Safety of oral Molnupiravir administration for hospitalized elderly COVID-19 patients aged 80 years old or older

Safety of oral Molnupiravir administration for hospitalized elderly COVID-19 patients aged 80 years old or older | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Safety of oral Molnupiravir administration for hospitalized elderly COVID-19 patients aged 80 years old or older Kenji Gonda, Kouichi Suzuki, Koji Kono, Seiichi Takenoshita This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2022293/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: The number of elderly people with coronavirus disease 2019 (COVID-19) is increasing. To reduce the risk of progression of COVID-19, Molnupiravir, an oral small molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2, was administered. The targets of administration were 29 elderly people aged over 80 years old (median 87 years old, range 80-100). We evaluated the efficacy and safety of treatment with Molnupiravir; oral administration was started within 24 hours after the onset of signs or symptoms in hospitalized elderly patients with at least one confirmed risk factor for severe COVID-19.Molnupiravir (800 mg) was administered twice daily for 5 days. Results: There were no deaths within 28 days, and the treatment was effective. Adverse events occurred in only 55% of the target patients within 7 days after oral administration, but only nausea was observed, and no serious side effects were observed; thus, the drug could be safely administered to elderly patients. Early treatment with Molnupiravir reduced the risk of death in elderly individuals at risk for COVID-19. TRN: ISRCTN79981540, Registration date: 15/07/2022 Covid-19 100 years old Molnupiravir Figures Figure 1 Introduction The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 530 million confirmed cases and more than 6.2 million deaths around the world [ 1 ]. In particular, elderly inpatients infected with COVID-19 in the hospital need to start treatment as soon as possible to reduce the risk of progression after the onset of symptoms, and easy-to-administer antiviral therapy is desirable. Molnupiravir is a small molecule ribonucleoside prodrug of N-hydroxycytidine (NHC), and after oral administration, NHC circulates systemically and is phosphorylated into NHC triphosphate in cells. NHC triphosphate is incorporated into viral ribonucleic acid (RNA) by viral RNA polymerase and then induces viral polymerase to erroneously incorporate either guanosine or adenosine during viral replication. This results in harmful errors throughout the virus genome, ultimately making the virus noninfectious and incapable of replicating [ 2 ]. Oral Molnupiravir has been found to be effective in the treatment of COVID-19 if it is initiated within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults who were at risk of progression to serious disease, without obvious safety concerns [ 3 ]. We evaluated the efficacy and safety of the oral administration of Molnupiravir for hospitalized elderly patients. Methods The subjects were 29 elderly people over 80 years of age (median 87 years old, range 80–100) (Table 1 ). Polymerase chain reaction (PCR) tests were performed using the Applied Biosystems™ QuantStudio Real-Time PCR Systems Product (Code. 15731248), and cycle threshold (Ct) values were measured as an infectivity assessment [ 4 ]. On the first day a patient and/or their roommate had a fever, nasopharyngeal swab samples were collected, and SARS-CoV-2 RNA quantification by PCR and baseline virus genotyping using next-generation sequencing were performed in the central laboratory. Hospitalization conditions and vital sign evaluations, clinical examinations and physical examinations were also conducted on the first day of fever. In the analysis of the pharyngeal samples, SARS-CoV-2 delta, gamma, and mu variants could not be identified. Within 24 hours after the onset of signs or symptoms, 800 mg of Molnupiravir was administered as four 200 mg capsules twice daily for 5 days [ 5 , 6 ]. The follow-up observation period was 28 days during the treatment period and after the end of the treatment period. The mortality rate was evaluated as a measure of efficacy, and the adverse event incidence rate was evaluated as a measure of safety. In addition, the possibility of drug-induced liver injury was evaluated according to changes in platelet levels and liver enzymes. Target elderly patients had at least one on the following risk factors according to the guidance of Food and Drug Administration and World Health Organization (WHO): age > 60 years, active cancer, chronic kidney disease, chronic obstructive pulmonary disease, obesity defined by a body mass index (the weight in kilograms divided by the square of the height in meters) ≥ 30, serious heart conditions (heart failure, coronary artery disease, or cardiomyopathies), and diabetes mellitus. Patients undergoing dialysis, patients with an estimated glomerular filtration rate of 30 ml/minute/1.73 m 2 or less, pregnant patients, neutropenia patients (neutrophil count of < 500/ml), patients with a platelet count < 100,000/microliter, patients with monoclonal antibodies, and patients using remdesivir were excluded. Standard-of-care treatment with antipyretic agents, anti-inflammatory agents, glucocorticoids or a combination thereof was allowed. Table 1 Clinical characteristics of the patients Characteristic Molnupiravir (N = 29) Female - no. (%) 12 (41) Male - no. (%) 17 (59) Age group - no. (%) 80–90 years 23 (79) 91 60 years 25 (86) Diabetes mellitus 5 (17) Serious heart condition 13 (45) Chronic kidney disease 4 (14) Chronic obstructive pulmonary disease 5 (17) Active cancer 1 4 (14) Others bone fracture 13 (45) artificial joint replacement 5 (17) cerebral infarction, encephalorrhagia 10 (34) tube feeding 6 (21) disuse atrophy 21 (72) Vaccination 2 11 (38) Ct value 21 (72) 1 colon cancer, prostate cancer, lung cancer, lymphoma 2 More than one year had passed since vaccination Results The target patients who had quantifiable RNAs in the nasopharyngeal sample took Molnupiravir orally for 5 days according to the standard protocol. Fever is one of the most common symptoms of COVID-19. However, people