Early fungal colonization and infection as an independent predictor of in-hospital mortality in mechanically ventilated COVID-19 patients: A nationwide target trial emulation study in Taiwan.

PURPOSE: To evaluate the impact of fungal colonization and infection phenotypes and other prognostic factors on in-hospital mortality among mechanically ventilated COVID-19 patients (n = 376) admitted to ICUs during the first wave of the pandemic in Taiwan.

MATERIALS AND

METHODS

A target trial emulation framework was used to minimize immortal time bias. Patients were matched 1:1:2 for age and gender and classified into three groups: 94 in the "Early" group (fungal colonization or infection within 10 days), 94 in the "Late" group (10-30 days), and 188 in the "No" group (no fungal colonization or infection within 30 days). In-hospital mortality and clinical outcomes were compared across groups.

RESULTS

Patients in the "Early" group received higher cumulative corticosteroid doses, had lower PaO2/FiO2 ratios, and exhibited higher rates of comorbidities, cytomegalovirus viremia, and lung, heart, and kidney complications. They also had a longer duration of ventilator use, ICU stay, and total hospitalization compared to the "Late" and "No" groups. Time-dependent multivariate Cox regression analysis identified the "Early" phenotype as a strong predictor of in-hospital mortality (adjusted hazard ratio [aHR]= 3.992, 95 % CI: 2.676-5.956, p < 0.001). Additional independent risk factors included Charlson Comorbidity Index (aHR = 1.213, 95 % CI: 1.113-1.323, p < 0.001) and APACHE II score (aHR = 1.028, 95 % CI: 1.011-1.045, p = 0.001). In contrast, higher PaO2/FiO2 ratios (aHR = 0.998, 95 % CI: 0.997-1.000, p = 0.021) and ganciclovir use (aHR = 0.419, 95 % CI: 0.245-0.717, p = 0.002) were associated with reduced mortality.

CONCLUSIONS

"Early" fungal colonization and infection within 10 days of corticosteroid initiation is an independent risk factor for in-hospital mortality in mechanically ventilated COVID-19 patients. Future research should explore early intervention strategies, including antifungal prophylaxis, optimized corticosteroid dosing, and immune modulation, to improve survival outcomes.