BACKGROUND: Data regarding the importance of multidimensional frailty to guide clinical decision making for remdesivir use in older patients with coronavirus disease 2019 (COVID-19) are largely unexplored. OBJECTIVE: The aim of this research was to evaluate if the Multidimensional Prognostic Index (MPI), a multidimensional frailty tool based on the Comprehensive Geriatric Assessment (CGA), may help physicians in identifying older hospitalized patients affected by COVID-19 who might benefit from the use of remdesivir. METHODS: This was a multicenter, prospective study of older adults hospitalized for COVID-19 in 10 European hospitals, followed-up for 90 days after hospital discharge. A standardized CGA was performed at hospital admission and the MPI was calculated, with a final score ranging between 0 (lowest mortality risk) and 1 (highest mortality risk). We assessed survival with Cox regression, and the impact of remdesivir on mortality (overall and in hospital) with propensity score analysis, stratified by MPI = 0.50. RESULTS: Among 496 older adults hospitalized for COVID-19 (mean age 80 years, female 59.9%), 140 (28.2% of patients) were treated with remdesivir. During the 90 days of follow-up, 175 deaths were reported, 115 in hospital. Remdesivir treatment significantly reduced the risk of overall mortality (hazard ratio [HR] 0.54, 95% confidence interval CI 0.35-0.83 in the propensity score analysis) in the sample as whole. Stratifying the population, based on MPI score, the effect was observed only in less frail participants (HR 0.47, 95% CI 0.22-0.96 in propensity score analysis), but not in frailer subjects. In-hospital mortality was not influenced by remdesivir use. CONCLUSIONS: MPI could help to identify less frail older adults hospitalized for COVID-19 who could benefit more from remdesivir treatment in terms of long-term survival.

Ageing Clinical Research Department 2 of Internal Medicine and Center for Molecular Medicine University of Cologne Cologne Germany

Department of Geriatric Care Orthogeriatrics and Rehabilitation Galliera Hospital Genoa Italy

Department of Geriatrics 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Interdisciplinary Medicine University of Bari Aldo Moro Bari Italy

Division of Geriatrics University Medical Center Goettingen Goettingen Germany

Faculty of Health and Social Sciences University of South Bohemia Ceske Budejovice Czech Republic

Geriatric Unit Department of Internal Medicine and Geriatrics University of Palermo via del Vespro 141 90127 Palermo Italy

Geriatrics Unit Mater Salutis Hospital Legnago ULSS 9 Scaligera Verona Italy

Geriatrics Unit Pugliese Ciaccio Hospital Catanzaro Italy

Infectious Disease Unit Sanremo Hospital ASL 1 Imperiese Sanremo Italy

Klinikum Oldenburg AöR Oldenburg University Oldenburg Germany

Neurology Unit Department of Clinical and Experimental Sciences University of Brescia Brescia Italy

Servicio de Geriatría Hospital Universitario Ramón y Cajal Madrid Spain

Serviço de Medicina Interna Hospital Curry Cabral Centro Hospitalar Universitário Lisboa Central Universidade Nova de Lisboa Lisbon Portugal

Zobrazit více v PubMed

National Center for Health Statistics. Provisional COVID-19 deaths by sex and age. 2022. https://data.cdc.gov/d/9bhg-hcku. Cited 2 Dec 2022.

Yao TT, Qian JD, Zhu WY, Wang Y, Wang GQ. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus—a possible reference for coronavirus disease-19 treatment option. J Med Virol. 2020;92(6):556–563. doi: 10.1002/jmv.25729. PubMed DOI PMC

Kokic G, Hillen HS, Tegunov D, Dienemann C, Seitz F, Schmitzova J, et al. Mechanism of SARS-CoV-2 polymerase stalling by remdesivir. Nat Commun. 2021;12(1):1–7. doi: 10.1038/s41467-020-20542-0. PubMed DOI PMC

Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the treatment of covid-19—final report. N Engl J Med. 2020;383(19):1813–1826. doi: 10.1056/NEJMoa2007764. PubMed DOI PMC

Consortium WHOST, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, et al. Repurposed antiviral drugs for covid-19—interim WHO solidarity trial results. N Engl J Med. 2021;384(6):497–511. PubMed PMC

Young B, Tan TT, Leo YS. The place for remdesivir in COVID-19 treatment. Lancet Infect Dis. 2021;21(1):20–21. doi: 10.1016/S1473-3099(20)30911-7. PubMed DOI PMC

Ansems K, Grundeis F, Dahms K, Mikolajewska A, Thieme V, Piechotta V, et al. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2021;8(8):CD014962. PubMed PMC

Therapeutics and COVID-19: living guideline, 16 September 2022. 2022. WHO/2019-nCoV/therapeutics/2022.5.

