Indexed in MEDLINE, SCI & KoreaMed
pISSN 1011-8934   eISSN 1598-6357
Open Access, Peer-reviewed, Weekly
J Korean Med Sci. 2025 May 26;40(20):e82. English.
Published online Feb 04, 2025.
https://doi.org/10.3346/jkms.2025.40.e82
© 2025 The Korean Academy of Medical Sciences.
Original Article

Association of Extended Steroid Treatment With Bloodstream Infection in Critically Ill Patients With COVID-19: A National, Multicenter, Propensity Score-Matched Study

Seohyun Kim,1 Jiwon Ryoo,2 Hyeong Jun Cho,3 Seok Chan Kim,3 Sunghoon Park,4 Su Hwan Lee,5 view all
    • 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
    • 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
    • 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
    • 4Division of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.
    • 5Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
    • 6BioMedical Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
    • 7Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Internal Medicine, Transplant Research Center, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
    • 8Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea.
  • Address for Correspondence: Jongmin Lee, MD, PhD. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. Email: dibs01@catholic.ac.kr
Received May 20, 2024; Accepted November 14, 2024.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

AbstractGraphical AbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONNotesACKNOWLEDGMENTSReferences

Abstract

Background

The impact of steroid treatment on mortality outcomes in patients with coronavirus disease 2019 (COVID-19) has been widely demonstrated, while its effect on secondary infections, such as bloodstream infections (BSIs), is controversial. Recent studies have reported the survival benefits of using steroids for a standard duration compared to extended use, though their impact on the risk of BSIs remains debated. This study investigated whether extended steroid use is associated with the risk of BSIs and mortality in critically ill patients with COVID-19.

Methods

This national multicenter retrospective study conducted at 22 university-affiliated hospitals evaluated the effect of steroid treatment duration in hospitalized patients with COVID-19 treated with more than high-flow nasal cannula therapy. Patients were divided into two groups according to the duration of corticosteroid treatment: extended (> 10 days) and standard (≤ 10 days). Propensity score matching was performed by adjusting for covariates. Baseline characteristics and clinical outcomes were compared between the two groups.

Results

Among 1,114 patients, 378 with a hospital length of stay (LOS) exceeding 10 days were included. Each group of the propensity score–matched cohort had 189 patients, with no significant differences in demographic characteristics between the two groups, except for the incidence of BSIs (extended group vs. standard group, 49.7% vs. 36.0%, P = 0.043). After adjusting for confounding factors, extended use of steroids remained significantly associated with BSIs (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.25–4.04; P = 0.007). The use of a mechanical ventilator, extracorporeal membrane oxygenation, continuous renal replacement therapy, and a longer hospital LOS were associated with BSIs. In-hospital mortality was associated with an older age, higher body mass index, higher sequential organ failure assessment score at admission, and the presence of a BSI (OR, 2.47; 95% CI, 1.50–4.05; P < 0.001). Kaplan-Meier survival analysis demonstrated no significant difference in in-hospital mortality between the extended and standard groups.

Conclusion

Extended steroid therapy was significantly associated with a higher incidence of BSIs in critically ill patients with COVID-19.

Keywords
Coronavirus; Adrenal Cortex Hormones; COVID-19; SARS-CoV-2; Steroids; Bloodstream Infections; Korea

Most patients with coronavirus disease 2019 (COVID-19) experience a mild course of the disease; however, a minority may develop severe pneumonia, leading to life-threatening respiratory failure or acute respiratory distress syndrome. Currently, the standard treatment for COVID-19 is stratified based on the severity of the disease.1

Systemic steroids have been widely administered during the COVID-19 pandemic. In recent studies, such as the RECOVERY trial and several meta-analyses, reduced mortality was observed with steroid treatment in patients with COVID-19, especially in those who required oxygen support with or without a mechanical ventilator.2, 3, 4 Based on these results, guidelines recommend the use of steroids in hospitalized patients with severe illness who require high-flow nasal cannula oxygen delivery, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).1, 4, 5 The RECOVERY trial evaluated the administration of 6 mg of dexamethasone once daily for up to 10 days, which is the current recommended dose for hospitalized adults with COVID-19.2 Although there is clear evidence that steroids can benefit some patients with COVID-19 who require oxygen therapy, many unresolved issues remain.

