Preprint Brief Report Version 1 Preserved in Portico This version is not peer-reviewed

Mechanical Ventilation Stimulates Expression of the SARS-Cov-2 Receptor ACE2 in the Lung and May Trigger a Vicious Cycle

Version 1 : Received: 20 May 2020 / Approved: 26 May 2020 / Online: 26 May 2020 (11:26:52 CEST)

How to cite: Huang, S.; Kaipainen, A.; Strasser, M.; Baranzini, S. Mechanical Ventilation Stimulates Expression of the SARS-Cov-2 Receptor ACE2 in the Lung and May Trigger a Vicious Cycle. Preprints 2020, 2020050429 (doi: 10.20944/preprints202005.0429.v1). Huang, S.; Kaipainen, A.; Strasser, M.; Baranzini, S. Mechanical Ventilation Stimulates Expression of the SARS-Cov-2 Receptor ACE2 in the Lung and May Trigger a Vicious Cycle. Preprints 2020, 2020050429 (doi: 10.20944/preprints202005.0429.v1).

Abstract

The SARS-Cov-2 virus, which causes COVID 19, uses the cell surface protein ACE2 as receptor for entry into cells. Critically ill COVID-19 patients often require prolonged mechanical ventilation which can cause mechanical stress to lung tissue. In vitro studies have shown that expression of ACE2 in alveolar cells is increased following mechanical stretch and inflammation. Therefore, we analyzed transcriptome datasets of 480 (non-COVID-19) lung tissues in the GTex tissue gene expression database. We found that mechanical ventilation of the tissue donors increased the expression of ACE2 by more than two-fold (p<10-6). Analyses of transcriptomes of mechanically ventilated mice in the GEO database indicate that this alveolar cell response to stretch and inflammation is mediated by the chemokine midkine. Using a novel big knowledge network approach (SPOKE) we also found in transcriptomes of pharmacological perturbations (LINCS) that corticosteroids down-regulate midkine in pulmonal cells, and confirmed this in GEO transcriptomes of animal studies. Thus, mechanical ventilation of patients with COVID-19 pneumonia may eo ipso facilitate viral propagation in the lung, further accelerating the pulmonal pathology that has necessitated mechanical ventilation in the first place. This vicious cycle presents a rationale for the temporary treatment with corticosteroids to modulate the midkine-ACE2 axis in ventilated COVID19 patients and for gentler ventilation protocols.

Subject Areas

mechanical stress; vicious cycle; midkine; ARDS; GTEx

Comments (1)

Comment 1
Received: 22 July 2020
Commenter: SUI HUANG
The commenter has declared there is no conflict of interests.
Comment: A recent report that confirms these findings at the protein level (ACE2 increase in ventilated patients) - here: https://www.medrxiv.org/content/10.1101/2020.07.05.20140467v1
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