Premortem Skin Biopsy Assessing Microthrombi, Interferon Type I Antiviral and Regulatory Proteins, and Complement Deposition Correlates with Coronavirus Disease 2019 Clinical Stage.
Journal
The American journal of pathology
ISSN: 1525-2191
Titre abrégé: Am J Pathol
Pays: United States
ID NLM: 0370502
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
02
03
2022
revised:
20
05
2022
accepted:
23
05
2022
pubmed:
1
6
2022
medline:
9
9
2022
entrez:
31
5
2022
Statut:
ppublish
Résumé
Apart from autopsy, tissue correlates of coronavirus disease 2019 (COVID-19) clinical stage are lacking. In the current study, cutaneous punch biopsy specimens of 15 individuals with severe/critical COVID-19 and six with mild/moderate COVID-19 were examined. Evidence for arterial and venous microthrombi, deposition of C5b-9 and MASP2 (representative of alternative and lectin complement pathways, respectively), and differential expression of interferon type I-driven antiviral protein MxA (myxovirus resistance A) versus SIN3A, a promoter of interferon type I-based proinflammatory signaling, were assessed. Control subjects included nine patients with sepsis-related acute respiratory distress syndrome (ARDS) and/or acute kidney injury (AKI) pre-COVID-19. Microthrombi were detected in 13 (87%) of 15 patients with severe/critical COVID-19 versus zero of six patients with mild/moderate COVID-19 (P < 0.001) and none of the nine patients with pre-COVID-19 ARDS/AKI (P < 0.001). Cells lining the microvasculature staining for spike protein of severe acute respiratory syndrome coronavirus 2, the etiologic agent of COVID-19, also expressed tissue factor. C5b-9 deposition occurred in 13 (87%) of 15 patients with severe/critical COVID-19 versus zero of six patients with mild/moderate COVID-19 (P < 0.001) and none of the nine patients with pre-COVID-19 ARDS/AKI (P < 0.001). MASP2 deposition was also restricted to severe/critical COVID-19 cases. MxA expression occurred in all six mild/moderate versus two (15%) of 13 severe/critical cases (P < 0.001) of COVID-19. In contrast, SIN3A was restricted to severe/critical COVID-19 cases co-localizing with severe acute respiratory syndrome coronavirus 2 spike protein. SIN3A was also elevated in plasma of patients with severe/critical COVID-19 versus control subjects (P ≤ 0.02). In conclusion, the study identified premortem tissue correlates of COVID-19 clinical stage using skin. If validated in a longitudinal cohort, this approach could identify individuals at risk for disease progression and enable targeted interventions.
Identifiants
pubmed: 35640675
pii: S0002-9440(22)00149-3
doi: 10.1016/j.ajpath.2022.05.006
pmc: PMC9144849
pii:
doi:
Substances chimiques
Antiviral Agents
0
Complement Membrane Attack Complex
0
Interferon Type I
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
MASP2 protein, human
EC 3.4.21.-
Mannose-Binding Protein-Associated Serine Proteases
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1282-1294Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148123
Pays : United States
Informations de copyright
Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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