Effects and infection risks of baricitinib in combination with nirmatrelvir/ritonavir in elderly patients with severe or critical COVID-19: a retrospective observational cohort study

Baricitinib was shown to reduce the mortality of COVID-19 patients, but real world data about baricitinib in combination with nirmatrelvir/ritonavir for the treatment of elderly patients with severe or critical COVID-19 were limited. The aim of the study was to determine the effects and hospital-acquired infections occurrence after combined medication in these patients. We included severe or critical COVID-19 patients treated at Beijing Chaoyang Hospital from December 2022 to February 2023. We investigated duration of hospital stay, factors associated with reduced mortality risk, IL-6 levels and the characteristics of hospital-acquired infections in patients treated with baricitinib with nirmatrelvir/ritonavir. The median age of the 117 included patients was 79 (interquartile range [IQR]: 70–85) years. Thirty-six patients received baricitinib with nirmatrelvir/ritonavir, 16 of whom died. The factors associated with reduced mortality were the administration of baricitinib with nirmatrelvir/ritonavir (hazard ratio [HR]: 0.405 (95% CI: 0.183–0.90), p = 0.026)). The IL-6 levels were 0.75 (IQR: 0.55–1.82) log 10 pg/mL before or within 2 days of baricitinib administration, and it was 1.45 (IQR: 0.94–2.07) log 10 pg/mL after baricitinib administration for 6 to 8 days. A mixed-effects model showed a statistically significant effect of Time on IL-6 levels (F(1, 20.757) = 6.299, p = 0.020). The fixed effects estimates indicated that each one-day increase during the treatment period, IL-6 levels increased by an average of 0.081 units ( B = 0.081, SE = 0.032, t (20.757) = 2.510, p = 0.020, 95% CI (0.014, 0.148)). In patients treated with baricitinib, carbapenem-resistant Acinetobacter baumannii (2), carbapenem-resistant Klebsiella pneumoniae (2), and K. pneumoniae (2) were more common pathogens detected in the respiratory tract. Carbapenem-resistant K. pneumoniae (1), Enterococcus faecium (1), and Staphylococcus epidermidis (1) were detected in blood. Enterococcus faecium (2) and K. pneumoniae (1) were identified via urine culture. Baricitinib combined with nirmatrelvir/ritonavir was associated with lower mortality in elderly patients with severe or critical COVID-19 in the real world. Carbapenem-resistant A.baumannii and carbapenem-resistant K. pneumoniae were more common pathogens detected in the respiratory tract in these patients. Not applicable.