Objective
Limited data are available on the use of antiviral drugs among oldest-old patients. This study investigates the effect of Jinhua Qinggan Granule (JHQG) , a compound Chinese herbal medicine, on the efficacy and safety of nirmatrelvir/ritonavir in oldest-old patients with coronavirus disease 2019 (COVID-19).

Methods
A total of 180 oldest-old patients with confirmed COVID-19 at the Chinese PLA General Hospital from July 2023 to July 2024 were enrolled in this retrospective cohort study and were divided into a monotherapy group (nirmatrelvir/ritonavir, n = 89) and a combination therapy group (nirmatrelvir/ritonavir plus JHQG, n = 91) according to the treatments received. The primary outcome was the cumulative rate of nucleic acid negative conversion (NANC) on the fifth day after initiation of treatment. The secondary outcomes included the rates of improvement in the main symptoms, the duration of fever, and variations in clinical laboratory indices. The safety outcomes included the incidence of adverse drug reactions (ADRs) and indicators of liver and kidney function.

Results
Among the 180 oldest-old patients participating in the study, the median (P25, P75) age was 93.0 (86.0, 96.0) years, and 94.44% were male. The rate of NANC within five days was significantly higher in the combination therapy group than in the monotherapy group (80.22% vs 66.29%, P = 0.035). The addition of JHQG was significantly associated with NANC within five days in the multivariable analysis (odds ratio [OR] = 2.216; 95% confidence interval [CI]: 1.066–4.607; P = 0.033). Furthermore, compared with nirmatrelvir/ritonavir alone, combination therapy had better effects on the recovery rates of various symptoms, including fever, cough, expectoration, and all respiratory symptoms, as well as the time to recovery from fever (P < 0.05). There were also significant differences between the two groups in terms of improvement in C-reactive protein (P < 0.05). Moreover, no significant differences were observed in the incidence of ADRs or in liver and kidney function indicators (P > 0.05).

Conclusion
Among oldest-old patients with COVID-19, the addition of JHQG to nirmatrelvir/ritonavir significantly improves early clinical recovery without increasing safety concerns.

Key words: COVID-19, Nirmatrelvir/ritonavir, Jinhua Qinggan Granule, Oldest-old patients, Cohort study