with COVID-19 sometimes have a low-grade fever or no fever at all. In general, a fever is a temperature of above 100.4°F (38°C) ([℃(Celsius)×1.8] + 32=℉[Fahrenheit]). Patients were grouped according to the presence of a fever of 38 ℃ one time (Group A), two times (Group B), and three or more times (Group C) at 10 days after oral administration (Fig. 1 ). There were no significant differences in the Ct values of the A group, the B group, or the C group. However, there were differences in symptoms during and after oral administration (Table 2 ). No deaths were observed during the observation period. No exacerbation of the risk factor was observed in patients with at least one risk factor. Compared to before administration, there was no myelosuppression, such as thrombocytopenia, during the observation after administration, and no hepatic dysfunction or renal dysfunction was observed. No significant changes in blood pressure or pulse were observed. Patients in the A group had a fever of 38 ℃ or higher that was then reduced to 36 ℃ or lower and did not had a subsequent fever. Nausea and anaphylaxis were observed in 1 patient, each occurring within 14 days after the start of oral administration. Two patients experienced substantial disturbances: one had hypoglycemic symptoms, and one tube-fed patient required sputum aspiration for 12 days but improved with the use of antiemetics and antihistamines. Two patients with tube feeding resumed rehabilitation without any adverse events. Patients in the B Group had a fever of 38 ℃ or higher that then decreased to 36 ℃ or lower and had only one fever of 38℃ or higher during the 10 days after administration. No fever occurred after the administration of acetaminophen. During oral administration, one patient developed nausea, and another developed vomiting. It improved with the use of antiemetics. In the 14 days after the start of oral administration, 2 people discharged a large amount of sputum, and suction was needed. One of them was a patient who experienced vomiting. Aspiration was suspected. Two patients had poor appetites, and one had nausea. In addition to these patients, one patient had an SaO2 (Arterial oxygen saturation) of 90% or less and required oxygen administration (0.5-1 L/min). No increase in white blood cells (WBCs) or C-reactive protein (CRP) was observed. X-ray examinations and computerized tomography (CT) scan examinations could not be performed due to the spread of infection. After administration, one tube-fed patient could eat without fever and resumed rehabilitation without accidents. Patients in the C group had a fever of 38 ℃ or higher that then decreased to 36 degrees or lower and also had a fever of 38 ℃ or higher two or more times within 10 days. No fever occurred after the administration of acetaminophen. However, symptoms were noted in seven patients who did not have a fever. 1. During oral administration, one person felt dizzy, but no numbness, paralysis, nystagmus, or pupil abnormalities were observed in the extremities, and their condition improved without medication. 2. During oral administration, one person had headaches, which improved with the use of acetaminophen. The CT scan showed no abnormalities. 3. One patient had diarrhea after the oral administration but they improved without antidiarrheal or other drugs to relieve intestinal ailments. 4. One of the two patients with diarrhea, experienced nausea during administration, discharged a large amount of sputum, and was given oxygen. The patient was unable to eat orally but improved with a one-week-long infusion and regained the ability to eat orally. 5. One patient with chronic obstructive pulmonary disease discharged more sputum after infection and was given oxygen. After dosing, nausea and vomiting were observed but improved with the use of antiemetics. However, the patient developed difficulty eating and received nutrition from a nasogastric tube. 6. One patient with chronic interstitial pneumonia had a large discharge of sputum during the oral administration and was given oxygen. This patient then vomited and developed difficulty eating and was fed from a nasogastric tube. 7. One patient had melena during oral administration, but there was a possibility of colorectal cancer, and a colonoscopic examination was planned. Table 2 Incidence of Adverse Events Patients over 80 years (n = 29) < 5 d 1 < 7 d < 14 d < 21 d < 28 d Actual number of patients A (n = 13) nausea 0 1 0 0 0 1 anaphylaxis 0 1 0 0 0 1 with facial rash disturbance 1 1 0 0 0 2 with disturbances IGT 2 1 0 0 0 0 1 with hypoglycemia sputum 1 1 1 0 0 1 with sputum suction B (n = 9) nausea 1 0 0 0 0 1 vomiting 1 0 0 0 0 1 substantial amount of sputum 2 1 0 0 0 2 with sputum suction poor appetite 1 2 1 0 0 2 with difficulty eating hypoxia 1 1 0 0 0 1 with oxygen administration C (n = 7) feeling dizzy 1 0 0 0 0 1 headaches 1 0 0 0 0 1 diarrhea 1 1 0 0 0 2 with diarrhea nausea 1 1 0 0 0 2 with nausea vomiting 0 2 0 0 0 2 with vomiting substantial amount of sputum 3 3 3 1 0 3 with sputum suction inedia 0 3 2 2 2 2 with tube feeding management hypoxia 3 3 3 2 2 3 with oxygen administration melena 1 0 0 0 0 1 1 d: days 2 IGT: impaired glucose tolerance In the 14 days after the start of administration, 3 patients discharged a large amount of sputum, and suction was needed. Two of them were patients who experienced vomiting and aspiration was suspected. These two patients became unable to eat orally due to difficulty swallowing and underwent tube feeding management. At the same time, swallowing training was conducted, and as a result, the patients were able to eat. Oxygen was administered (1–3 L/min) to 3 patients who had an SaO2 of 87% or lower. Two of them were patients who required sputum aspiration. These two patients had elevated WBC and CRP levels, had a history of sepsis, suspected bacterial pneumonia, received a loxoprofen antipyretic, and were administered meropenem antibiotics for improvement. One patient ended oxygen administration, and the other continued to receive oxygen due to a history of brainstem infarction. One patient had a history of interstitial pneumonia, which was improved by steroid administration for 3 days, and the oxygen dose was reduced (0.5-1 L/min). They had an SaO2 of 95% or higher. If it worsened, we planned to manage the ventilator considering the need for endotracheal intubation. Rehabilitation was resumed for all patients except for these 3 patients. Discussion Okinawa Prefecture is located in the southernmost part of Japan and is known as a prefecture with a population longevity of over 90 years [ 7 ]. At this stage, the number of COVID-19-infected people per 100,000 people in Okinawa Prefecture is the worst among all prefectures in Japan. There are many healthy elderly people in Okinawa Prefecture, but there are also many elderly people who are being treated in hospitals. This hospital is a rehabilitation facility for elderly individuals, and it is required to help these patients maintain good health and return to home by rehabilitation. This time, 30 nosocomial infections occurred in 60 wards. It was necessary to reduce the risk of death due to infection death for elderly patients in the same ward and to return them to early rehabilitation. Focusing on elderly patients who are most likely to require antiviral treatment, a more rapid evaluation of the therapeutic effect of oral Molnupiravir in elderly patients is needed. In addition, due to the explosive pandemic, detention at the core hospital could not be maintained, and transfer and treatment requests were restricted, so in-hospital treatment was indispensable. Certainly, vaccination is effective. In the A group, more than 1 year ago, 4 out of 13 patients were vaccinated 3 or more times, and 2 patients were vaccinated twice. In the B group, 2 out of 9 patients were vaccinated 3 times or more, and 1 patient was vaccinated twice, and in the C group, 1 patient was vaccinated twice. None of them experienced any serious symptoms after infection or after oral administration. The patient who was vaccinated within 3 months was a 90-year-old female patient who was hospitalized in the same ward but was not infected even after being in the same room as the infected person. The clinical symptoms after oral administration shown in Table 2 could not be determined to be a side effect of Molnupiravir; however, in patients with a history of disuse syndrome with cancer and/or interstitial pneumonia, unstable fever was observed, and thus, caution is required for observation and treatment after oral administration. Additionally, thanks to the medication, it was possible to prevent infection of other patients in the ward. Furthermore, at present, this ward accepts infected patients from other wards in the hospital as an infected ward that provide rehabilitation measures, but the administration of Molnupiravir not only improved the patient themselves but also avoided infection for other patients in the same ward. The oral administration of Molnupiravir in elderly individuals aged 80 years and older is effective and is considered to have potentially significant improvements in outcomes because it can prevent patient-to-patient and patient-to-medical personnel transmission. Limitations In this study, our data from elderly people infected with COVID-19 during hospitalization showed that Molnupiravir, which was started within 24 hours after the onset of symptoms, reduced the risk of inpatients of any cause or death by Day 28. It was also shown that Molnupiravir can be safely administered to patients aged 90 to 100 years. However, this sample size was small and, thus, not sufficient to provide solid evidence. Thus, these findings are preliminary and should be supplemented by further studies with a larger number of subjects. Abbreviations COVID-19 coronavirus disease 2019 SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 NHC N-hydroxycytidine RNA ribonucleic acid PCR polymerase chain reaction Ct Cycle threshold ℃ Celsius SaO2 Arterial oxygen saturation WBC white blood cell CRP C-reactive protein CT computerized tomography Declarations Ethics approval and consent to participate Molnupiravir was distributed with the approval of the Ministry of Health, Labor and Welfare of Japan. The medication was approved by the in-hospital clinical trial review committee, ethics committee, and regulatory authorities in accordance with the medical guidelines of the Ministry of Health, Labor and Welfare in Japan. The study was conducted according to the guidelines of the Declaration of Helsinki, and it was registered and approved by the Institutional Review Board of Daido Central Hospital (protocol code number: No.35, June 2022). Written informed consent was obtained from all patients and their families. If serious side effects were observed during oral administration, the administration was stopped immediately. Safety monitoring was performed by the Data Monitoring Committee. Data were collected by the investigators and attending physicians and interpreted by the authors. Data on adverse events were collected until the end of the follow-up observation period, and all patients and their families approved the storage, analysis, utilization, and publication of the data. The authors guarantee the accuracy and integrity of the data and the fidelity of the test protocol. In accordance with the Personal Protection Law, no patient name or family name will be published, and the subject patients will not be tracked or specified in this article. Consent for publication Not applicable. Availability of data and materials The data collected for this study may be available from the corresponding author upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding There was no sponsor. Authors' contributions Study concept and design: KG. Study supervision: KG, KS. Acquisition, analysis, or interpretation of data: KG, KS, KK, ST Drafting of the manuscript: KG. Critical revision of the manuscript for intellectual content: KG, KK, ST. All authors have read and approved the final manuscript. Acknowledgments The authors would also like to thank the Okinawan patients for their participation in this study. This study was part of the Okinawa–Fukushima Obesity Project. Author information Authors and Affiliations Daido Central Hospital, Naha, Okinawa, Japan Kenji Gonda and Kouichi Suzuki Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan Kenji Gonda and Koji Kono Department of