%0 Randomized Controlled Trial
%T Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial.
%A Fragoso-Saavedra S
%A Núñez I
%A Audelo-Cruz BM
%A Arias-Martínez S
%A Manzur-Sandoval D
%A Quintero-Villegas A
%A Benjamín García-González H
%A Carbajal-Morelos SL
%A PoncedeLeón-Rosales S
%A Gotés-Palazuelos J
%A Maza-Larrea JA
%A Rosales-de la Rosa JJ
%A Diaz-Rivera D
%A Luna-García E
%A Piten-Isidro E
%A Del Río-Estrada PM
%A Fragoso-Saavedra M
%A Caro-Vega Y
%A Batina I
%A Islas-Weinstein L
%A Iruegas-Nunez DA
%A Calva JJ
%A Belaunzarán-Zamudio PF
%A Sierra-Madero J
%A Crispín JC
%A Valdés-Ferrer SI
%J Mol Med
%V 28
%N 1
%D 11 2022 8
%M 36348276
%F 6.376
%R 10.1186/s10020-022-00553-x
%X Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19.<BR>We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described.<BR>We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively).<BR>Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.