Differences in COVID-19 Outpatient Antiviral Treatment Among Adults Aged ≥65 Years by Age Group — National Patient-Centered Clinical Research Network, United States, April 2022–September 2023

Quinlan et al., MMWR. Morbidity and Mortality Weekly Report, doi:10.15585/mmwr.mm7339a3

Oct 2024

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Retrospective 393,390 COVID-19 patients aged ≥65 years showing underutilization of antiviral treatment, with lower use for older patients at higher risk for severe outcomes.

Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-10. Multiple analyses have identified variants potentially created by molnupiravir11-15.

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Study covers molnupiravir and paxlovid.

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2. Hadj Hassine et al., Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity, Viruses, doi:10.3390/v14040841.mdpi.com, doi.org.

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5. Zibat et al., N4-hydroxycytidine, the active compound of Molnupiravir, promotes SARS-CoV-2 mutagenesis and escape from a neutralizing nanobody, iScience, doi:10.1016/j.isci.2023.107786.sciencedirect.com, doi.org.

6. Shiraki et al., Convenient screening of the reproductive toxicity of favipiravir and antiviral drugs in Caenorhabditis elegans, Heliyon, doi:10.1016/j.heliyon.2024.e35331.sciencedirect.com, doi.org.

7. Gruber et al., Molnupiravir increases SARS‐CoV‐2 genome diversity and complexity: A case‐control cohort study, Journal of Medical Virology, doi:10.1002/jmv.29642.wiley.com, doi.org.

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9. 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.oup.com, doi.org.

10. 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.asianmedjam.com.

11. Focosi et al., The fitness of molnupiravir-signed SARS-CoV-2 variants: imputation analysis based on prescription counts and GISAID analyses by country, Intervirology, doi:10.1159/000540282.karger.com, doi.org.

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Quinlan et al., 3 Oct 2024, retrospective, USA, peer-reviewed, 17 authors, study period April 2022 - September 2023.

This Paper Molnupiravir All

Differences in COVID-19 Outpatient Antiviral Treatment Among Adults Aged ≥65 Years by Age Group -National Patient-Centered Clinical Research Network, United States

MD Claire M Quinlan, MD Melisa M Shah, MPH Carol E Desantis, MD ; J Bradford Bertumen, Christine Draper, ; Faraz, MD S Ahmad, MD Jonathan Arnold, MD Kenneth H Mayer, PhD Thomas W Carton, PhD Lindsay G Cowell, Samantha Smith, PhD Sharon Saydah, MD Jefferson M Jones, MD Pragna Patel, MD Melissa Briggs Hagen, MD Jason Block, MD Emily H Koumans

Adults aged ≥65 years experience the highest risk for COVID-19-related hospitalization and death, with risk increasing with increasing age; outpatient antiviral treatment reduces the risk for these severe outcomes. Despite the proven benefit of COVID-19 antiviral treatment, information on differences in use among older adults with COVID-19 by age group is limited. Nonhospitalized patients aged ≥65 years with COVID-19 during April 2022-September 2023 were identified from the National Patient-Centered Clinical Research Network. Differences in use of antiviral treatment among patients aged 65-74, 75-89, and ≥90 years were assessed. Multivariable logistic regression was used to estimate the association between age and nonreceipt of antiviral treatment. Among 393,390 persons aged ≥65 years, 45.9% received outpatient COVID-19 antivirals, including 48.4%, 43.5%, and 35.2% among those aged 65-75, 76-89, and ≥90 years, respectively. Patients aged 75-89 and ≥90 years had 1.17 (95% CI = 1.15-1.19) and 1.54 (95% CI = 1.49-1.61) times the adjusted odds of being untreated, respectively, compared with those aged 65-74 years. Among 12,543 patients with severe outcomes, 2,648 (21.1%) had received an outpatient COVID-19 antiviral medication, compared with 177,874 (46.7%) of 380,847 patients without severe outcomes. Antiviral use is underutilized among adults ≥65 years; the oldest adults are least likely to receive treatment. To prevent COVID-19-associated morbidity and mortality, increased use of COVID-19 antiviral medications among older adults is needed. * PCORnet is a national network that facilitates access to health care data and interoperability through the use of a common data model across participating health care systems. The PCORnet Common Data Model includes demographic characteristics, diagnoses, prescriptions, procedures, and laboratory test results, among other inpatient and outpatient elements, from approximately 30 million patients. https://pcornet.org/data † LOINC is a code system that includes identifiers, names, and codes for clinical and laboratory observations, health care screening instruments, and document types. https://loinc.org § https://www.cdc.gov/nchs/icd/icd-10-cm/files.html ¶ Nirmatrelvir-ritonavir and molnupiravir are taken orally; remdesivir and monoclonal antibodies are administered intravenously. The only monoclonal antibody available for outpatient treatment during the study period was bebtelovimab. However, on November 30, 2022, the Food and Drug Administration announced that bebtelovimab was not authorized because it was not expected to neutralize the variants in circulation at that time.

