ABSTRACT
Recent works have demonstrated a significant reduction in cholesterol levels and increased oxidative stress in patients with coronavirus disease 2019 (COVID-19). The cause of this alteration is not well known. This study aimed to comprehensively evaluate their possible association during the evolution of COVID-19. This is an observational prospective study. The primary endpoint was to analyze the association between lipid peroxidation, lipid, and inflammatory profiles in COVID-19 patients. A multivariate regression analysis was employed. The secondary endpoint included the long-term follow-up of lipid profiles. COVID-19 patients presented significantly lower values in their lipid profile (total, low, and high-density lipoprotein cholesterol) with greater oxidative stress and inflammatory response compared to the healthy controls. Lipid peroxidation was the unique oxidative parameter with a significant association with the total cholesterol (OR: 0.982; 95% CI: 0.969-0.996; p = 0.012), IL1-RA (OR: 0.999; 95% CI: 0.998-0.999; p = 0.021) IL-6 (OR: 1.062; 95% CI: 1.017-1.110; p = 0.007), IL-7 (OR: 0.653; 95% CI: 0.433-0.986; p = 0.042) and IL-17 (OR: 1.098; 95% CI: 1.010-1.193; p = 0.028). Lipid abnormalities recovered after the initial insult during long-term follow-up (IQR 514 days); however, those with high LPO levels at hospital admission had, during long-term follow-up, an atherogenic lipid profile. Our study suggests that oxidative stress in COVID-19 is associated with derangements of the lipid profile and inflammation. Survivors experienced a recovery in their lipid profiles during long-term follow-up, but those with stronger oxidative responses had an atherogenic lipid profile.
Subject(s)
Atherosclerosis , COVID-19 , Dyslipidemias , Humans , Follow-Up Studies , Prospective Studies , Inflammation , Oxidative Stress , Cholesterol, HDLABSTRACT
Coronavirus disease (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with systemic organ damage in the most severe forms. Long-term complications of SARS-CoV-2 appear to be restricted to severe presentations of COVID-19, but many patients with persistent symptoms have never been hospitalized. Post-acute sequelae of COVID-19 (PASC) represents a heterogeneous group of symptoms characterized by cardiovascular, general, respiratory, and neuropsychiatric sequelae. The pace of evidence acquisition with PASC has been rapid, but the mechanisms behind it are complex and not yet fully understood. In particular, exercise intolerance shares some features with other classic respiratory and cardiac disorders. However, cardiopulmonary exercise testing (CPET) provides a comprehensive assessment and can unmask the pathophysiological mechanism behind exercise intolerance in gray-zone PASC. This mini-review explores the utility of CPET and aims to provide a comprehensive assessment of PASC by summarizing the current evidence.
ABSTRACT
Coronavirus disease (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with systemic organ damage in the most severe forms. Long-term complications of SARS-CoV-2 appear to be restricted to severe presentations of COVID-19, but many patients with persistent symptoms have never been hospitalized. Post-acute sequelae of COVID-19 (PASC) represents a heterogeneous group of symptoms characterized by cardiovascular, general, respiratory, and neuropsychiatric sequelae. The pace of evidence acquisition with PASC has been rapid, but the mechanisms behind it are complex and not yet fully understood. In particular, exercise intolerance shares some features with other classic respiratory and cardiac disorders. However, cardiopulmonary exercise testing (CPET) provides a comprehensive assessment and can unmask the pathophysiological mechanism behind exercise intolerance in gray-zone PASC. This mini-review explores the utility of CPET and aims to provide a comprehensive assessment of PASC by summarizing the current evidence. Graphical
ABSTRACT
Background Hypertension is a prevalent condition among SARS-CoV-2 infected patients. Whether renin–angiotensin–aldosterone system (RAAS) inhibitors are beneficial or harmful is controversial. Methods We have performed a national retrospective, nonexperimental comparative study from two tertiary hospitals to evaluate the impact of chronic use of RAAS inhibitors in hypertensive COVID-19 patients. A meta-analysis was performed to strengthen our findings. Results Of 849 patients, 422 (49.7%) patients were hypertensive and 310 (73.5%) were taking RAAS inhibitors at baseline. Hypertensive patients were older, had more comorbidities, and a greater incidence of respiratory failure (−0.151 [95% CI −0.218, −0.084]). Overall mortality in hypertensive patients was 28.4%, but smaller among those with prescribed RAAS inhibitors before (−0.167 [95% CI −0.220, −0.114]) and during hospitalization (0.090 [−0.008,0.188]). Similar findings were observed after two propensity score matches that evaluated the benefit of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers among hypertensive patients. Multivariate logistic regression analysis of hypertensive patients found that age, diabetes mellitus, C-reactive protein, and renal failure were independently associated with all-cause mortality. On the contrary, ACEIs decreased the risk of death (OR 0.444 [95% CI 0.224–0.881]). Meta-analysis suggested a protective benefit of RAAS inhibitors (OR 0.6 [95% CI 0.42–0.8]) among hypertensive COVID-19. Conclusion Our data suggest that RAAS inhibitors may play a protective role in hypertensive COVID-19 patients. This finding was supported by a meta-analysis of the current evidence. Maintaining these medications during hospital stay may not negatively affect COVID-19 outcomes.
