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J Clin Invest
. 2025 Mar 17;135(6):e181136.
doi: 10.1172/JCI181136. Post-transfusion activation of coagulation pathways during severe COVID-19 correlates with COVID-19 convalescent plasma antibody profiles
Svenja Weiss 1 , ****-Mo Lin 2 , Eric Acosta 1 , Natalia L Komarova 3 , Ping Chen 1 , Dominik Wodarz 4 , Ian Baine 5 , Ralf Duerr 6 7 8 , Ania Wajnberg 9 , Adrian Gervais 10 11 12 , Paul Bastard 10 11 12 , Jean-Laurent Casanova 10 11 12 13 , Suzanne A Arinsburg 14 , Talia H Swartz 1 , Judith A Aberg 1 , Nicole M Bouvier 1 15 , Sean Th Liu 1 15 , Raymond A Alvarez 1 , Benjamin K Chen 1
Affiliations
Early antibody therapy can prevent severe SARS-CoV-2 infection (COVID-19). However, the effectiveness of COVID-19 convalescent plasma (CCP) therapy in treating severe COVID-19 remains inconclusive. To test a hypothesis that some CCP units are associated with a coagulopathy hazard in severe disease that offsets its benefits, we tracked 304 CCP units administered to 414 hospitalized COVID-19 patients to assess their association with the onset of unfavorable post-transfusion D-dimer trends. CCP recipients with increasing or persistently elevated D-dimer trajectories after transfusion experienced higher mortality than those whose D-dimer levels were persistently low or decreasing after transfusion. Within the CCP donor-recipient network, recipients with increasing or persistently high D-dimer trajectories were skewed toward association with a minority of CCP units. In in vitro assays, CCP from "higher-risk" units had higher cross-reactivity with the spike protein of human seasonal betacoronavirus OC43. "Higher-risk" CCP units also mediated greater Fcγ receptor IIa signaling against cells expressing SARS-CoV-2 spike compared with "lower-risk" units. This study finds that post-transfusion activation of coagulation pathways during severe COVID-19 is associated with specific CCP antibody profiles and supports a potential mechanism of immune complex-activated coagulopathy.
Keywords: Adaptive immunity; COVID-19; Immunoglobulins; Immunology; Immunotherapy.
. 2025 Mar 17;135(6):e181136.
doi: 10.1172/JCI181136. Post-transfusion activation of coagulation pathways during severe COVID-19 correlates with COVID-19 convalescent plasma antibody profiles
Svenja Weiss 1 , ****-Mo Lin 2 , Eric Acosta 1 , Natalia L Komarova 3 , Ping Chen 1 , Dominik Wodarz 4 , Ian Baine 5 , Ralf Duerr 6 7 8 , Ania Wajnberg 9 , Adrian Gervais 10 11 12 , Paul Bastard 10 11 12 , Jean-Laurent Casanova 10 11 12 13 , Suzanne A Arinsburg 14 , Talia H Swartz 1 , Judith A Aberg 1 , Nicole M Bouvier 1 15 , Sean Th Liu 1 15 , Raymond A Alvarez 1 , Benjamin K Chen 1
Affiliations
- PMID: 40091845
- DOI: 10.1172/JCI181136
Early antibody therapy can prevent severe SARS-CoV-2 infection (COVID-19). However, the effectiveness of COVID-19 convalescent plasma (CCP) therapy in treating severe COVID-19 remains inconclusive. To test a hypothesis that some CCP units are associated with a coagulopathy hazard in severe disease that offsets its benefits, we tracked 304 CCP units administered to 414 hospitalized COVID-19 patients to assess their association with the onset of unfavorable post-transfusion D-dimer trends. CCP recipients with increasing or persistently elevated D-dimer trajectories after transfusion experienced higher mortality than those whose D-dimer levels were persistently low or decreasing after transfusion. Within the CCP donor-recipient network, recipients with increasing or persistently high D-dimer trajectories were skewed toward association with a minority of CCP units. In in vitro assays, CCP from "higher-risk" units had higher cross-reactivity with the spike protein of human seasonal betacoronavirus OC43. "Higher-risk" CCP units also mediated greater Fcγ receptor IIa signaling against cells expressing SARS-CoV-2 spike compared with "lower-risk" units. This study finds that post-transfusion activation of coagulation pathways during severe COVID-19 is associated with specific CCP antibody profiles and supports a potential mechanism of immune complex-activated coagulopathy.
Keywords: Adaptive immunity; COVID-19; Immunoglobulins; Immunology; Immunotherapy.