To date, there are no definitive answers regarding the optimal dose and type of steroids, timing of initiation, and duration of administration in patients with severe COVID-19. Furthermore, steroids can cause various adverse effects. Generally, steroid administration is associated with hyperglycemia, steroid-induced neuromyopathy, gastrointestinal bleeding, and secondary infections.6, 7, 8, 9 Critically ill patients are particularly susceptible to secondary infections. This increased vulnerability is due to the frequent performance of invasive procedures, such as mechanical ventilation, and the use of central venous catheters.10, 11 Several clinical trials have aimed to investigate secondary infection as an adverse event during steroid treatment in patients with COVID-19; however, most were discontinued after the release of the results of the RECOVERY trial or did not show sufficient statistical power.12, 13, 14 Additionally, studies addressing the relationship between the duration of steroid use and the risk of bloodstream infection (BSI) in patients with severe COVID-19 are lacking.

In this study, using data from critically ill patients with COVID-19 treated at 22 university-affiliated hospitals across South Korea, we investigated the risk factors for BSI in these patients who received steroid treatment, including the duration of steroid use, and examined the factors influencing their prognosis.

Study population

This was a nationwide, multicenter, retrospective observational cohort study using data collected from patients admitted to 22 university-affiliated hospitals between January 2020 and August 2021. The eligible subjects were hospitalized patients with COVID-19 aged ≥ 19 years who had received high-flow nasal cannula oxygen, mechanical ventilation, or ECMO. Patient registration protocols dictated the exclusion of patients who were not hospitalized in the intensive care unit (ICU), did not undergo blood cultures, did not receive oxygen therapy, or received only low-flow oxygen therapy. Among the original cohort, patients with missing values in matching covariants or those with a hospital length of stay (LOS) and ICU LOS shorter than 10 days were excluded from the study.

Data collection and definitions

The following data were collected by trained coordinators at each center: 1) demographic data, including age, sex, body mass index (BMI), laboratory findings, comorbidities, the Clinical Frailty Scale, COVID-19 vaccination status, timing of COVID-19 diagnosis, and sequential organ failure assessment (SOFA) score at hospital admission; 2) initial dose of steroids and duration of steroid treatment; 3) ICU admission treatment and information regarding the use of rescue therapies, including remdesivir, tocilizumab, vasopressors, ECMO, and continuous renal replacement therapy (CRRT); 4) cultured pathogens during hospitalization; and 5) clinical outcomes, such as in-hospital mortality and hospital and ICU LOS.

Patients were divided into two groups according to the duration of steroid treatment: extended (> 10 days) and standard (≤ 10 days). BSI development was defined as a positive blood culture for one or more bacterial or fungal organisms occurring at least 48 hours after ICU admission, and multiple infections in one individual were counted as one BSI case. Polymicrobial infections were not separately specified. Data were reviewed by two separate investigators to determine whether the organism was clinically significant or a contaminant. Isolates from blood cultures were excluded if they were considered contaminants and not true causes of BSI, based on clinical and microbiological data, and in accordance with CDC criteria.15, 16 In cases of disagreement between the two investigators, the discordant cases were discussed with an infectious disease specialist, and a final decision was made. The initial steroid dose was defined as the dexamethasone-equivalent dose.

Propensity score matching

Propensity score matching was performed to mitigate the potential bias caused by confounding variables, acknowledging the likelihood of uneven baseline patient characteristics between the extended and standard groups. After excluding patients with missing values in the matching covariates, propensity score matching was performed using the nearest-neighbor method to produce balanced cohorts and evaluate the effects of steroid duration. Patients were matched 1:1 by propensity score using the covariates of age, sex, BMI, COVID-19 vaccination status, comorbidities such as diabetes mellitus, cardiovascular disease, chronic lung disease, chronic neurological disease, an immunocompromised state, connective tissue disease, hematologic malignancy and solid tumor, absolute neutrophil count, partial pressure of oxygen (PaO2), fraction of inspired oxygen (FiO2), SOFA score at admission, Clinical Frailty Scale score at admission, hospital LOS, use of mechanical ventilation, use of ECMO, use of CRRT, tocilizumab treatment, and initial dose of steroids as the confounding factors.

