Impact of regional heterogeneity on the severity of COVID-19.
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ABSTRACT:
SUBMITTER: Tsuzuki S
PROVIDER: S-EPMC8730489 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical manifestations in disease-ridden patients. Differences in the severity of COVID-19 ranges from asymptomatic infections and mild cases to the severe form, leading to acute respiratory distress syndrome (ARDS) and multiorgan failure with poor survival. MiRNAs can regulate various cellular processes, including proliferation, apoptosis, and differentiation, by binding to the 3′UTR of target mRNAs inducing their degradation, thus serving a fundamental role in post-transcriptional repression. Alterations of miRNA levels in the blood have been described in multiple inflammatory and infectious diseases, including SARS-related coronaviruses. We used microarrays to delineate the miRNAs and snoRNAs signature in the peripheral blood of severe COVID-19 cases (n=9), as compared to mild (n=10) and asymptomatic (n=10) patients, and identified differentially expressed transcripts in severe versus asymptomatic, and others in severe versus mild COVID-19 cases. A cohort of 29 male age-matched patients were selected. All patients were previously diagnosed with COVID-19 using TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Waltham, Massachusetts), or Cobas SARS-CoV-2 Test (Roche Diagnostics, Rotkreuz, Switzerland), with a CT value < 30. Additional criterion for selection was age between 35 and 75 years. Participants were grouped into severe, mild and asymptomatic. Classifying severe cases was based on requirement of high-flow oxygen support and ICU admission (n=9). Whereas mild patients were identified based on symptoms and positive radiographic findings with pulmonary involvement (n=10). Patients with no clinical presentation were labelled as asymptomatic cases (n=10).
2022-03-01 | E-MTAB-10970 | biostudies-arrayexpress
Project description:We investigated the effect of IL-13 neutralization on COVID-19 disease progression in mice.
2021-07-23 | GSE180557 | GEO
Project description:BackgroundThe ongoing Coronavirus disease of 2019 (COVID-19) pandemic has hit Brazil hard in period of different dominant variants. Different COIVD-19 variants have swept through the region, resulting that the total number of cases in Brazil is the third highest in the world. This study is aimed at investigating the regional heterogeneity of in-hospital mortality of COVID-19 in Brazil and the effects of vaccination and social inequality.MethodsWe fitted a multivariate mixed-effects Cox model to a national database of inpatient data in Brazil who were admitted for COVID-19 from February 27, 2020 to March 15, 2022. The in-hospital mortality risks of vaccinated and unvaccinated patients were compared, with adjustment for age, state, ethnicity, education and comorbidities. And the effects of variables to in-hospital mortality were also compared. Stratified analysis was conducted across different age groups and vaccine types.ResultsBy fitting the multivariate mixed-effects Cox model, we concluded that age was the most important risk factor for death. With regards to educational level, illiterate patients (hazard ratio: 1.63, 95% CI: 1.56-1.70) had a higher risk than those with a university or college degree. Some common comorbidities were more dangerous for hospitalized patients, such as liver disease (HR: 1.46, 95% CI: 1.34-1.59) and immunosuppression (HR:1.32, 95% CI: 1.26-1.40). In addition, the states involving Sergipe (HR: 1.75, 95% CI: 1.46-2.11), Roraima (HR: 1.65, 95% CI: 1.43-1.92), Maranhão (HR: 1.57, 95% CI: 1.38-1.79), Acre (HR: 1.44, 95% CI: 1.12-1.86), and Rondônia (HR: 1.26, 95% CI: 1.10-1.44) in the north and the northeast region tended to have higher hazard ratios than other area. In terms of vaccine protection, vaccination did not significantly reduce mortality among hospitalized patients. Sinovac and AstraZeneca offered different protection in different regions, and no vaccine provided high protection in all regions.ConclusionThe study revealed the regional heterogeneity of in-hospital mortality of Covid-19 in Brazil and the effects of vaccination and social inequality. We found that ethnic concentrations were consistent with higher proportion of death cases relative to population size. White Brazilians had more frequent international travel opportunities. As race revealed the intersection of social connections, we speculated that uneven interactions with residential communities partially contribute to the spread of the epidemic. Additionally, the vaccine showed different protection in different regions. In the northern and northeastern regions, AstraZeneca was much more protective than Sinovac, while Sinovac was more protective for hospitalized patients with varying numbers of comorbidities in the Central-west, Southeast and South regions.
