Co-exposure to urban particulate matter and aircraft noise adversely impacts the cerebro-pulmonary-cardiovascular axis in mice

Worldwide, up to 8.8 million excess deaths/year have been attributed to air pollution, mainly due to the exposure to fine particulate matter (PM). Traffic-related noise is an additional contributor to global mortality and morbidity. Both health risk factors substantially contribute to cardiovascular, metabolic and neuropsychiatric sequelae. Studies on the combined exposure are rare and urgently needed because of frequent co-occurrence of both risk factors in urban and industrial settings. To study the synergistic effects of PM and noise, we used an exposure system equipped with aerosol generator and loud-speakers, where C57BL/6 mice were acutely exposed for 3d to either ambient PM (NIST particles) and/or noise (aircraft landing and take-off events). The combination of both stressors caused endothelial dysfunction, increased blood pressure, oxidative stress and inflammation. An additive impairment of endothelial function was observed in isolated aortic rings and even more pronounced in cerebral and retinal arterioles. The increase in oxidative stress and inflammation markers together with RNA sequencing data indicate that noise particularly affects the brain and PM particularly affects the lungs. Noise also increased levels of circulating stress hormones adrenaline and noradrenaline, while PM increased levels of circulating cytokines CD68 and MCP-1. The combination of both stressors has additive adverse effects on the cardiovascular system that are based on PM-induced systemic inflammation and noise-triggered stress hormone signaling. We demonstrate an additive upregulation of ACE-2 in the lung, suggesting that there may be an increased vulnerability to COVID-19 infection. The data warrant further mechanistic studies to characterize the propagation of primary target tissue damage (lung, brain) to remote organs such as aorta and heart by combined noise and PM exposure.Copyright © 2023

Trends and risk factors of in-hospital mortality of patients with COVID-19 in Germany

Background: Unselected data of nationwide studies of hospitalized patients with COVID-19 is still sparse, but these data are of outstanding interest not to exceed hospital capacities and to avoid overloading of national health-care systems. Purpose(s): Thus, we sought to analyze seasonal/regional trends, predictors of in-hospital case-fatality and mechanical ventilation (MV) in patients with COVID-19 in Germany. Method(s): We used the German nationwide inpatient sample to analyze all hospitalized patients with confirmed COVID-19 diagnosis in Germany between January 1st and December 31st in 2020 (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2020, own calculations). Covid-19-inpatients with MV vs. without MV and survivors vs. non-survivors were compared. Logistic regression models were calculated to investigate associations between patients' characteristics as well as adverse events and i) necessity of MV and ii) in-hospital death. Result(s): We analyzed data of 176,137 hospitalizations of patients with confirmed COVID-19-infection. Among those, 31,607 (17.9%) died, whereby in-hospital case-fatality grew exponentially with age. Cardiovascular comorbidities were common in hospitalized patients with confirmed COVID-19-infections: Overall, almost half of the patients (46.8%;n=82,480) had arterial hypertension and 25,574 (14.4%) had a diagnosis of coronary artery disease. In 60.7% (n=106,913) of the hospitalizations, pneumonia was reported, 8.6% (n=15,061) had an acute infection of the upper or lower airways other than pneumonia, and 6.6% (n=11,594) suffered from an acute respiratory distress syndrome (ARDS) during hospitalization Age >=70 years (OR 5.91, 95% CI 5.70-6.13, P<0.001), pneumonia (OR 4.58, 95% CI 4.42-4.74, P<0.001) and acute respiratory distress syndrome (OR 8.51, 95% CI 8.12-8.92, P<0.001) were strong predictors of in-hospital death. Most COVID-19-patients were treated in hospitals in urban areas (n=92,971) associated with lowest case-fatality (17.5%) as compared to hospitals in suburban (18.3%) or rural areas (18.8%). MV demand was highest in November/December 2020 (32.3%, 20.3%) in patients between 6th and 8th age-decade. In the first age-decade, 78 of 1861 children (4.2%) with COVID-19-infection were treated with MV and five of them died (0.3%). Conclusion(s): The results of our study indicate seasonal and regional variations concerning number of COVID-19-patients, necessity of MV and casefatality in Germany. These findings may help to ensure flexible allocation of intensive care (human) resources, which is essential for managing enormous societal challenges worldwide to avoid overloaded regional healthcare systems.

