Premortem skin biopsy assessing microthrombi, IFN I antiviral & regulatory proteins and complement correlates with Covid19 clinical stage, 2022

Premortem Skin Biopsy Assessing Microthrombi, Interferon I Antiviral and Regulatory Proteins, and Complement Deposition Correlates with Coronavirus Disease 2019 Clinical Stage
Jeffrey Laurence, Gerard Nuovo, Sabrina E. Racine-Brzostek, Madhav Seshadri, Sonia Elhadad, A. Neil Crowson, J. Justin Mulvey, Joanna Harp, Jasimuddin Ahamed, Cynthia Magrox

Apart from autopsy, tissue correlates of coronavirus disease 2019 (COVID-19) clinical stage are lacking.

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 severe/critical COVID-19 patients versus zero of six mild/moderate COVID-19 patients (P < 0.001) and none of the nine pre-COVID-19 ARDS/AKI patients (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 severe/critical versus zero of six mild/moderate COVID-19 patients (P < 0.001) and none of the nine pre-COVID-19 ARDS/AKI patients (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 and co-localized with severe acute respiratory syndrome coronavirus 2 spike protein. SIN3A was also elevated in plasma of severe/critical COVID-19 patients versus control subjects (P = 0.0128).

In conclusion, we 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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Per the title, these index patients were pretty sick. These microthrombi don't sound the same as the putative Pretorius microclots. The paper suggests they are generally platelet aggregates. However, they reference fibrin thrombi in their prior autopsy paper.