Zinc Deficiency And sTNF-RII Are Associated With Worse COVID-19 Outcomes.

BACKGROUND: Zinc (Zn) is known for its substantial involvement in the immune response as an antioxidant and anti-inflammatory agent. Zn plasma levels' clinical significance in coronavirus disease (COVID) diagnosis is not yet fully established. OBJECTIVE: We assessed the association between Zn deficiency, gut integrity, inflammation, and COVID-19 outcomes. METHODS: A prospective observational cohort in which plasma Zn, soluble tumor necrosis factor alpha receptor II (sTNF-RII) intestinal fatty-acid binding protein (IFABP; marker of intestinal integrity), and zonulin levels (intestinal permeability) were collected from participants during the acute phase of a confirmed COVID-19 diagnosis. Zn was modeled as continuous and binary, categorized as Zn deficiency (Zn < 75 µg/dL) and Zn sufficiency (Zn ≥ 75 µg/dL). COVID-19 outcomes were classified according to the World Health Organization clinical progression scale. We used cumulative probit regression to assess if suboptimal Zn levels, gut, and inflammatory markers increase the likelihood of worse COVID-19 outcomes. RESULTS: Zn deficiency was independently associated with 63% higher predicted odds of worse COVID outcomes. Increases in sTNF-RII {unadjusted odds ratio (uOR): 3.43 [95% confidence interval (CI): 2.02, 5.82]} and zonulin [uOR: 1.83 (95% CI: 1.21, 2.76)] levels were associated with greater odds of worse COVID outcomes. IFABP was not associated with worse COVID outcomes [uOR: 1.12 (95% CI: 0.82, 1.53)] or acute Zn deficiency [uOR: 1.35 (95% CI: 0.79, 2.35)]. The adjusted predicted odds of worse COVID outcomes are 3-fold higher (P = 0.04) for every one-unit decrease in Zn and is more than 2 times greater odds of COVID severity (P = 0.01) for every 1-unit increase in sTNF-RII. CONCLUSION: Zn deficiency and inflammation were independently associated with greater odds of worse COVID outcomes.

Synchronous versus staged carotid artery stenting and coronary artery bypass graft for patients with concomitant severe coronary and carotid artery stenosis: A systematic review and meta-analysis.

BACKGROUND: Coronary artery disease requiring coronary artery bypass graft (CABG) frequently coexists with critical carotid stenosis. The most optimized strategy for treating concomitant carotid and coronary artery disease remains debatable. OBJECTIVE: The aim of this meta-analysis was to compare synchronous CAS and CABG versus staged CAS and CABG for patients with concomitant coronary artery disease and carotid artery stenosis in terms of peri-operative (30-day) and long-term clinical outcomes. METHODS: This study was performed according to the PRISMA guidelines. Eligible studies were identified through a search of PubMed, Scopus and Cochrane database until December 2019. A meta-analysis was conducted with the use of a random effects model. The I-square statistic was used to assess heterogeneity. RESULTS: Four studies comprising 357 patients were included in this meta-analysis. Patients who were treated with the synchronous approach had a statistically significant higher risk for peri-operative stoke (OR: 3.71; 95% CI: 1.00-13.69; I2 = 0%) compared tο the staged group. Peri-operative mortality (OR: 4.50; 95% CI: 0.88-23.01; I2 = 0%), myocardial infarction (MI) (OR: 1.54; 95% CI: 0.18- 13.09; I2 = 0%), postoperative bleeding (OR: 0.27;95% CI: 0.02-3.12; I2 = 0%), transient ischemic attacks (TIA) (OR: 0.60; 95% CI: 0.04- 9.20; I2 = 0.0%), acute kidney injury (AKI) (OR: 0.34; 95% CI: 0.03-4.03; I2 = 0.0%) and atrial fibrillation rates (OR:0.27; 95% CI: 0.02-3.12; I2 = 0.0%) were similar between the two groups. Synchronous CAS-CABG and staged CAS followed by CABG were associated with similar rates of late mortality (OR: 3.75; 95% CI: 0.50-27.94; I2 = 0.0%), MI (OR: 0.33; 95% CI: 0.01-12.03; I2 = 0.0%) and stroke (OR:3.58; 95% CI:0.84-15.20; I2 = 0.0%) after a mean follow-up of 47 months. CONCLUSION: The simultaneous approach was associated with an increased risk of 30-day stroke compared to staged CAS and CABG. However, no statistically significant difference was found in long-term results of mortality, MI and stroke between the two approaches. Future studies are warranted to validate our results.

