Absence of SARS‑CoV‑2 RNA in COVID‑19‑associated intestinal endothelialitis

Absence of SARS‑CoV‑2 RNA in COVID‑19‑associated intestinal endothelialitis

SPRINGER NATURE
Intensive Care Med https://doi.org/10.1007/s00134-020-06326-6
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Recent reports that SARS-CoV-2 virus particles could be visualized by electron microscopy (EM) in endothelial cells of various organs gave rise to the hypothesis that endothelial injury and micro-thrombosis, which are central elements of coronavirus disease 2019 (COVID-19) pathophysiology.

However, these observations have been challenged, as intracellular structures such as the endoplasmatic reticulum (ER) may mimic SARS-CoV-2 particles on EM

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

ANALYSIS

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)Nevertheless, the development of NOMI in severe COVID-19 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.

Fig. 1 Fluorescent in situ hybridization using RNA-SARS-CoV-2 HuluFISH PLUS probe tagged with Atto565 (MetaSystems Probes, Altlussheim, Germany).

Abundant positive signals can be seen in lung specimen of a patient who died from Covid-19 pneumonia (red signals, a).

In the gut specimens of our patient, vessels including those with severe endothelialitis were completely negative (b); only single signals in cells located within interstitium can be seen (c) (micrographs by courtesy of Jessica Schmitz, Nephropathology Unit, Institute of Pathology, MHH)