Complex Thrombo-Inflammatory Responses versus Outcomes of Non-COVID-19 Community-Acquired Pneumonia and COVID-19

J Innate Immun. 2024;16(1):529-552. doi: 10.1159/000542420. Epub 2024 Dec 3.

Abstract

Introduction: The thrombo-inflammatory response and outcomes of community-acquired pneumonia (CAP) 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 2,485 patients (non-COVID-19 CAP, n = 719; COVID-19 patients, n = 2,157), non-COVID-19 CAP patients had significantly lower 28-day mortality (CAP vs. COVID-19 waves 1 and 2; 10% vs. 18% and 16%, respectively), intensive care unit admission (CAP vs. all waves; 15% vs. 39%, 37%, 33%, and 24%, respectively), invasive ventilation (CAP vs. waves 1, 2, and 3 patients; 11% vs. 25%, 20%, and 16%), vasopressor use (CAP 12% vs. 23%, 21%, and 18%), and renal replacement therapy use (CAP 3% vs. 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. Pooling all COVID-19 waves increased complexity with seven clusters on admission.

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.

Keywords: COVID-19; Coagulation factors; Community-acquired pneumonia; Cytokines; Hierarchical clustering; Mortality.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • COVID-19* / immunology
  • COVID-19* / mortality
  • Canada / epidemiology
  • Community-Acquired Infections* / immunology
  • Community-Acquired Infections* / mortality
  • Cytokines / blood
  • Female
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Pneumonia / immunology
  • Pneumonia / mortality
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / mortality
  • SARS-CoV-2* / immunology
  • Thromboinflammation / immunology

Substances

  • Cytokines

Grants and funding

This study was funded by Canadian Institutes of Health Research (CIHR) (Grant No. 439993) and St. Paul’s Foundation. The funders had no role in the design, data collection, data analysis, and reporting of this study.