Statistical analysis

Continuous variables are expressed as medians and interquartile ranges and categorical variables as numbers and percentages. Baseline characteristics were compared using the χ2 test or Fisher’s exact test for categorical variables and the t-test or Mann-Whitney U test for continuous variables. Multivariate logistic regression analyses were performed to investigate the association between patient characteristics and in-hospital mortality or the presence of BSI. In addition to the duration of steroid use, the model included clinically meaningful variables (age, BMI, initial steroid dose, PaO2/FiO2 ratio, SOFA score, use of mechanical ventilation, ECMO use, CRRT use, and hospital LOS). Clinical parameters with a P value of 0.05 in the univariate logistic regression were included in the multivariate logistic regression. To evaluate the goodness-of-fit of the logistic regression model, we used the Hosmer-Lemeshow test.17 The test results indicated an adequate fit between the model and the observed data. The goodness-of-fit was computed to assess the relevance of the logistic regression model. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. The probabilities of in-hospital survival for each group were estimated using the Kaplan-Meier method and compared using the log-rank test. All tests were two-sided, and P values < 0.05 were considered statistically significant. All statistical analyses were performed using R version 4.2.2 (R Foundation for Statistical Computing, Vienna, Austria).

Ethics statement

This study was conducted in accordance with the relevant legislation and the protocol was approved by the Ethics Committee of Seoul St. Mary’s Hospital (KC23RIDI0860). The study complies with the principles of the Declaration of Helsinki and Good Clinical Practice Guidelines, and the requirement for informed consent was waived due to the retrospective design of the study.

Baseline characteristics

Among 1,114 patients with COVID-19, 166 were excluded. A total of 948 patients were included in the final study (Fig. 1). The baseline patient characteristics are presented in Table 1. All the patients included in this study were prescribed steroids. The median duration of steroid use was 13.0 days (10.0–22.0) and the initial dexamethasone-equivalent dose was 6 mg (6.0–10.0). BSI occurred in 192 cases, with ICU and in-hospital mortality observed in 205 (21.6%) and 236 cases (24.9%), respectively.

Fig. 1
Study flow diagram.
COVID-19 = coronavirus disease 2019, ICU = intensive care unit, LOS = length of stay.

Table 1
Baseline characteristics of the overall study population

Clinical characteristics and outcomes before and after propensity score matching according to duration of steroid treatment

The clinical characteristics and outcomes of the short and extended steroid treatment groups are shown in Table 2. In this study, 608 patients (64.1%) were treated with steroids for more than 10 days. The proportion of patients with cardiovascular disease and hematological malignancy in the extended group was higher than that in the standard group (13.5% vs. 7.6%, P = 0.009 and 2.3% vs. 0.0%, P = 0.011, respectively). Additionally, the extended group exhibited a higher proportion of patients who received tocilizumab (10.7% vs. 5.9%, P = 0.019) and a higher initial steroid dosage (6.0 mg [6.0–11.7] vs. 6.0 mg [6.0–6.0], P < 0.001). The PaO2/FiO2 ratio was lower (131.2 [91.0–196.8] vs. 147.5 [101.3–241.1], P = 0.004) and the SOFA score was higher (4.0 [3.0–6.0] vs. 4.0 [3.0–5.0], P = 0.007) in the extended group. Moreover, a greater percentage of patients in the extended group required mechanical ventilation (66.6% vs. 50.3%, P < 0.001) and there was a higher incidence of BSI (23.2% vs. 15.0%, P = 0.003). Furthermore, both ICU LOS (17.0 days [11.0–34.0] vs. 14.0 [10.0–24.0], P < 0.001) and hospital LOS (25.0 days [17.0–46.0] vs. 20.0 [13.0–29.5], P < 0.001) were significantly longer in the extended group.

