Premortem skin biopsy assessing microthrombi, interferon type I antiviral and regulatory proteins, and complement deposition correlates with coronavirus disease 2019 clinical stage Journal Article


Authors: Laurence, J.; Nuovo, G.; Racine-Brzostek, S. E.; Seshadri, M.; Elhadad, S.; Crowson, A. N.; Mulvey, J. J.; Harp, J.; Ahamed, J.; Magro, C.
Article Title: Premortem skin biopsy assessing microthrombi, interferon type I antiviral and regulatory proteins, and complement deposition correlates with coronavirus disease 2019 clinical stage
Abstract: 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 syn-drome (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 depo-sition 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.& nbsp; <comment>Superscript/Subscript Available</comment
Keywords: covid-19
Journal Title: American Journal of Pathology
Volume: 192
Issue: 9
ISSN: 0002-9440
Publisher: Elsevier Science, Inc.  
Date Published: 2022-09-01
Start Page: 1282
End Page: 1294
Language: English
ACCESSION: WOS:000859598300006
DOI: 10.1016/j.ajpath.2022.05.006
PROVIDER: wos
PMCID: PMC9144849
PUBMED: 35640675
Notes: Article -- Source: Wos
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  1. Joseph Justin Mulvey
    14 Mulvey