Exploring Paxlovid Efficacy in COVID-19 Patients with MAFLD: Insights from a Single-Center Prospective Cohort Study

Abstract

This study investigates the intricate interplay between Metabolic-associated Fatty Liver Disease (MAFLD) and COVID-19, exploring the impact of MAFLD on disease severity, outcomes, and the efficacy of the antiviral agent Paxlovid (nirmatrelvir/ritonavir). MAFLD, affecting a quarter of the global population, emerges as a potential risk factor for severe COVID-19, yet the underlying pathophysiological mechanisms remain elusive. This study focuses on the clinical significance of Paxlovid, the first orally bioavailable antiviral agent granted Emergency Use Authorization in the United States. Notably, outcomes from phase II/III trials exhibit an 88% relative risk reduction in COVID-19-associated hospitalization or mortality among high-risk patients. Despite conflicting data on the association between MAFLD and COVID-19 severity, this research strives to bridge the gap by evaluating the effectiveness of Paxlovid in MAFLD patients with COVID-19, addressing the scarcity of relevant studies.

Keywords: COVID-19; MAFLD; Paxlovid; nirmatrelvir.

Figure 1

(a) ROC curve characterizing the dependence of the probability of the need for oxygen supply on the value of logistic function P. This ROC curve assesses the quality of logistic regression for predicting the primary outcome. It was created using the prediction results of the regression model and the category we are trying to predict. (b) Cut-off plot with the best cut-off point to maximize specificity and sensitivity indicators.

Figure 2

Comparison of the medians of four groups: patients treated with standard therapy vs. those treated with Paxlovid (disregarding the presence of MALFD) on the left; patients with and without MAFLD (disregarding the treatment) on the right. Data are presented as medians and p-values were calculated using the Mann–Whitney test. IQR—25–75% interquartile range.

Figure 3

Comparison of the medians of four groups (COVID-19—standard treatment, COVID-19—Paxlovid treatment, COVID-19 with MAFLD—standard treatment, and COVID-19 with MAFLD—Paxlovid treatment) during hospitalization. Data are presented as medians and p-values were calculated using the Mann–Whitney test. IQR—25–75% interquartile range.

Figure 4

Comparison of the medians of four groups: patients treated with standard therapy vs. those treated with Paxlovid (disregarding the presence of MALFD) on the left; patients with and without MAFLD (disregarding the treatment) on the right. Data are presented as medians and p-values were calculated using the Mann–Whitney test. IQR—25–75% interquartile range.

Figure 5

Comparison of the medians of four groups (COVID-19—standard treatment, COVID-19—Paxlovid treatment, COVID-19 with MAFLD—standard treatment, and COVID-19 with MAFLD—Paxlovid treatment) during hospitalization. Data are presented as medians and p-values were calculated using the Mann–Whitney test. IQR—25–75% interquartile range.

Figure 6

Comparison of the medians of four groups: patients treated with standard therapy vs. those treated with Paxlovid (disregarding the presence of MALFD) on the left; patients with and without MAFLD (disregarding the treatment) on the right. Data are presented as medians and p-values were calculated using the Mann–Whitney test. IQR—25–75% interquartile range.

Figure 7

Comparison of the medians of four groups (COVID-19—standard treatment, COVID-19—Paxlovid treatment, COVID-19 with MAFLD—standard treatment, and COVID-19 with MAFLD—Paxlovid treatment) during hospitalization. Data are presented as medians and p-values were calculated using the Mann–Whitney test. IQR—25–75% interquartile range.

Figure 8

Comparison of the medians of four groups: patients treated with standard therapy vs. those treated with Paxlovid (disregarding the presence of MALFD) on the left; patients with and without MAFLD (disregarding the treatment) on the right. Data are presented as medians and p-values were calculated using the Mann–Whitney test. IQR—25–75% interquartile range.

Figure 9

Comparison of the medians of four groups (COVID-19—standard treatment, COVID-19—Paxlovid treatment, COVID-19 with MAFLD—standard treatment, and COVID-19 with MAFLD—Paxlovid treatment) during hospitalization. Data are presented as medians and p-values were calculated using the Mann–Whitney test. IQR—25–75% interquartile range.

Figure 10

The difference in the medians of the clinical and laboratory findings in patients with Paxlovid and standard therapy at discharge compared with admission. Data are presented as medians with IQR, and p-values were calculated using Wilcoxon matched-pairs test. IQR—5–75% interquartile range.

Figure 11

The difference in the medians of the clinical and laboratory findings in patients with Paxlovid and standard therapy at discharge compared with admission. Data are presented as medians with IQR, and p-values were calculated using Wilcoxon matched-pairs test. IQR—25–75% interquartile range.

Figure 12

The difference in the medians of the clinical and laboratory findings in patients with Paxlovid and standard therapy at discharge compared with admission. Data are presented as medians with IQR, and p-values were calculated using Wilcoxon matched-pairs test. IQR—25–75% interquartile range.

Figure 13

Correlation correlogram. Spearman’s correlation was used with two continuous variables, point-biserial correlation between binary and continuous data, the Chi-square test between two binary data. The color at the intersection of those variables represents the strength of the correlation between two variables. Colors range from crimson (strong negative correlation; r = −1.0) to cyan blue (strong positive correlation; r = 1.0). Results were not represented if p > 0.05.

Figure 14

Association of time to recovery with Paxlovid prescription using Kaplan–Meier curves in patients with COVID-19. Hazard ratios (HR) with 95% confidence intervals and p-values were calculated using the log-rank test. We defined the probability of hospital discharge in a given length of time while considering time in many small intervals. The day of discharge from the hospital was considered the target event. p > 0.05 shows statistically significant difference between medians of hospital discharge (standard therapy—11 days vs. Paxlovid therapy—9 days).

Figure 15

(a) ROC curve characterizing the dependence of the probability of the need for oxygen supply on value of logistic function P. This ROC curve assesses the quality of logistic regression for predicting the primary outcome. It was created using the prediction results of the regression model and the category we are trying to predict; (b) cut-off plot with the best cut-off point to maximize specificity and sensitivity indicators.