The Association of Post-COVID-19 Conditions With Mortality in Sepsis

Introduction: COVID-19 is associated with lasting immune dysfunction, an evolving spectrum of post-COVID-19 conditions (PCC), and increased risk of subsequent sepsis-related hospitalizations. We examined the population-level association of PCC with mortality in sepsis.


Methods: We used a statewide dataset to identify hospitalizations aged ≥18 years with sepsis in Texas during 2022-2023. Sepsis was defined by the SEP-1 ICD-10 code taxonomy and PCC by ICD-10 code U099. Hospitalizations with COVID-19 were excluded. Hierarchical logistic models were fit to estimate the association of PCC with short-term mortality (In-hospital death or discharge to hospice) in sepsis overall and on sensitivity analyses of sepsis hospitalizations of patients aged ≥65 years, the mechanically ventilated, and strata of sepsis severity (non-severe sepsis, severe sepsis without shock, and septic shock.)


Results: Of 518,852 sepsis hospitalizations, 1,215 (0.2%) had PCC. Compared to those without PCC, those with PCC were similarly aged ≥65 years (49.5% vs 51.1%), had lower mean [SD] Deyo Comorbidity Index (2.1 [1.9] vs 2.3 [2.4]), similar number of organ dysfunctions (1.7 [1.3] vs 1.5 [1.4]), and higher frequency of mechanical ventilation (11.3% vs 7.8%). Short-term mortality among sepsis hospitalizations with and without PCC was 16.4% vs 16.1%, respectively. On adjusted analyses, PCC was not associated with short-term mortality (adjusted odds ratio [aOR] 1.16 [95% CI 0.94-1.43]) overall and largely on sensitivity analyses. However, PCC were associated with increased odds of short-term mortality among sepsis hospitalizations who were mechanically ventilated (aOR 1.80 [95% CI 1.18-2.74]) and those with septic shock, though the estimate was not statistically significant among the latter (aOR 1.36 [95% CI 0.99 to 1.89]).


Conclusions: PCC were not associated with mortality in sepsis overall. However, PCC appear to be associated with increased odds of death among the more severe strata of sepsis hospitalizations. Our findings suggest likely underestimation of PCC in administrative data, while underscoring ongoing uncertainties about its clinical phenotyping and documentation by frontline clinicians. Further studies are warranted to explore the mechanisms underlying the differential prognostic associations of PCC in sepsis.