Table 2
Baseline characteristics and outcomes before and after propensity score matching

After 1:1 propensity score matching of 378 patients using the nearest-neighbor method (189 each in the extended and standard groups), the study groups were well-balanced in terms of baseline characteristics and disease severity (Table 2, Fig. 2). After matching, the median duration of steroid treatment in the extended group was significantly longer at 19.0 days (14.0–29.0) compared to 10.0 days (7.0–10.0) in the standard group (P < 0.001). There were no significant differences in demographic characteristics, comorbidities, or initial disease severity represented by vital signs, except for systolic blood pressure, laboratory data, SOFA score, PaO2/FiO2 ratio, and COVID-19 treatments such as remdesivir and tocilizumab (Table 2). Regarding clinical outcomes, there were no significant differences in ICU and hospital LOS, ICU mortality, or in-hospital mortality between the two groups. However, the rate of BSI development was higher in the extended group than in the standard group (36.0% vs. 20.6%, P = 0.001).

Fig. 2
Distribution before (A) and after (B) PSM between the standard and extended steroid treatment group. (C) Region of common support between the standard and extended steroid treatment group.
PSM = propensity score matching.

BSI

The characteristics of the identified BSI pathogens are listed in Table 3. In the propensity score-matched cohort, bacteria constituted the largest portion of BSI in both the extended and standard groups (89.7% and 75.0%, respectively). Gram-positive cocci were the most frequently identified bacteria, followed by Gram-negative bacteria. Candida spp. accounted for the majority of the fungi. Although fungemia was more frequent in the extended group, it was not statistically significant (30.0% vs. 16.2%, P = 0.231).

Table 3
Identified pathogen of blood stream infection

Fig. 3 shows the results of the multivariate analysis of the clinical factors associated with the occurrence of BSI, presented on a logarithmic scale to accommodate the asymmetric CIs. According to the analysis, the usage of steroids for more than 10 days was significantly associated with the occurrence of BSI (OR, 2.77; 95% CI, 1.59–4.80; P < 0.001). Other independent risk factors for the occurrence of BSI were the use of mechanical ventilation (OR, 2.81; 95% CI, 1.11–7.13; P = 0.029), use of ECMO (OR, 2.80; 95% CI, 1.44–5.45; P = 0.002), use of CRRT (OR, 4.04; 95% CI, 2.09–7.84; P < 0.001), and hospital LOS (OR, 1.02; 95% CI, 1.01–1.03; P < 0.001).

Fig. 3
Multivariable analysis of factors independently associated with blood stream infection among critically ill patients with coronavirus disease 2019.
MV = mechanical ventilation, ECMO = extracorporeal membrane oxygenation, CRRT = continuous renal replacement therapy, LOS = length of stay, CI = confidence interval.

Risk factors for in-hospital mortality

Table 4 shows the clinical characteristics based on in-hospital mortality in the propensity score–matched cohort. Notably, the proportion of patients with BSI (41.3% vs. 21.8%, P < 0.001), median age (70.0 years [61.0–78.0] vs. 74.0 years [66.0–81.0], P = 0.001), prevalence of chronic kidney disease (2.8% vs. 7.9%, P = 0.044), white blood cell counts (7.4 [5.4–10.7] vs. 8.6 [6.3–13.9] × 109 cells/L, P = 0.007), absolute neutrophil counts (6.2 [4.1–9.1] vs. 7.5 [5.2–12.1] × 109 cells/L, P = 0.004), SOFA score (4.0 [3.0–5.0] vs. 5.0 [3.0–7.0], P < 0.001), use of mechanical ventilation (96.8% vs. 65.1%, P < 0.001), use of ECMO (38.1% vs. 7.5%, P < 0.001), use of CRRT (43.7% vs. 4.8%, P < 0.001), and ICU LOS (26.0 days [18.0–42.0] vs. 20.0 days [15.0–29.0], P < 0.001) were significantly higher among the deceased patients. In contrast, the Glasgow Coma Scale score (15.0 [15.0–15.0] vs. 15.0 [13.0–15.0], P = 0.002) and PaO2/FiO2 ratio (144.2 [101.8–208.2] vs. 130.2 [79.0–171.3], P = 0.004) were notably lower in patients who did not survive.

