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

Yao Kuang Wu; Hsueh Wen Chung; Wei Chih Chen; Kuang Yao Yang; Lun Yu Jao; Hou Tai Chang; Chien Hua Tseng; Tzu Tao Chen; Shih Chi Ku; Thomas Tao Min Huang; Tzu Hsuan Chiu; Kuo Chin Kao; Chieh Jen Wang; Chiao Hung Wang; Tse Bin Yang; Chi Won Suk; Chung Kan Peng; Chih Hao Shen; Yu San Chien; Li kuo Kuo; Chen Chun Lin; Chia Mo Lin; Wei Lun Liu; Huang Pin Wu; Ming Huang Chiu; Ming Cheng Chan; Chieh Mo Lin; Chung Shu Lee; Chia Hao Chang; Li Ta Keng; Hsing Chun Chen; Yi Ting Chen; Shih Chieh Chang; Yi Chun Lai; Chin Ming Chen; Wen Feng Fang; Wen Lin Su

doi:10.1016/j.jiph.2025.102767

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

Yao Kuang Wu, Hsueh Wen Chung, Wei Chih Chen, Kuang Yao Yang, Lun Yu Jao, Hou Tai Chang, Chien Hua Tseng, Tzu Tao Chen, Shih Chi Ku, Thomas Tao Min Huang, Tzu Hsuan Chiu, Kuo Chin Kao, Chieh Jen Wang, Chiao Hung Wang, Tse Bin Yang, Chi Won Suk, Chung Kan Peng, Chih Hao Shen, Yu San Chien, Li kuo KuoChen Chun Lin, Chia Mo Lin, Wei Lun Liu, Huang Pin Wu, Ming Huang Chiu, Ming Cheng Chan, Chieh Mo Lin, Chung Shu Lee, Chia Hao Chang, Li Ta Keng, Hsing Chun Chen, Yi Ting Chen, Shih Chieh Chang, Yi Chun Lai, Chin Ming Chen, Wen Feng Fang, Wen Lin Su

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	102767
Journal	Journal of Infection and Public Health
Volume	18
Issue number	7
DOIs	https://doi.org/10.1016/j.jiph.2025.102767
Publication status	Published - Jul 2025

Keywords

Corticosteroid
COVID-19
Fungal colonization
Mortality
Phenotype
Prognostic factor

ASJC Scopus subject areas

Public Health, Environmental and Occupational Health
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jiph.2025.102767

Cite this

Wu, Y. K., Chung, H. W., Chen, W. C., Yang, K. Y., Jao, L. Y., Chang, H. T., Tseng, C. H., Chen, T. T., Ku, S. C., Huang, T. T. M., Chiu, T. H., Kao, K. C., Wang, C. J., Wang, C. H., Yang, T. B., Suk, C. W., Peng, C. K., Shen, C. H., Chien, Y. S., ... Su, W. L. (2025). 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. Journal of Infection and Public Health, 18(7), Article 102767. https://doi.org/10.1016/j.jiph.2025.102767

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. / Wu, Yao Kuang; Chung, Hsueh Wen; Chen, Wei Chih et al.
In: Journal of Infection and Public Health, Vol. 18, No. 7, 102767, 07.2025.

Research output: Contribution to journal › Article › peer-review

Wu, YK, Chung, HW, Chen, WC, Yang, KY, Jao, LY, Chang, HT, Tseng, CH , Chen, TT, Ku, SC, Huang, TTM, Chiu, TH, Kao, KC, Wang, CJ, Wang, CH, Yang, TB, Suk, CW, Peng, CK, Shen, CH, Chien, YS, Kuo, LK, Lin, CC, Lin, CM, Liu, WL, Wu, HP, Chiu, MH, Chan, MC, Lin, CM, Lee, CS, Chang, CH, Keng, LT, Chen, HC, Chen, YT, Chang, SC, Lai, YC, Chen, CM, Fang, WF & Su, WL 2025, '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', Journal of Infection and Public Health, vol. 18, no. 7, 102767. https://doi.org/10.1016/j.jiph.2025.102767