Bioregulation and Pharmacological Medicine, Fukushima Medical University, Fukushima, Japan Kenji Gonda and Kouichi Suzuki Department of Drug Research for Astatine-221 Targeted Alfa Therapy, Fukushima Medical University, Fukushima, Japan Kenji Gonda and Seiichi Takenoshita References WHO Coronavirus (COVID-19) Dashboard https://covid19.who.int Merck and Ridgeback’s Investigational Oral Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19 in Positive Interim Analysis of Phase 3 Study. https://www.merck.com/news/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-by-approximately-50-percent-compared-to-placebo-for-patients-with-mild-or-moderat/ Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2022;386(6):509-520. Thermo Fisher Scientific Inc. QuantStudio 5 qPCR System https://www.fishersci.se/shop/products/quantstudio-5-qpcr-system-1/15731248 COVID-19: developing drugs and biological products for treatment or prevention: guidance for industry. Silver Spring, MD: Food and Drug Administration, May 2020 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/covid-19-developing-drugs-and-biological-products-treatment-or-prevention WHO COVID-19 case definitions. Geneva: World Health Organization, December 16, 2020 https://apps.who.int/iris/rest/bitstreams/1322790/retrieve Amos Duo. Why do Okinawans live longer: The Secret To Long Life. 2021. https://therealrealreviews.com/why-do-okinawans-live-longer-the-secret-to-long-life/ Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2022293","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":133880893,"identity":"15c7e807-7861-4a82-bfd2-965f632958ca","order_by":0,"name":"Kenji Gonda","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxklEQVRIiWNgGAWjYJACCYYDDHLsDRAOM9FajHkOkKolsecAsY6Sd+89eOPHGZv0HrEzBgw/ahjYzQlpMTxzLtmy50Zabo90jgFjzzEGZssGQlpm5JhJ8Hw4nLsfqIWBt4GB2YCQC0FaJP98+J/OA7LlLzFa5CVyzKR5bhxIAGlhJsoWA54zxtYyZ5INe6TTCg7LHJMg7Bf59h7Dm2+O2cnzSCdvfPimxiaZYIihOAPIlkg2IKRFHt0ZdgS1jIJRMApGwYgDADVuPPU1SOdjAAAAAElFTkSuQmCC","orcid":"","institution":"Daido Central Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Kenji","middleName":"","lastName":"Gonda","suffix":""},{"id":133880894,"identity":"d981836d-b98a-44f3-8721-c5f6f49c193a","order_by":1,"name":"Kouichi Suzuki","email":"","orcid":"","institution":"Daido Central Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kouichi","middleName":"","lastName":"Suzuki","suffix":""},{"id":133880895,"identity":"ac5f4723-5eee-4b8a-9b20-d9361fd1c6e3","order_by":2,"name":"Koji Kono","email":"","orcid":"","institution":"Fukushima Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Koji","middleName":"","lastName":"Kono","suffix":""},{"id":133880896,"identity":"9dfa5ddc-375e-4242-8c2a-553860fe2c91","order_by":3,"name":"Seiichi Takenoshita","email":"","orcid":"","institution":"Fukushima Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Seiichi","middleName":"","lastName":"Takenoshita","suffix":""}],"badges":[],"createdAt":"2022-09-01 14:29:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2022293/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2022293/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":26780346,"identity":"0a1926aa-c73f-4009-b610-cac3356a9f8d","added_by":"auto","created_at":"2022-09-21 18:12:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":189857,"visible":true,"origin":"","legend":"\u003cp\u003eThe patient's thermal form was divided into three types of waveforms.\u003c/p\u003e\n\u003cp\u003eWithin 10 days after the start of the oral administration of Molnupiravir, the thermal type was divided into unimodal mountain peaks (Group A (a) 88 years, male, (b) 100 years, female), bimodal mountain peaks (Group B (a) 87 years, male, (b) 86 years, male), and three-peaked mountain peaks (Group C (a) 96 years, female, (b) 85 years, female). ℃: Celsius\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-2022293/v1/c7355731d840e3e0574a4628.png"},{"id":38482901,"identity":"6a09b125-b490-4973-b59b-c5eb97733e43","added_by":"auto","created_at":"2023-06-13 15:44:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":265220,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2022293/v1/166d959f-c11f-45fd-8a93-e88f48e76a5f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Safety of oral Molnupiravir administration for hospitalized elderly COVID-19 patients aged 80 years old or older","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 530\u0026nbsp;million confirmed cases and more than 6.2\u0026nbsp;million deaths around the world [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In particular, elderly inpatients infected with COVID-19 in the hospital need to start treatment as soon as possible to reduce the risk of progression after the onset of symptoms, and easy-to-administer antiviral therapy is desirable. Molnupiravir is a small molecule ribonucleoside prodrug of N-hydroxycytidine (NHC), and after oral administration, NHC circulates systemically and is phosphorylated into NHC triphosphate in cells. NHC triphosphate is incorporated into viral ribonucleic acid (RNA) by viral RNA polymerase and then induces viral polymerase to erroneously incorporate either guanosine or adenosine during viral replication. This results in harmful errors throughout the virus genome, ultimately making the virus noninfectious and incapable of replicating [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Oral Molnupiravir has been found to be effective in the treatment of COVID-19 if it is initiated within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults who were at risk of progression to serious disease, without obvious safety concerns [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. We evaluated the efficacy and safety of the oral administration of Molnupiravir for hospitalized elderly patients.