Table 4
Clinical characteristics according to in-hospital mortality in propensity score-matched cohort

The occurrence of BSI was independently associated with in-hospital mortality (adjusted OR, 2.47; 95% CI, 1.50–4.05; P < 0.001) in the multivariate logistic regression analysis after adjusting for potential confounding factors (Table 5). Other independent risk factors for in-hospital mortality included an older age (adjusted OR, 1.04; 95% CI, 1.01–1.06; P < 0.001), higher BMI (adjusted OR, 1.06; 95% CI, 1.00–1.12, P = 0.044), and higher SOFA score (adjusted OR, 1.18; 95% CI, 1.08–1.29; P < 0.001).

Table 5
Multivariable logistic regression analysis of risk factors for in-hospital mortality

Finally, Kaplan-Meier survival analysis demonstrated no significant difference in the in-hospital mortality rate between the extended and standard groups (log-rank test, P = 0.121) (Fig. 4).

Fig. 4
Kaplan-Meier survival analysis plot for in-hospital mortality between the standard and extended steroid treatment group.

In this nationwide multicenter propensity score–matched study, we evaluated the effects of prolonged steroid therapy on the outcomes of critically ill patients with COVID-19. Our results indicate that extended steroid use, which is commonly prescribed but does not enhance in-hospital survival, is associated with the occurrence of BSI. Furthermore, BSI occurrence was significantly correlated with increased in-hospital mortality among these patients, even after adjusting for various clinical and laboratory parameters. To the best of our knowledge, this is the first multicenter investigation focusing on the adverse effects of extended steroid treatment in this patient group.

In this study, the occurrence of BSI was associated with extended steroid use. Furthermore, it was also significantly correlated with increased in-hospital mortality. Secondary infections commonly occur as complications in patients with acute respiratory failure or acute respiratory distress syndrome caused by viral infections.18, 19 Critically ill patients are susceptible to secondary infections due to immunosuppression associated with severe illness, the use of invasive life support devices, and prolonged hospitalization.20, 21, 22 Secondary infections occur in approximately 5–40% of critically ill patients with COVID-19.13, 23, 24 Recent studies have shown that the overall rate of BSI in patients with COVID-19 varies from 5.3% to 43.6%.25, 26, 27 In some patients with COVID-19, however, there has been no clear evidence on steroid-causing BSI. Buetti et al.28 have reported that while the use of agents such as tocilizumab and anakinra in patients with COVID-19 was associated with the occurrence of BSI, steroid use did not influence the occurrence of BSI. However, another multicenter retrospective study has reported an association between the occurrence of BSI and a combination of steroid and tocilizumab therapy.25 Additionally, the use of steroids increases the odds of any secondary infection in critically ill patients with COVID-19,29, 30 and another single-center retrospective study has reported findings consistent with our research, indicating that the extended use of steroids is associated with the occurrence of BSI.31 BSIs induce a critical complication of sepsis and septic shock. Previous studies have also reported the significant impact of BSI on morbidity and mortality in critically ill patients with COVID-19.10, 25 Our study supports these findings and expands upon the aforementioned results.

In this study, extended steroid use did not reduce in-hospital mortality. The use of steroids has shown benefits in the treatment of critically ill patients with COVID-19 and has been widely adopted, with current guidelines recommending use for up to 10 days.1, 4 However, real-world applications often involve longer treatment,32 as seen in the present study. Despite this, there is limited systematic research on the consequences of prolonged steroid use that might increase the risk of adverse events, such as delayed viral clearance, particularly in critically ill patients with COVID-19.33 Although the study did not exclusively focus on critically ill patients, a recent meta-analysis indicated that using steroids for > 7 days did not offer a survival benefit in hospitalized patients with COVID-19.34 Given these findings, it is crucial to consider the potential risks of extended steroid use, necessitating further targeted research to optimize the therapies for critically ill patients.