| S-EPMC9250816 | biostudies-literature
Project description:BackgroundThe ongoing Coronavirus disease of 2019 (COVID-19) pandemic has hit Brazil hard in period of different dominant variants. Different COIVD-19 variants have swept through the region, resulting that the total number of cases in Brazil is the third highest in the world. This study is aimed at investigating the regional heterogeneity of in-hospital mortality of COVID-19 in Brazil and the effects of vaccination and social inequality.MethodsWe fitted a multivariate mixed-effects Cox model to a national database of inpatient data in Brazil who were admitted for COVID-19 from February 27, 2020 to March 15, 2022. The in-hospital mortality risks of vaccinated and unvaccinated patients were compared, with adjustment for age, state, ethnicity, education and comorbidities. And the effects of variables to in-hospital mortality were also compared. Stratified analysis was conducted across different age groups and vaccine types.ResultsBy fitting the multivariate mixed-effects Cox model, we concluded that age was the most important risk factor for death. With regards to educational level, illiterate patients (hazard ratio: 1.63, 95% CI: 1.56-1.70) had a higher risk than those with a university or college degree. Some common comorbidities were more dangerous for hospitalized patients, such as liver disease (HR: 1.46, 95% CI: 1.34-1.59) and immunosuppression (HR:1.32, 95% CI: 1.26-1.40). In addition, the states involving Sergipe (HR: 1.75, 95% CI: 1.46-2.11), Roraima (HR: 1.65, 95% CI: 1.43-1.92), Maranhão (HR: 1.57, 95% CI: 1.38-1.79), Acre (HR: 1.44, 95% CI: 1.12-1.86), and Rondônia (HR: 1.26, 95% CI: 1.10-1.44) in the north and the northeast region tended to have higher hazard ratios than other area. In terms of vaccine protection, vaccination did not significantly reduce mortality among hospitalized patients. Sinovac and AstraZeneca offered different protection in different regions, and no vaccine provided high protection in all regions.ConclusionThe study revealed the regional heterogeneity of in-hospital mortality of Covid-19 in Brazil and the effects of vaccination and social inequality. We found that ethnic concentrations were consistent with higher proportion of death cases relative to population size. White Brazilians had more frequent international travel opportunities. As race revealed the intersection of social connections, we speculated that uneven interactions with residential communities partially contribute to the spread of the epidemic. Additionally, the vaccine showed different protection in different regions. In the northern and northeastern regions, AstraZeneca was much more protective than Sinovac, while Sinovac was more protective for hospitalized patients with varying numbers of comorbidities in the Central-west, Southeast and South regions.
| S-EPMC9250816 | biostudies-literature
Project description:BackgroundThe ongoing Coronavirus disease of 2019 (COVID-19) pandemic has hit Brazil hard in period of different dominant variants. Different COIVD-19 variants have swept through the region, resulting that the total number of cases in Brazil is the third highest in the world. This study is aimed at investigating the regional heterogeneity of in-hospital mortality of COVID-19 in Brazil and the effects of vaccination and social inequality.MethodsWe fitted a multivariate mixed-effects Cox model to a national database of inpatient data in Brazil who were admitted for COVID-19 from February 27, 2020 to March 15, 2022. The in-hospital mortality risks of vaccinated and unvaccinated patients were compared, with adjustment for age, state, ethnicity, education and comorbidities. And the effects of variables to in-hospital mortality were also compared. Stratified analysis was conducted across different age groups and vaccine types.ResultsBy fitting the multivariate mixed-effects Cox model, we concluded that age was the most important risk factor for death. With regards to educational level, illiterate patients (hazard ratio: 1.63, 95% CI: 1.56-1.70) had a higher risk than those with a university or college degree. Some common comorbidities were more dangerous for hospitalized patients, such as liver disease (HR: 1.46, 95% CI: 1.34-1.59) and immunosuppression (HR:1.32, 95% CI: 1.26-1.40). In addition, the states involving Sergipe (HR: 1.75, 95% CI: 1.46-2.11), Roraima (HR: 1.65, 95% CI: 1.43-1.92), Maranhão (HR: 1.57, 95% CI: 1.38-1.79), Acre (HR: 1.44, 95% CI: 1.12-1.86), and Rondônia (HR: 1.26, 95% CI: 1.10-1.44) in the north and the northeast region tended to have higher hazard ratios than other area. In terms of vaccine protection, vaccination did not significantly reduce mortality among hospitalized patients. Sinovac and AstraZeneca offered different protection in different regions, and no vaccine provided high protection in all regions.ConclusionThe study revealed the regional heterogeneity of in-hospital mortality of Covid-19 in Brazil and the effects of vaccination and social inequality. We found that ethnic concentrations were consistent with higher proportion of death cases relative to population size. White Brazilians had more frequent international travel opportunities. As race revealed the intersection of social connections, we speculated that uneven interactions with residential communities partially contribute to the spread of the epidemic. Additionally, the vaccine showed different protection in different regions. In the northern and northeastern regions, AstraZeneca was much more protective than Sinovac, while Sinovac was more protective for hospitalized patients with varying numbers of comorbidities in the Central-west, Southeast and South regions.