Pilotto A, Custodero C, Maggi S, Polidori MC, Veronese N, Ferrucci L. A multidimensional approach to frailty in older people. Ageing Res Rev. 2020;60:101047. doi: 10.1016/j.arr.2020.101047. PubMed DOI PMC

Heyns A, Dupont J, Gielen E, Flamaing J, Peers K, Gosselink R, et al. Impact of COVID-19: urging a need for multi-domain assessment of COVID-19 inpatients. Eur Geriatr Med. 2021;12(4):741–748. doi: 10.1007/s41999-021-00486-4. PubMed DOI PMC

Pilotto A, Azzini M, Cella A, Cenderello G, Castagna A, Pilotto A, et al. The multidimensional prognostic index (MPI) for the prognostic stratification of older inpatients with COVID-19: a multicenter prospective observational cohort study. Arch Gerontol Geriatr. 2021;95:104415. doi: 10.1016/j.archger.2021.104415. PubMed DOI PMC

Pilotto A, Topinkova E, Michalkova H, Polidori MC, Cella A, Cruz-Jentoft A, et al. Can the multidimensional prognostic index improve the identification of older hospitalized patients with COVID-19 likely to benefit from mechanical ventilation? An observational, prospective, multicenter study. J Am Med Dir Assoc. 2022;23(9):1608.e1–e8. doi: 10.1016/j.jamda.2022.06.023. PubMed DOI PMC

Agarwal A, Rochwerg B, Lamontagne F, Siemieniuk RA, Agoritsas T, Askie L, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020;370:m3379. PubMed

von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guildelines for reporting observational studies. J Clin Epidemiol. 2008;61(4):344–349. doi: 10.1016/j.jclinepi.2007.11.008. PubMed DOI

Cavaleri M, Sweeney F, Gonzalez-Quevedo R, Carr M. Shaping EU medicines regulation in the post COVID-19 era. Lancet Reg Health Europe. 2021;9:100192. doi: 10.1016/j.lanepe.2021.100192. PubMed DOI PMC

Pilotto A, Ferrucci L, Franceschi M, D'Ambrosio LP, Scarcelli C, Cascavilla L, et al. Development and validation of a multidimensional prognostic index for one-year mortality from comprehensive geriatric assessment in hospitalized older patients. Rejuven Res. 2008;11(1):151–161. doi: 10.1089/rej.2007.0569. PubMed DOI PMC

Katz S, Downs TD, Cash HR, Grotz RC. Progress in development of the index of ADL. Gerontologist. 1970;10(1):20–30. doi: 10.1093/geront/10.1_Part_1.20. PubMed DOI

Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9(3):179–186. doi: 10.1093/geront/9.3_Part_1.179. PubMed DOI

Pfeiffer E. A Short Portable Mental Status Questionnaire (SPMSQ) J Am Geriatr Soc. 1975;23(10):1975. doi: 10.1111/j.1532-5415.1975.tb00927.x. PubMed DOI

Linn BS, Linn MW, Gurel L. Cumulative illness rating scale. J Am Geriatr Soc. 1968;16(5):622–626. doi: 10.1111/j.1532-5415.1968.tb02103.x. PubMed DOI

Guigoz Y, Vellas B. The Mini Nutritional Assessment (MNA) for grading the nutritional state of elderly patients: presentation of the MNA, history and validation. In: Nestle nutrition workshop series clinical & performance programme, vol. 1. 1999. pp. 3–11 (discussion-2). PubMed

Bliss MR, McLaren R, Exton-Smith AN. Mattresses for preventing pressure sores in geriatric patients. Mon Bull Minist Health Public Health Lab Serv. 1966;25:238–268. PubMed

Pilotto A, Veronese N, Daragjati J, Cruz-Jentoft AJ, Polidori MC, Mattace-Raso F, et al. Using the multidimensional prognostic index to predict clinical outcomes of hospitalized older persons: a prospective, multicenter, international study. J Gerontol Ser A. 2019;74(10):1643–1649. doi: 10.1093/gerona/gly239. PubMed DOI PMC

