Recent reports that SARS-CoV-2 virus particles could be visualized by electron microscopy (EM) in endothelial cells of various organs [1] gave rise to the hypothesis that endothelial injury and micro-thrombosis, which are central elements of coronavirus disease 2019 (COVID-19) pathophysiology [2], might be a consequence of direct endothelial cell infection by SARS-CoV-2. However, these observations have been challenged, as intracellular structures such as the endoplasmatic reticulum (ER) may mimic SARS-CoV-2 particles on EM [3].
In a recent issue of Intensive Care Medicine, we published images of the resected colon of a COVID-19 patient presenting with non-occlusive mesenteric ischemia (NOMI). The specimens demonstrated severe endothelialitis and EM showed intracellular structures resembling SARS-CoV-2 [4].
The present discussion regarding potential false positive EM findings with regard to SARS-CoV-2 drove us to re-examine our specimens. For this purpose, we established an in situ hybridization technique (SARS-CoV-2 Hulu-FISH probe, MetaSystems). The technique was confirmed using lung tissue from a deceased COVID-19 patient as a positive control (Fig. 1a). Interestingly, the gut endothelium from our original patient was indeed negative for SARS-CoV-2 RNA (Fig. 1b, c). We therefore believe that the Corona-like structures shown by EM in our patient are “morphological look-alikes” of genuine corona viruses (including coated vesicles, multi-vesicular bodies and cross-sections of the rough ER) [5].
Nevertheless, the development of NOMI in severe COVID-19 [1, 4] together with the histological demonstration of massive intestinal endothelialitis and microvascular thrombosis is of high clinical relevance for intensivists fighting COVID-19. Evidently, some patients with severe COVID-19 develop a systemic vasculitis, the pathogenesis of which is not yet understood but might be triggered by indirect effects rather than direct viral infection.
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Stahl, K., Bräsen, J.H., Hoeper, M.M. et al. Absence of SARS-CoV-2 RNA in COVID-19-associated intestinal endothelialitis. Intensive Care Med 47, 359–360 (2021). https://doi.org/10.1007/s00134-020-06326-6
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DOI: https://doi.org/10.1007/s00134-020-06326-6