The present study has some limitations. First, it was a secondary analysis of a retrospective cohort study. Therefore, the reasons for the prolonged use of steroids have not been properly determined. Some patients may have been deliberately treated with extended steroids, whereas others may have received extended steroids for therapeutic immunomodulation under different conditions. These differences may have influenced the patient outcomes. Secondly, we did not consider the cumulative dose of steroids administered. However, in patients with COVID-19, where immunosuppression over a certain period is necessary to prevent immune-mediated inflammation, the duration of steroid treatment can affect outcomes independently of the cumulative dosage. Third, this study focused only on BSIs. Our findings did not include other secondary infections, such as ventilator-associated pneumonia or urinary tract infections. Fourth, there might be a potential bias for patients who, owing to their severe condition and subsequent rapid deterioration after admission, either did not have the opportunity to be treated with steroids or were administered steroids for an insufficient duration. However, we endeavored to address this by only including patients who were hospitalized in the ICU for 10 days or more in our study.

In this study, the extended use of steroids was associated with an increased risk of BSI in critically ill patients with COVID-19. In addition, the presence of BSIs was associated with a higher mortality risk. However, no correlation was observed between extended steroid use and in-hospital mortality. These findings have important clinical implications, as they suggest that clinicians should be cautious about prolonged steroid use in critically ill COVID-19 patients and closely monitor for signs of BSI. Further prospective studies are required to clarify the effect of prolonged steroid use in critically ill patients with COVID-19.

AbstractGraphical AbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONNotesACKNOWLEDGMENTSReferences
Notes

Funding:This study was supported by a grant (KATRD-S-2021-2) from the Korean Academy of Tuberculosis and Respiratory Diseases.

Disclosure:The authors have no potential conflicts of interest to disclose.

Author Contributions:

  • Conceptualization: Kim S, Lee J.

  • Data curation: Ryoo J, Cho HJ, Kim SC, Park S, Lee SH, Park O, Kim T, Yeo HJ, Cho WH, Lee J.

  • Writing - original draft: Kim S, Lee J.

  • Writing - review & editing: Kim S, Lee J.

Members of The Korean Intensive Care Study Group, excluding the authors: Jin-Won Huh (Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine), Sang-Min Lee (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine), Chi Ryang Chung (Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine), Jung Soo Kim (Division of Critical Care Medicine, Department of Hospital Medicine, Inha Collage of Medicine), Sung Yoon Lim (Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul National University Bundang Hospital), Ae-Rin Baek (Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital), Jung-Wan Yoo (Department of Internal Medicine, Gyeongsang National University Hospital), Ho Cheol Kim (Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine), Eun Young Choi (Division of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center), Chul Park (Division of Pulmonology and Critical Care Medicine, Wonkwang University Hospital), Tae-Ok Kim (Division of Pulmonary, and Critical Care Medicine, Department of Internal Medicine, Chonnam National University Hospital), Do Sik Moon (Department of Pulmonology and Critical Care Medicine, Chosun University Hospital), Song-I Lee (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungnam National University School of Medicine, Chungnam National University Hospital), Jae Young Moon (Department of Internal Medicine, Chungnam National University College of Medicine, Chungnam National University Sejong Hospital), Sun Jung Kwon (Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Konyang University Hospital), Gil Myeong Seong (Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine), Won Jai Jung (Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Anam Hospital), Moon Seong Baek (Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine).

AbstractGraphical AbstractINTRODUCTIONMETHODSRESULTSDISCUSSIONNotesACKNOWLEDGMENTSReferences

