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      The influence of gender on COVID-19 infections and mortality in Germany: Insights from age- and gender-specific modeling of contact rates, infections, and deaths in the early phase of the pandemic

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          Abstract

          Recent research points towards age- and gender-specific transmission of COVID-19 infections and their outcomes. The effect of gender, however, has been overlooked in past modelling approaches of COVID-19 infections. The aim of our study is to explore how gender-specific contact behavior affects gender-specific COVID-19 infections and deaths. We consider a compartment model to establish short-term forecasts of the COVID-19 epidemic over a time period of 75 days. Compartments are subdivided into different age groups and genders, and estimated contact patterns, based on previous studies, are incorporated to account for age- and gender-specific social behaviour. The model is fitted to real data and used for assessing the effect of hypothetical contact scenarios all starting at a daily level of 10 new infections per million population. On day 75 after the end of the lockdown, infection rates are highest among the young and working-age, but they also have increased among the old. Sex ratios reveal higher infection risks among women than men at working ages; the opposite holds true at old age. Death rates in all age groups are twice as high for men as for women. Small changes in contact rates at working and young ages have a considerable effect on infections and mortality at old age, with elderly men being always at higher risk of infection and mortality. Our results underline the high importance of the non-pharmaceutical mitigation measures (NPMM) in low-infection phases of the pandemic to prevent that an increase in contact rates leads to higher mortality among the elderly, even if easing measures take place among the young. At young and middle ages, women’s contribution to increasing infections is higher due to their higher number of contacts. Gender differences in contact rates may be one pathway that contributes to the spread of the disease and results in gender-specific infection rates and their mortality outcome. To further explore possible pathways, more data on contact behavior and COVID-19 transmission is needed, which includes gender- and socio-demographic information.

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          Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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            Estimates of the severity of coronavirus disease 2019: a model-based analysis

            Summary Background In the face of rapidly changing data, a range of case fatality ratio estimates for coronavirus disease 2019 (COVID-19) have been produced that differ substantially in magnitude. We aimed to provide robust estimates, accounting for censoring and ascertainment biases. Methods We collected individual-case data for patients who died from COVID-19 in Hubei, mainland China (reported by national and provincial health commissions to Feb 8, 2020), and for cases outside of mainland China (from government or ministry of health websites and media reports for 37 countries, as well as Hong Kong and Macau, until Feb 25, 2020). These individual-case data were used to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the case fatality ratio by relating the aggregate distribution of cases to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for demography and age-based and location-based under-ascertainment. We also estimated the case fatality ratio from individual line-list data on 1334 cases identified outside of mainland China. Using data on the prevalence of PCR-confirmed cases in international residents repatriated from China, we obtained age-stratified estimates of the infection fatality ratio. Furthermore, data on age-stratified severity in a subset of 3665 cases from China were used to estimate the proportion of infected individuals who are likely to require hospitalisation. Findings Using data on 24 deaths that occurred in mainland China and 165 recoveries outside of China, we estimated the mean duration from onset of symptoms to death to be 17·8 days (95% credible interval [CrI] 16·9–19·2) and to hospital discharge to be 24·7 days (22·9–28·1). In all laboratory confirmed and clinically diagnosed cases from mainland China (n=70 117), we estimated a crude case fatality ratio (adjusted for censoring) of 3·67% (95% CrI 3·56–3·80). However, after further adjusting for demography and under-ascertainment, we obtained a best estimate of the case fatality ratio in China of 1·38% (1·23–1·53), with substantially higher ratios in older age groups (0·32% [0·27–0·38] in those aged <60 years vs 6·4% [5·7–7·2] in those aged ≥60 years), up to 13·4% (11·2–15·9) in those aged 80 years or older. Estimates of case fatality ratio from international cases stratified by age were consistent with those from China (parametric estimate 1·4% [0·4–3·5] in those aged <60 years [n=360] and 4·5% [1·8–11·1] in those aged ≥60 years [n=151]). Our estimated overall infection fatality ratio for China was 0·66% (0·39–1·33), with an increasing profile with age. Similarly, estimates of the proportion of infected individuals likely to be hospitalised increased with age up to a maximum of 18·4% (11·0–7·6) in those aged 80 years or older. Interpretation These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death. Funding UK Medical Research Council.
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              The reproductive number of COVID-19 is higher compared to SARS coronavirus

