Study finds nirmatrelvir-ritonavir reduces severe COVID-19 and long COVID risks in high-risk patients

By Vijay Kumar MalesuReviewed by Lily Ramsey, LLMOct 30 2024

New research highlights the effectiveness of nirmatrelvir-ritonavir in lowering hospitalization rates and long COVID symptoms in non-hospitalized, high-risk COVID-19 patients.

Study: Nirmatrelvir plus ritonavir reduces COVID-19 hospitalization and prevents long COVID in adult outpatients. Image Credit: Simplylove/Shutterstock.com

In a recent study published in the Scientific Reports, a group of researchers evaluated the effectiveness of nirmatrelvir plus ritonavir in preventing severe disease progression and long coronavirus disease 2019 (COVID-19) symptoms in non-hospitalized adults with mild to moderate COVID-19, particularly in the context of the Omicron variant.

Background 

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated COVID-19 pose ongoing global health challenges, particularly for patients with underlying conditions like diabetes, cardiovascular disease, and obesity, who face heightened risks of severe illness and long-term complications. Effective oral treatments are essential for preventing disease progression.

In December 2021, the Food and Drug Administration (FDA) granted Emergency Use Authorization for nirmatrelvir plus ritonavir for treating mild to moderate COVID-19 in high-risk populations.

Although preliminary studies suggest benefits, substantial gaps in real-world clinical data, especially regarding the Omicron variant and long COVID prevention, necessitate the need for further research.

About the study

In the present study, administrative data from the Smart and Advanced Logistics Automated Management Architecture (SALAMA) healthcare system in Dubai was analyzed to evaluate the effects of nirmatrelvir-ritonavir on COVID-19 outcomes. SALAMA serves as the unified electronic medical record system for hospitals and clinics under the Dubai Health Authority.

Data was collected from patients treated with oral nirmatrelvir-ritonavir and those who did not receive antiviral treatment for COVID-19 between May 22, 2022, and April 30, 2023. Information included demographics, SARS-CoV-2 test results, symptoms, oxygen saturation levels, and medical history.

Ethical approval was granted by the Dubai Scientific Research Ethics Committee, ensuring that all patient records were anonymized and eliminating the need for written consent. The study targeted adults aged 18 and older who tested positive for SARS-CoV-2 with mild to moderate symptoms.

Patients requiring hospitalization were excluded. Treatment selection was based on national protocols and physician discretion, particularly targeting high-risk individuals.

The primary outcome was the risk of hospitalization within 28 days, while secondary outcomes focused on long-term COVID symptoms reported during family medicine visits. Statistical analyses, including Cox proportional hazards models and Kaplan-Meier survival curves, were performed using various software tools, revealing significant findings regarding treatment efficacy and outcomes. 

Study results

Among the 7,290 non-hospitalized adults with COVID-19 identified in the SALAMA healthcare system, 672 received nirmatrelvir-ritonavir, while 6,618 did not receive any antiviral treatment.

Baseline characteristics of the patients indicated that those in the nirmatrelvir-ritonavir group were significantly older, with a mean age of 54 years, compared to 37 years in the no-treatment group (P < 0.001). Gender distribution was similar across both groups, with approximately half of the patients being male (48% in the nirmatrelvir-ritonavir group and 45% in the no-treatment group; P = 0.102).

Ethnic demographics showed that around two-thirds of patients identified as Caucasian (81% in the nirmatrelvir-ritonavir group and 78% in the no-treatment group; P = 0.090). 

Clinical guidelines outline the most common risk factors for COVID-19 progression, including age 65 or older, diabetes, cardiovascular disease, hypertension, obesity, asthma, and immunocompromised states.

These risk factors were more prevalent in the nirmatrelvir-ritonavir group, where 32% of patients were aged 65 and older, compared to 12% in the no-treatment group (P < 0.001). The presence of diabetes was noted in 28% of the nirmatrelvir-ritonavir group versus 10% in the no-treatment group (P < 0.001).

Other notable differences included obesity rates at 16% in the nirmatrelvir-ritonavir group compared to 8% in the no-treatment group (P < 0.001) and cardiovascular disease at 11% versus 4%, respectively (P < 0.001).

In terms of hospitalization outcomes, a total of 170 COVID-19-related hospitalizations lasting more than 24 hours were recorded during the 28-day follow-up period, representing 2.3% of the total cohort. Of these, 8 (1.1%) occurred in the nirmatrelvir-ritonavir group, while 162 (2.4%) occurred in the no-treatment group.

Cox regression analysis revealed that nirmatrelvir-ritonavir significantly reduced the risk of hospitalization compared to no treatment, with an adjusted hazard ratio of 0.39 (95% CI: 0.18–0.85, P = 0.019).

Regarding long COVID symptoms, 208 patients (2.8%) required a follow-up visit to the family medicine department due to ongoing symptoms. Eight patients (1.1%) were from the nirmatrelvir-ritonavir group, while 200 patients (3%) were in the no-treatment group (P = 0.015).

The most frequently reported long COVID symptoms included fatigue (17.8%), muscle pain (12%), and upper respiratory symptoms (8.2%).

Adjusted Cox regression analysis indicated that nirmatrelvir-ritonavir treatment was associated with a reduced risk of developing long COVID symptoms, with an adjusted hazard ratio of 0.42 (95% CI: 0.19-0.95, P = 0.037).

Conclusions 

To summarize, the results of this study demonstrate that early administration of nirmatrelvir-ritonavir effectively reduced COVID-19-related hospitalization by day 28 in high-risk patients. Given that the predominant variant was Omicron, these findings indicate the treatment's efficacy against this strain.

The study also revealed that nirmatrelvir-ritonavir was associated with a decreased risk of developing long COVID symptoms, likely due to its role in reducing viral load.