COVID-19 infection and its impact on case-fatality in patients with pulmonary embolism

Background: Although a high prevalence of pulmonary embolism (PE) has been reported as a complication during severe COVID-19 infections in critical ill patients, nationwide data of hospitalized patients with COVID-19 with PE is still limited. Thus, we sought to analyze seasonal trends and predictors of in-hospital case-fatality in patients with COVID-19 and PE in Germany. Method(s): We used the German nationwide inpatient sample to analyze all data on hospitalizations for COVID-19 patients with and without PE in Germany during the year 2020 and to compare changes of PE prevalence to 2019. Result(s):We analyzed data of 176,137 hospitalizations because of COVID- 19 in 2020. Among those, PE was recorded in 1.9% (n=3,362) of discharge or death certificates. Almost one third of patients with COVID-19 and PE died during the in-hospital course (28.7%). The case-fatality rate increased with patients' age peaking in the 9th life-decade. Regardless of COVID-19, 196,203 inpatients were diagnosed with PE in Germany between 2019 and 2020. The number of PE hospitalizations were widely equally distributed between both years (98,485 vs. 97,718), while the case-fatality rate of all patients with PE was slightly lower in 2019 compared to 2020 (12.7% vs. 13.1%, P<0.001). In contrast, considerable differences in prevalence and case-fatality were demonstrated in 2020 regarding PE patients with and without COVID-19 infection (28.7% vs. 13.1%, P<0.001) (Figure 1). A COVID-19-infection was associated with a 2.8-fold increased risk of casefatality in patients with PE (OR 2.81, 95% CI 1.66-2.12, P<0.001). Conclusion(s): In Germany, the prevalence of PE events complicating hospitalizations was similar in 2019 and 2020. However, the fatality rate among patients with COVID-19-associated PE was substantially higher than that in those without either COVID-19 or PE, indicating an additive prognostic effect of these two conditions.

Air pollution as important cofactor in COVID-19 deaths

Background: The mortality from COVID-19 is increased in the presence of cardiopulmonary comorbidities. Air pollution is also associated with increased mortality, primarily mediated by cardiopulmonary diseases. Observations at the beginning of the COVID-19 pandemic showed that mortality from COVID-19 was increased, especially in regions with higher levels of air pollution. The influence of air pollution on the course of the disease in COVID-19 is unclear. Method: A selective literature search of studies up to the beginning of April 2021 was carried out in PubMed on the association between air pollution and COVID-19 mortality using the search terms “air pollution AND/OR COVID-19/coronavirus/SARS-CoV‑2 AND/OR mortality”. Results: Current research shows that around 15% of global COVID-19 deaths are due to air pollution. The proportion of COVID-19 deaths from air pollution is 19% in Europe, 17% in North America and 27% in East Asia. This role of air pollution in COVID-19 deaths has now been confirmed by various studies from the USA, Italy and England. Air pollution and COVID-19 result in similar damage to the cardiopulmonary system, which may explain the link between air pollution and increased COVID-19 mortality. Conclusion: The environmental aspect of the COVID-19 pandemic shown here calls for greater efforts to be made towards effective measures to reduce anthropogenic emissions, which cause both air pollution and climate change.

Endothelium, Vascular Function and COVID-19

The global involvement of coronavirus disease 19 (COVID-19) provokes multiple findings about the clinical course in three phases, the infection pathway and the vascular function. Severe course of SARS- CoV-2- infection is defined as massive inflammatory reaction with elevated pro-inflammatory cytokines resulting in acute respiratory stress syndrome and the involvement of secondary organ damages with even life-threatening cardiovascular and pulmonary complications. Mechanistically, SARS-CoV-2 invades human cells with binding at angiotensin converting enzyme 2 and following another secondary pathway with ADAM17-mediated systemic release of cytokines and pro-inflammatory markers. Systemic inflammation and vasoconstriction lead to hypoxia and pro-thrombotic complications. Microvascular dysfunction, microangiopathy of small lung vessels and endotheliitis may provide new approaches for systemic inflammation due to SARS- CoV-2 infection.