              Introduction In Wuhan, China, a novel and alarmingly contagious primary atypical (viral) pneumonia broke out in December 2019. It has since been identified as a zoonotic coronavirus, similar to SARS coronavirus and MERS coronavirus and named COVID-19. As of 8 February 2020, 33 738 confirmed cases and 811 deaths have been reported in China. Here we review the basic reproduction number (R 0) of the COVID-19 virus. R 0 is an indication of the transmissibility of a virus, representing the average number of new infections generated by an infectious person in a totally naïve population. For R 0 > 1, the number infected is likely to increase, and for R 0 < 1, transmission is likely to die out. The basic reproduction number is a central concept in infectious disease epidemiology, indicating the risk of an infectious agent with respect to epidemic spread. Methods and Results PubMed, bioRxiv and Google Scholar were accessed to search for eligible studies. The term ‘coronavirus & basic reproduction number’ was used. The time period covered was from 1 January 2020 to 7 February 2020. For this time period, we identified 12 studies which estimated the basic reproductive number for COVID-19 from China and overseas. Table 1 shows that the estimates ranged from 1.4 to 6.49, with a mean of 3.28, a median of 2.79 and interquartile range (IQR) of 1.16. Table 1 Published estimates of R 0 for 2019-nCoV Study (study year) Location Study date Methods Approaches R 0 estimates (average) 95% CI Joseph et al. 1 Wuhan 31 December 2019–28 January 2020 Stochastic Markov Chain Monte Carlo methods (MCMC) MCMC methods with Gibbs sampling and non-informative flat prior, using posterior distribution 2.68 2.47–2.86 Shen et al. 2 Hubei province 12–22 January 2020 Mathematical model, dynamic compartmental model with population divided into five compartments: susceptible individuals, asymptomatic individuals during the incubation period, infectious individuals with symptoms, isolated individuals with treatment and recovered individuals R 0 = \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\beta$\end{document} / \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\alpha$\end{document} \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\beta$\end{document} = mean person-to-person transmission rate/day in the absence of control interventions, using nonlinear least squares method to get its point estimate \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}$\alpha$\end{document} = isolation rate = 6 6.49 6.31–6.66 Liu et al. 3 China and overseas 23 January 2020 Statistical exponential Growth, using SARS generation time = 8.4 days, SD = 3.8 days Applies Poisson regression to fit the exponential growth rateR 0 = 1/M(−𝑟)M = moment generating function of the generation time distributionr = fitted exponential growth rate 2.90 2.32–3.63 Liu et al. 3 China and overseas 23 January 2020 Statistical maximum likelihood estimation, using SARS generation time = 8.4 days, SD = 3.8 days Maximize log-likelihood to estimate R 0 by using surveillance data during a disease epidemic, and assuming the secondary case is Poisson distribution with expected value R 0 2.92 2.28–3.67 Read et al. 4 China 1–22 January 2020 Mathematical transmission model assuming latent period = 4 days and near to the incubation period Assumes daily time increments with Poisson-distribution and apply a deterministic SEIR metapopulation transmission model, transmission rate = 1.94, infectious period =1.61 days 3.11 2.39–4.13 Majumder et al. 5 Wuhan 8 December 2019 and 26 January 2020 Mathematical Incidence Decay and Exponential Adjustment (IDEA) model Adopted mean serial interval lengths from SARS and MERS ranging from 6 to 10 days to fit the IDEA model, 2.0–3.1 (2.55) / WHO China 18 January 2020 / / 1.4–2.5 (1.95) / Cao et al. 6 China 23 January 2020 Mathematical model including compartments Susceptible-Exposed-Infectious-Recovered-Death-Cumulative (SEIRDC) R = K 2 (L × D) + K(L + D) + 1L = average latent period = 7,D = average latent infectious period = 9,K = logarithmic growth rate of the case counts 4.08 / Zhao et al. 7 China 10–24 January 2020 Statistical exponential growth model method adopting serial interval from SARS (mean = 8.4 days, SD = 3.8 days) and MERS (mean = 7.6 days, SD = 3.4 days) Corresponding to 8-fold increase in the reporting rateR 0 = 1/M(−𝑟)𝑟 =intrinsic growth rateM = moment generating function 2.24 1.96–2.55 Zhao et al. 7 China 10–24 January 2020 Statistical exponential growth model method adopting serial interval from SARS (mean = 8.4 days, SD = 3.8 days) and MERS (mean = 7.6 days, SD = 3.4 days) Corresponding to 2-fold increase in the reporting rateR 0 = 1/M(−𝑟)𝑟 =intrinsic growth rateM = moment generating function 3.58 2.89–4.39 Imai (2020) 8 Wuhan January 18, 2020 Mathematical model, computational modelling of potential epidemic trajectories Assume SARS-like levels of case-to-case variability in the numbers of secondary cases and a SARS-like generation time with 8.4 days, and set number of cases caused by zoonotic exposure and assumed total number of cases to estimate R 0 values for best-case, median and worst-case 1.5–3.5 (2.5) / Julien and Althaus 9 China and overseas 18 January 2020 Stochastic simulations of early outbreak trajectories Stochastic simulations of early outbreak trajectories were performed that are consistent with the epidemiological findings to date 2.2 Tang et al. 10 China 22 January 2020 Mathematical SEIR-type epidemiological model incorporates appropriate compartments corresponding to interventions Method-based method and Likelihood-based method 6.47 5.71–7.23 Qun Li et al. 11 China 22 January 2020 Statistical exponential growth model Mean incubation period = 5.2 days, mean serial interval = 7.5 days 2.2 1.4–3.9 Averaged 3.28 CI, Confidence interval. Figure 1 Timeline of the R 0 estimates for the 2019-nCoV virus in China The first studies initially reported estimates of R 0 with lower values. Estimations subsequently increased and then again returned in the most recent estimates to the levels initially reported (Figure 1). A closer look reveals that the estimation method used played a role. The two studies using stochastic methods to estimate R 0, reported a range of 2.2–2.68 with an average of 2.44. 