Paxlovid is 80% effective when taken within 5 days of severe COVID

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Mar 21 2023

In a recent study published in The Lancet’s Infectious Diseases, researchers in the United States evaluated nirmatrelvir–ritonavir treatment effectiveness against hospitalizations and deaths among coronavirus disease 2019 (COVID-19) outpatients in the United States of America (USA).

Study: Effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system. Image Credit:  WESTOCK PRODUCTIONS / Shutterstock

Background

The continual emergence of increasingly transmissible and immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has challenged the therapeutic efficacy of COVID-19 vaccines, monoclonal antibodies, and antiviral agents, warranting the development of substances effective against variant mutations.

The evaluation of protease inhibition for COVID-19 in high-risk patients (EPIC-HR) trial findings indicated that orally administered nirmatrelvir-ritonavir (Paxlovid) lowered COVID-19-associated hospitalization risks by 89%. When nirmatrelvir-ritonavir was administered within 28 days of treatment among unvaccinated adult COVID-19 outpatients prone to severe COVID-19 outcomes, this result was observed.

Subsequently, nirmatrelvir-ritonavir was authorized by the US Food and Drug Administration for emergency usage among high-risk individuals with mild-moderate SARS-CoV-2 infections aged ≥12 years. However, further research is required to evaluate nirmatrelvir-ritonavir’s effectiveness in preventing COVID-19 severity outcomes in the real world.

About the study

In the present observational retrospective cohort study, researchers estimated nirmatrelvir–ritonavir effectiveness in preventing COVID-19-associated hospitalizations and deaths in outpatient settings.

The study comprised individuals registered with the Kaiser Permanente healthcare system of South California (CA). The team retrieved data from the electronic medical records and via structured questionnaires of non-hospitalized patients aged ≥12 years.

These individuals had a SARS-CoV-2-positive polymerase chain reaction (PCR) report (index COVID-19 test date) between 8 April and 7 October 2022 without any such positive reports in the previous 90.0 days. In addition, included individuals were not hospitalized at the time of index testing or the week prior and were registered with the KPSC system for ≥1.0 years before the index test.

COVID-19 outcomes were compared between individuals receiving nirmatrelvir-ritonavir treatment. Individuals who were not administered the combination matched for the testing date, sex, age, clinical COVID-19 status (healthcare received, acute SARS-CoV-2 infections, symptoms at PCR testing, and duration between symptom onset and PCR testing), COVID-19 vaccination status, comorbid conditions, healthcare encounters in the prior year, and body mass index (BMI).

The prime study exposures were outpatient receipt of nirmatrelvir-ritonavir (300.0 mg nirmatrelvir and 100.0 mg ritonavir orally two times daily over five days) within five days of the onset of symptoms and outpatient receipt of nirmatrelvir-ritonavir any time after testing positive for SARS-CoV-2 by PCR.

The prime study endpoint comprised the estimated nirmatrelvir-ritonavir effectiveness against COVID-19-associated hospitalizations or deaths within 30.0 days of positive SARS-CoV-2 test reports.

The secondary study endpoints comprised intensive care unit (ICU) admission, mechanical ventilation requirements, or deaths within 60.0 days of the index date, indicating progression toward severe COVID-19. Cox proportional hazards modeling was performed, and the adjusted hazard ratios were calculated, adjusting for covariates such as age, comorbidities, obesity, vaccination status, smoking habits, and body mass index.

Treatment effectiveness percentages were calculated using hazard ratios. Subgroup analysis was performed among two-dose and three-dose COVID-19 vaccinees, and exploratory analysis was performed for individuals treated ≤3.0 days post-symptom onset, treated ≥6 days post-symptom onset, and at any time post-symptom onset.

Results

In total, 7,274 and 126,152 nirmatrelvir-ritonavir treatment recipients and non-recipients, respectively. When the SARS-CoV-2-positive test reports were analyzed, 75% (n=5,472) and 67% (n=4,657) were recipients and non-recipients, respectively, who underwent tests within five days of COVID-19 symptom onset. Compared to non-recipients, nirmatrelvir–ritonavir recipients showed a greater likelihood of being older, having comorbidities, having more emergency department (ED) encounters, and having received ≥2.0 doses of COVID-19 vaccines.

The estimated nirmatrelvir-ritonavir effectiveness in preventing hospitalizations and/or deaths within 30.0 days of SARS-CoV-2-positive reports was 54%, increasing to 80% when the combination medication was administered within five days of the onset of symptoms.

In the subgroup analysis, including individuals undergoing SARS-CoV-2 testing within five days of the onset of symptoms, who were administered treatment at testing, the estimated nirmatrelvir-ritonavir effectiveness was 90%. However, no significant protection was conferred by treatment against the secondary outcomes for nirmatrelvir-ritonavir administered within five days of symptom onset.

For treatment administered at any time during COVID-19, the estimated treatment effectiveness against the endpoint was 84%. Among individuals who received ≥2.0 SARS-CoV-2 vaccine doses, the estimated nirmatrelvir–ritonavir effectiveness against hospitalizations and deaths within 30.0 days was 55%. Among vaccinees treated within five days of symptom onset was 83%. The corresponding estimates for individuals who received ≥3.0 doses were 67% and 92%, respectively, and for high-risk individuals, the estimates were 52% and 81%, respectively.

Among individuals receiving nirmatrelvir–ritonavir at index testing and within five days of symptom onset, the estimated treatment effectiveness against hospitalizations and deaths were 78%, and 90%, respectively. The findings indicated that early initiation of treatment conferred a maximal therapeutic benefit, underscoring the importance of prompt SARS-CoV-2 testing and therapy administration to high-risk individuals to reduce the global COVID-19 burden.

The study findings showed that in the high SARS-CoV-2 vaccine-uptake scenario, nirmatrelvir–ritonavir treatment effectively lowered COVID-19 severity outcome risks, including hospitalizations and deaths within 30.0 days of a SARS-CoV-2-positive result, among COVID-19 outpatients.