Prognostic factors for mortality, intensive care unit and hospital admission due to SARS-CoV-2: a systematic review and meta-analysis of cohort studies in Europe.

BACKGROUND: As mortality from coronavirus disease 2019 (COVID-19) is strongly age-dependent, we aimed to identify population subgroups at an elevated risk for adverse outcomes from COVID-19 using age-/gender-adjusted data from European cohort studies with the aim to identify populations that could potentially benefit from booster vaccinations. METHODS: We performed a systematic literature review and meta-analysis to investigate the role of underlying medical conditions as prognostic factors for adverse outcomes due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including death, hospitalisation, intensive care unit (ICU) admission and mechanical ventilation within three separate settings (community, hospital and ICU). Cohort studies that reported at least age and gender-adjusted data from Europe were identified through a search of peer-reviewed articles published until 11 June 2021 in Ovid Medline and Embase. Results are presented as odds ratios with 95% confidence intervals and absolute risk differences in deaths per 1000 COVID-19 patients. FINDINGS: We included 88 cohort studies with age-/gender-adjusted data from 6 653 207 SARS-CoV-2 patients from Europe. Hospital-based mortality was associated with high and moderate certainty evidence for solid organ tumours, diabetes mellitus, renal disease, arrhythmia, ischemic heart disease, liver disease and obesity, while a higher risk, albeit with low certainty, was noted for chronic obstructive pulmonary disease and heart failure. Community-based mortality was associated with a history of heart failure, stroke, diabetes and end-stage renal disease. Evidence of high/moderate certainty revealed a strong association between hospitalisation for COVID-19 and solid organ transplant recipients, sleep apnoea, diabetes, stroke and liver disease. INTERPRETATION: The results confirmed the strong association between specific prognostic factors and mortality and hospital admission. Prioritisation of booster vaccinations and the implementation of nonpharmaceutical protective measures for these populations may contribute to a reduction in COVID-19 mortality, ICU and hospital admissions.

Causal inference regarding infectious aetiology of chronic conditions: a systematic review.

BACKGROUND: The global burden of disease has shifted from communicable diseases in children to chronic diseases in adults. This epidemiologic shift varies greatly by region, but in Europe, chronic conditions account for 86% of all deaths, 77% of the disease burden, and up to 80% of health care expenditures. A number of risk factors have been implicated in chronic diseases, such as exposure to infectious agents. A number of associations have been well established while others remain uncertain. METHODS AND FINDINGS: We assessed the body of evidence regarding the infectious aetiology of chronic diseases in the peer-reviewed literature over the last decade. Causality was assessed with three different criteria: First, the total number of associations documented in the literature between each infectious agent and chronic condition; second, the epidemiologic study design (quality of the study); third, evidence for the number of Hill's criteria and Koch's postulates that linked the pathogen with the chronic condition. We identified 3136 publications, of which 148 were included in the analysis. There were a total of 75 different infectious agents and 122 chronic conditions. The evidence was strong for five pathogens, based on study type, strength and number of associations; they accounted for 60% of the associations documented in the literature. They were human immunodeficiency virus, hepatitis C virus, Helicobacter pylori, hepatitis B virus, and Chlamydia pneumoniae and were collectively implicated in the aetiology of 37 different chronic conditions. Other pathogens examined were only associated with very few chronic conditions (≤ 3) and when applying the three different criteria of evidence the strength of the causality was weak. CONCLUSIONS: Prevention and treatment of these five pathogens lend themselves as effective public health intervention entry points. By concentrating research efforts on these promising areas, the human, economic, and societal burden arising from chronic conditions can be reduced.

Social determinants of tuberculosis in Europe: a prospective ecological study.

