Association of Right Ventricular Dilation and Dysfunction on Echocardiogram with In-Hospital Mortality Among Patients Hospitalized with COVID-19 Compared with Other Acute Respiratory Illness

BackgroundAlthough right ventricular (RV) dysfunction is associated with mortality in acute COVID-19, the role of RV dilation is uncertain. The prognostic significance of RV dilation and dysfunction among hospitalized patients with acute COVID-19 compared to other respiratory illnesses. MethodsWe conducted a retrospective cohort study to examine 225 consecutive adults admitted for acute COVID-19 and 6,150 control adults admitted for influenza, pneumonia or ARDS who had a clinical echocardiogram performed. We used logistic regression models to assess associations between RV parameters and in-hospital mortality adjusted for confounders. ResultsAmong those with COVID-19, 48/225 (21.3%) died during the index hospitalization compared to 727/6150 (11.8%) with other respiratory illness (p=0.001). Independent of COVID-19, mild and moderate to severe RV dilation were associated with 1.4 and 2.0 times higher risk of inpatient mortality, respectively (95%CI 1.17 to 1.69; p=0.0003; 95%CI 1.62 to 2.47; p<0.0001, respectively). Similarly, mild and moderate RV dysfunction were associated with 1.4 and 1.7 times higher risk of inpatient mortality (95%CI 1.10 to 1.77; p=0.007; 95%CI 1.17 to 2.42; p=0.005, respectively). Relative to normal RV size and non-COVID-19 acute respiratory illness, mild and moderate RV dilation were associated with 1.4 times and 2.0 times higher risk among those without COVID-19 and 1.9 times higher and 3.0 times higher risk among those with COVID-19, with similar findings for RV dysfunction. Having both RV dilation and dysfunction or RV dilation alone were associated with 1.7 times higher risk while RV dysfunction alone was associated with 1.4 times higher risk compared to normal RV size and function. ConclusionsRV dilation and dysfunction are associated with increased risk of inpatient mortality among those with COVID-19 and other respiratory illnesses. Abnormal RV findings may identify those at higher risk of short-term mortality from acute respiratory illness including COVID-19 beyond other risk markers.

Cardiopulmonary exercise testing to evaluate post-acute sequelae of COVID-19 ("Long COVID"): a systematic review and meta-analysis

ImportanceReduced exercise capacity is commonly reported among individuals with Long COVID (LC). Cardiopulmonary exercise testing (CPET) is the gold-standard to measure exercise capacity to identify causes of exertional intolerance. ObjectivesTo estimate the effect of SARS-CoV-2 infection on exercise capacity including those with and without LC symptoms and to characterize physiologic patterns of limitations to elucidate possible mechanisms of LC. Data SourcesWe searched PubMed, EMBASE, and Web of Science, preprint severs, conference abstracts, and cited references in December 2021 and again in May 2022. Study SelectionWe included studies of adults with SARS-CoV-2 infection at least three months prior that included CPET measured peak VO2. 3,523 studies were screened independently by two blinded reviewers; 72 (2.2%) were selected for full-text review and 36 (1.2%) met the inclusion criteria; we identified 3 additional studies from preprint servers. Data Extraction and SynthesisData extraction was done by two independent reviewers according to PRISMA guidelines. Data were pooled with random-effects models. Main Outcomes and MeasuresA priori primary outcomes were differences in peak VO2 (in ml/kg/min) among those with and without SARS-CoV-2 infection and LC. ResultsWe identified 39 studies that performed CPET on 2,209 individuals 3-18 months after SARS-CoV-2 infection, including 944 individuals with LC symptoms and 246 SARS-CoV-2 uninfected controls. Most were case-series of individuals with LC or post-hospitalization cohorts. By meta-analysis of 9 studies including 404 infected individuals, peak VO2 was 7.4 ml/kg/min (95%CI 3.7 to 11.0) lower among infected versus uninfected individuals. A high degree of heterogeneity was attributable to patient and control selection, and these studies mostly included previously hospitalized, persistently symptomatic individuals. Based on meta-analysis of 9 studies with 464 individuals with LC, peak VO2 was 4.9 ml/kg/min (95%CI 3.4 to 6.4) lower compared to those without symptoms. Deconditioning was common, but dysfunctional breathing, chronotropic incompetence, and abnormal oxygen extraction were also described. Conclusions and RelevanceThese studies suggest that exercise capacity is reduced after SARS-CoV-2 infection especially among those hospitalized for acute COVID-19 and individuals with LC. Mechanisms for exertional intolerance besides deconditioning may be multifactorial or related to underlying autonomic dysfunction.

