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      Magnitude and determinants of excess total, age-specific and sex-specific all-cause mortality in 24 countries worldwide during 2020 and 2021: results on the impact of the COVID-19 pandemic from the C-MOR project

      research-article
      1 , 1 , 1 , 2 , 1 , 3 , 1 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 10 , 11 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 21 , 22 , 23 , 24 , 25 , 26 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 1 ,
      BMJ Global Health
      BMJ Publishing Group
      COVID-19, Public Health, Vaccines, Control strategies, Epidemiology

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          Abstract

          Introduction

          To examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age.

          Methods

          Total, age-specific and sex-specific weekly all-cause mortality was collected for 2015–2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015–2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models.

          Results

          Excess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively.

          Conclusion

          This study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.

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          Most cited references48

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          Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2)

          Estimation of the prevalence and contagiousness of undocumented novel coronavirus (SARS-CoV2) infections is critical for understanding the overall prevalence and pandemic potential of this disease. Here we use observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics associated with SARS-CoV2, including the fraction of undocumented infections and their contagiousness. We estimate 86% of all infections were undocumented (95% CI: [82%–90%]) prior to 23 January 2020 travel restrictions. Per person, the transmission rate of undocumented infections was 55% of documented infections ([46%–62%]), yet, due to their greater numbers, undocumented infections were the infection source for 79% of documented cases. These findings explain the rapid geographic spread of SARS-CoV2 and indicate containment of this virus will be particularly challenging.
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            Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility

            Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents. Methods We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic. Results Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide. Conclusions Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.
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              Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission

              Anecdotal evidence suggests that Coronavirus disease 2019 (COVID-19), caused by the coronavirus SARS-CoV-2, exhibits differences in morbidity and mortality between sexes. Here, we present a meta-analysis of 3,111,714 reported global cases to demonstrate that, whilst there is no difference in the proportion of males and females with confirmed COVID-19, male patients have almost three times the odds of requiring intensive treatment unit (ITU) admission (OR = 2.84; 95% CI = 2.06, 3.92) and higher odds of death (OR = 1.39; 95% CI = 1.31, 1.47) compared to females. With few exceptions, the sex bias observed in COVID-19 is a worldwide phenomenon. An appreciation of how sex is influencing COVID-19 outcomes will have important implications for clinical management and mitigation strategies for this disease.
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                Author and article information

