Evaluation of outpatient treatment for non-hospitalised patients with COVID-19: The experience of a regional centre in the UK
et al., PLOS ONE, doi:10.1371/journal.pone.0281915, Mar 2023
Retrospective 604 outpatients in the UK, showing lower risk of hospitalization with molnupiravir treatment, without statistical significance due to the small number of hospitalizations.
Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-15. Multiple analyses have identified variants potentially created by molnupiravir16-20.
Standard of Care (SOC) for COVID-19 in the study country,
the United Kingdom, is very poor with very low average efficacy for approved treatments21.
The United Kingdom focused on expensive high-profit treatments, approving only one low-cost early treatment, which required a prescription and had limited adoption. The high-cost prescription treatment strategy reduces the probability of early treatment due to access and cost barriers, and eliminates complementary and synergistic benefits seen with many low-cost treatments.
Study covers molnupiravir and sotrovimab.
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risk of death, 110.0% higher, RR 2.10, p = 0.47, treatment 1 of 80 (1.2%), control 2 of 336 (0.6%).
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risk of hospitalization, 58.0% lower, RR 0.42, p = 0.70, treatment 1 of 80 (1.2%), control 10 of 336 (3.0%), NNT 58, COVID-19 related.
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risk of hospitalization, 53.3% lower, RR 0.47, p = 0.39, treatment 2 of 80 (2.5%), control 18 of 336 (5.4%), NNT 35, all cause.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
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Zhou et al., β-D-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells, The Journal of Infectious Diseases, doi:10.1093/infdis/jiab247.
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Chamod et al., Molnupiravir Metabolite--N4-hydroxycytidine Causes Cytotoxicity and DNA Damage in Mammalian Cells in vitro: N4-hydroxycytidine Induced Cytotoxicity DNA Damage, Asian Medical Journal and Alternative Medicine, 23:3, asianmedjam.com/index.php/amjam/article/view/1448.
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Standing et al., Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients, Nature Communications, doi:10.1038/s41467-024-45641-0.
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Mori et al., Reactive oxygen species-mediated cytotoxic and DNA-damaging mechanism of N4-hydroxycytidine, a metabolite of the COVID-19 therapeutic drug molnupiravir, Free Radical Research, doi:10.1080/10715762.2025.2469738.
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Goodwin et al., 15 Mar 2023, retrospective, United Kingdom, peer-reviewed, 3 authors, study period 22 December, 2021 - 20 February, 2022.
Contact: amanda.goodwin@nottingham.ac.uk.
Evaluation of outpatient treatment for non-hospitalised patients with COVID-19: The experience of a regional centre in the UK
PLOS ONE, doi:10.1371/journal.pone.0281915
Introduction Antivirals, such as molnupiravir, and SARS-CoV-2 neutralising monoclonal antibodies (nMAbs), such as sotrovimab, reduced the risk of hospitalisation and death in clinical trials of high-risk non-hospitalised patients with Covid-19. However, the real-world benefits of these drugs are unclear.
Aims To evaluate the characteristics and outcomes of high-risk patients referred for outpatient antiviral or nMAb treatment for symptomatic Covid-19.
Methods The records of patients referred to a large UK Covid Medicines Delivery Unit (CMDU) over nine weeks (December 2021-February 2022) were reviewed. Data were collected on demographics, referral indications, vaccination, deprivation, treatment, complications, hospital admission, and mortality.
Results 1820 patients were referred to the CMDU, with 604 (33.2%) suitable for further assessment. 169 patients received sotrovimab, 80 patients received molnupiravir, 70 patients declined treatment, and 266 were ineligible for treatment because of resolving symptoms. There were trends towards higher proportions of female and white patients, lower deprivation scores, and malignancy-or transplant-related indications in the groups receiving treatment compared with untreated patients. Covid-19-related hospitalisations occurred in 1.2% of the treated group and 3.0% of the untreated group indicating a potential treatment effect, however Covid-related hospitalisations were lower than reported in the original clinical trials (2.2% compared with 7-10%).
Conclusion The referral pathways for outpatient treatment of Covid-19 are inefficient, and the UK system may not be serving all groups equitably. Hospitalisation with Covid-19 was rare
References
Bernal, Da Silva, Musungaie, Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients, N Eng J Med, doi:10.1056/NEJMoa2116044
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Chavarot, Melenotte, Amrouche, Early treatment with sotrovimab monoclonal antibody in kidney transplant recipients with Omicron infection, Kidney Int, doi:10.1016/j.kint.2022.04.003
Deng, Heybati, Ba, Differential efficacy and safety of anti-SARS-CoV-2 antibody therapies for the management of COVID-19: a systematic review and network meta-analysis, Infection, doi:10.1007/s15010-022-01825-8
Dhand, Okumura, Wolfe, Sotrovimab for treatment of COVID-19 in solid organ transplant recipients, Transplantation, doi:10.1097/TP.0000000000004136
Gupta, Gonzales-Rojas, Juarez, Early treatment for Covid-19 with SARS-CoV-2 Neutralizing antibody sotrovimab, N Engl J Med, doi:10.1056/NEJMoa2107934
Gupta, Gonzales-Rojas, Juarez, Effect of sotrovimab on hospitalisation or death among high-risk patients with mild to moderate COVID-19: a randomized clinical trial, JAMA, doi:10.1001/jama.2022.2832
Nhs England, Statistical work areas: COVID-19 therapeutics (antivirals, neutralising monoclonal antibodies, and interleukin 6 inhibitors
Scobie, Morris, Quality and inequality: digging deeper
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"abstract": "<jats:sec id=\"sec001\">\n<jats:title>Introduction</jats:title>\n<jats:p>Antivirals, such as molnupiravir, and SARS-CoV-2 neutralising monoclonal antibodies (nMAbs), such as sotrovimab, reduced the risk of hospitalisation and death in clinical trials of high-risk non-hospitalised patients with Covid-19. However, the real-world benefits of these drugs are unclear.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Aims</jats:title>\n<jats:p>To evaluate the characteristics and outcomes of high-risk patients referred for outpatient antiviral or nMAb treatment for symptomatic Covid-19.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods</jats:title>\n<jats:p>The records of patients referred to a large UK Covid Medicines Delivery Unit (CMDU) over nine weeks (December 2021-February 2022) were reviewed. Data were collected on demographics, referral indications, vaccination, deprivation, treatment, complications, hospital admission, and mortality.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results</jats:title>\n<jats:p>1820 patients were referred to the CMDU, with 604 (33.2%) suitable for further assessment. 169 patients received sotrovimab, 80 patients received molnupiravir, 70 patients declined treatment, and 266 were ineligible for treatment because of resolving symptoms. There were trends towards higher proportions of female and white patients, lower deprivation scores, and malignancy- or transplant-related indications in the groups receiving treatment compared with untreated patients. Covid-19-related hospitalisations occurred in 1.2% of the treated group and 3.0% of the untreated group indicating a potential treatment effect, however Covid-related hospitalisations were lower than reported in the original clinical trials (2.2% compared with 7–10%).</jats:p>\n</jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion</jats:title>\n<jats:p>The referral pathways for outpatient treatment of Covid-19 are inefficient, and the UK system may not be serving all groups equitably. Hospitalisation with Covid-19 was rare regardless of treatment. Ongoing service evaluation is required to ensure efficient use of resources for the outpatient management of Covid-19.</jats:p>\n</jats:sec>",
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