Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these ...associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients.
Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group.
The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1β, MCP 1, and VEGF levels, total lymphocyte counts, and CD8
CD38
mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8
CD38
T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8
HLA-DR
CD38
cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR
CD38
cells.
Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying ...mechanism has not been fully elucidated.
Methods
All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury.
Results
The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8
+
CD38
+
mean fluorescence intensity (MFI), and percentage of CD8
+
human leukocyte antigen DR isotope (HLA-DR)
+
CD38
–
cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)
+
MFI, percentage of CD8
+
CD38
+
cells, CD8
+
HLA-DR
+
MFI, CD8
+
NKG2A
+
MFI, and percentage of CD8
+
HLA-DR
–
CD38
+
cells. On multivariate regression, the CD8
+
HLA-DR
+
MFI, CD8
+
CD38
+
MFI, and total lymphocyte count were associated significantly with myocardial injury.
Conclusion
Our findings suggest that lymphopenia, CD8
+
CD38
+
MFI, and CD8
+
HLA-DR
+
MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Cyoablation is a ablation technique underutilized except in parahissian pathways and atrial fibrillation ablation. Ablation inside venous coronary sinus remains a dreaded incursion, and cryoablation ...is rarely used. We present the case of a 43 YO female who had a recurrent wolff parkinson white syndrome due to an epicardial pathway inside the coronary sinus successfully treated with a large bore(8mm) cryocatheter. We also review literature and describe the advantages and similar reports of use of cryo in low flow recesses inside the heart.
Myocardial injury (MI), defined by troponin elevation, has been associated with increased mortality and adverse outcomes in patients with coronavirus disease 2019 (COVID-19), but the role of this ...biomarker as a risk predictor remains unclear. Data from adult patients hospitalized with COVID-19 were recorded prospectively. A multiple logistic regression model was used to quantify associations of all variables with in-hospital mortality, including the calculation of odds ratios (ORs) and confidence intervals (CI). Troponin measurement was performed in 1476 of 4628 included patients, and MI was detected in 353 patients, with a prevalence of 23.9%; 95% CI, 21.8–26.1%. The total in-hospital mortality rate was 10.9% 95% CI, 9.8–12.0%. The mortality was much higher among patients with MI than among those without MI, with a prevalence of 22.7% 95% CI, 18.5–27.3% vs. 5.5% 95% CI, 4.3–7.0% and increased with each troponin level. After adjustment for age and comorbidities, the model revealed that the mortality risk was greater for patients with MI OR = 2.99; 95% CI, 2.06–4.36%, and for those who did not undergo troponin measurement OR = 2.2; 95% CI, 1.62–2.97%, compared to those without MI. Our data support the role of troponin as an important risk predictor for these patients, capable of discriminating between those with a low or increased mortality rate. In addition, our findings suggest that this biomarker has a remarkable negative predictive value in COVID-19.
IMPORTANCE: It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in ...patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020). INTERVENTIONS: Discontinuation (n = 334) or continuation (n = 325) of ACEIs or ARBs. MAIN OUTCOMES AND MEASURES: The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression. RESULTS: Among 659 patients, the median age was 55.1 years (interquartile range IQR, 46.1-65.0 years), 14.7% were aged 70 years or older, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days SD, 8 days) vs patients in the continuation group (mean, 22.9 days SD, 7.1 days) and the mean ratio was 0.95 (95% CI, 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs 2.8% for the continuation group; odds ratio OR, 0.97 95% CI, 0.38-2.52), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95 95% CI, 0.19-42.12), or COVID-19 progression (38.3% vs 32.3%; OR, 1.30 95% CI, 0.95-1.80). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%). CONCLUSIONS AND RELEVANCE: Among patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04364893
In the present study, we investigated the protein levels and phosphorylation status of the insulin receptor and insulin receptor substrates (IRS-1, IRS-2, and IRS-3) as well as their association with ...PI(3)-kinase in the rat adipose tissue of two models of insulin resistance: dexamethasone treatment and aging. AKT and atypical PKC phosphorylation detection were also performed. Both models showed decreased insulin-induced IRS-1 and IRS-2 tyrosine phosphorylation, accompanied by reduced protein levels of IRS-1 and IRS-2. Nevertheless, IRS-3 protein level was unchanged in aging but increased in dexamethasone-treated rats. PI(3)-kinase association with IRS-1 was reduced in aged rats, whereas dexamethasone-treated rats showed a reduced IRS-2/ PI(3)-kinase association. However, IRS-3 association with PI(3)-kinase was reduced in both models, as well as insulin-induced AKT and PKC phosphorylation. The alterations described in the present study show that the action of insulin is differently impaired depending on the origin of insulin resistance. These differences might be directly linked to the singular metabolic features of the models we tested.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Cyoablation is a ablation technique underutilized except in parahissian pathways and atrial fibrillation ablation. Ablation inside venous coronary sinus remains a dreaded incursion, and cryoablation ...is rarely used. We present the case of a 43 YO female who had a recurrent wolff parkinson white syndrome due to an epicardial pathway inside the coronary sinus successfully treated with a large bore(8mm) cryocatheter. We also review literature and describe the advantages and similar reports of use of cryo in low flow recesses inside the heart.
Cyoablation is a ablation technique underutilized except in parahissian pathways and atrial fibrillation ablation. Ablation inside venous coronary sinus remains a dreaded incursion, and cryoablation ...is rarely used. We present the case of a 43 YO female who had a recurrent wolff parkinson white syndrome due to an epicardial pathway inside the coronary sinus successfully treated with a large bore(8mm) cryocatheter. We also review literature and describe the advantages and similar reports of use of cryo in low flow recesses inside the heart.
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