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Register a new userSex Differences in Severity and Mortality Among Patients With COVID-19: Evidence from Pooled Literature Analysis and Insights from Integrated Bioinformatic Analysis
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Objective: To conduct a meta-analysis of current studies that examined sex differences in severity and mortality in patients with COVID-19, and identify potential mechanisms underpinning these differences. Methods: We performed a systematic review to collate data from observational studies examining associations of sex differences with clinical outcomes of COVID-19. PubMed, Web of Science and four preprint servers were searched for relevant studies. Data were extracted and analyzed using meta-analysis where possible, with summary data presented otherwise. Publicly available bulk RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq) data were analyzed to explore the potential mechanisms underlying the observed association. Results: 39 studies met inclusion criteria, representing 77932 patients, of which 41510 (53.3%) were males. Men were at a markedly increased risk of developing severe cases compared with women. Furthermore, the pooled odds ratio (OR) of mortality for male group compared with the female group indicated significant higher mortality rate for male. Data from scRNA-seq suggest that men have a higher amount of ACE2-expressing pulmonary alveolar type II cells than women. Sex-based immunological differences exist. The expression of androgen receptor (AR) is positively correlated with ACE2, and there is evidence that AR may directly regulate the expression of ACE2. Conclusions: This meta-analysis detected an increased severity and mortality rate in the male populations with COVID-19, which might be attributable to the sex-based differences in cellular compositions and immunological microenvironments of the lung. The host cell receptor ACE2 is likely regulated by AR signaling pathway, which is identified as a potential target for prevention and treatment of SARS-Cov-2 infections in men.
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As the second wave in India mitigates, COVID-19 has now infected about 29 million patients countrywide, leading to more than 350 thousand people dead. As the infections surged, the strain on the medical infrastructure in the country became apparent. While the country vaccinates its population, opening up the economy may lead to an increase in infection rates. In this scenario, it is essential to effectively utilize the limited hospital resources by an informed patient triaging system based on clinical parameters. Here, we present two interpretable machine learning models predicting the clinical outcomes, severity, and mortality, of the patients based on routine non-invasive surveillance of blood parameters from one of the largest cohorts of Indian patients at the day of admission. Patient severity and mortality prediction models achieved 86.3% and 88.06% accuracy, respectively, with an AUC-ROC of 0.91 and 0.92. We have integrated both the models in a user-friendly web app calculator, https://triage-COVID-19.herokuapp.com/, to showcase the potential deployment of such efforts at scale.
The SIR evolutionary model predicts too sharp a decrease of the fractions of people infected with COVID-19 in France after the start of the national lockdown, compared to what is observed. I fit the daily hospital data: arrivals in regular and critical care units, releases and deaths, using extended SEIR models. These involve ratios of evolutionary timescales to branching fractions, assumed uniform throughout a country, and the basic reproduction number, $R_0$, before and during the national lockdown, for each region of France. The joint-region Bayesian analysis allows precise evaluations of the time/fraction ratios and pre-hospitalized fractions. The hospital data are well fit by the models, except the arrivals in critical care, which decrease faster than predicted, indicating better treatment over time. Averaged over France, the analysis yields $R_0$= 3.4$pm$0.1 before the lockdown and 0.65$pm$0.04 (90% c.l.) during the lockdown, with small regional variations. On 11 May 2020, the Infection Fatality Rate in France was 4 $pm$1% (90% c.l.), while the Feverish vastly outnumber the Asymptomatic, contrary to the early phases. Without the lockdown nor social distancing, over 2 million deaths from COVID-19 would have occurred throughout France, while a lockdown that would have been enforced 10 days earlier would have led to less than 1000 deaths. The fraction of immunized people reached a plateau below 1% throughout France (3% in Paris) by late April 2020 (95% c.l.), suggesting a lack of herd immunity. The widespread availability of face masks on 11 May, when the lockdown was partially lifted, should keep $R_0$ below unity if at least 46% of the population wear them outside their home. Otherwise, without enhanced other social distancing, a second wave is inevitable and cause the number of deaths to triple between early May and October (if $R_0$=1.2) or even late June (if $R_0$=2).
We develop a novel hybrid epidemiological model and a specific methodology for its calibration to distinguish and assess the impact of mobility restrictions (given by Apples mobility trends data) from other complementary non-pharmaceutical interventions (NPIs) used to control the spread of COVID-19. Using the calibrated model, we estimate that mobility restrictions contribute to 47 % (US States) and 47 % (worldwide) of the overall suppression of the disease transmission rate using data up to 13/08/2020. The forecast capacity of our model was evaluated doing four-weeks ahead predictions. Using data up to 30/06/20 for calibration, the mean absolute percentage error (MAPE) of the prediction of cumulative deceased individuals was 5.0 % for the United States (51 states) and 6.7 % worldwide (49 countries). This MAPE was reduced to 3.5% for the US and 3.8% worldwide using data up to 13/08/2020. We find that the MAPE was higher for the total confirmed cases at 11.5% worldwide and 10.2% for the US States using data up to 13/08/2020. Our calibrated model achieves an average R-Squared value for cumulative confirmed and deceased cases of 0.992 using data up to 30/06/20 and 0.98 using data up to 13/08/20.
COVID-19 pandemic represents an unprecedented global health crisis in the last 100 years. Its economic, social and health impact continues to grow and is likely to end up as one of the worst global disasters since the 1918 pandemic and the World Wars. Mathematical models have played an important role in the ongoing crisis; they have been used to inform public policies and have been instrumental in many of the social distancing measures that were instituted worldwide. In this article we review some of the important mathematical models used to support the ongoing planning and response efforts. These models differ in their use, their mathematical form and their scope.
In this work, we adapt the epidemiological SIR model to study the evolution of the dissemination of COVID-19 in Germany and Brazil (nationally, in the State of Paraiba, and in the City of Campina Grande). We prove the well posedness and the continuous dependence of the model dynamics on its parameters. We also propose a simple probabilistic method for the evolution of the active cases that is instrumental for the automatic estimation of parameters of the epidemiological model. We obtained statistical estimates of the active cases based the probabilistic method and on the confirmed cases data. From this estimated time series we obtained a time-dependent contagion rate, which reflects a lower or higher adherence to social distancing by the involved populations. By also analysing the data on daily deaths, we obtained the daily lethality and recovery rates. We then integrate the equations of motion of the model using these time-dependent parameters. We validate our epidemiological model by fitting the official data of confirmed, recovered, death, and active cases due to the pandemic with the theoretical predictions. We obtained very good fits of the data with this method. The automated procedure developed here could be used for basically any population with a minimum of extra work. Finally, we also propose and validate a forecasting method based on Markov chains for the evolution of the epidemiological data for up to two weeks.
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