TargetingT-cell senescence and cytokinestorm with rapamycin to prevent severe progression in COVID-19

TargetingT-cellsenescenceandcytokinestormwithrapamycintopreventsevereprogressioninCOVID-19Letter to the editor of Elsevier 23 April 2020 (accepted 10 May 2020).

"In COVID-19, the serine/threonine kinase mTOR (mechanistic Target Of Rapamycin) pathways may offer valuable targets to control cell injury, oxidative stress, and the onset of hyperinflammation [5].mTOR is a central regulator of inflammation within the immune system[6,7] and a sensor of oxidative stress [8]. mTOR forms two complexes:mTORC1 mediates TH1 and TH17 differentiation at the time of viralantigenic presentation by dendritic cells (DC) [9]; mTORC2 mediatesTH2 differentiation; while both complexes restrict regulatory T-cell(Treg) differentiation [7]. With regards to T cells, mTORC1 activation is consequence of oxidative stress, which can be blocked by N-acet-ylcysteine in Systemic Lupus Erythematosus (SLE) patients [10]. Con-sistent with its role in pro-inflammatory T-cell differentiation, mTORC1activation is involved in SLE patients which can be blocked by rapa-mycin [7]. In addition, mTORC1 is thus known as the rapamycin-sen-sitive complex [9].
The aim of this letter is to discuss the potentiality for rapamycin (sirolimus), an mTOR inhibitor, to restore T-cell functionality and de-crease cytokine storm."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217787/pdf/main.pdf

"To date, there is one registered clinical trial of rapamycin:“Sirolimus Treatment in Hospitalized Patients With COVID-19 Pneumonia (SCOPE)” (NCT04341675)".

https://clinicaltrials.gov/ct2/show/NCT04341675

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