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Objective: To compare mortality trends in patients requiring Extracorporeal Membrane Oxygenation (ECMO) support between the first quarters of 2019 and 2020 and determine whether these trends might have predicted the severe acute respiratory syndrome coronavirus-2 (SARS)-Cov-2 pandemic in the United States. Methods: We analyzed 5% Medicare claims data at aggregate, state, hospital, and encounter levels using MS-DRG (Medicare Severity-Diagnosis Related Group) codes for ECMO, combining state-level data with national census data. Necessity and sufficiency relations associated with change in mortality between the 2 years were modeled using qualitative comparative analysis (QCA). Multilevel, generalized linear modeling was used to evaluate mortality trends. Results: Based on state-level data, there was a 3.36% increase in mortality between 2019 and 2020. Necessity and sufficiency evaluation of aggregate data at state and institutional levels did not identify any association or combinations of risk factors associated with this increase in mortality. However, multilevel and generalized linear models using disaggregated patient-level data to evaluate institution mortality and patient death, identified statistically significant differences between the first (p =.019) and second (p =.02) months of the 2 years, the first and second quarters (p <.001 and p =.042, respectively), and the first 6 months (p <.001) of 2019 and 2020. Conclusion: Mortality in ECMO patients increased significantly during the first quarter of 2020 and may have served as an early warning of the SARS-Cov-2 pandemic. Granular data shared in real-time may be used to better predict public health threats. [ABSTRACT FROM AUTHOR]