Pericyte alteration sheds light on micro-vasculopathy in COVID-19 infection
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LETTER
Pericyte alteration sheds light on micro‑vasculopathy in COVID‑19 infection Nathalie Cardot‑Leccia1, Thomas Hubiche2, Jean Dellamonica3, Fanny Burel‑Vandenbos1 and Thierry Passeron2,4* © 2020 Springer-Verlag GmbH Germany, part of Springer Nature
Dear Editor, Understanding the mechanisms involved in SARS-CoV-2 infection is crucial to provide more efficient therapeutic approaches. Here, we report the histological patterns of skin and lung post-mortem analysis in patients hospitalized in intensive care unit that revealed a micro-vasculopathy secondary to pericyte alteration. After family consent, we performed in-depth histological analysis, with a special focus on micro-vascularization, of post-mortem biopsies from COVID-19 positive patients hospitalized in intensive care unit. (Lung biopsies were taken from 2 patients, and skin biopsies from 4 patients.) The normal lung tissue used as control was from a 16-year-old patient cured for pneumothorax. Detailed methods are available in Supplementary Appendix. As previously reported, we observed in the lung, patterns of diffuse alveolar damage (DAD) including exudative and proliferative changes. Interestingly, walls of venules and alveolar capillaries were thickened as compared to normal pulmonary vessels (Supplementary Fig. 1a, b, c). We did not observe any thrombi, and CD34 immunostaining showed no alteration of endothelial cells of those venules and capillaries (Supplementary Fig. 1d). At the contrary, pericytes were dramatically decreased in alveolar capillaries in COVID + lung, while they were abundant in normal parenchyma (Fig. 1a, b). Cleaved caspase 3 immunostaining revealed apoptosis of pericytes (Fig. 1c). The thickening of venules and capillaries and the loss of pericytes were observed not only in DAD *Correspondence: [email protected] 2 Department of Dermatology, Université Côte D’Azur. CHU Nice, Nice, France Full author information is available at the end of the article Nathalie Cardot-Leccia and Thomas Hubiche equal contribution.
territories, but also in non-inflammatory areas. Biopsies of apparent normal skin of the same two patients and two additional ones also showed a mild thickening of smallsized vessel wall in superficial dermis without inflammation (Supplementary Fig. 1e). In the skin, we did not observe a pericyte loss, but a mild hyperplasia of pericytes was noted (Supplementary Fig. 1f, g). There are increasing data supporting a vascular involvement in COVID-19 patients. MRI performed in patients with neurologic signs revealed perfusion abnormalities in 100% of cases [1]. Dual-energy CT performed in COVID-19 pneumonia showed profound vascular and perfusion abnormalities without pulmonary emboli [2]. So far, studies emphasized thrombotic events or searched for endothelial cell alteration [3]. The lack of thrombi in our samples might be explained by the curative anticoagulation that our patients received. Sprouting and intussusceptive angiogenesis along with disruption of intercellular junctions, cell swelling, and a loss of contact with
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