#5505 EFFICACY OF PAXLOVID WITHIN 5 DAYS VERSUS 5 DAYS AFTER DIAGNOSIS IN COVID-19 PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Yu Wenjuan , Zhang Xiao , Fu Sha , Shu Ting , Chen Junzhe , Tang Ying 
Published: June 2023

Abstract

Background and Aims
With the liberalization of COVID-19 control policies in mainland China, the majority of the Chinese population has experienced Omicron infection since mid-December 2022. Paxlovid is a commonly used antiviral drug for patients with COVID-19, but there are few studies in patients with chronic kidney disease (CKD).Therefore, we conducted a retrospective cohort study to explore the drug efficacy of Paxlovid in patients with CKD at different time points after COVID-19 infection.

Method
70 CKD patients who were admitted to the Department of Nephrology, the Third Affiliated Hospital of Southern Medical University before January 07, 2023 and diagnosed with COVID-19 were included.The patients were divided into three groups: No Paxlovid group, Paxlovid group within 5 days of diagnosis, Paxlovid group after 5 days of diagnosis, each patient was followed-up for at least 4 weeks. The primary outcome measures included all-cause mortality, length of hospital stay, PCR positive duration and the aggravation of the disease requires ICU admission or mechanical ventilation, or the initiation of renal replacement therapy, and re-hospitalization. The t test or non-parametric test was used to compare the quantitative data, the chi-square test was used to compare the rates, and the K-M curve and Cox regression model were used for survival analysis.

Results
Among the 70 patients (mean age 65.8±15.90 years, male sex 67.7%), Paxlovid was not used in 35 patients (50%), used in 16 patients (22.9%) within 5 days of diagnosis, and in 19 patients (27.1%) after 5 days. At the start of follow-up, there were no significant differences in age, gender, eGFR, comorbidities, COVID-19 severity and laboratory parameters between patients who used Paxlovid within 5 days and after 5 days of diagnosis. However, patients who used Paxlovid had more severe disease than those who did not use Paxlovid (P&lt;0.001), and patients were more likely to use glucocorticoids (74.3% vs 17.1%, P&lt; 0.001), as well as lower lymphocyte count (0.54*10^9/L vs 0.85*10^9/L, P = 0.016) and percentage (9.5% vs 14.2%, P = 0.009), Higher levels of IL-6 (68.57 pg/ml vs 14.66 pg/ml, P = 0.015) and CRP(113.36 mg/L vs 24.57 mg/L, P = 0.001). After a median follow-up of 45 days, we found that patients used Paxlovid had significantly longer hospital stays and higher rehospitalization rates, with subgroup analysis finding that the increased length of stay and rehospitalization rates were mainly attributable to Paxlovid use after 5 days of diagnosis. Patients who used Paxlovid after 5 days had longer nucleic acid positive time (25 days vs 7 days, P = 0.001) and longer hospital stay (16 days vs 10 days, P = 0.008) compared with those who used Paxlovid earlier. At the end of follow-up, a total of nine patients had died. The K-M survival curve was drawn after the exclusion of mild patients, which showed that patients who used Paxlovid within 5 days had the lowest risk of death, those who did not use Paxlovid had the highest risk of death, and those who used Paxlovid after 5 days fell in between. However, due to the small sample size, the difference was not statistically significant (P = 0.155). The Cox regression analysis showed that IL-6 (HR 1.009; 95% CI: 1.004-1.014, P = 0.001)was the best predictor of death risk in COVID-19 patients with CKD after adjusting other factors.

Conclusion
The risk of death in CKD patients infected with COVID-19 is significantly higher than that in the general population. Early use of Paxlovid to inhibit virus replication has a good therapeutic effect on these patients, which can greatly reduce the risk of death, admission to ICU or emergency renal replacement therapy. Delayed use of Paxlovid may increase the time of nucleic acid positive and the length of hospital stay.