Hui Shi1,2, Gautam Sule1, Kelsey Gockman1, Jacqueline A. Madison1, Melanie Zuo3, Vinita Yadav4, Jintao Wang5, Wrenn Woodard6, Sean P. Lezak6, Njira L. Lugogo7, Stephanie A. Smith8, James H. Morrissey8, Yogendra Kanthi4,5,‡ and Jason S. Knight1,‡

 

1Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

2Division of Rheumatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

3Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

4Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

5Division of Intramural Research National Heart, Lung and Blood Institute Bethesda, Maryland 20892, USA.

6Michigan Clinical Research Unit, University of Michigan, Ann Arbor, Michigan 48109, USA,

7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.

8Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.

↵‡Yogendra Kanthi and Jason S. Knight are co-corresponding authors. Email: yogen.kanthi@nih.gov, jsknight@umich.edu

 

1.  ‡Yogendra Kanthi and Jason S. Knight are co-corresponding authors. Email: yogen.kanthi@nih.govjsknight@umich.edu

Hide authors and affiliations

Science Translational Medicine  02 Nov 2020:

eabd3876

 

Abstract

Patients with COVID-19 are at high risk for thrombotic arterial and venous occlusions. Lung histopathology often reveals fibrin-based occlusions in the small blood vessels of patients who succumb to the disease. Antiphospholipid syndrome is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies targeting phospholipids and phospholipid-binding proteins (aPL antibodies). Case series have recently detected aPL antibodies in patients with COVID-19. Here, we measured eight types of aPL antibodies in serum samples from 172 patients hospitalized with COVID-19. These aPL antibodies included anticardiolipin IgG, IgM and IgA; anti-β2 glycoprotein I IgG, IgM, and IgA; and anti-phosphatidylserine/ prothrombin (aPS/PT) IgG and IgM. We detected aPS/PT IgG in 24% of serum samples, anticardiolipin IgM in 23% of samples, and aPS/PT IgM in 18% of samples. Antiphospholipid autoantibodies were present in 52% of serum samples using the manufacturer’s threshold and in 30% using a more stringent cutoff (≥40 ELISA-specific units). Higher titers of aPL antibodies were associated with neutrophil hyperactivity including the release of neutrophil extracellular traps (NETs), higher platelet counts, more severe respiratory disease, and lower clinical estimated glomerular filtration rate. Similar to IgG from patients with antiphospholipid syndrome, IgG fractions isolated from COVID-19 patients promoted NET release from neutrophils isolated from healthy individuals.

Furthermore, injection of IgG purified from COVID-19 patient serum into mice accelerated venous thrombosis in two mouse models. These findings suggest that half of patients hospitalized with COVID-19 become at least transiently positive for aPL antibodies and that these autoantibodies are potentially pathogenic.

 

View Full-Text

 

Related Links:

 

Dipyridamole to Prevent Coronavirus Exacerbation of Respiratory Status in COVID-19 (DICER)

 

New Cause of COVID-19 Blood Clots Identified

 

Scientific Updates Sponsored by Endothelix Inc.

LATEST SCIENTIFIC UPDATES