Effectiveness of a nation-wide COVID-19 vaccination program in Mexico

BACKGROUNDVaccination has been effective in ameliorating the impact of COVID-19. However, estimation of vaccine effectiveness (VE) is still unavailable for some widely used vaccines and underrepresented groups. Here, we report on the effectiveness of a nation-wide COVID-19 vaccination program in Mexico. METHODSWe used a test-negative design within a national COVID-19 surveillance system to assess VE of the BNT162b2, mRNA-12732, Gam-COVID-Vac, Ad5-nCoV, Ad26.COV2.S, ChAdOx1 and CoronaVac vaccines, against SARS-CoV-2 infection, COVID-19 related hospitalization and death for adults [≥]18 years in Mexico. VE was estimated using Cox proportional hazard models considering time-varying vaccination status in partial and fully vaccinated individuals compared to unvaccinated adults, adjusted by age, sex, comorbidities and municipality. We also estimated VE for adults [≥]60 years, for cases with diabetes and comparing periods with predominance of variants B.1.1.519 and B.1.617.2. RESULTSWe assessed 793,487 vaccinated compared to 4,792,338 unvaccinated adults between December 24th, 2020, and September 27th, 2021. VE against SARS-CoV-2 infection was highest for fully vaccinated individuals with mRNA-12732 (91.5%, 95%CI 90.3-92.4) and Ad26.COV2.S (82.2%, 95%CI 81.4-82.9), whereas for COVID-19 related hospitalization were BNT162b2 (84.3%, 95%CI 83.6-84.9) and Gam-COVID-Vac (81.4% 95%CI 79.5-83.1) and for mortality BNT162b2 (89.8%, 95%CI 89.2-90.2) and mRNA-12732 (93.5%, 95%CI 86.0-97.0). VE for all evaluated vaccines was reduced for adults [≥]60 years, people with diabetes, and in periods of Delta variant predominance. CONCLUSIONSAll evaluated vaccines were effective against SARS-CoV-2 infection and COVID-19 related hospitalization and death. Mass vaccination campaigns with multiple vaccine products are feasible and effective to maximize vaccination coverage.

Pyridostigmine in adults with severe SARS-CoV-2 infection: the PISCO trial

BackgroundHospitalized patients with severe COVID-19 have an increased risk of developing severe systemic inflammatory response, pulmonary damage, and acute respiratory distress syndrome (ARDS), resulting in end-organ damage and death. Acetylcholine modulates the acute inflammatory response through a neuro-immune mechanism known as the inflammatory reflex. Pyridostigmine, an acetylcholine-esterase inhibitor, increases the half-life of endogenous ACh, chemically stimulating the inflammatory reflex. This trial aimed to evaluate whether pyridostigmine could decrease invasive mechanical ventilation (IMV) and death in patients with severe COVID-19. MethodsWe performed a parallel-group, multicenter, double-blinded, placebo-controlled, randomized clinical trial to evaluate if add-on pyridostigmine to standard treatment reduced the composite outcome of initiation of IMV and 28-day all-cause mortality among hospitalized patients with severe COVID-19. Results188 participants were randomly assigned to placebo (n=94) or pyridostigmine (n=94). The composite outcome occurred in 22 (23.4%) vs. 11 (11.7%) participants, respectively (hazard ratio 0.46, 95% confidence interval 0.22-0.96, p=0.03). Most of the adverse events were mild to moderate, with no serious adverse events related to pyridostigmine; discontinuation of the study drugs was similar in both groups. ConclusionsWe provide evidence indicating that the addition of pyridostigmine to standard treatment resulted in a clinically significant reduction in the composite outcome (IMV/death) among patients hospitalized for severe COVID-19. (Funded by Consejo Nacional de Ciencia y Tecnologia, Mexico; ClinicalTrials.gov number: NCT04343963).

Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19

The biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19, at the time of diagnosis. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.799, p-value = 4.2e-6; multi-class AUCvalidation = 0.773, p-value = 7.7e-6). Features of this high-dimensional model recapitulated recent COVID-19 related observations of immune perturbations, and revealed novel biological signatures of severity, including the mobilization of elements of the renin-angiotensin system and primary hemostasis, as well as dysregulation of JAK/STAT, MAPK/mTOR, and NF-{kappa}B immune signaling networks. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for the prevention of COVID-19 progression. SummaryFeyaerts et al. demonstrate that an integrated analysis of plasma and single-cell proteomics differentiates COVID-19 severity and reveals severity-specific biological signatures associated with the dysregulation of the JAK/STAT, MAPK/mTOR, and NF-{kappa}B immune signaling networks and the mobilization of the renin-angiotensin and hemostasis systems.