References

    1. COVID-19 Treatment Guidelines Panel. Coronavirus disease 2019 (COVID-19) treatment guidelines. [Updated 2023]. [Accessed October 29, 2023].
      https://www.covid19treatmentguidelines.nih.gov/.
    1. RECOVERY Collaborative Group. Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med 2021;384(8):693–704.
    1. van Paassen J, Vos JS, Hoekstra EM, Neumann KMI, Boot PC, Arbous SM. Corticosteroid use in COVID-19 patients: a systematic review and meta-analysis on clinical outcomes. Crit Care 2020;24(1):696.
    1. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA 2020;324(13):1330–1341.
    1. Chalmers JD, Crichton ML, Goeminne PC, Cao B, Humbert M, Shteinberg M, et al. Management of hospitalised adults with coronavirus disease 2019 (COVID-19): a European Respiratory Society living guideline. Eur Respir J 2021;57(4):2100048
    1. Stern A, Skalsky K, Avni T, Carrara E, Leibovici L, Paul M. Corticosteroids for pneumonia. Cochrane Database Syst Rev 2017;12(12):CD007720
    1. Cronin L, Cook DJ, Carlet J, Heyland DK, King D, Lansang MA, et al. Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med 1995;23(8):1430–1439.
    1. Narum S, Westergren T, Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open 2014;4(5):e004587
    1. Surmachevska N, Tiwari V. In: Corticosteroid Induced Myopathy. Petersburg, FL, USA: StatPearls; 2023.
    1. Kurt AF, Mete B, Urkmez S, Demirkiran O, Dumanli GY, Bozbay S, et al. Incidence, risk factors, and prognosis of bloodstream infections in COVID-19 patients in intensive care: a single-center observational study. J Intensive Care Med 2022;37(10):1353–1362.
    1. Garnacho-Montero J, Aldabó-Pallás T, Palomar-Martínez M, Vallés J, Almirante B, Garcés R, et al. Risk factors and prognosis of catheter-related bloodstream infection in critically ill patients: a multicenter study. Intensive Care Med 2008;34(12):2185–2193.
    1. Villar J, Añón JM, Ferrando C, Aguilar G, Muñoz T, Ferreres J, et al. Efficacy of dexamethasone treatment for patients with the acute respiratory distress syndrome caused by COVID-19: study protocol for a randomized controlled superiority trial. Trials 2020;21(1):717.
    1. Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, Rosa RG, Veiga VC, et al. Effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and COVID-19: the CoDEX randomized clinical trial. JAMA 2020;324(13):1307–1316.
    1. Munch MW, Granholm A, Kjaer MN, Aksnes TS, Sølling CG, Christensen S, et al. Long-term mortality and health-related quality of life in the COVID STEROID trial. Acta Anaesthesiol Scand 2022;66(4):543–545.
    1. Garcia RA, Spitzer ED, Beaudry J, Beck C, Diblasi R, Gilleeny-Blabac M, et al. Multidisciplinary team review of best practices for collection and handling of blood cultures to determine effective interventions for increasing the yield of true-positive bacteremias, reducing contamination, and eliminating false-positive central line-associated bloodstream infections. Am J Infect Control 2015;43(11):1222–1237.
    1. Centers for Disease Control and Prevention (US). Blood culture contamination: an overview for infection control and antibiotic stewardship programs working with the clinical laboratory. [Updated 2022]. [Accessed October 29, 2023].
      https://www.cdc.gov/antibiotic-use/core-elements/pdfs/fs-bloodculture-508.pdf.
    1. Lemeshow S, Hosmer DW Jr. A review of goodness of fit statistics for use in the development of logistic regression models. Am J Epidemiol 1982;115(1):92–106.
    1. De Bruyn A, Verellen S, Bruckers L, Geebelen L, Callebaut I, De Pauw I, et al. Secondary infection in COVID-19 critically ill patients: a retrospective single-center evaluation. BMC Infect Dis 2022;22(1):207.
    1. Metzger DW, Sun K. Immune dysfunction and bacterial coinfections following influenza. J Immunol 2013;191(5):2047–2052.
