Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases
By C. Magro, J. J. Mulvey, D. Berlin, G. Nuovo, S. Salvatore, J. Harp, Amelia Baxter-Stoltzfus, J. Laurence. Translational Research: The Journal of Laboratory and Clinical Medicine, 2020
2,065 citations recorded by the source corpus.
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.
Subfields: Immunology, Infectious Diseases, Surgery
View Paper: https://www.semanticscholar.org/paper/88320e88d3eeb2442be0ef9c6bbf66c7ebc42b66
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Immunology
In Infectious Diseases
Citations in the corpus
- SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract (2020, positive): “Our autopsy studies also provide early insights into the variable nature of the severity and pathogenesis related to postCOVID-19 lung health or function (Atri et al., 2020; Kollias et al., 2020; Magro et al., 2020).”
- Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis (2020, background): “Our findings are in agreement with recent evidence demonstrating markedly higher plasma levels of sC5b-9 and C5a in severely affected patients with COVID-19 and widespread complement deposition along with microvascular thrombosis in lung and skin tissue samples (7, 24, 25).”
- Postmortem examination of COVID‐19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction (2020, result): “They corroborate the above-mentioned observation and are consistent with complement-mediated microvascular injury in the lung and/or skin.(13) One patient with superimposed bronchopneumonia showed florid vasculitis of small veins and capillaritis, which has previously been described in individual SA”
- COVID-19 update: Covid-19-associated coagulopathy (2020, background): “[19] reported on the autopsy findings from five decedents with severe Covid-19 infections and ARDS.”