ABSTRACT
Background: Hypertension is a prevalent condition among SARS-CoV-2 infected patients. Whether renin-angiotensin-aldosterone system (RAAS) inhibitors are beneficial or harmful is controversial. Methods: We have performed a national retrospective, nonexperimental comparative study from two tertiary hospitals to evaluate the impact of chronic use of RAAS inhibitors in hypertensive COVID-19 patients. A meta-analysis was performed to strengthen our findings. Results: Of 849 patients, 422 (49.7%) patients were hypertensive and 310 (73.5%) were taking RAAS inhibitors at baseline. Hypertensive patients were older, had more comorbidities, and a greater incidence of respiratory failure (-0.151 [95% CI -0.218, -0.084]). Overall mortality in hypertensive patients was 28.4%, but smaller among those with prescribed RAAS inhibitors before (-0.167 [95% CI -0.220, -0.114]) and during hospitalization (0.090 [-0.008,0.188]). Similar findings were observed after two propensity score matches that evaluated the benefit of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers among hypertensive patients. Multivariate logistic regression analysis of hypertensive patients found that age, diabetes mellitus, C-reactive protein, and renal failure were independently associated with all-cause mortality. On the contrary, ACEIs decreased the risk of death (OR 0.444 [95% CI 0.224-0.881]). Meta-analysis suggested a protective benefit of RAAS inhibitors (OR 0.6 [95% CI 0.42-0.8]) among hypertensive COVID-19. Conclusion: Our data suggest that RAAS inhibitors may play a protective role in hypertensive COVID-19 patients. This finding was supported by a meta-analysis of the current evidence. Maintaining these medications during hospital stay may not negatively affect COVID-19 outcomes.
Introducción: La hipertensión es una condición prevalente entre los pacientes infectados por el SARS-CoV-2. Es controvertido si los inhibidores del sistema renina-angiotensina-aldosterona (SRAA) son beneficiosos o perjudiciales. Métodos: Hemos desarrollado un estudio comparativo nacional retrospectivo y no experimental en 2 hospitales terciarios para evaluar el impacto del uso crónico de inhibidores del SRAA en pacientes hipertensos con COVID-19. Se realizó un metaanálisis para reforzar los hallazgos. Resultados: De 849 pacientes, 422 (49,7%) eran hipertensos y 310 (73,5%) tomaban inhibidores del SRAA al inicio del estudio. Los pacientes hipertensos eran mayores, tenían más comorbilidades y una mayor incidencia de insuficiencia respiratoria (−0,151; IC 95%: [−0,218; −0,084]). La mortalidad global en los pacientes hipertensos fue del 28,4%, pero fue menor entre los que tenían prescritos inhibidores del SRAA antes (−0,167; IC 95%: [−0,220; −0,114]) y durante la hospitalización (0,090; [−0,008; 0,188]). Se observaron hallazgos similares tras 2 emparejamientos de puntuación de propensión que evaluaron el beneficio de los inhibidores de la enzima convertidora de angiotensina y los bloqueadores de los receptores de angiotensina entre los pacientes hipertensos. El análisis de regresión logística multivariante de los pacientes hipertensos reveló que la edad, la diabetes mellitus, la proteína C reactiva y la insuficiencia renal se asociaban de forma independiente con la mortalidad por todas las causas. Por el contrario, los inhibidores de la enzima convertidora de angiotensina disminuyeron el riesgo de muerte (OR 0,444; IC 95%: 0,224-0,881). El metaanálisis indicó un beneficio protector de los inhibidores del SRAA (OR 0,6; IC 95%: 0,42-0,8) entre los hipertensos con COVID-19. Conclusión: Nuestros datos indican que los inhibidores del SRAA pueden desempeñar un papel protector en los pacientes hipertensos con COVID-19. Este hallazgo fue apoyado por un metaanálisis de la evidencia actual. Su mantenimiento durante la estancia hospitalaria puede no afectar negativamente a los resultados de la COVID-19.