\u003c/p\u003e"},{"header":"Methods ","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003cp\u003eThe subjects were 29 elderly people over 80 years of age (median 87 years old, range 80\u0026ndash;100) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Polymerase chain reaction (PCR) tests were performed using the Applied Biosystems\u0026trade; QuantStudio Real-Time PCR Systems Product (Code. 15731248), and cycle threshold (Ct) values were measured as an infectivity assessment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. On the first day a patient and/or their roommate had a fever, nasopharyngeal swab samples were collected, and SARS-CoV-2 RNA quantification by PCR and baseline virus genotyping using next-generation sequencing were performed in the central laboratory. Hospitalization conditions and vital sign evaluations, clinical examinations and physical examinations were also conducted on the first day of fever. In the analysis of the pharyngeal samples, SARS-CoV-2 delta, gamma, and mu variants could not be identified. Within 24 hours after the onset of signs or symptoms, 800 mg of Molnupiravir was administered as four 200 mg capsules twice daily for 5 days [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The follow-up observation period was 28 days during the treatment period and after the end of the treatment period. The mortality rate was evaluated as a measure of efficacy, and the adverse event incidence rate was evaluated as a measure of safety. In addition, the possibility of drug-induced liver injury was evaluated according to changes in platelet levels and liver enzymes. Target elderly patients had at least one on the following risk factors according to the guidance of Food and Drug Administration and World Health Organization (WHO): age\u0026thinsp;\u0026gt;\u0026thinsp;60 years, active cancer, chronic kidney disease, chronic obstructive pulmonary disease, obesity defined by a body mass index (the weight in kilograms divided by the square of the height in meters)\u0026thinsp;\u0026ge;\u0026thinsp;30, serious heart conditions (heart failure, coronary artery disease, or cardiomyopathies), and diabetes mellitus. Patients undergoing dialysis, patients with an estimated glomerular filtration rate of 30 ml/minute/1.73 m\u003csup\u003e2\u003c/sup\u003e or less, pregnant patients, neutropenia patients (neutrophil count of \u0026lt;\u0026thinsp;500/ml), patients with a platelet count\u0026thinsp;\u0026lt;\u0026thinsp;100,000/microliter, patients with monoclonal antibodies, and patients using remdesivir were excluded. Standard-of-care treatment with antipyretic agents, anti-inflammatory agents, glucocorticoids or a combination thereof was allowed.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of the patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMolnupiravir (N\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale - no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale - no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge group - no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e80\u0026ndash;90 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (79)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e91\u0026thinsp;\u0026lt;\u0026thinsp;years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age (range) - years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87 (80\u0026ndash;100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRisk factors for severe COVID-19 - no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAt least one risk factor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (86)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObesity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026gt;\u0026thinsp;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (86)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerious heart condition\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic kidney disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic obstructive pulmonary disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eActive cancer \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ebone fracture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eartificial joint replacement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecerebral infarction, encephalorrhagia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003etube feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (21)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003edisuse atrophy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaccination \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCt value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e1 colon cancer, prostate cancer, lung cancer, lymphoma\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e2 More than one year had passed since vaccination\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe target patients who had quantifiable RNAs in the nasopharyngeal sample took Molnupiravir orally for 5 days according to the standard protocol. Fever is one of the most common symptoms of COVID-19. However, people with COVID-19 sometimes have a low-grade fever or no fever at all. In general, a fever is a temperature of above 100.4\u0026deg;F (38\u0026deg;C) ([℃(Celsius)\u0026times;1.8]\u0026thinsp;+\u0026thinsp;32=℉[Fahrenheit]). Patients were grouped according to the presence of a fever of 38 ℃ one time (Group A), two times (Group B), and three or more times (Group C) at 10 days after oral administration (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). There were no significant differences in the Ct values of the A group, the B group, or the C group. However, there were differences in symptoms during and after oral administration (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). No deaths were observed during the observation period. No exacerbation of the risk factor was observed in patients with at least one risk factor. Compared to before administration, there was no myelosuppression, such as thrombocytopenia, during the observation after administration, and no hepatic dysfunction or renal dysfunction was observed. No significant changes in blood pressure or pulse were observed. Patients in the A group had a fever of 38 ℃ or higher that was then reduced to 36 ℃ or lower and did not had a subsequent fever. Nausea and anaphylaxis were observed in 1 patient, each occurring within 14 days after the start of oral administration. Two patients experienced substantial disturbances: one had hypoglycemic symptoms, and one tube-fed patient required sputum aspiration for 12 days but improved with the use of antiemetics and