Premortem Skin Biopsy Assessing Microthrombi, Interferon Type I Antiviral and Regulatory Proteins, and Complement Deposition Correlates with Coronavirus Disease 2019 Clinical Stage

• Published in: The American journal of pathology Vol. 192; no. 9; pp. 1282 - 1294
• Main Authors: Laurence, Jeffrey, Nuovo, Gerard, Racine-Brzostek, Sabrina E., Seshadri, Madhav, Elhadad, Sonia, Crowson, A. Neil, Mulvey, J. Justin, Harp, Joanna, Ahamed, Jasimuddin, Magro, Cynthia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2022; American Society for Investigative Pathology
• Subjects: Acute Kidney Injury; Antiviral Agents; Biopsy; Complement Membrane Attack Complex; COVID-19; Humans; Interferon Type I; Mannose-Binding Protein-Associated Serine Proteases; Regular; Respiratory Distress Syndrome; Spike Glycoprotein, Coronavirus; Thrombosis
• ISSN: 0002-9440; 1525-2191; 1525-2191
• DOI: 10.1016/j.ajpath.2022.05.006

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.