@article{c3dee950a4744b3fbf110ecb9719d055,

title = "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",

abstract = "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.",

keywords = "Corticosteroid, COVID-19, Fungal colonization, Mortality, Phenotype, Prognostic factor",

author = "Wu, {Yao Kuang} and Chung, {Hsueh Wen} and Chen, {Wei Chih} and Yang, {Kuang Yao} and Jao, {Lun Yu} and Chang, {Hou Tai} and Tseng, {Chien Hua} and Chen, {Tzu Tao} and Ku, {Shih Chi} and Huang, {Thomas Tao Min} and Chiu, {Tzu Hsuan} and Kao, {Kuo Chin} and Wang, {Chieh Jen} and Wang, {Chiao Hung} and Yang, {Tse Bin} and Suk, {Chi Won} and Peng, {Chung Kan} and Shen, {Chih Hao} and Chien, {Yu San} and Kuo, {Li kuo} and Lin, {Chen Chun} and Lin, {Chia Mo} and Liu, {Wei Lun} and Wu, {Huang Pin} and Chiu, {Ming Huang} and Chan, {Ming Cheng} and Lin, {Chieh Mo} and Lee, {Chung Shu} and Chang, {Chia Hao} and Keng, {Li Ta} and Chen, {Hsing Chun} and Chen, {Yi Ting} and Chang, {Shih Chieh} and Lai, {Yi Chun} and Chen, {Chin Ming} and Fang, {Wen Feng} and Su, {Wen Lin}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s)",

year = "2025",

month = jul,

doi = "10.1016/j.jiph.2025.102767",

language = "English",

volume = "18",

journal = "Journal of Infection and Public Health",

issn = "1876-0341",

publisher = "Elsevier Ltd",

number = "7",

}

TY - JOUR

T1 - Early fungal colonization and infection as an independent predictor of in-hospital mortality in mechanically ventilated COVID-19 patients

T2 - A nationwide target trial emulation study in Taiwan

AU - Wu, Yao Kuang

AU - Chung, Hsueh Wen

AU - Chen, Wei Chih

AU - Yang, Kuang Yao

AU - Jao, Lun Yu

AU - Chang, Hou Tai

AU - Tseng, Chien Hua

AU - Chen, Tzu Tao

AU - Ku, Shih Chi

AU - Huang, Thomas Tao Min

AU - Chiu, Tzu Hsuan

AU - Kao, Kuo Chin

AU - Wang, Chieh Jen

AU - Wang, Chiao Hung

AU - Yang, Tse Bin

AU - Suk, Chi Won

AU - Peng, Chung Kan

AU - Shen, Chih Hao

AU - Chien, Yu San

AU - Kuo, Li kuo

AU - Lin, Chen Chun

AU - Lin, Chia Mo

AU - Liu, Wei Lun

AU - Wu, Huang Pin

AU - Chiu, Ming Huang

AU - Chan, Ming Cheng

AU - Lin, Chieh Mo

AU - Lee, Chung Shu

AU - Chang, Chia Hao

AU - Keng, Li Ta

AU - Chen, Hsing Chun

AU - Chen, Yi Ting

AU - Chang, Shih Chieh

AU - Lai, Yi Chun

AU - Chen, Chin Ming

AU - Fang, Wen Feng

AU - Su, Wen Lin

PY - 2025/7

Y1 - 2025/7

N2 - 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.

AB - 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.

KW - Corticosteroid

KW - COVID-19

KW - Fungal colonization

KW - Mortality

KW - Phenotype

KW - Prognostic factor

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U2 - 10.1016/j.jiph.2025.102767

DO - 10.1016/j.jiph.2025.102767

M3 - Article

AN - SCOPUS:105002148348

SN - 1876-0341

VL - 18

JO - Journal of Infection and Public Health

JF - Journal of Infection and Public Health

IS - 7

M1 - 102767

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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