HIV and race are independently associated with endothelial dysfunction.

OBJECTIVE: Evaluating the vascular function in HIV-infected compared with HIV uninfected with assessment of body composition, inflammation, and gut integrity markers. DESIGN: A noninvasive test that measures the endothelial function. METHODS: We included participants at least 18 years old, with peripheral arterial tonometry testing (EndoPAT2000) between 2014 and 2022. Persons with HIV (PWH) had documented infection, a stable ART regimen, and a viral load less than 400 copies/ml. We measured the vessel's function with the reactive hyperemia index (RHI) (normal >1.67) and Augmentation Index. Lower Augmentation Index reflect better arterial elasticity. We assessed markers of systemic inflammation, immune activation, and gut integrity. We used linear mixed models to estimate endothelial dysfunction with a significant P value less than 0.05. RESULTS: Overall, 511 participants (296 HIV-infected; 215 HIV-uninfected controls) were included. Estimated RHI among PWH was 13% lower (P = 0.01) compared with persons without HIV. In nonwhite race, the estimated RHI was 9% lower (P = 0.001) than white race. For every 1% increase in BMI, we would expect RHI to increase 0.17% (P = 0.01). At the time of EndoPAT, the estimated RHI was 8% lower (P = 0.04) among protease inhibitor users compared with PWH who were not taking protease inhibitors. The estimated odds of abnormal RHI ≤1.67) is 1.56 times greater [95% confidence interval (CI) 1.05-2.31] in nonwhite race compared with white race, independent of HIV status [OR = 1.4 (95% CI 0.94-2.13)]. There was not enough evidence to suggest that inflammation, gut, or monocyte markers, current or nadir CD4+ cell count, or duration of HIV were associated with endothelial dysfunction. CONCLUSION: HIV, nonwhite race, and protease inhibitor use are independently associated with endothelial dysfunction.

Increase in gut permeability and oxidized ldl is associated with post-acute sequelae of SARS-CoV-2.

Background: Post-acute sequelae of SARS-CoV-2 (PASC) is marked by persistent or newly developing symptoms beyond 4 weeks of infection. Investigating gut integrity, oxidized lipids and inflammatory markers is important for understanding PASC pathogenesis. Methods: A cross-sectional study including COVID+ with PASC, COVID+ without PASC, and COVID-negative (COVID-) participants. We measured plasma markers by enzyme-linked immunosorbent assay to assess intestinal permeability (ZONULIN), microbial translocation (lipopolysaccharide-binding protein or LBP), systemic inflammation (high-sensitivity C-reactive protein or hs-CRP), and oxidized low-density lipoprotein (Ox-LDL). Results: 415 participants were enrolled in this study; 37.83% (n=157) had prior COVID diagnosis and among COVID+, 54% (n=85) had PASC. The median zonulin among COVID- was 3.37 (IQR: 2.13, 4.91) mg/mL, 3.43 (IQR: 1.65, 5.25) mg/mL among COVID+ no PASC, and highest [4.76 (IQR: 3.2, 7.35) mg/mL] among COVID+ PASC+ (p<.0001). The median ox-LDL among COVID- was 47.02 (IQR: 35.52, 62.77) U/L, 57.24 (IQR: 40.7, 75.37) U/L among COVID+ No PASC, and the highest [76.75 (IQR: 59.95, 103.28) U/L] among COVID+ PASC+ (p<.0001). COVID+ PASC+ was positively associated with zonulin (p=0.0002) and ox-LDL (p<.0001), and COVID- was negatively associated with ox-LDL (p=0.01), compared to COVID+ No PASC. Every unit increase in zonulin was associated with 44% higher predicted odds of having PASC [aOR: 1.44 (95%CI: 1.1, 1.9)] and every one-unit increase in ox-LDL was associated with more than four-fold increased odds of having PASC [aOR: 2.44 (95%CI: 1.67, 3.55)]. Conclusions: PASC is associated with increased gut permeability and oxidized lipids. Further studies are needed to clarify whether these relationships are causal which could lead to targeted therapeutics.

