Targeting inflammation with collagen.

Tissue damage caused by an infection oran autoimmune disease triggers degradation of collagen in the extracellular matrix (ECM), which further enhances inflammation. Therefore, improving ECM in aninflamed tissue can be exploited as a potential therapeutic target. A recentstudy emphasised an innovative approach against COVID-19 using polymerised type I collagen (PTIC) that improves disease severity through a hitherto unknownmechanism. In this paper, we provide an overview of potential mechanism thatmay explain the anti-inflammatory effect of collagen peptides. In addition,the paper includes a brief summary of possible side effect of collagendeposition in inflammatory diseases. Altogether, current knowledge suggeststhat collagen may potentially reduce the residual risk in inflammatorydiseases; however, the detailed mechanism remains elusive.

Incidence and predictors of cardiac arrhythmias in patients with COVID-19 induced ARDS.

INTRODUCTION: Recent studies suggest cardiac involvement with an increased incidence of arrhythmias in the setting of coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the risk of potentially lethal arrhythmias and atrial fibrillation in patients with COVID-19-induced acute respiratory distress syndrome (ARDS) and to elicit possible predictors of arrhythmia occurrence. METHODS AND RESULTS: A total of 107 patients (82 male, mean age 60 ±â€¯12 years, median body mass index 28 kg/m2) treated for COVID-19-induced ARDS in a large tertiary university hospital intensive care unit between March 2020 and February 2021 were retrospectively analyzed. Eighty-four patients (79%) had at least moderate ARDS, 88 patients (83%) were mechanically ventilated, 35 patients (33%) received vvECMO. Forty-three patients (40%) died during their hospital stay. Twelve patients (11%) showed potentially lethal arrhythmias (six ventricular tachycardia, six significant bradycardia). Atrial fibrillation occurred in 27 patients (25%). In a multivariate logistic regression analysis, duration of hospitalization was associated with the occurrence of potentially lethal arrhythmias (p = 0.006). There was no association between possible predictive factors and the occurrence of atrial fibrillation. Invasive ventilation, antipsychotics, and the QTc interval were independently associated with acute in-hospital mortality, but this was not arrhythmia-driven as there was no association between the occurrence of arrhythmias and mortality. CONCLUSION: In this relatively young population with COVID-19-induced ARDS, the incidence of potentially lethal arrhythmias was low. While overall mortality was high in these severely affected patients, cardiac involvement and arrhythmia occurrence was not a significant driver of mortality.

Dexamethasone Improves Cardiovascular Outcomes in Critically Ill COVID-19, a Real World Scenario Multicenter Analysis.

BACKGROUND: Severe COVID-19 pneumonia requiring intensive care treatment remains a clinical challenge to date. Dexamethasone was reported as a promising treatment option, leading to a reduction of mortality rates in severe COVID-19 disease. However, the effect of dexamethasone treatment on cardiac injury and pulmonary embolism remains largely elusive. METHODS: In total 178 critically ill COVID-19 patients requiring intensive care treatment and mechanical ventilation were recruited in three European medical centres and included in the present retrospective study. One hundred thirteen patients (63.5%) were treated with dexamethasone for a median duration of 10 days (IQR 9-10). Sixty five patients (36.5%) constituted the non-dexamethasone control group. RESULTS: While peak inflammatory markers were reduced by dexamethasone treatment, the therapy also led to a significant reduction in peak troponin levels (231 vs. 700% indicated as relative to cut off value, p = 0.001). Similar, dexamethasone resulted in significantly decreased peak D-Dimer levels (2.16 mg/l vs. 6.14 mg/l, p = 0.002) reflected by a significant reduction in pulmonary embolism rate (4.4 vs. 20.0%, p = 0.001). The antithrombotic effect of dexamethasone treatment was also evident in the presence of therapeutic anticoagulation (pulmonary embolism rate: 6 vs. 34.4%, p < 0.001). Of note, no significant changes in baseline characteristics were observed between the dexamethasone and non-dexamethasone group. CONCLUSION: In severe COVID-19, anti-inflammatory effects of dexamethasone treatment seem to be associated with a significant reduction in myocardial injury. Similar, a significant decrease in pulmonary embolism, independent of anticoagulation, was evident, emphasizing the beneficial effect of dexamethasone treatment in severe COVID-19.