Tuberculosis (TB) is considered to be a disease of poverty, since its incidence is exacerbated by socioeconomic factors, inconsistent or partial treatment practices, and immigration from endemic countries. A prospective country level study, using a comprehensive dataset of TB incidence and prevalence taken from countries within the World Health Organization (WHO) European region, was conducted. We employed quintile regression to investigate the prospective association between baseline (measured in 2000) and a nation's wealth, level of egalitarianism, migration rate, health-related lifestyle and social capital with TB incidence and prevalence over a 10-yr period (2000-2009). We found that ∼50% of TB variation is accounted for by a nation's wealth and level of egalitarianism. We observed a negative prospective association between logged gross domestic product and TB rates, and a positive prospective association between income inequality and TB. National income levels per capita and income inequality are important predictors for TB incidence and prevalence in the WHO European region. They account for 50% of country-level variation, indicating the importance of a combined absolute and relative socioeconomic disadvantage in the development of TB. These findings also provide a tool for forecasting potential fluctuations in the level of TB epidemics in the WHO European region, with respect to socioeconomic changes.

Breast cancer risk and methylenetetrahydrofolate reductase polymorphism.

OBJECTIVE: Methylenetetrahydrofolate reductase (MTHFR), a polymorphic enzyme involved in folate metabolism, plays a role in DNA biosynthesis, methylation, and repair in actively dividing cells. Because breast-cell division occurs in women with active ovulatory cycles, polymorphisms in the MTHFR gene could be a risk factor for breast cancer. METHODS: We genotyped 352 clinic-based study subjects for MTHFR, 105 subjects with breast cancer and 247 with benign breast disease, histopathologically classified as high-risk or low-risk for breast cancer. Questionnaire data were collected prior to biopsy to blind subjects and interviewers to diagnoses. RESULTS: Premenopausal women with the MTHFR polymorphism had a threefold increased breast cancer risk (OR = 2.8; 95%CI: 1.02-7.51) compared to the clinic-based controls with benign breast disease. Results were similar using either low- or high-risk controls. However, risk for postmenopausal women was not elevated (OR = 0.8; 95%CI 0.4-1.4). No significant interaction between genotype and smoking or alcohol was found, but polymorphic MTHFR decreased the likelihood of drinking alcohol (OR = 0.5; 95%CI 0.3-0.9). CONCLUSION: These data suggest that polymorphic MTHFR increases risk of premenopausal, but not postmenopausal, breast cancer. These findings should be explored with a larger sample size in order to analyze gene-environment interactions between MTHFR and folate. Once the intricate relationship between diet and breast cancer has been elucidated, new cancer control initiatives can be considered such as folate chemoprevention trials in high-risk individuals.

Risk factors for acute myeloid leukemia and multiple myeloma: a combination of GIS and case-control studies.

Risk factors for acute myeloid leukemia (AML) and multiple myeloma (MM) include exposure to toxic chemicals present in tobacco smoke, as well as to emissions from industrial operations and petroleum refinery waste dumps. The study reported here identified these risk factors among case patients and control patients in Orange County, California, from 1984 to 1993 and determined the significance of the risk factors in the study population. A case-control study was performed for 604 cases of AML and 643 cases of MM; there were 7,112 control subjects who had colon cancer. The model included the variables smoking history, occupational history, and residence in a census tract with a petroleum refinery waste dump. A geographic information system (GIS) analysis also was performed to correlate the incidence of AML and MM with proximity to the six dump sites that received large amounts of petroleum refinery waste. Current smokers were found to be at an increased risk of AML with an odds ratio of 2.0. Laborer/equipment cleaners and transportation workers/movers were at risk of AML with odds ratios of 3.5 and 2.4, respectively. Construction/resource extraction workers were at risk of MM with an odds ratio of 2.8. GIS analysis determined that the risk for MM was 1.6 cases per mile for 10 or more years of residence near a large chemical dump. The authors were able to identify census tracts with a high incidence of AML and MM, and to perform distance analysis using a statistical measure of spatial randomness. The case-control study identified occupational and lifestyle risk factors for AML and MM that were not apparent from census-tract-level data.