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COVID-19 severity determinants inferred through ecological and epidemiological modeling.

ABSTRACT: Understanding variations in the severity of infectious diseases is essential for planning proper mitigation strategies. Determinants of COVID-19 clinical severity are commonly assessed by transverse or longitudinal studies of the fatality counts. However, the fatality counts depend both on disease clinical severity and transmissibility, as more infected also lead to more deaths. Instead, we use epidemiological modeling to propose a disease severity measure that accounts for the underlying disease dynamics. The measure corresponds to the ratio of population-averaged mortality and recovery rates (m/r), is independent of the disease transmission dynamics (i.e., the basic reproduction number), and has a direct mechanistic interpretation. We use this measure to assess demographic, medical, meteorological, and environmental factors associated with the disease severity. For this, we employ an ecological regression study design and analyze different US states during the first disease outbreak. Principal Component Analysis, followed by univariate, and multivariate analyses based on machine learning techniques, is used for selecting important predictors. The usefulness of the introduced severity measure and the validity of the approach are confirmed by the fact that, without using prior knowledge from clinical studies, we recover the main significant predictors known to influence disease severity, in particular age, chronic diseases, and racial factors. Additionally, we identify long-term pollution exposure and population density as not widely recognized (though for the pollution previously hypothesized) significant predictors. The proposed measure is applicable for inferring severity determinants not only of COVID-19 but also of other infectious diseases, and the obtained results may aid a better understanding of the present and future epidemics. Our holistic, systematic investigation of disease severity at the human-environment intersection by epidemiological dynamical modeling and machine learning ecological regressions is aligned with the One Health approach. The obtained results emphasize a syndemic nature of COVID-19 risks.

SUBMITTER: Markovic S

PROVIDER: S-EPMC8626896 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveWe aimed to identify the country-level determinants of the severity of the first wave of the COVID-19 pandemic.DesignEcological study of publicly available data. Countries reporting >25 COVID-19 related deaths until 8 June 2020 were included. The outcome was log mean mortality rate from COVID-19, an estimate of the country-level daily increase in reported deaths during the ascending phase of the epidemic curve. Potential determinants assessed were most recently published demographic parameters (population and population density, percentage population living in urban areas, population >65 years, average body mass index and smoking prevalence); economic parameters (gross domestic product per capita); environmental parameters (pollution levels and mean temperature (January-May); comorbidities (prevalence of diabetes, hypertension and cancer); health system parameters (WHO Health Index and hospital beds per 10 000 population); international arrivals; the stringency index, as a measure of country-level response to COVID-19; BCG vaccination coverage; UV radiation exposure; and testing capacity. Multivariable linear regression was used to analyse the data.Primary outcomeCountry-level mean mortality rate: the mean slope of the COVID-19 mortality curve during its ascending phase.ParticipantsThirty-seven countries were included: Algeria, Argentina, Austria, Belgium, Brazil, Canada, Chile, Colombia, the Dominican Republic, Ecuador, Egypt, Finland, France, Germany, Hungary, India, Indonesia, Ireland, Italy, Japan, Mexico, the Netherlands, Peru, the Philippines, Poland, Portugal, Romania, the Russian Federation, Saudi Arabia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the UK and the USA.ResultsOf all country-level determinants included in the multivariable model, total number of international arrivals (beta 0.033 (95% CI 0.012 to 0.054)) and BCG vaccination coverage (-0.018 (95% CI -0.034 to -0.002)), were significantly associated with the natural logarithm of the mean death rate.ConclusionsInternational travel was directly associated with the mortality slope and thus potentially the spread of COVID-19. Very early restrictions on international travel should be considered to control COVID-19 outbreaks and prevent related deaths.

Project description:Using RNA-seq and high-resolution mass spectrometry we performed a comprehensive systems analysis on 128 plasma and leukocyte samples from hospitalized patients with or without COVID-19 (n=102 and 26 respectively) and with differing degrees of disease severity. We generated abundance measurements for over 17,000 transcripts, proteins, metabolites, and lipids and compiled them with clinical data into a curated relational database. This resource offers the unique opportunity to perform systems analysis and cross-ome correlations to both molecules and patient outcomes. In total 219 molecular features were mapped with high significance to COVID-19 status and severity, including those involved in processes such as complement system activation, dysregulated lipid transport, and B cell activation. In one example, we detected a trio of covarying molecules – citrate, plasmenyl-phosphatidylcholines, and gelsolin (GSN) – that offer both pathophysiological insight and potential novel therapeutic targets. Further, our data revealed in some cases, and supported in others, that several biological processes were dysregulated in COVID-19 patients including vessel damage, platelet activation and degranulation, blood coagulation, and acute phase response. For example, we observed that the coagulation-related protein, cellular fibronectin (cFN), was highly increased within COVID-19 patients and provide new evidence that the upregulated proteoform stems from endothelial cells, consistent with endothelial injury as a major activator of the coagulation cascade. The abundance of prothrombin, which is cleaved to form thrombin during clotting, was significantly reduced and correlated with severity and might help to explain the hyper coagulative environment of SARS-CoV-2 infection. From transcriptomic analysis of leukocytes, we concluded that COVID-19 patients with acute respiratory distress syndrome (ARDS) demonstrated a phenotype that overlapped with, but was distinct from, that found in patients with non-COVID-19-ARDS. To aid in the global efforts toward elucidation of disease pathophysiology and therapeutic development, we created a web-based tool with interactive visualizations allowing for easy navigation of this systems-level compendium of biomolecule abundance in relation to COVID-19 status and severity. Finally, we leveraged these multi-omic data to predict COVID-19 patient outcomes with machine learning, which highlighted the predictive power of these expansive molecular measurements beyond the standardized clinical estimate of 10-year survival Charlson score.

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COVID-19 severity determinants inferred through ecological and epidemiological modeling.

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