                Journal
                BMJ Glob Health
                BMJ Glob Health
                bmjgh
                bmjgh
                BMJ Global Health
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2059-7908
                2024
                18 April 2024
                : 9
                : 4
                : e013018
                Affiliations
                [1 ] departmentDepartment of Primary Care and Population Health , Ringgold_486462University of Nicosia Medical School , Nicosia, Cyprus
                [2 ] Ringgold_2167Massachusetts Institute of Technology , Cambridge, Massachusetts, USA
                [3 ] departmentHealth Monitoring Unit , Ringgold_63524Government of the Republic of Cyprus Ministry of Health , Nicosia, Cyprus
                [4 ] departmentDepartment of Biostatistics and Epidemiology , Rutgers School of Public Health , Piscataway, New Jersey, USA
                [5 ] departmentDepartment of Epidemiology , Harvard TH Chan School of Public Health , Boston, Massachusetts, USA
                [6 ] departmentDepartment of Environmental Health , Harvard T.H. Chan School of Public Health , Boston, Massachusetts, USA
                [7 ] departmentSchool of Information Technologies , University of Limassol , Limassol, Cyprus
                [8 ] Ringgold_54504European Commission Joint Research Centre , Ispra, Italy
                [9 ] departmentInstitute for Health Transformation , Ringgold_2104Deakin University , Burwood, Victoria, Australia
                [10 ] departmentDepartment of Epidemiology , Ringgold_213862Medical University of Vienna Center for Public Health , Vienna, Austria
                [11 ] departmentDepartment of Epidemiology and Public Health , Ringgold_54513Sciensano , Brussels, Belgium
                [12 ] departmentDepartment of Epidemiology and Biostatistics, Institute of Collective Health (ISC) , Ringgold_28110Federal Fluminense University , Niteroi, Brazil
                [13 ] departmentInstitute of Studies in Collective Health (IESC) , Ringgold_28125Federal University of Rio de Janeiro , Rio de Janeiro, Brazil
                [14 ] departmentMethods and Analysis Department , Ringgold_4303Statistics Denmark , Copenhagen Oe, Denmark
                [15 ] departmentPopulation Health Research Institute , Ringgold_4915St George's University of London , London, UK
                [16 ] departmentDivision of Health Services Research and Management , School of Health and Psychological Sciences, University of London, City , London, UK
                [17 ] departmentDepartment of Registries , Ringgold_241808National Institute for Health Development , Tallinn, Estonia
                [18 ] departmentUMR CNRS 6051 - INSERM U1309 , Ecole des Hautes Etudes en Santé Publique , Rennes, France
                [19 ] departmentDepartment of Medical Statistics , Ringgold_443716National Center for Disease Control and Public Health , Tbilisi, Georgia
                [20 ] departmentLaboratory for Health Technology Assessment , Ringgold_523391University of West Attica , Athens, Greece
                [21 ] departmentIsraeli Center of Disease Control , Ringgold_26737State of Israel Ministry of Health , Ramat Gan, Israel
                [22 ] departmentDepartment of Medicine, Public Health Section , Ringgold_199927University of Perugia, School of Medicine , Perugia, Italy
                [23 ] departmentDepartment of Cardiology , Ringgold_60250University of Perugia School of Medicine , Perugia, Italy
                [24 ] departmentRector Administration , Ringgold_186045Asfendiyarov Kazakh National Medical University , Almaty, Kazakhstan
                [25 ] departmentDepartment of Epidemiology, Evidence-Based Medicine and Biostatistics , Ringgold_98799Al-Farabi Kazakh National University , Almaty, Kazakhstan
                [26 ] departmentDepartment of Medicine , Ringgold_475509University of Mauritius Faculty of Science , Reduit, Mauritius
                [27 ] departmentDepartment of Health Management and Health Economics , Ringgold_6305University of Oslo , Oslo, Norway
                [28 ] departmentDepartamento de Ingeniería , Ringgold_42693Universidad del Pacifico , Lima, Peru
                [29 ] departmentDepartamento de Economia , Ringgold_42693Universidad del Pacifico , Lima, Peru
                [30 ] departmentDepartment of Health Economics , Ringgold_49577Nicolaus Copernicus University in Torun , Bydgoszcz, Poland
                [31 ] departmentPublic Health School , Ringgold_68920National Institute of Public Health of the Republic of Slovenia , Ljubljana, Slovenia
                [32 ] departmentUnit for Research in Emergency and Disaster, Department of Medicine , Ringgold_90195University of Oviedo , Oviedo, Spain
                [33 ] departmentDepartment of Global Public Health , Ringgold_27106Karolinska Institutet , Stockholm, Sweden
                [34 ] departmentDepartment of Internal Medicine , Ringgold_123498Bogomolets National Medical University , Kyiv, Ukraine
                [35 ] departmentDepartment of Medical Sciences , Ringgold_486462University of Nicosia Medical School , Nicosia, Cyprus
                [36 ] departmentCenter for Rural Health Research , College of Public Health, East Tennessee State University , Johnson City, TN, USA
                [37 ] Ringgold_121343University of Nicosia , Nicosia, Cyprus
                [38 ] Ringgold_486462University of Nicosia Medical School , Nicosia, Cyprus
                Author notes
                [Correspondence to ] Dr Christiana A. Demetriou; demetriou.chri@ 123456unic.ac.cy
                Author information
                http://orcid.org/0000-0001-6781-9684
                http://orcid.org/0000-0002-1688-9225
                http://orcid.org/0000-0002-6934-1925
                http://orcid.org/0000-0002-5825-5079
                Article
                bmjgh-2023-013018
                10.1136/bmjgh-2023-013018
                11029481
                38637119
                28f6cf97-28e2-4beb-85a5-5990f9d421d3
                © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 01 June 2023
                : 06 January 2024
                Funding
                Funded by: The University of Nicosia Medical School;
                Categories
                Original Research
                1506
                2474
                Custom metadata
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                covid-19,public health,vaccines,control strategies,epidemiology

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