Reduced Exercise Capacity, Chronotropic Incompetence, Inflammation and Symptoms in Post-Acute COVID-19

BACKGROUNDMechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 "PASC" or "Long COVID") remain unclear. The purpose of this study was to elucidate the pathophysiology of cardiopulmonary PASC using multimodality cardiovascular imaging including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring. METHODSWe performed CMR, CPET, and ambulatory rhythm monitoring among adults > 1 year after PCR-confirmed SARS-CoV-2 infection in the UCSF Long-Term Impact of Infection with Novel Coronavirus cohort (LIINC; NCT04362150) and correlated findings with previously measured biomarkers. We used logistic regression to estimate associations with PASC symptoms (dyspnea, chest pain, palpitations, and fatigue) adjusted for confounders and linear regression to estimate differences between those with and without symptoms adjusted for confounders. RESULTSOut of 120 participants in the cohort, 46 participants (unselected for symptom status) had at least one advanced cardiac test performed at median 17 months following initial SARS-CoV-2 infection. Median age was 52 (IQR 42-61), 18 (39%) were female, and 6 (13%) were hospitalized for severe acute infection. On CMR (n=39), higher extracellular volume was associated with symptoms, but no evidence of late-gadolinium enhancement or differences in T1 or T2 mapping were demonstrated. We did not find arrhythmias on ambulatory monitoring. In contrast, on CPET (n=39), 13/23 (57%) with cardiopulmonary symptoms or fatigue had reduced exercise capacity (peak VO2<85% predicted) compared to 2/16 (13%) without symptoms (p=0.008). The adjusted difference in peak VO2 was 5.9 ml/kg/min lower (-9.6 to -2.3; p=0.002) or -21% predicted (-35 to -7; p=0.006) among those with symptoms. Chronotropic incompetence was the primary abnormality among 9/15 (60%) with reduced peak VO2. Adjusted heart rate reserve <80% was associated with reduced exercise capacity (OR 15.6, 95%CI 1.30-187; p=0.03). Inflammatory markers (hsCRP, IL-6, TNF-) and SARS-CoV-2 antibody levels measured early in PASC were negatively correlated with peak VO2 more than 1 year later. CONCLUSIONSCardiopulmonary symptoms and elevated inflammatory markers present early in PASC are associated with objectively reduced exercise capacity measured on cardiopulmonary exercise testing more than 1 year following COVID-19. Chronotropic incompetence may explain reduced exercise capacity among some individuals with PASC. Clinical PerspectiveWhat is New? O_LIElevated inflammatory markers in early post-acute COVID-19 are associated with reduced exercise capacity more than 1 year later. C_LIO_LIImpaired chronotropic response to exercise is associated with reduced exercise capacity and cardiopulmonary symptoms more than 1 year after SARS-CoV-2 infection. C_LIO_LIFindings on ambulatory rhythm monitoring point to perturbed autonomic function, while cardiac MRI findings argue against myocardial dysfunction and myocarditis. C_LI Clinical ImplicationsO_LICardiopulmonary testing to identify etiologies of persistent symptoms in post-acute sequalae of COVID-19 or "Long COVID" should be performed in a manner that allows for assessment of heart rate response to exercise. C_LIO_LITherapeutic trials of anti-inflammatory and exercise strategies in PASC are urgently needed and should include assessment of symptoms and objective testing with cardiopulmonary exercise testing. C_LI

The effect of probiotics on serum lipid levels in non-obese healthy adults with hyperlipidemia: a systematic review and meta-analysis of randomized controlled trials / El efecto de los probióticos sobre los niveles de lípidos séricos en adultos sanos no obesos con hiperlipidemia: revisión sistemática y metaanálisis de ensayos controlados y aleatorizados