Higher Incidence of Stroke in Severe COVID-19 Is Not Associated With a Higher Burden of Arrhythmias: Comparison With Other Types of Severe Pneumonia

Aims: Thromboembolic events, including stroke, are typical complications of COVID-19. Whether arrhythmias, frequently described in severe COVID-19, are disease-specific and thus promote strokes is unclear. We investigated the occurrence of arrhythmias and stroke during rhythm monitoring in critically ill patients with COVID-19, compared with severe pneumonia of other origins. Methods and Results: This retrospective study included 120 critically ill patients requiring mechanical ventilation in three European tertiary hospitals, including n =60 COVID-19, matched according to risk factors for the occurrence of arrhythmias in n = 60 patients from a retrospective consecutive cohort of severe pneumonia of other origins. Arrhythmias, mainly atrial fibrillation (AF), were frequent in COVID-19. However, when compared with non-COVID-19, no difference was observed with respect to ventricular tachycardias (VT) and relevant bradyarrhythmias (VT 10.0 vs. 8.4 %, p = ns and asystole 5.0 vs. 3.3%, p = ns) with consequent similar rates of cardiopulmonary resuscitation (6.7 vs. 10.0%, p = ns). AF was even more common in non-COVID-19 (AF 18.3 vs. 43.3%, p = 0.003;newly onset AF 10.0 vs. 30.0%, p = 0.006), which resulted in a higher need for electrical cardioversion (6.7 vs. 20.0%, p = 0.029). Despite these findings and comparable rates of therapeutic anticoagulation (TAC), the incidence of stroke was higher in COVID-19 (6.7.% vs. 0.0, p = 0.042). These events also happened in the absence of AF (50%) and with TAC (50%). Conclusions: Arrhythmias were common in severe COVID-19, consisting mainly of AF, yet less frequent than in matched pneumonia of other origins. A contrasting higher incidence of stroke independent of arrhythmias also observed with TAC, seems to be an arrhythmia-unrelated disease-specific feature of COVID-19.

Deadly COVID-19 among the elderly: Innate immune memory helping those most in need.

Age is a key risk factor associated with the severity of symptoms caused by SARS-CoV-2, and there is an urgent need to reduce COVID-19 morbidity and mortality in elderly individuals. We discuss evidence suggesting that trained immunity elicited by BCG vaccination may improve immune responses and can serve as a strategy to combat COVID-19 in this population.

Myocardial injury in severe COVID-19 is similar to pneumonias of other origin: results from a multicentre study.

AIMS: COVID-19, a respiratory viral disease causing severe pneumonia, also affects the heart and other organs. Whether its cardiac involvement is a specific feature consisting of myocarditis, or simply due to microvascular injury and systemic inflammation, is yet unclear and presently debated. Because myocardial injury is also common in other kinds of pneumonias, we investigated and compared such occurrence in severe pneumonias due to COVID-19 and other causes. METHODS AND RESULTS: We analysed data from 156 critically ill patients requiring mechanical ventilation in four European tertiary hospitals, including all n = 76 COVID-19 patients with severe disease course requiring at least ventilatory support, matched to n = 76 from a retrospective consecutive patient cohort of severe pneumonias of other origin (matched for age, gender, and type of ventilator therapy). When compared to the non-COVID-19, mortality (COVID-19 = 38.2% vs. non-COVID-19 = 51.3%, P = 0.142) and impairment of systolic function were not significantly different. Surprisingly, myocardial injury was even more frequent in non-COVID-19 (96.4% vs. 78.1% P = 0.004). Although inflammatory activity [C-reactive protein (CRP) and interleukin-6] was indifferent, d-dimer and thromboembolic incidence (COVID-19 = 23.7% vs. non-COVID-19 = 5.3%, P = 0.002) driven by pulmonary embolism rates (COVID-19 = 17.1% vs. non-COVID-19 = 2.6%, P = 0.005) were higher. CONCLUSIONS: Myocardial injury was frequent in severe COVID-19 requiring mechanical ventilation, but still less frequent than in similarly severe pneumonias of other origin, indicating that cardiac involvement may not be a specific feature of COVID-19. While mortality was also similar, COVID-19 is characterized with increased thrombogenicity and high pulmonary embolism rates.

Altered Cholesterol and Lipid Synthesis Mediates Hyperinflammation in COVID-19.

Recent data have revealed that fructose-rich diet triggers inflammation and lipid synthesis. Furthermore, lipid metabolism, cholesterol synthesis and sterol regulatory element binding protein-2 (SREBP-2) activation correlates with coronavirus disease 2019 (COVID-19)-induced cytokine storm. High fructose consumption result in SREBPs activation, altered cholesterol and lipid synthesis and may establish an innate immune memory in the cells, leading to severe COVID-19 in patients with obesity.