Seroepidemiology of SARS-CoV-2 in Healthcare Personnel Working at the Largest Tertiary COVID-19 Referral Hospitals in Mexico City (preprint)

Background: We performed a longitudinal SARS-CoV-2 seroepidemiologic study in healthcare personnel of the two largest tertiary referral hospitals in Mexico City. Methods: Participants answered a computer-assisted self-administered interview and donated blood samples for antibody testing every three weeks from October 2020 to June 2021. Findings: 290/883 participants had a positive result in any of the antibody tests, yielding an overall adjusted prevalence in the study period of 33·5%. 235 positive tests were identified at baseline (prevalent cases), the remaining 55 positive tests were incident cases. Prevalent cases showed associations with both occupational (institution 2 vs. 1: adjusted odds ratio [aOR]=2·24, 95% confidence interval [CI]: 1·54, 3·25; laboratory technician vs. medical doctor: aOR=4·38, 95% CI: 1·75, 10·93) and community risk (municipality of residence Xochimilco vs. Tlalpan: aOR=2·03, 95% CI: 1·09, 3·79). The incidence rate was 3·0 cases per 100 person-months. Incident cases were mainly associated with community-acquired risk, due to contact with suspect/confirmed COVID-19 cases (HR=2·45, 95% CI: 1·21, 5·00).Interpretation: We observed similar level of exposure to SARS-CoV-2 in healthcare workers of the two largest tertiary COVID-19 referral centers in Mexico City to the general population. Most variables associated with exposure in this setting pointed toward community rather than occupational risk.Funding: Consejo Nacional de Ciencia y Tecnología (CONACyT) (Fondo FORDECYT-PRONACES) and the Mexican Government (Programa Presupuestal P016; Anexo 13 del Decreto del Presupuesto de Egresos de la Federación).Declaration of Interest: None to declare. Ethical Approval: The study was reviewed and approved by the Institutional Review Boards of both participating institutions.

Delay of molecular SARS-CoV-2 testing and turnaround time in Mexico and Colombia (preprint)

Objective: To 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. Methods: We 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. Results: In 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. Conclusion: POC 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.

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

Background: Hospitalized 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. Methods: We 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. Results: 188 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. Conclusions: We 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).

Corrected Estimation of COVID-19 Cases in Mexico: A Nation-Wide Open Data Modelling Study (preprint)

Background: 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. We estimated the corrected number of COVID-19 confirmed cases, ICU admissions and deaths in Mexico accounting for the probabilities of false-negative tests. Methods: We used a publicly available, national database of all SARS-CoV-2 tests performed at public laboratories in Mexico between February 27th and August 31st, 2020. We used the estimated probabilities of false negatives tests based on the day of clinical sample collection after symptom initiation previously calculated by Kucirca et al. Applying results derived from the false negative estimation model on the government official dataset, we estimated the daily corrected number of cases, ICU admissions and deaths at the National level and for each of the 32 States. Results: There were 1 343 730 people tested between February 27th and August 31st, 2020. We included 1 280 910 patients with available results. There were 604 376 confirmed cases, 13 038 ICU admissions and 64 360 deaths due to COVID-19. We estimated a total of 838 377 (95% CL 734 605 – 1 057 164) positive cases (39% higher than confirmed cases); 15 085 ICU admissions and 69 835 deaths (about 16% and 9% more than reported). In our corrected estimates, 50 000 cases were reached by May 11th, while the official count reached that number at May 18th. The magnitude of difference between official counts and corrected estimates varied between states . Interpretation: Accounting for SARS-CoV-2 RT-PCR based diagnostic tests precision 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. Funding: The authors received no funding for this study.Declaration of Interests: All authors state they have no conflict of interests.Ethics Approval Statement: The ethics committee of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán reviewed and approved the study.

Impact of false negative results of RT-PCR test for SARS-CoV-2 in COVID-19 case count as applied to Mexico (preprint)

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.