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      Age-related mortality in 61,993 confirmed COVID-19 cases over three epidemic waves in Aragon, Spain. Implications for vaccination programmes

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          Abstract

          Background

          Risk for severe COVID-19 increases with age. Different vaccination strategies are currently being considered, including those aimed at slowing down transmission and those aimed at providing direct protection to those most at risk.

          Methods

          The objectives of the current study were i) to assess age-related incidence and survival between PCR-diagnosed COVID-19 cases (n = 61,993) in the Autonomous Community of Aragon from March to November 2020, and ii) to characterize age differences regarding the course of the disease in hospitalized patients in a tertiary university hospital.

          Results

          We found a similar incidence of COVID-19 in individuals between 10 and 79 years. Incidence increased in those over 80 years possibly because of the elevated transmission within the nursing homes. We observed a profound disparity among age groups; case fatality rates (CFRs) were near 0 in cases younger than 39 years throughout different waves. In contrast, there was an age-dependent and progressive increase in the CFRs, especially during the first pandemic wave. SARS-CoV-2 infection caused a more severe and rapid progression in older patients. The elderly required faster hospitalization, presented more serious symptoms on admission, and had a worse clinical course. Hospitalized older individuals, even without comorbidities, had an increased mortality risk directly associated with their age. Lastly, the existence of comorbidities dramatically increased the CFRs in the elderly, especially in males.

          Conclusion

          The elevated incidence of COVID-19 and the vulnerability of the elderly call for their prioritization in vaccination and targeted prevention measures specifically focused on this aged population.

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          Most cited references49

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

            Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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              The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

              Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                9 December 2021
                2021
                9 December 2021
                : 16
                : 12
                : e0261061
                Affiliations
                [1 ] Gastroenterology Department, Miguel Servet University Hospital, Zaragoza, Spain
                [2 ] Instituto de Investigación Sanitaria (IIS) Aragon, Zaragoza, Spain
                [3 ] Internal Medicine Department, Miguel Servet University Hospital, Zaragoza, Spain
                [4 ] Translational Research Unit, Miguel Servet University Hospital, Instituto Aragonés de Ciencias de la Salud, Zaragoza, Spain
                [5 ] Centro de Investigación Biomédica en Red Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, Madrid, Spain
                Azienda Ospedaliero Universitaria Careggi, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0001-6883-8940
                https://orcid.org/0000-0002-8982-3737
                Article
                PONE-D-21-03877
                10.1371/journal.pone.0261061
                8659616
                34882740
                bf274d78-5341-4a78-8962-246f9ff3b586
                © 2021 Casas-Deza et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 4 February 2021
                : 23 November 2021
                Page count
                Figures: 4, Tables: 1, Pages: 13
                Funding
                Funded by: Instituto de Salud Carlos III (ES)
                Award ID: PI17/02268
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100010067, Gobierno de Aragón;
                Award ID: B03_20R
                Award Recipient :
                JMA-M is partially supported by the project PI17/02268 (Instituto de Salud Carlos III and co-financed by Fondo Europeo de Desarrollo Regional (FEDER): “Una manera de hacer Europa”) and by the DGA Group Biology of adipose tissue and metabolic complications (B03_20R), co-financed with the FEDER Aragón 2014-2020: “Construyendo Europa desde Aragón”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Medicine and Health Sciences
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                Infectious Diseases
                Viral Diseases
                Covid 19
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                Geriatric Care
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                Custom metadata
                The authors cannot disclose individual level data as part of the agreement with the BIGAN repository and with our Ethics Committee. The dataset with epidemiological data from Aragón from this study is held by BIGAN at the Aragón Institute of Health Sciences (IACS). Access may be granted to those who meet pre-specified criteria for confidential access, available at https://www.iacs.es/instituto-aragones-ciencias-la-salud/oficina-virtual/solicitud-de-acceso-a-datos-para-realizacion-de-un-proyecto-de-investigacion-rpi01-3a All aggregated data and analyses behind Figs 2 and 3 could be replicable with publicly available dataset ( https://cnecovid.isciii.es/covid19/resources/casos_hosp_uci_def_sexo_edad_provres.csv) provided by the Spanish epidemiological surveillance network (Red de Vigilancia Epidemiológica) at https://cnecovid.isciii.es/covid19/#documentación-y-datos. The anonymized dataset for the hospitalized patients is mantiened IACS repository. It can be requested at https://www.iacs.es/instituto-aragones-ciencias-la-salud/oficina-virtual/solicitud-de-acceso-a-datos-para-realizacion-de-un-proyecto-de-investigacion-rpi01-3a/ with prior authorization by the Ethics Committee of Aragon (CEIC-A) which can be obtained at https://www.iacs.es/investigacion/comite-de-etica-de-la-investigacion-de-aragon-ceica/ceica-evaluaciones-y-otras-presentaciones/.
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