Introduction: probiotics might have a potential effect to manage serum lipid levels as nutraceuticals. Objective: this systematic review was conducted to explore whether probiotics have an efficient result in non-obese healthy adults with hyperlipidemia. Methods: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science were searched for randomized controlled trials (from their commencement to January 2021). This meta-analysis was performed by Review Manager 5.3 and STATA 15.1. Changes in serum lipid levels after the intervention were used to evaluate the effect of the probiotics, which were expressed as the weighted mean difference (WMD) with a 95 % confidence interval (CI). Results: a total of 16 studies, which could be regarded as 21 independent trials with 1429 participants, were included in this meta-analysis following our inclusion criteria. It could be observed that probiotics could significantly lower total cholesterol (TC) (WMD: -0.34 mmol/L, 95 % CI: -0.45 to -0.23 mmol/L; p < 0.001, I2 = 73.9 %) and low-density lipoprotein cholesterol (LDL-C) (WMD: -0.26 mmol/L, 95 % CI: -0.36 to -0.17 mmol/L; p < 0.001, I2 = 79.0 %) levels in non-obese healthy adults with hyperlipidemia, while no significant effect between the probiotic intervention and control groups was observed on high-density lipoprotein cholesterol (HDL-C) (WMD: 0.00 mmol/L, 95 % CI: -0.02 to 0.02 mmol/L; p = 0.001, I2 = 56.6 %) and triglyceride (TG) (WMD: -0.08 mmol/L, 95 % CI: -0.18 to 0.01 mmol/L; p = 0.003, I2 = 52.4 %) levels. Conclusion: this systematic review showed that probiotics may provide a promising way to reduce serum lipid levels in non-obese healthy adults with hyperlipidemia, but their specific effect still needs more clinical experiments to be proven (AU)

Introducción: los probióticos podrían tener efecto para controlar los niveles de lípidos séricos como nutracéuticos. Objetivo: esta revisión sistemática se realizó para explorar si los probióticos tienen un resultado eficiente en adultos sanos no obesos con hiperlipidemia. Métodos: se realizaron búsquedas de ensayos controlados aleatorios en PubMed, Embase, el Registro Cochrane Central de Ensayos Controlados y Web of Science (desde su inicio hasta enero de 2021). Este metanálisis fue realizado mediante Review Manager 5.3 y STATA 15.1. Los cambios de los niveles de lípidos séricos después de la intervención se utilizaron para evaluar el efecto de los probióticos, que se expresaron como la diferencia de medias ponderada (DMP) con un intervalo de confianza (IC) del 95 %. Resultados: en este metaanálisis se incluyeron un total de 16 estudios, que podrían considerarse 21 ensayos independientes con 1429 participantes, siguiendo nuestros criterios de inclusión. Se pudo observar que los probióticos podían reducir significativamente el colesterol total (CT) (DMP: -0,34 mmol/L, IC del 95 %: -0,45 a -0,23 mmol/L; p < 0,001, I2 = 73,9 %) y el colesterol de lipoproteínas de baja densidad (C-LDL) (DMP: -0,26 mmol/L, IC del 95 %: -0,36 a -0,17 mmol/L; p < 0,001, I2 = 79,0 %) en los adultos sanos no obesos con hiperlipidemia, mientras que no hubo efectos significativos entre los grupos de intervención y de control en el colesterol de lipoproteínas de alta densidad (HDL-C) (DMP: 0,00 mmol/L, IC del 95 %: -0,02 a 0,02 mmol/L; p = 0,001, I2 = 56,6 %) y los triglicéridos (TG) (DMP: -0,08 mmol/L, IC del 95 %: -0,18 a 0,01 mmol/L; p = 0,003, I2 = 52,4 %). Conclusión: esta revisión sistemática manifestó que los probióticos podrían suponer una forma prometedora de reducir los niveles de lípidos séricos en los adultos sanos no obesos con hiperlipidemia, pero se necesitan más experimentos clínicos para demostrar su efecto específico (AU)

Role of antibodies, inflammatory markers, and echocardiographic findings in post-acute cardiopulmonary symptoms after SARS-CoV-2 infection

