Differences in Outcomes and Factors Associated With Mortality Among Patients With SARS-CoV-2 Infection and Cancer Compared With Those Without Cancer A Systematic Review and Meta-analysis

IMPORTANCE: SARS-CoV-2 infection has been associated with more severe disease and death in patients with cancer. However, the implications of certain tumor types, treatments, and the age and sex of patients with cancer for the outcomes of COVID-19 remain unclear. OBJECTIVE: To assess the differences in clinical outcomes between patients with cancer and SARS-CoV-2 infection and patients without cancer but with SARS-CoV-2 infection, and to identify patients with cancer at particularly high risk for a poor outcome. DATA SOURCES: PubMed, Web of Science, and Scopus databases were searched for articles published in English until June 14, 2021. References in these articles were reviewed for additional studies. STUDY SELECTION: All case-control or cohort studies were included that involved 10 or more patients with malignant disease and SARS-CoV-2 infection with or without a control group (defined as patients without cancer but with SARS-CoV-2 infection). Studies were excluded if they involved fewer than 10 patients, were conference papers or abstracts, were preprint reports, had no full text, or had data that could not be obtained from the corresponding author. DATA EXTRACTION AND SYNTHESIS: Two investigators independently performed data extraction using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Meta-analysis was performed using a random-effects model. MAIN OUTCOMES AND MEASURES: The difference in mortality between patients with cancer and SARS-CoV-2 infection and control patients as well as the difference in outcomes for various tumor types and cancer treatments. Pooled case fatality rates, a random-effects model, and random-effects meta-regressions were used. RESULTS: A total of 81 studies were included, involving 61 532 patients with cancer. Among 58 849 patients with available data, 30 557 male individuals (52%) were included and median age ranged from 35 to 74 years. The relative risk (RR) of mortality from COVID-19 among patients with vs without cancer when age and sex were matched was 1.69 (95% CI, 1.46-1.95; P < .001; I(2) = 51.0%). The RR of mortality in patients with cancer vs control patients was associated with decreasing age (exp [b], 0.96; 95% CI, 0.92-0.99; P = .03). Compared with other cancers, lung cancer (RR, 1.68; 95% CI, 1.45-1.94; P < .001; I(2) = 32.9%), and hematologic cancer (RR, 1.42; 95% CI, 1.31-1.54; P < .001; I(2) = 6.8%) were associated with a higher risk of death. Although a higher point estimate was found for genitourinary cancer (RR, 1.11; 95% CI, 1.00-1.24; P = .06; I2 = 21.5%), the finding was not statistically significant. Breast cancer (RR, 0.51; 95% CI, 0.36-0.71; P < .001; I(2) = 86.2%) and gynecological cancer (RR, 0.76; 95% CI, 0.62-0.93; P = .009; I(2) = 0%) were associated with a lower risk of death. Chemotherapy was associated with the highest overall pooled case fatality rate of 30% (95% CI, 25%-36%; I(2) = 86.97%; range, 10%-100%), and endocrine therapy was associated with the lowest at 11% (95% CI, 6%-16%; I(2) = 70.68%; range, 0%-27%). CONCLUSIONS AND RELEVANCE: Results of this study suggest that patients with cancer and SARS-CoV-2 infection had a higher risk of death than patients without cancer. Younger age, lung cancer, and hematologic cancer were also risk factors associated with poor outcomes from COVID-19

Deliberative Democracy in the EU. Countering Populism with Participation and Debate. CEPS Paperback

Elections are the preferred way to freely transfer power from one term to the next and from one political party or coalition to another. They are an essential element of democracy. But if the process of power transfer is corrupted, democracy risks collapse. Reliance on voters, civil society organisations and neutral observers to fully exercise their freedoms as laid down in international human rights conventions is an integral part of holding democratic elections. Without free, fair and regular elections, liberal democracy is inconceivable. Elections are no guarantee that democracy will take root and hold, however. If the history of political participation in Europe over the past 800 years is anything to go by, successful attempts at gaining voice have been patchy, while leaders’ attempts to silence these voices and consolidate their own power have been almost constant (Blockmans, 2020). Recent developments in certain EU member states have again shown us that democratically elected leaders will try and use majoritarian rule to curb freedoms, overstep the constitutional limits of their powers, protect the interests of their cronies and recycle themselves through seemingly free and fair elections. In their recent book How Democracies Die, two Harvard professors of politics write: “Since the end of the Cold War, most democratic breakdowns have been caused not by generals and soldiers but by elected governments themselves” (Levitsky and Ziblatt, 2018)

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that -80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAFPeer reviewe

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts