Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: A retrospective cohort study

Evans, Andrew; Qi, Cathy Huaqing; Adebayo, Jubril Omololu; Underwood, Jonathan; Coulson, James; Bailey, Rowena; Lyons, Ronan A; Edwards, Adrian; Cooper, Alison; John, Gareth; Akbari, Ashley

doi:10.1016/j.jinf.2023.02.012

Cited by 29 publications

(60 citation statements)

References 20 publications

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“…Real world effectiveness studies from Israel, Hong Kong, and the UK provided evidence of the effectiveness of nirmatrelvir during the early days of the omicron surge when BA.1 or BA.2 was the predominant subvariant. 3 4 5 SARS-CoV-2 is mutating rapidly, and new variants and subvariants are replacing previous ones every few months. Whereas BA.1 was the predominant subvariant of omicron in the US at the beginning of our study on 3 January 2022, BA.2 was predominant between 20 March and 25 June 2022, and the BA.5 subvariant between 26 June and 5 November 2022 (our study ended on 30 November 2022, and follow-up ended on 12 December 2022).…”

Section: Discussionmentioning

confidence: 99%

“…Real world evidence studies from Israel, Hong Kong, and the UK suggested that nirmatrelvir was associated with a reduced risk of admission to hospital or death during the early days of the omicron surge. 3 4 5 Omicron has since replaced previous variants, has spawned subvariants, many people recently infected have been vaccinated, and many people have been reinfected (ie, had a previous SARS-CoV-2 infection). 6 7 8 The effectiveness of nirmatrelvir in reducing the risk of admission to hospital or death by vaccination status and by previous history of SARS-CoV-2 infection is not known.…”

Section: Introductionmentioning

confidence: 99%

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Nirmatrelvir and risk of hospital admission or death in adults with covid-19: emulation of a randomized target trial using electronic health records

Bowe

Al‐Aly

2023

BMJ

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Objective To estimate the effectiveness of nirmatrelvir, compared with no treatment, in reducing admission to hospital or death at 30 days in people infected with the SARS-CoV-2 virus and at risk of developing severe disease, according to vaccination status and history of previous SARS-CoV-2 infection. Design Emulation of a randomized target trial with electronic health records. Setting Healthcare databases of the US Department of Veterans Affairs Participants 256 288 participants with a SARS-CoV-2 positive test result and at least one risk factor for developing severe covid-19 disease, between 3 January and 30 November 2022. 31 524 were treated with nirmatrelvir within five days of testing positive for SARS-CoV-2 and 224 764 received no treatment. Main outcome measures The effectiveness of starting nirmatrelvir within five days of a positive SARS-CoV-2 test result versus no treatment in reducing the risk of admission to hospital or death at 30 days was estimated in those who were not vaccinated, in those who received one or two doses of vaccine, and those who received a vaccine booster and, separately, in participants with a primary SARS-CoV-2 infection or reinfection. The inverse probability weighting method was used to balance personal and health characteristics between the groups. Relative risk and absolute risk reduction were computed from cumulative incidence at 30 days, estimated by weighted Kaplan-Meier estimator. Results Among people who were not vaccinated (n=76 763; 5338 nirmatrelvir and 71 425 no treatment), compared with no treatment, the relative risk of nirmatrelvir in reducing admission to hospital or death at 30 days was 0.60 (95% confidence interval 0.50 to 0.71); the absolute risk reduction was 1.83% (95% confidence interval 1.29% to 2.49%). The relative risk and absolute risk reduction, compared with no treatment, were 0.65 (0.57 to 0.74) and 1.27% (0.90% to 1.61%), respectively, in people who received one or two doses of vaccine (n=84 620; 7989 nirmatrelvir and 76 631 no treatment); 0.64 (0.58 to 0.71) and 1.05% (0.85% to 1.27%) in individuals who received a booster dose of vaccine (n=94 905; 18 197 nirmatrelvir and 76 708 no treatment); 0.61 (0.57 to 0.65) and 1.36% (1.19% to 1.53%) in participants with a primary SARS-CoV-2 infection (n=228 081; 26 350 nirmatrelvir and 201 731 no treatment); and 0.74 (0.63 to 0.87) and 0.79% (0.36% to 1.18%) in participants who were reinfected with the SARS-CoV-2 virus (n=28 207; 5174 nirmatrelvir and 23 033 no treatment). Nirmatrelvir was associated with a reduced risk of admission to hospital or death in those aged ≤65 years and > 65 years; in men and women; in black and white participants; in those with 1-2, 3-4, and ≥5 risk factors for progression to severe covid-19 illness; and in those infected during the omicron BA.1 or BA.2 predominant era, and the BA.5 predominant era. Conclusions In people with SARS-CoV-2 infection who were at risk of developing severe disease, compared with no treatment, nirmatrelvir was associated with a reduced risk of admission to hospital or death at 30 days in people who were not vaccinated, vaccinated, and had received a booster vaccine, and in those with a primary SARS-CoV-2 infection and reinfection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nirmatrelvir and risk of hospital admission or death in adults with covid-19: emulation of a randomized target trial using electronic health records

Bowe

Al‐Aly

2023

BMJ

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“…Previous real-world effectiveness studies showed that molnupiravir use was associated with a lower risk of hospitalization in treated patients compared to non-recipients, including studies by Evans et al (HR 0.49), Paraskevis et al (OR 0.40), and Wai et al (OR 0.72) [13, 14, 15]. In a study conducted among U.S. veterans aged 65 years and older, receipt of molnupiravir was associated with a lower 30-day risk of hospitalization or death (RR 0.67, 95% CI 0.46 to 0.99), but the overall result between treated and untreated patients was similar [16].…”

Section: Discussionmentioning

confidence: 99%

Molnupiravir’s real-world effectiveness in COVID-19 non-hospitalized patients at high risk of severe disease: a single-center study

Gmizić¹,

Todorovic²,

Sabanovic³

et al. 2023

Preprint

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ObjectiveTo assess the real-world effectiveness of molnupiravir (MOL) in reducing the need for hospitalization in at-risk, non-hospitalized patients with confirmed COVID-19.MethodsA single-center, non-randomized, observational retrospective study of non-hospitalized patients with confirmed COVID-19 treated at the Clinic for Infectious and Tropical Diseases, University Clinical Center in Belgrade, Serbia.ResultsBetween December 15th, 2021, and February 15th, 2022, 320 patients were eligible for inclusion in the study. Of these, 165 received treatment with molnupiravir (51.6%), while both groups were similar in gender and age distribution. The treatment group had a higher proportion of vaccination (75.2% vs. 51%, p<0.001) but was similar to the control group in terms of multiple comorbidity predomination (65.5% vs. 65.2%, p 0.956). The majority of patients who received MOL didn’t require hospitalization (92.7 vs. 24.5%, p<0.001) and needed oxygen supplementation less frequently than those in the control group (0.6% vs. 31%, p<0.001). During the follow-up period of 12.12±3.5 days, none of the patients on MOL were admitted to the Intensive Care Unit (vs. 10.3%, p<0.001). Molnupiravir significantly reduced the risk of hospitalization by 97.9% (HR 0.021, p<0.001).ConclussionOur study has proven the effectiveness of molnupiravir in preventing hospitalization in a population at risk for developing severe forms of COVID-19.

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“…We read with great interest the recent article published in the Journal of Infection investigating the effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab in preventing hospital admission or death among COVID-19 patients. 1 We noticed that despite the use of broad-spectrum antivirals (e.g. remdesivir), monoclonal antibodies, corticosteroids, hydroxychloroquine 2 being attempted, only limited effectiveness have been shown in reducing mortality, along with financial and logistical limitations, preventing their wide-spread use.…”

mentioning

confidence: 99%

Molnupiravir and nirmatrelvir–ritonavir reduce mortality risk during post-acute COVID-19 phase

Wan

Wang

Mathur

et al. 2023

Journal of Infection

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Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: A retrospective cohort study

Cited by 29 publications

References 20 publications

Nirmatrelvir and risk of hospital admission or death in adults with covid-19: emulation of a randomized target trial using electronic health records

Nirmatrelvir and risk of hospital admission or death in adults with covid-19: emulation of a randomized target trial using electronic health records

Molnupiravir’s real-world effectiveness in COVID-19 non-hospitalized patients at high risk of severe disease: a single-center study

Molnupiravir and nirmatrelvir–ritonavir reduce mortality risk during post-acute COVID-19 phase

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