Supplementary Material for: COMPLEX THROMBO-INFLAMMATORY RESPONSES VERSUS OUTCOMES OF NON-COVID-19 COMMUNITY-ACQUIRED PNEUMONIA AND COVID-19

Introduction: The thrombo-inflammatory response and outcomes of community-acquired pneumonia due to various organisms (non-COVID-19 CAP) versus CAP due to a single virus, SARS-CoV-2 (i.e., COVID-19) may differ.
Methods: Adults hospitalized with non-COVID-19 CAP (December 1, 2021-June 15, 2023) or COVID-19 (March 2, 2020 – June 15, 2023) in Canada. We compared non-COVID-19 CAP and COVID-19 baseline, thrombo-inflammatory response, and mortality. We measured plasma cytokine and coagulation factor levels in a sample of patients, did hierarchical clustering, and compared cytokine and coagulation factor levels.
Results: In 2485 patients (non-COVID-19 CAP n= 719; COVID-19 patients n=2157), non-COVID-19 CAP patients had significantly lower 28-day mortality (CAP versus COVID-19 waves 1 and 2; 10% versus 18% and 16% respectively), ICU admission (CAP versus all waves; 15% versus 39%, 37%, 33% and 24% respectively), invasive ventilation (CAP versus waves 1, 2 and 3 patients; 11% versus 25%, 20% and 16%), vasopressor use (CAP 12% versus 23%, 21% and 18%), and renal replacement therapy use (CAP 3% versus Omicron 7%). Complexity of hierarchical clustering aligned directly with mortality: COVID-19 wave 1 and 2 patients had six clusters at admission and higher mortality than non-COVID-19 CAP and Omicron that had three clusters at admission. Hierarchical clustering displayed pro-inflammatory and non-pro-inflammatory endotypes.
Conclusion: Complex thrombo-inflammatory responses aligned with mortality of CAP. At a fundamental level, the human thrombo-inflammatory response to a brand new virus was “confused” whereas humans had eons of time to develop a more concise efficient thrombo-inflammatory host response to CAP.