antihistamines. Two patients with tube feeding resumed rehabilitation without any adverse events. Patients in the B Group had a fever of 38 ℃ or higher that then decreased to 36 ℃ or lower and had only one fever of 38℃ or higher during the 10 days after administration. No fever occurred after the administration of acetaminophen. During oral administration, one patient developed nausea, and another developed vomiting. It improved with the use of antiemetics. In the 14 days after the start of oral administration, 2 people discharged a large amount of sputum, and suction was needed. One of them was a patient who experienced vomiting. Aspiration was suspected. Two patients had poor appetites, and one had nausea. In addition to these patients, one patient had an SaO2 (Arterial oxygen saturation) of 90% or less and required oxygen administration (0.5-1 L/min). No increase in white blood cells (WBCs) or C-reactive protein (CRP) was observed. X-ray examinations and computerized tomography (CT) scan examinations could not be performed due to the spread of infection. After administration, one tube-fed patient could eat without fever and resumed rehabilitation without accidents. Patients in the C group had a fever of 38 ℃ or higher that then decreased to 36 degrees or lower and also had a fever of 38 ℃ or higher two or more times within 10 days. No fever occurred after the administration of acetaminophen. However, symptoms were noted in seven patients who did not have a fever. 1. During oral administration, one person felt dizzy, but no numbness, paralysis, nystagmus, or pupil abnormalities were observed in the extremities, and their condition improved without medication. 2. During oral administration, one person had headaches, which improved with the use of acetaminophen. The CT scan showed no abnormalities. 3. One patient had diarrhea after the oral administration but they improved without antidiarrheal or other drugs to relieve intestinal ailments. 4. One of the two patients with diarrhea, experienced nausea during administration, discharged a large amount of sputum, and was given oxygen. The patient was unable to eat orally but improved with a one-week-long infusion and regained the ability to eat orally. 5. One patient with chronic obstructive pulmonary disease discharged more sputum after infection and was given oxygen. After dosing, nausea and vomiting were observed but improved with the use of antiemetics. However, the patient developed difficulty eating and received nutrition from a nasogastric tube. 6. One patient with chronic interstitial pneumonia had a large discharge of sputum during the oral administration and was given oxygen. This patient then vomited and developed difficulty eating and was fed from a nasogastric tube. 7. One patient had melena during oral administration, but there was a possibility of colorectal cancer, and a colonoscopic examination was planned.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIncidence of Adverse Events\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients over 80 years (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5 d\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;7 d\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;14 d\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;21 d\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;28 d\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eActual number of patients\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA (n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eanaphylaxis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 with facial rash\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003edisturbance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 with disturbances\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIGT\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 with hypoglycemia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esputum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 with sputum suction\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003evomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esubstantial amount of sputum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 with sputum suction\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epoor appetite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 with difficulty eating\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ehypoxia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 with oxygen administration\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC (n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003efeeling dizzy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eheadaches\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ediarrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 with diarrhea\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 with nausea\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003evomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 with vomiting\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esubstantial amount of sputum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3 with sputum suction\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003einedia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 with tube feeding management\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ehypoxia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3 with oxygen administration\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emelena\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e1 d: days\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e2 IGT: impaired glucose tolerance\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the 14 days after the start of administration, 3 patients discharged a large amount of sputum, and suction was needed. Two of them were patients who experienced vomiting and aspiration was suspected. These two patients became unable to eat orally due to difficulty swallowing and underwent tube feeding management. At the same time, swallowing training was conducted, and as a result, the patients were able to eat. Oxygen was administered (1\u0026ndash;3 L/min) to 3 patients who had an SaO2 of 87% or lower. Two of them were patients who required sputum aspiration. These two patients had elevated WBC and CRP levels, had a history of sepsis, suspected bacterial pneumonia, received a loxoprofen antipyretic, and were administered meropenem antibiotics for improvement. One patient ended oxygen administration, and the other continued to receive oxygen due to a history of brainstem infarction. One patient had a history of interstitial pneumonia, which was improved by steroid administration for 3 days, and the oxygen dose was reduced (0.5-1 L/min). They had an SaO2 of 95% or higher. If it worsened, we planned to manage the ventilator considering the need for endotracheal intubation. Rehabilitation was resumed for all patients except for these 3 patients.