Arterial Stiffness and Oxidized LDL Independently Associated With Post-Acute Sequalae of SARS-CoV-2.

OBJECTIVE: COVID-19 survivors can experience lingering symptoms known as post-acute sequelae of SARS-CoV-2 (PASC) that appear in different phenotypes, and its etiology remains elusive. We assessed the relationship of endothelial dysfunction with having COVID and PASC. METHODS: Data was collected from a prospectively enrolled cohort (n=379) of COVID-negative and COVID-positive participants with and without PASC. Primary outcomes, endothelial function (measured by reactive hyperemic index [RHI]), and arterial elasticity (measured by augmentation index standardized at 75 bpm [AI]), were measured using the FDA approved EndoPAT. Patient characteristics, labs, metabolic measures, markers of inflammation, and oxidized LDL (ox-LDL) were collected at each study visit, and PASC symptoms were categorized into 3 non-exclusive phenotypes: cardiopulmonary, neurocognitive, and general. COVID-negative controls were propensity score matched to COVID-negative-infected cases using the greedy nearest neighbor method. RESULTS: There were 14.3% of participants who were fully recovered COVID positive and 28.5% who were COVID positive with PASC, averaging 8.64 ± 6.26 total number of symptoms. The mean RHI was similar across the cohort and having COVID or PASC was not associated with endothelial function (P=0.33). Age (P<0.0001), female sex (P<0.0001), and CRP P=0.04) were positively associated with arterial stiffness, and COVID positive PASC positive with neurological and/or cardiopulmonary phenotypes had the worst arterial elasticity (highest AI). Values for AI (P=0.002) and ox-LDL (P<0.0001) were independently and positively associated with an increased likelihood of having PASC. CONCLUSION: There is evidence of an independent association between PASC, ox-LDL, and arterial stiffness with neurological and/or cardiopulmonary phenotypes having the worst arterial elasticity. Future studies should continue investigating the role of oxidative stress in the pathophysiology of PASC.

The Protective Effect of Coronavirus Disease 2019 (COVID-19) Vaccination on Postacute Sequelae of COVID-19: A Multicenter Study From a Large National Health Research Network.

Background: Coronavirus disease 2019 (COVID-19) vaccines have been proven to decrease the severity of acute-phase infection; however, little is known about their effect on postacute sequelae of COVID-19 (PASC). Methods: Patients with confirmed COVID-19 diagnosis and minimum age of 18 years with 3-month follow-up postdiagnosis between 21 September 2020 and 14 December 2021 were identified from the TriNetX Research Network platform. The primary outcomes consisted of new-onset or persistent symptoms, new-onset diagnoses, and death and were compared between vaccine and no-vaccine groups. Results: At baseline, 1 578 719 patients with confirmed COVID-19 were identified and 1.6% (n = 25 225) completed vaccination. After matching, there were no differences (P > .05) in demographics or preexisting comorbidities. At 28 days following COVID-19 diagnosis, the incidence of hypertension was 13.52 per 1000, diabetes was 5.98 per 1000, thyroid disease was 3.80 per 1000, heart disease was 15.41 per 1000, and mental disorders was 14.77 per 1000 in the vaccine cohort. At 90 days following COVID-19 diagnosis, the relative risk of hypertension was 0.33 (95% confidence interval [CI], .26-.42), diabetes was 0.28 (95% CI, .20-.38), heart disease was 0.35 (95% CI, .29-.44), and death was 0.21 (95% CI, .16-.27). Differences in both 28- and 90-day risk between the vaccine and no-vaccine cohorts were observed for each outcome, and there was enough evidence (P < .05) to suggest that these differences were attributed to the vaccine. Conclusions: Our data suggest that COVID-19 vaccine is protective against PASC symptoms, new onset of health conditions, and mortality.