1 , 9 The six studies using mathematical methods to estimate R 0 produced a range from 1.5 to 6.49, with an average of 4.2. 2 , 4–6 , 8 , 10 The three studies using statistical methods such as exponential growth estimated an R 0 ranging from 2.2 to 3.58, with an average of 2.67. 3 , 7 , 11 Discussion Our review found the average R 0 to be 3.28 and median to be 2.79, which exceed WHO estimates from 1.4 to 2.5. The studies using stochastic and statistical methods for deriving R 0 provide estimates that are reasonably comparable. However, the studies using mathematical methods produce estimates that are, on average, higher. Some of the mathematically derived estimates fall within the range produced the statistical and stochastic estimates. It is important to further assess the reason for the higher R 0 values estimated by some the mathematical studies. For example, modelling assumptions may have played a role. In more recent studies, R 0 seems to have stabilized at around 2–3. R 0 estimations produced at later stages can be expected to be more reliable, as they build upon more case data and include the effect of awareness and intervention. It is worthy to note that the WHO point estimates are consistently below all published estimates, although the higher end of the WHO range includes the lower end of the estimates reviewed here. R 0 estimates for SARS have been reported to range between 2 and 5, which is within the range of the mean R 0 for COVID-19 found in this review. Due to similarities of both pathogen and region of exposure, this is expected. On the other hand, despite the heightened public awareness and impressively strong interventional response, the COVID-19 is already more widespread than SARS, indicating it may be more transmissible. Conclusions This review found that the estimated mean R 0 for COVID-19 is around 3.28, with a median of 2.79 and IQR of 1.16, which is considerably higher than the WHO estimate at 1.95. These estimates of R 0 depend on the estimation method used as well as the validity of the underlying assumptions. Due to insufficient data and short onset time, current estimates of R 0 for COVID-19 are possibly biased. However, as more data are accumulated, estimation error can be expected to decrease and a clearer picture should form. Based on these considerations, R 0 for COVID-19 is expected to be around 2–3, which is broadly consistent with the WHO estimate. Author contributions J.R. and A.W.S. had the idea, and Y.L. did the literature search and created the table and figure. Y.L. and A.W.S. wrote the first draft; A.A.G. drafted the final manuscript. All authors contributed to the final manuscript. Conflict of interest None declared.
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                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: 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
                2022
                6 May 2022
                6 May 2022
                : 17
                : 5
                : e0268119
                Affiliations
                [1 ] Department of Economics, University of Rostock, Rostock, Germany
                [2 ] Department of Sociology and Demography, University of Rostock, Rostock, Germany
                Nanyang Technological University, SINGAPORE
                Author notes

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

                Author information
                https://orcid.org/0000-0001-9297-3675
                Article
                PONE-D-21-03904
                10.1371/journal.pone.0268119
                9075634
                35522614
                0cbaf805-41bf-44af-80bd-e8232ba73201
                © 2022 Doerre, Doblhammer

                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
                : 22 April 2022
                Page count
                Figures: 9, Tables: 4, Pages: 20
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Viral Diseases
                Covid 19
                Biology and Life Sciences
                Population Biology
                Population Metrics
                Death Rates
                Medicine and Health Sciences
                Epidemiology
                Infectious Disease Epidemiology
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                Infectious Diseases
                Infectious Disease Epidemiology
                Medicine and Health Sciences
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                Pharmacology
                Pharmacologic Analysis
                Pharmacokinetic Analysis
                Compartment Models
                People and Places
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                All data and implementation files are available from the following public repository: https://github.com/AchimDoerre/Covid-19.
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