Background: Coronavirus disease 19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin-converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to the accumulation of bradykinin. Methods: In this case control study, we tested two pharmacological inhibitors of the kinin–kallikrein system that are currently approved for the treatment of hereditary angioedema, icatibant, and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Results: Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in changes in time to clinical improvement. However, both compounds were safe and promoted the significant improvement of lung computed tomography scores and increased blood eosinophils, which are indicators of disease recovery. Conclusions: In this small cohort, we found evidence for safety and a beneficial role of pharmacological inhibition of the kinin–kallikrein system in two markers that indicate improved disease recovery.

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Background SARS-CoV-2, the virus that causes COVID-19, enters the cells through a mechanism dependent on its binding to angiotensin-converting enzyme 2 (ACE2), a protein highly expressed in the lungs. The putative viral-induced inhibition of ACE2 could result in the defective degradation of bradykinin, a potent inflammatory substance. We hypothesize that increased bradykinin in the lungs is an important mechanism driving the development of pneumonia and respiratory failure in COVID-19. Methods This is a phase II, single-center, three-armed parallel-group, open-label, active control superiority randomized clinical trial. One hundred eighty eligible patients will be randomly assigned in a 1:1:1 ratio to receive either the inhibitor of C1e/kallikrein 20 U/kg intravenously on day 1 and day 4 plus standard care; or icatibant 30 mg subcutaneously, three doses/day for 4 days plus standard care; or standard care alone, as recommended in the clinical trials published to date, which includes supplemental oxygen, non-invasive and invasive ventilation, antibiotic agents, anti-inflammatory agents, prophylactic antithrombotic therapy, vasopressor support, and renal replacement therapy. Discussion Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough. In animal models, the inactivation of ACE2 leads to severe acute pneumonitis in response to lipopolysaccharide (LPS), and the inhibition of bradykinin almost completely restores the lung structure. We believe that inhibition of bradykinin in severe COVID-19 patients could reduce the lung inflammatory response, impacting positively on the severity of disease and mortality rates. Trial registration Brazilian Clinical Trials Registry Universal Trial Number (UTN) U1111-1250-1843. Registered on May/5/2020.

Whether the content of saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA) could differently influence postprandial triglycerides (TG) is unknown. We examined possible differences in the postprandial TG response to fat tolerance tests (FTTs), in which SFA or unsaturated fatty acids were used. Crossover clinical trials investigating the effects of FTTs containing SFA and unsaturated fats on postprandial triglyceridemia in databases from 1994 until 2016 were searched. Of 356 studies, 338 were excluded and 18 were considered. TG net incremental areas under the curve were calculated using time-points or changes from baseline. Pooled effects of standardized mean differences and I2 test were used. Results: In 12 studies, responses to SFA versus PUFA meals, and in 16 studies versus MUFA meals were compared. Over 4 h, no differences between SFA and unsaturated fats were observed. Over 8 h a lower response to PUFA (SMD −2.28; 95% CI −4.16, −0.41) and a trend to lower response to MUFA (SMD −0.89, 95% CI −1.82, 0.04) were detected. FTTs shorter than 8 h may not be sufficient to differentiate postprandial TG after challenges with distinct fatty acids. Clinical significance of different postprandial TG responses on cardiovascular risk in the long-term deserves investigation.

BackgroundDietary guidelines of 5 servings per day of fruits and vegetables (FV) offer a reasonable amount of vitamins to control organic processes, which may contribute to a favorable cardiometabolic profile. This study aimed at investigating whether the intake of the FV group as well as pro-vitamin A carotenoids and vitamins C and E were associated with circulating markers of oxidative stress, inflammation and insulin resistance in Brazilians individuals at cardiometabolic risk.MethodsThis cross-sectional study included 205 individuals screened for diabetes prevention program in a healthcare center from the School of Public Health, University of São Paulo, conducted in 2008. Possible associations of consumption of FV group, as well as pro-vitamin A carotenoids and vitamins C and E, with circulating markers of oxidative stress (superoxide dismutase – SOD and oxidized LDL – oxLDL), inflammation (C reactive protein, TNF-α and adiponectin) and insulin resistance (HOMA-IR) were investigated. Pearson correlation coefficient, ANOVA and multiple linear regression were employed.ResultsThe sample (64.7% women) had a mean age of 54.1 ± 12.7 years and body mass index of 30.7 ± 5.7 kg/m2. Dietary, physical activity, anthropometric and laboratory data were obtained. Participants consumed a mean of 3.8 servings/day of FV; their FV intake was categorized into three groups: <2.5, 2.5-5.0 and >5.0 servings/day. Significant trends for lower waist circumference (103.4 ± 13.6 vs. 100.1 ± 12.2 vs. 98.2 ± 12.7 cm, p-trend <0.05) and higher adiponectin concentrations (10.4 ± 1.8 vs. 11.9 ± 1.9 vs. 13.6 ± 2.1 ng/mL, p-trend <0.05) were detected across categories. Associations between SOD concentrations (β 0.172 [0.110-0.688]) with FV consumption and between oxLDL concentrations with vitamins C (β -0.333 [−2.568 – -0.218]) and E (β -0.354 [−1.131– -0.110]) intakes, adjusted for age, gender, BMI, saturated fat intake, smoking and physical activity were found. Similar results were observed for the associations between oxLDL and FV intake, but significance disappeared adding adjustment for saturated fat, smoking and physical activity.ConclusionOur data suggest that the intake of FV or selected vitamins may be useful for identifying the oxidative stress and inflammation involved in the genesis of cardiometabolic diseases and for motivating at-risk patients for changing dietary habits.