found that prevalence of receipt of antivirals decreased progressively and substantially with increasing age in persons aged 65 to ≥90 years, after controlling for the number of underlying medical conditions and other demographic factors. Several real-world studies, including those conducted since the emergence of SARS-CoV-2 Omicron variant in January 2022, have demonstrated that COVID-19 antivirals are effective in preventing hospitalization and death (3). Because older age is a strong risk factor for severe COVID-19-associated outcomes, and COVID-19 hospitalizations continue to disproportionately affect older patients (1-4), treatment of COVID-19, including cases in older adults, is critical to the prevention of severe outcomes. Among older patients, frequent self-reported reasons for nonuse of antivirals include the presence of mild signs and symptoms, lack of awareness of eligibility, and absence of a provider recommendation (8) . Other potential barriers to treatment among older patients include delays in seeking treatment after symptom onset and missing the treatment window (5-7 days after symptom onset) (8) . Challenges to COVID-19 antiviral use include obtaining testing (9) , acquiring an antiviral prescription after receiving a positive SARS-CoV-2 test result, and accessing treatment, with each step potentially requiring a separate visit to a health care facility. Older age is associated with increasing numbers of comorbidities and potentially related medications,..

References

Ahmad, Cisewski, Xu, Anderson, COVID-19 mortality update-United States, 2022, MMWR Morb Mortal Wkly Rep, doi:10.15585/mmwr.mm7218a4

Benchimol-Elkaim, Dryden-Peterson, Miller, Koh, Geller, Oral antiviral therapy utilization among adults with recent COVID-19 in the United States, J Gen Intern Med, doi:10.1007/s11606-023-08106-6

Boehmer, Koumans, Skillen, Racial and ethnic disparities in outpatient treatment of COVID-19-United States, January-July 2022, MMWR Morb Mortal Wkly Rep, doi:10.15585/mmwr.mm7143a2

Dryden-Peterson, Kim, Kim, Nirmatrelvir plus ritonavir for early COVID-19 in a large US health system: a population-based cohort study, Ann Intern Med, doi:10.7326/M22-2141

Smith, Lambrou, Patel, SARS-CoV-2 rebound with and without use of COVID-19 oral antivirals, MMWR Morb Mortal Wkly Rep, doi:10.15585/mmwr.mm7251a1

Sun, Hua, Qiu, Brown, Determinants of COVID-19 testing among late middle-aged and older adults: applying the health belief model, Aging Health Res, doi:10.1016/j.ahr.2022.100066

Sun, Rogers, Her, Adaptation and validation of the combined comorbidity score for ICD-10-CM, Med Care, doi:10.1097/MLR.0000000000000824

Taylor, Patel, Pham, COVID-19-associated hospitalizations among U.S. adults aged ≥18 years-COVID-NET, 12 states, October 2023, MMWR Morb Mortal Wkly Rep

Wilcock, Kissler, Mehrotra, Clinical risk and outpatient therapy utilization for COVID-19 in the Medicare population, JAMA Health Forum, doi:10.1001/jamahealthforum.2023.5044

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