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Premortem Skin Biopsy Assessing Microthrombi, Interferon Type I Antiviral and Regulatory Proteins, and Complement Deposition Correlates with Coronavirus Disease 2019 Clinical Stage.
Laurence, Jeffrey; Nuovo, Gerard; Racine-Brzostek, Sabrina E; Seshadri, Madhav; Elhadad, Sonia; Crowson, A Neil; Mulvey, J Justin; Harp, Joanna; Ahamed, Jasimuddin; Magro, Cynthia.
  • Laurence J; Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York. Electronic address: jlaurenc@med.cornell.edu.
  • Nuovo G; The Ohio State University Comprehensive Cancer Center, Columbus, Ohio; Discovery Life Sciences, Inc., Powell, Ohio.
  • Racine-Brzostek SE; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
  • Seshadri M; Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York.
  • Elhadad S; Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, New York.
  • Crowson AN; Department of Pathology, Regional Medical Laboratories, Tulsa, Oklahoma.
  • Mulvey JJ; Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Harp J; Department of Dermatology, Weill Cornell Medicine, New York, New York.
  • Ahamed J; Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
  • Magro C; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Am J Pathol ; 192(9): 1282-1294, 2022 09.
Article in English | MEDLINE | ID: covidwho-1944048
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 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Thrombosis / Interferon Type I / Acute Kidney Injury / COVID-19 Type of study: Cohort study / Etiology study / Observational study / Prognostic study Limits: Humans Language: English Journal: Am J Pathol Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Thrombosis / Interferon Type I / Acute Kidney Injury / COVID-19 Type of study: Cohort study / Etiology study / Observational study / Prognostic study Limits: Humans Language: English Journal: Am J Pathol Year: 2022 Document Type: Article