| S-EPMC9250816 | biostudies-literature
Project description:Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA-Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups.
2022-07-19 | E-MTAB-10926 | biostudies-arrayexpress
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.
2020-08-29 | GSE157103 | GEO
Project description:Genome-wide DNA methylation analysis of COVID-19 severity using the Illumina HumanMethylationEPIC microarray platform to analyze over 850,000 methylation sites, comparing COVID-19 patients with patients presenting with respiratory symptoms, but negative for COVID-19, using whole blood tissue.
2021-05-31 | GSE174818 | GEO
Project description:COVID-19 is an outbreak of viral pneumonia which became a global health crisis, and the risk of morbidity and mortality of people with obesity are higher. SARS-CoV-2, the pathogen of COVID-19, enters into cells through binding to the Angiotensin Converting Enzyme (ACE) homolog-2 (ACE2). ACE2 is a regulator of two contrary pathways in renin angiotensin system (RAS): ACE-Ang-II-AT1R axis and ACE2-Ang 1-7-Mas axis. Viral entry process eventuates in downregulation of ACE2 and subsequent activation of ACE-Ang-II-AT1R axis. ACE-Ang II-AT1R axis increases lipid storage, reduces white-to-beige fat conversion and plays role in obesity. Conversely, adipose tissue is an important source of angiotensin, and obesity results in increased systemic RAS. ACE-Ang-II-AT1R axis, which has proinflammatory, profibrotic, prothrombotic, and vasoconstrictive effects, is potential mechanism of more severe SARS-CoV-2 infection. The link between obesity and severe COVID-19 may be attributed to ACE2 consumption and subsequent ACE-Ang-II-AT1R axis activation. Therefore, patients with SARS-CoV-2 infection may benefit from therapeutic strategies that activate ACE2-Ang 1-7-Mas axis, such as Ang II receptor blockers (ARBs), ACE inhibitors (ACEIs), Mas receptor agonists and ACE2.
| S-EPMC7361069 | biostudies-literature
Project description:A strong association between obesity and COVID-19 complications and a lack of prognostic factors that explain the unpredictable severity among these patients still exist despite the various vaccination programs. The expression of angiotensin converting enzyme 2 (ACE2), the main receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is enhanced in obese individuals. The occurrence of frequent genetic single nucleotide polymorphisms (SNPs) in ACE2 is suggested to increase COVID-19 severity. Accordingly, we hypothesize that obesity-associated ACE2 polymorphisms increase the severity of COVID-19. In this study, we profiled eight frequently reported ACE2 SNPs in a cohort of lean and obese COVID-19 patients (n = 82). We highlight the significant association of rs2285666, rs2048683, rs879922, and rs4240157 with increased severity in obese COVID-19 patients as compared to lean counterparts. These co-morbid-associated SNPs tend to positively correlate, hence proposing possible functional cooperation to ACE2 regulation. In obese COVID-19 patients, rs2285666, rs879922, and rs4240157 are significantly associated with increased blood nitrogen urea and creatinine levels. In conclusion, we highlight the contribution of ACE2 SNPs in enhancing COVID-19 severity in obese individuals. The results from this study provide a basis for further investigations required to shed light on the underlying mechanisms of COVID-19 associated SNPs in COVID-19 obese patients.
| S-EPMC9748040 | biostudies-literature