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOkinawa Prefecture is located in the southernmost part of Japan and is known as a prefecture with a population longevity of over 90 years [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. At this stage, the number of COVID-19-infected people per 100,000 people in Okinawa Prefecture is the worst among all prefectures in Japan. There are many healthy elderly people in Okinawa Prefecture, but there are also many elderly people who are being treated in hospitals. This hospital is a rehabilitation facility for elderly individuals, and it is required to help these patients maintain good health and return to home by rehabilitation. This time, 30 nosocomial infections occurred in 60 wards. It was necessary to reduce the risk of death due to infection death for elderly patients in the same ward and to return them to early rehabilitation. Focusing on elderly patients who are most likely to require antiviral treatment, a more rapid evaluation of the therapeutic effect of oral Molnupiravir in elderly patients is needed. In addition, due to the explosive pandemic, detention at the core hospital could not be maintained, and transfer and treatment requests were restricted, so in-hospital treatment was indispensable. Certainly, vaccination is effective. In the A group, more than 1 year ago, 4 out of 13 patients were vaccinated 3 or more times, and 2 patients were vaccinated twice. In the B group, 2 out of 9 patients were vaccinated 3 times or more, and 1 patient was vaccinated twice, and in the C group, 1 patient was vaccinated twice. None of them experienced any serious symptoms after infection or after oral administration. The patient who was vaccinated within 3 months was a 90-year-old female patient who was hospitalized in the same ward but was not infected even after being in the same room as the infected person. The clinical symptoms after oral administration shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e could not be determined to be a side effect of Molnupiravir; however, in patients with a history of disuse syndrome with cancer and/or interstitial pneumonia, unstable fever was observed, and thus, caution is required for observation and treatment after oral administration. Additionally, thanks to the medication, it was possible to prevent infection of other patients in the ward. Furthermore, at present, this ward accepts infected patients from other wards in the hospital as an infected ward that provide rehabilitation measures, but the administration of Molnupiravir not only improved the patient themselves but also avoided infection for other patients in the same ward. The oral administration of Molnupiravir in elderly individuals aged 80 years and older is effective and is considered to have potentially significant improvements in outcomes because it can prevent patient-to-patient and patient-to-medical personnel transmission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, our data from elderly people infected with COVID-19 during hospitalization showed that Molnupiravir, which was started within 24 hours after the onset of symptoms, reduced the risk of inpatients of any cause or death by Day 28. It was also shown that Molnupiravir can be safely administered to patients aged 90 to 100 years. However, this sample size was small and, thus, not sufficient to provide solid evidence. Thus, these findings are preliminary and should be supplemented by further studies with a larger number of subjects.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOVID-19\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecoronavirus disease 2019\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSARS-CoV-2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esevere acute respiratory syndrome coronavirus 2\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNHC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eN-hydroxycytidine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRNA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eribonucleic acid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epolymerase chain reaction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCt\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCycle threshold\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e℃\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCelsius\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSaO2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eArterial oxygen saturation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ewhite blood cell\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eC-reactive protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecomputerized tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eMolnupiravir was distributed with the approval of the Ministry of Health, Labor and Welfare of Japan. The medication was approved by the in-hospital clinical trial review committee, ethics committee, and regulatory authorities in accordance with the medical guidelines of the Ministry of Health, Labor and Welfare in Japan. The study was conducted according to the guidelines of the Declaration of Helsinki, and it was registered and approved by the Institutional Review Board of Daido Central Hospital (protocol code number: No.35, June 2022). Written informed consent was obtained from all patients and their families. If serious side effects were observed during oral administration, the administration was stopped immediately. Safety monitoring was performed by the Data Monitoring Committee. Data were collected by the investigators and attending physicians and interpreted by the authors. Data on adverse events were collected until the end of the follow-up observation period, and all patients and their families approved the storage, analysis, utilization, and publication of the data. The authors guarantee the accuracy and integrity of the data and the fidelity of the test protocol. In accordance with the Personal Protection Law, no patient name or family name will be published, and the subject patients will not be tracked or specified in this article.