ABSTRACT
ObjectiveTo quantify the delay in SARS-CoV-2 real time polymerase chain reaction (RT-PCR) testing and test result reporting in Mexico and Colombia, and to assess the relation between margination status and these delays. MethodsWe quantified time in days from symptom onset until testing (latency one) and delay in test results report (latency two) using freely available country-wide open data from Mexico and Colombia. Directed acyclic graphs were built to determine which associations were appropriate to assess. Stratification by margination status, state and hospitalization status was used to determine corresponding associations. ResultsIn almost all the study period latency two was longer than latency one. Median latency one was 3 (IQR 0-6) days and latency two 7 (IQR 4-11) days in Colombia, while in Mexico they were 3 (IQR 1-5) days and 4 (IQR 3-6) days. In Colombia, worse margination status prolonged latency two. In Mexico, a lower number and percentage of point-of-care (POC) tests in areas with worse margination. ConclusionPOC tests must be used as a widespread means to reduce latency two, and until then should be prioritized in areas with longer latency two. An unequal distribution of this resource should be avoided.
ABSTRACT
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).
ABSTRACT
Underestimation of the number of cases during the COVID-19 pandemic has been a constant concern worldwide. Case confirmation is based on identification of SARS-CoV-2 RNA using real time polymerase chain reaction (RT-PCR) in clinical samples. However, these tests have suboptimal sensitivity, especially during the early and late course of infection. Using open data, we estimated that among 1 343 730 people tested in Mexico since February 27th, there were 838 377 (95% CL 734 605 - 1 057 164) cases, compared with 604 376 considering only positive tests. ICU admissions and deaths were around 16% and 9% higher than reported. Thus, we show that accounting for the sensitivity of SARS-Cov-2 RT-PCR diagnostic tests is a simple way to improve estimations for the true number of COVID-19 cases in tested people, particularly in high-prevalence populations. This could aid to better inform public health measures and reopening policies.