Abstract: medRxiv preprint doi: https://doi.org/10.1101/2021.05.28.21258012; this version posted May 31, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic Leon G. Smith1, Nicolas Mendoza1, David Dobesh2, & Stephen M. Smith1 1 – Smith Center for Infectious Diseases & Urban Health, East Orange, New Jersey 2 – Saint Barnabas Medical Center, Livingston, New Jersey NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2021.05.28.21258012; this version posted May 31, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Introduction: This observational study looked at 255 COVID19 patients who required invasive mechanical ventilation (IMV) during the first two months of the US pandemic. Through comprehensive, longitudinal evaluation and new consideration of all the data, we were able to better describe and understand factors affecting outcome after intubation. Methods: All vital signs, laboratory values, and medication administrations (time, date, dose, and route) were collected and organized. Further, each patient’s prior medical records, including PBM data and available ECG, were reviewed by a physician. These data were incorporated into time-series database for statistical analysis. Results: By discharge or Day 90, 78.2% of the cohort expired. The most common pre-existing conditions were hypertension, (63.5%), diabetes (59.2%) and obesity (50.4%). Age correlated with death. Comorbidities and clinical status on presentation were not predictive of outcome. Admission markers of inflammation were universally elevated (>96%). The cohort’s weight range was nearly 7-fold. Causal modeling establishes that weightadjusted HCQ and AZM therapy improves survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serum levels. Discussion: This detailed approach gives us better understanding of risk factors, prognostic indicators, and outcomes of Covid patients needing IMV. Few variables were related to outcome. By considering more factors and using new methods, we found that when increased doses of co-administered HCQ and AZM were associated with >100% increase in survival. Comparison of absolute with weight-adjusted cumulative doses proves administration ≥80 mg/kg of HCQ with > 1 gm AZM increases survival in IMV-requiring Covid patients by over 100%. According to our data, HCQ is not associated with prolongation. Studies, which reported QTc prolongation secondary to HCQ, need to be re-evaluated more stringently and with controls. The weight ranges of Covid patient cohorts are substantially greater than those of most antibiotic RCTs. Future clinical trials need to consider the weight variance of hospitalized Covid patients and need to study therapeutics more thoughtfully. 2 medRxiv preprint doi: https://doi.org/10.1101/2021.05.28.21258012; this version posted May 31, 2021. The copyright holder for this preprint (which was not..