tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Hung-Mo Lin[SUP] 2 [/SUP], Eric Acosta[SUP] 1 [/SUP], Natalia L Komarova[SUP] 3 [/SUP], Ping Chen[SUP] 1 [/SUP], Dominik Wodarz[SUP] 4 [/SUP], Ian Baine[SUP] 5 [/SUP], Ralf Duerr[SUP] 6 7 8 [/SUP], Ania Wajnberg[SUP] 9 [/SUP], Adrian Gervais[SUP] 10 11 12 [/SUP], Paul Bastard[SUP] 10 11 12 [/SUP], Jean-Laurent Casanova[SUP] 10 11 12 13 [/SUP], Suzanne A Arinsburg[SUP] 14 [/SUP], Talia H Swartz[SUP] 1 [/SUP], Judith A Aberg[SUP] 1 [/SUP], Nicole M Bouvier[SUP] 1 15 [/SUP], Sean Th Liu[SUP] 1 15 [/SUP], Raymond A Alvarez[SUP] 1 [/SUP], Benjamin K Chen[SUP] 1 [/SUP]
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[SUP] 1 [/SUP], Hung-Mo Lin[SUP] 2 [/SUP], Eric Acosta[SUP] 1 [/SUP], Natalia L Komarova[SUP] 3 [/SUP], Ping Chen[SUP] 1 [/SUP], Dominik Wodarz[SUP] 4 [/SUP], Ian Baine[SUP] 5 [/SUP], Ralf Duerr[SUP] 6 7 8 [/SUP], Ania Wajnberg[SUP] 9 [/SUP], Adrian Gervais[SUP] 10 11 12 [/SUP], Paul Bastard[SUP] 10 11 12 [/SUP], Jean-Laurent Casanova[SUP] 10 11 12 13 [/SUP], Suzanne A Arinsburg[SUP] 14 [/SUP], Talia H Swartz[SUP] 1 [/SUP], Judith A Aberg[SUP] 1 [/SUP], Nicole M Bouvier[SUP] 1 15 [/SUP], Sean Th Liu[SUP] 1 15 [/SUP], Raymond A Alvarez[SUP] 1 [/SUP], Benjamin K Chen[SUP] 1 [/SUP]
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.