BACKGROUNDShortness of breath, chest pain, and palpitations occur as post-acute sequelae of COVID-19 (PASC), but whether symptoms are associated with echocardiographic abnormalities, cardiac biomarkers, or markers of systemic inflammation remains unknown. METHODSIn a cross-sectional analysis, we assessed symptoms, performed echocardiograms, and measured biomarkers among adults >8 weeks after PCR-confirmed SARS-CoV-2 infection. We modeled associations between symptoms and baseline characteristics, echocardiographic findings, and biomarkers using logistic regression. RESULTSWe enrolled 102 participants at a median 7.2 months (IQR 4.1-9.1) following COVID-19 onset; 47 individuals reported dyspnea, chest pain, or palpitations. Median age was 52 years (range 24-86) and 41% were women. Female sex (OR 2.55, 95%CI 1.13-5.74) and hospitalization during acute infection (OR 3.25, 95%CI 1.08-9.82) were associated with symptoms. IgG antibody to SARS-CoV-2 receptor binding domain (OR 1.38 per doubling, 95%CI 1.38-1.84) and high-sensitivity C-reactive protein (OR 1.31 per doubling, 95%CI 1.00-1.71) were associated with symptoms. Regarding echocardiographic findings, 4/47 (9%) with symptoms had pericardial effusions compared to 0/55 without symptoms (p=0.038); those with pericardial effusions had a median 4 symptoms compared to 1 without (p<0.001). There was no strong evidence for a relationship between symptoms and echocardiographic functional parameters (including left ventricular ejection fraction and strain, right ventricular strain, pulmonary artery pressure) or high-sensitivity troponin, NT-pro-BNP, interleukin-10, interferon-gamma, or tumor necrosis factor-alpha. CONCLUSIONSAmong adults in the post-acute phase of SARS-CoV-2 infection, SARS-CoV-2 RBD antibodies, markers of inflammation and, possibly, pericardial effusions are associated with cardiopulmonary symptoms. Investigation into inflammation as a mechanism underlying PASC is warranted. FUNDINGThis work was supported by the UCSF Division of Cardiology at Zuckerberg San Francisco General, and the National Institutes of Health/National Heart Lung Blood Institute and National Institute of Allergy and Infectious Diseases. MSD is supported by NIH 5K12HL143961. MJP is supported on NIH T32 AI60530-12. JDK is supported by NIH K23AI135037. TJH is supported by NIH/NIAID 3R01A1141003-03S1. PYH is supported by NIH/NAID 2K24AI112393-06. This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1TR001872. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=169 HEIGHT=200 SRC="FIGDIR/small/21266834v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@7b2424org.highwire.dtl.DTLVardef@81d995org.highwire.dtl.DTLVardef@f3d6e5org.highwire.dtl.DTLVardef@a19373_HPS_FORMAT_FIGEXP M_FIG C_FIG

Association of HIV with COVID-19 Outcomes Among Hospitalized Adults

BackgroundWhether HIV infection is associated with differences in clinical outcomes among people hospitalized with COVID-19 is uncertain. ObjectiveTo evaluate the impact of HIV infection on COVID-19 outcomes among hospitalized patients. MethodsUsing the American Heart Associations COVID-19 Cardiovascular Disease registry, we used hierarchical mixed effects models to assess the association of HIV with in-hospital mortality accounting for patient demographics and comorbidities and clustering by hospital. Secondary outcomes included major adverse cardiac events (MACE), severity of illness, and length of stay (LOS). ResultsThe registry included 21,528 hospitalization records of people with confirmed COVID-19 from 107 hospitals in 2020, including 220 people living with HIV (PLWH). PLWH were younger (56.0+/-13.0 versus 61.3+/-17.9 years old) and more likely to be male (72.3% vs 52.7%), Non-Hispanic Black (51.4% vs 25.4%), on Medicaid (44.5% vs 24.5), and active tobacco users (12.7% versus 6.5%). Of the study population, 36 PLWH (16.4%) had in-hospital mortality compared with 3,290 (15.4%) without HIV (Risk ratio 1.06, 95%CI 0.79-1.43; risk difference 0.9%, 95%CI -4.2 to 6.1%; p=0.71). After adjustment for age, sex, race, and insurance, HIV was not associated with in-hospital mortality (aOR 1.13; 95%CI 0.77-1.6; p 0.54) even after adding body mass index and comorbidities (aOR 1.15; 95%CI 0.78-1.70; p=0.48). HIV was not associated with MACE (aOR 0.99, 95%CI 0.69-1.44, p=0.91), severity of illness (aOR 0.96, 95%CI 0.62-1.50, p=0.86), or LOS (aOR 1.03; 95% CI 0.76-1.66, p=0.21). ConclusionHIV was not associated with adverse outcomes of COVID-19 including in-hospital mortality, MACE, or severity of illness. Condensed AbstractWe studied 21,528 patients hospitalized with COVID-19 at 107 hospitals in AHAs COVID-19 registry to examine the association between HIV and COVID-19 outcomes. More patients with HIV were younger, male, non-Hispanic Black, on Medicaid and current smokers. HIV was not associated with worse COVID-19 in-hospital mortality (Risk ratio 1.06, 95%CI 0.79-1.43; p=0.71) even after adjustment (aOR 1.15; 95%CI 0.78-1.70; p=0.48). HIV was also not associated with MACE (aOR 0.99, 95%CI 0.69-1.44, p=0.91) or severity of illness (aOR 0.96, 95%CI 0.62-1.50, p=0.86. Our findings do not support that HIV is a major risk factor for adverse COVID-19 outcomes.