Bellelli G, Morandi A, Davis DH, Mazzola P, Turco R, Gentile S, et al. Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people. Age Ageing. 2014;43(4):496–502. doi: 10.1093/ageing/afu021. PubMed DOI PMC

Wong CK, Wong JY, Tang EH, Au CH, Wai AK. Clinical presentations, laboratory and radiological findings, and treatments for 11,028 COVID-19 patients: a systematic review and meta-analysis. Sci Rep. 2020;10(1):1–16. doi: 10.1038/s41598-020-74988-9. PubMed DOI PMC

Figliozzi S, Masci PG, Ahmadi N, Tondi L, Koutli E, Aimo A, et al. Predictors of adverse prognosis in COVID-19: a systematic review and meta-analysis. Eur J Clin Investig. 2020;50(10):e13362. doi: 10.1111/eci.13362. PubMed DOI

Fluss R, Faraggi D, Reiser B. Estimation of the Youden Index and its associated cutoff point. Biometr J. 2005;47(4):458–472. doi: 10.1002/bimj.200410135. PubMed DOI

Ohl ME, Miller DR, Lund BC, Kobayashi T, Richardson Miell K, Beck BF, et al. Association of remdesivir treatment with survival and length of hospital stay among US veterans hospitalized with COVID-19. JAMA Netw Open. 2021;4(7):e2114741. doi: 10.1001/jamanetworkopen.2021.14741. PubMed DOI PMC

Ramos-Rincon JM, Lopez-Carmona MD, Cobos-Palacios L, Lopez-Sampalo A, Rubio-Rivas M, Martin-Escalante MD, et al. Remdesivir in very old patients (>/=80 years) hospitalized with COVID-19: real world data from the SEMI-COVID-19 registry. J Clin Med. 2022;11(13). PubMed PMC

Yu M, Kim BI, Kim J, Gwack J. Clinical outcomes of remdesivir-treated COVID-19 patients in South Korea. Osong Public Health Res Perspect. 2022;13(5):370–376. doi: 10.24171/j.phrp.2022.0138. PubMed DOI PMC

Inzitari M, Arnal C, Ribera A, Hendry A, Cesari M, Roca S, et al. Comprehensive geriatric hospital at home: adaptation to referral and case-mix changes during the COVID-19 pandemic. J Am Med Dir Assoc. 2023;24(1):3–9.e1. doi: 10.1016/j.jamda.2022.11.003. PubMed DOI PMC

O'Hanlon S, Dhesi J, Aronson L, Inouye SK. Covid-19: a call for mobilizing geriatric expertise. Eur Geriatr Med. 2021;12(3):597–600. doi: 10.1007/s41999-021-00500-9. PubMed DOI PMC

Senderovich H, Vinoraj D, Stever M, Waicus S. Efficacy of COVID-19 treatments among geriatric patients: a systematic review. Ther Adv Infect Dis. 2022;9:20499361221095666. PubMed PMC

Pilotto A, Gallina P, Panza F, Copetti M, Cella A, Cruz-Jentoft A, et al. Relation of statin use and mortality in community-dwelling frail older patients with coronary artery disease. Am J Cardiol. 2016;118(11):1624–1630. doi: 10.1016/j.amjcard.2016.08.042. PubMed DOI PMC

Pilotto A, Panza F, Copetti M, Simonato M, Sancarlo D, Gallina P, et al. Statin treatment and mortality in community-dwelling frail older patients with diabetes mellitus: a retrospective observational study. PLoS ONE. 2015;10(6):e0130946. doi: 10.1371/journal.pone.0130946. PubMed DOI PMC

Pilotto A, Gallina P, Copetti M, Pilotto A, Marcato F, Mello AM, et al. Warfarin treatment and all-cause mortality in community-dwelling older adults with atrial fibrillation: a retrospective observational study. J Am Geriatr Soc. 2016;64(7):1416–1424. doi: 10.1111/jgs.14221. PubMed DOI PMC

D'Onofrio G, Sancarlo D, Addante F, Ciccone F, Cascavilla L, Paris F, et al. A pilot randomized controlled trial evaluating an integrated treatment of rivastigmine transdermal patch and cognitive stimulation in patients with Alzheimer's disease. Int J Geriatr Psychiatry. 2015;30(9):965–975. doi: 10.1002/gps.4247. PubMed DOI