Time-Varying Effects of Glucocorticoid Treatment in Critically III Patients with Severe Fever with Thrombocytopenia Syndrome: An Inverse Probability of Treatment Weighting Analysis

Peng Xia,1,2,&ast; Yun Liu,3,&ast; Jun Wang,3,&ast; Haopeng Li,4 Yu Zhai,3 Baoyan Wang,5 Hanwen Tong,3 Weihong Ge,1,5 Chenxiao Jiang1,5 1Department of Pharmacy, Nanjing Drum Tower Hospital, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Emergency Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Emergency Medicine, Nanjing Drum Tower Hospital, School of Clinical Medicine, Xuzhou Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chenxiao Jiang, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Zhongshan Road No. 321, Nanjing, Jiangsu, People’s Republic of China, Email [email protected] Weihong Ge, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Zhongshan Road No. 321, Nanjing, Jiangsu, People’s Republic of China, Email [email protected]: To evaluate the efficacy of glucocorticoid treatment in critically ill patients with severe fever with thrombocytopenia syndrome (SFTS) and to assess whether glucocorticoid use increases the risk of fungal infections.Patients and Methods: A retrospective cohort study was conducted involving confirmed SFTS patients from a tertiary hospital. After applying the Inverse Probability of Treatment Weights (IPTW), multivariable Cox regression and logistic regression analyses were utilized to assess the impact of glucocorticoids on the 28-day mortality rate and the risk of fungal infections. Additionally, landmark analysis and time-varying Cox regression were employed to evaluate the effects of glucocorticoids on mortality across different time intervals.Results: The study included 112 patients with severe SFTS, comprising 67 patients in the glucocorticoid (GC) group and 45 in the non-glucocorticoid (non-GC) group. While glucocorticoid treatment did not significantly alter the overall 28-day mortality in severe SFTS (aHR 0.92, 95% CI 0.44– 1.93, P = 0.828), it was associated with a notable reduction in mortality within the first 7 days of hospitalization (aHR 0.35, 95% CI 0.15– 0.82, P = 0.016) and an increased mortality risk between days 7 and 28 (aHR 4.92, 95% CI 1.30– 18.67, P = 0.019). Furthermore, glucocorticoid use was linked to a significantly higher risk of developing fungal infections (aOR 15.22, 95% CI 4.04– 57.38, P < 0.001).Conclusion: The effects of glucocorticoid treatment in severe SFTS patients vary depending on the disease stage, suggesting that the timing of glucocorticoid administration is crucial. Additionally, the increased risk of fungal infections warrants careful consideration when prescribing glucocorticoids in this population.Keywords: severe fever with thrombocytopenia syndrome, critical illness, glucocorticoid, mortality, fungal infections, time-varying