    1. Pène F, Pickkers P, Hotchkiss RS. Is this critically ill patient immunocompromised? Intensive Care Med 2016;42(6):1051–1054.
    1. Lee WC, Ho MC, Leu SW, Chang CC, Lin CK, Lin CM, et al. The impacts of bacterial co-infections and secondary bacterial infections on patients with severe influenza pneumonitis admitted to the intensive care units. J Crit Care 2022;72:154164
    1. Parienti JJ, Dugué AE, Daurel C, Mira JP, Mégarbane B, Mermel LA, et al. Continuous renal replacement therapy may increase the risk of catheter infection. Clin J Am Soc Nephrol 2010;5(8):1489–1496.
    1. Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect 2020;81(2):266–275.
    1. Rouzé A, Martin-Loeches I, Povoa P, Makris D, Artigas A, Bouchereau M, et al. Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study. Intensive Care Med 2021;47(2):188–198.
    1. Khatri A, Malhotra P, Izard S, Kim A, Oppenheim M, Gautam-Goyal P, et al. Hospital-acquired bloodstream infections in patients hospitalized with severe acute respiratory syndrome coronavirus 2 infection (coronavirus disease 2019): association with immunosuppressive therapies. Open Forum Infect Dis 2021;8(7):ofab339
    1. Engsbro AL, Israelsen SB, Pedersen M, Tingsgaard S, Lisby G, Andersen CO, et al. Predominance of hospital-acquired bloodstream infection in patients with COVID-19 pneumonia. Infect Dis (Lond) 2020;52(12):919–922.
    1. Ceccarelli G, Alessandri F, Oliva A, Dell’Isola S, Rocco M, Ruberto F, et al. Superinfections in patients treated with Teicoplanin as anti-SARS-CoV-2 agent. Eur J Clin Invest 2021;51(1):e13418
    1. Buetti N, Ruckly S, de Montmollin E, Reignier J, Terzi N, Cohen Y, et al. COVID-19 increased the risk of ICU-acquired bloodstream infections: a case-cohort study from the multicentric OUTCOMEREA network. Intensive Care Med 2021;47(2):180–187.
    1. Bardi T, Pintado V, Gomez-Rojo M, Escudero-Sanchez R, Azzam Lopez A, Diez-Remesal Y, et al. Nosocomial infections associated to COVID-19 in the intensive care unit: clinical characteristics and outcome. Eur J Clin Microbiol Infect Dis 2021;40(3):495–502.
    1. Ham SY, Lee S, Kim MK, Jeon J, Lee E, Kim S, et al. Incidence and temporal dynamics of combined infections in SARS-CoV-2-infected patients with risk factors for severe complications. J Korean Med Sci 2024;40(11):e38
    1. Dupper AC, Malik Y, Cusumano JA, Nadkarni D, Banga J, Berbel Caban A, et al. Longer steroid treatment increases secondary bloodstream infection risk among patients with COVID-19 requiring intensive care. Infect Dis Clin Pract (Baltim Md) 2022;30(4):IPC.0000000000001188
    1. Wang W, Snell LB, Ferrari D, Goodman AL, Price NM, Wolfe CD, et al. Real-world effectiveness of steroids in severe COVID-19: a retrospective cohort study. BMC Infect Dis 2022;22(1):776.
    1. Yu WC, Hui DS, Chan-Yeung M. Antiviral agents and corticosteroids in the treatment of severe acute respiratory syndrome (SARS). Thorax 2004;59(8):643–645.
    1. Ssentongo P, Yu N, Voleti N, Reddy S, Ingram D, Chinchilli VM, et al. Optimal duration of systemic corticosteroids in coronavirus disease 2019 treatment: a systematic review and meta-analysis. Open Forum Infect Dis 2023;10(3):ofad105
Publication Types
Multicenter Study
Original Article
MeSH Terms
Adrenal Cortex Hormones
Body Mass Index
Cannula
Cohort Studies
Coinfection
Continuous Renal Replacement Therapy
Coronavirus*
COVID-19*
Critical Illness*
Demography
Duration of Therapy
Extracorporeal Membrane Oxygenation
Hospital Mortality
Humans
Incidence
Length of Stay
Mortality
Organ Dysfunction Scores
Propensity Score
Retrospective Studies
SARS-CoV-2*
Sepsis*
Steroids
Steroids*
Therapeutics
Ventilators, Mechanical
Metrics
Share
Figures
slide
slide
slide
slide

1 / 4

Tables
slide
slide
slide
slide
slide

1 / 5

ORCID IDs
PERMALINK