Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, Baxter-Stoltzfus A, Laurence J, et al.
Translational research : the journal of laboratory and clinical medicine. Date of publication 2020 Jun 1;volume 220():1-13.
1. Transl Res. 2020 Jun;220:1-13. doi: 10.1016/j.trsl.2020.04.007. Epub 2020 Apr 15.
Complement associated microvascular injury and thrombosis in the pathogenesis of
severe COVID-19 infection: A report of five cases.
Magro C(1), Mulvey JJ(2), Berlin D(3), Nuovo G(4), Salvatore S(1), Harp J(5),
Baxter-Stoltzfus A(1), Laurence J(6).
Author information:
(1)Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New
York, New York.
(2)Department of Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, New
York, New York.
(3)Department of Medicine, Division of Pulmonary and Critical Care Medicine,
Weill Cornell Medicine, New York, New York.
(4)The Ohio State University Comprehensive Cancer Center, Columbus Ohio and
Discovery Life Sciences, Powell, Ohio.
(5)Department of Dermatology, Weill Cornell Medicine.
(6)Department of Medicine, Division of Hematology and Medical Oncology, Weill
Cornell Medicine, New York, New York. Electronic address:
jlaurenc@med.cornell.edu.
Acute respiratory failure and a systemic coagulopathy are critical aspects of the
morbidity and mortality characterizing infection with severe acute respiratory
distress syndrome-associated coronavirus-2, the etiologic agent of Coronavirus
disease 2019 (COVID-19). We examined skin and lung tissues from 5 patients with
severe COVID-19 characterized by respiratory failure (n= 5) and purpuric skin
rash (n = 3). COVID-19 pneumonitis was predominantly a pauci-inflammatory septal
capillary injury with significant septal capillary mural and luminal fibrin
deposition and permeation of the interalveolar septa by neutrophils. No viral
cytopathic changes were observed and the diffuse alveolar damage (DAD) with
hyaline membranes, inflammation, and type II pneumocyte hyperplasia, hallmarks of
classic acute respiratory distress syndrome, were not prominent. These pulmonary
findings were accompanied by significant deposits of terminal complement
components C5b-9 (membrane attack complex), C4d, and mannose binding lectin
(MBL)-associated serine protease (MASP)2, in the microvasculature, consistent
with sustained, systemic activation of the complement pathways. The purpuric skin
lesions similarly showed a pauci-inflammatory thrombogenic vasculopathy, with
deposition of C5b-9 and C4d in both grossly involved and normally-appearing skin.
In addition, there was co-localization of COVID-19 spike glycoproteins with C4d
and C5b-9 in the interalveolar septa and the cutaneous microvasculature of 2
cases examined. In conclusion, at least a subset of sustained, severe COVID-19
may define a type of catastrophic microvascular injury syndrome mediated by
activation of complement pathways and an associated procoagulant state. It
provides a foundation for further exploration of the pathophysiologic importance
of complement in COVID-19, and could suggest targets for specific intervention.
Copyright © 2020 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.trsl.2020.04.007
PMCID: PMC7158248
PMID: 32299776 [Indexed for MEDLINE]
