Examining the Impact of Nirmatrelvir–Ritonavir on Post-COVID-19 Condition in Hospitalized Patients


Investigating the long-term efficacy beyond short-term benefits.

covid hospital

Nurse and COVID patient in the hospital.

Image credits: Unsplash

This research revealed the prolonged advantages of nirmatrelvir–ritonavir in decreasing the likelihood of post-acute inpatient mortality, along with cardiovascular and respiratory issues among hospitalized COVID-19 patients.

136,973 individuals underwent screening for inclusion in the study, 50,055 met the eligibility criteria and were included in the analysis. Among these, 24,873 (49.7%) were female and 25,182 (50.3%) were male. Of the total, 15,242 patients were prescribed nirmatrelvir–ritonavir during acute COVID-19, while 23,756 patients formed the control group. However, 11,057 patients did not meet the criteria for either the exposed or unexposed groups.

3 Key Takeaways

  1. Extended advantages of nirmatrelvir–ritonavir in reducing post-acute mortality, and cardiovascular, and respiratory complications among hospitalized COVID-19 patients.
  2. Patients prescribed nirmatrelvir–ritonavir exhibited a notable decrease in the risk of post-acute inpatient death compared to the control group, extending beyond previous findings on short-term mortality benefits.
  3. Utilizing real-world data from Hong Kong's Hospital Authority and Department of Health, the study provides valuable insights into the efficacy of nirmatrelvir–ritonavir in managing post-COVID-19 conditions among hospitalized patients, emphasizing the need for further investigation to address potential limitations and elucidate underlying mechanisms.

“We showed that there was a significant reduction in the risk of post-acute inpatient death among the patients prescribed oral nirmatrelvir–ritonavir compared with the control group,” according to the investigators. “In addition to a previous study suggesting nirmatrelvir–ritonavir was effective in decreasing the risk of all-cause mortality within 28 days of COVID-19 infection in the same setting, we further showed the mortality benefit of nirmatrelvir–ritonavir extended to the post-acute phase of a SARS-CoV-2 infection among patients admitted to hospital.”

Patients were monitored for a median duration of 393 days (with an interquartile range of 317–489). In the nirmatrelvir–ritonavir group compared to the control group, there was a significantly reduced risk of post-acute inpatient mortality (hazard ratio 0.62 (95% confidence interval 0.57–0.68); p<0.0001), as well as lower incidences of congestive heart failure (0.70 (0.58–0.85); p=0.0002), atrial fibrillation (0.63 (0.52–0.760; p<0.0001), coronary artery disease (0.71 (0.59–0.85); p=0.0002), chronic pulmonary disease (0.68 (0.54–0.86); p=0.0011), acute respiratory distress syndrome (0.71 (0.58–0.86); p=0.0007), interstitial lung disease (0.17 90.04–0.750; p=0.020), and end-stage renal disease (0.37 (0.18–0.74); p=0.0049).

This study, based on real-world data from Hong Kong's Hospital Authority and Department of Health, examined patients aged 18 and above hospitalized with COVID-19 between March 11, 2022, and October 10, 2023. It compared those treated with nirmatrelvir–ritonavir within 5 days of symptom onset to a control group. The outcomes studied were post-acute inpatient death and 13 sequelae, such as heart issues and lung diseases. Standardized mortality ratio weights were used to balance factors, and Cox proportional hazards regression analyzed the relationship between nirmatrelvir–ritonavir and outcomes starting 21 days after a positive COVID-19 test.

“In our study, nirmatrelvir–ritonavir showed significantly reduced hazards associated with cardiovascular complications, including congestive heart failure, atrial fibrillation, and coronary artery disease compared with the control group,” according to the investigators. “This finding echo previous studies indicating a lower risk of dysrhythmia and long-term major adverse cardiovascular events among patients who were not admitted to hospital and were treated with nirmatrelvir–ritonavir compared with patients who did not receive nirmatrelvir–ritonavir.”

The study exhibits limitations, the cohort grouping relied on prescription records, which may have led to misclassification. The focus was on predefined sequelae documented using standardized ICD codes, rather than WHO-defined post-COVID-19 conditions. The investigation specifically targeted nirmatrelvir–ritonavir, omitting assessment of other antivirals such as molnupiravir. The definition of the post-acute period varied from other studies, potentially impacting comparability. Additionally, some sequelae had insufficient occurrences, possibly biasing the results. Lastly, unmeasured confounding variables and competing events related to post-acute inpatient death were not thoroughly addressed in the analysis.

Further investigation is essential to clarify the mechanisms behind these adverse correlations and to develop effective strategies for preventing the onset of post-acute sequelae.


Wang H, Wei Y, Hung C, et. al. Association of nirmatrelvir–ritonavir with post-acute sequelae and mortality in patients admitted to hospital with COVID-19: a retrospective cohort study. Published May 3, 2024. Accessed May 8, 2024. DOI: https://doi.org/10.1016/S1473-3099(24)00217-2 

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