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
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)