\u003c/p\u003e\n\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\n\u003cp\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe data collected for this study may be available from the corresponding author upon reasonable request.\u003c/p\u003e\n\n\u003cp\u003e\u003cem\u003eCompeting interests \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThere was no sponsor.\u003c/p\u003e\n\n\u003cp\u003e\u003cem\u003eAuthors\u0026apos; contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eStudy concept and design: KG. Study supervision: KG, KS. Acquisition, analysis, or interpretation of data: KG, KS, KK, ST Drafting of the manuscript: KG. Critical revision of the manuscript for intellectual content: KG, KK, ST. All authors have read and approved the final manuscript.\u003c/p\u003e\n\n\u003cp\u003e\u003cem\u003eAcknowledgments\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would also like to thank the Okinawan patients for their participation in this study. This study was part of the Okinawa\u0026ndash;Fukushima Obesity Project.\u003c/p\u003e\n\n\u003cp\u003e\u003cem\u003eAuthor information\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAuthors and Affiliations\u003c/p\u003e\n\u003cp\u003eDaido Central Hospital, Naha, Okinawa, Japan\u003c/p\u003e\n\u003cp\u003eKenji Gonda and Kouichi Suzuki\u003c/p\u003e\n\u003cp\u003eDepartment of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan\u003c/p\u003e\n\u003cp\u003eKenji Gonda and Koji Kono\u003c/p\u003e\n\u003cp\u003eDepartment of Bioregulation and Pharmacological Medicine, Fukushima Medical University, Fukushima, Japan\u003c/p\u003e\n\u003cp\u003eKenji Gonda and Kouichi Suzuki\u003c/p\u003e\n\u003cp\u003eDepartment of Drug Research for Astatine-221 Targeted Alfa Therapy, Fukushima Medical University, Fukushima, Japan\u003c/p\u003e\n\u003cp\u003eKenji Gonda and Seiichi Takenoshita\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWHO Coronavirus (COVID-19) Dashboard https://covid19.who.int\u003c/li\u003e\n\u003cli\u003eMerck and Ridgeback\u0026rsquo;s Investigational Oral Antiviral Molnupiravir Reduced the Risk of Hospitalization or Death by Approximately 50 Percent Compared to Placebo for Patients with Mild or Moderate COVID-19 in Positive Interim Analysis of Phase 3 Study. https://www.merck.com/news/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-by-approximately-50-percent-compared-to-placebo-for-patients-with-mild-or-moderat/\u003c/li\u003e\n\u003cli\u003eJayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2022;386(6):509-520.\u003c/li\u003e\n\u003cli\u003eThermo Fisher Scientific Inc. QuantStudio 5 qPCR System https://www.fishersci.se/shop/products/quantstudio-5-qpcr-system-1/15731248\u003c/li\u003e\n\u003cli\u003eCOVID-19: developing drugs and biological products for treatment or prevention: guidance for industry. Silver Spring, MD: Food and Drug Administration, May 2020 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/covid-19-developing-drugs-and-biological-products-treatment-or-prevention\u003c/li\u003e\n\u003cli\u003eWHO COVID-19 case definitions. Geneva: World Health Organization, December 16, 2020 https://apps.who.int/iris/rest/bitstreams/1322790/retrieve\u003c/li\u003e\n\u003cli\u003eAmos Duo. Why do Okinawans live longer: The Secret To Long Life. 2021. https://therealrealreviews.com/why-do-okinawans-live-longer-the-secret-to-long-life/\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Covid-19, 100 years old, Molnupiravir","lastPublishedDoi":"10.21203/rs.3.rs-2022293/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2022293/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e The number of elderly people with coronavirus disease 2019 (COVID-19) is increasing. To reduce the risk of progression of COVID-19, Molnupiravir, an oral small molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2, was administered. The targets of administration were 29 elderly people aged over 80 years old (median 87 years old, range 80-100). We evaluated the efficacy and safety of treatment with Molnupiravir; oral administration was started within 24 hours after the onset of signs or symptoms in hospitalized elderly patients with at least one confirmed risk factor for severe COVID-19.Molnupiravir (800 mg) was administered twice daily for 5 days.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e There were no deaths within 28 days, and the treatment was effective. Adverse events occurred in only 55% of the target patients within 7 days after oral administration, but only nausea was observed, and no serious side effects were observed; thus, the drug could be safely administered to elderly patients. Early treatment with Molnupiravir reduced the risk of death in elderly individuals at risk for COVID-19.\u003c/p\u003e\n\u003cp\u003eTRN: ISRCTN79981540, Registration date: 15/07/2022\u003c/p\u003e","manuscriptTitle":"Safety of oral Molnupiravir administration for hospitalized elderly COVID-19 patients aged 80 years old or older","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-09-21 18:12:13","doi":"10.21203/rs.3.rs-2022293/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"282f1d59-af3e-4528-a1f5-0ce6caede813","owner":[],"postedDate":"September 21st, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-06-13T15:44:17+00:00","versionOfRecord":[],"versionCreatedAt":"2022-09-21 18:12:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2022293","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2022293","identity":"rs-2022293","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}