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BACKGROUND AND AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19). METHODS AND RESULTS: We performed a retrospective single-center study of consecutively admitted patients between March 1st and May 15th, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19. A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14-3.31), C-reactive protein >88 mg/dl (HR 2.44; 95% CI, 1.41-4.23) and lymphopenia <1000 (HR 2.68; 95% CI, 1.91-3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Survivors presented with complete normalization of their lipid profiles on short-term follow-up. CONCLUSION: Hypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.
Subject(s)
COVID-19/blood , Cholesterol, LDL/blood , Dyslipidemias/blood , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Down-Regulation , Dyslipidemias/diagnosis , Dyslipidemias/mortality , Dyslipidemias/therapy , Female , Humans , Inflammation Mediators/blood , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Spain , Time FactorsABSTRACT
Influenza infection has been identified as a triggering or exacerbating factor for cardiovascular events. To analyse the effect of influenza vaccination on cardiovascular disease, a systematic search of studies published between 2009–2019 was conducted. All the studies that evaluated the effect of vaccination against influenza on cardiovascular events and their outcome were considered. Finally, 30 of the 1147 identified studies were included. These studies show a protective effect of the influenza vaccine on the development of cardiovascular events (myocardial infarction, cerebrovascular accidents, atrial fibrillation, and heart failure) and on the worsening of these conditions. Furthermore, the data showed that vaccinated patients have a lower risk of death from cardiovascular pathologies. Influenza vaccination is therefore an effective measure in the prevention of cardiovascular diseases both in patients with established cardiovascular disease and in the population without previous coronary pathology. Resumen La gripe se ha identificado como un factor desencadenante o agravante de los eventos cardiovasculares. Con el objetivo analizar el efecto de la vacunación antigripal en la enfermedad cardiovascular se realizó una búsqueda sistemática de estudios publicados entre 2009 y 2019. Se consideraron todos los trabajos que evaluaron el efecto de la vacunación frente a la gripe sobre eventos cardiovasculares y su evolución. Finalmente se incluyeron 30 de los 1.147 estudios identificados. Estos trabajos ponen de manifiesto el efecto protector de la vacuna antigripal tanto en el desarrollo de eventos cardiovasculares (infarto de miocardio, ictus, fibrilación auricular e insuficiencia cardíaca) como en el empeoramiento de estos procesos. Además, se demuestra que los pacientes vacunados presentan un menor riesgo de muerte por enfermedades cardiovasculares. La vacunación antigripal es, pues, una medida efectiva en la prevención de enfermedades cardiovasculares tanto en personas con enfermedad cardiovascular establecida como en aquellas sin patología previa.
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INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a systemic disease characterized by a disproportionate inflammatory response in the acute phase. This study sought to identify clinical sequelae and their potential mechanism. METHODS: We conducted a prospective single-center study (NCT04689490) of previously hospitalized COVID-19 patients with and without dyspnea during mid-term follow-up. An outpatient group was also evaluated. They underwent serial testing with a cardiopulmonary exercise test (CPET), transthoracic echocardiogram, pulmonary lung test, six-minute walking test, serum biomarker analysis, and quality of life questionaries. RESULTS: Patients with dyspnea (n = 41, 58.6%), compared with asymptomatic patients (n = 29, 41.4%), had a higher proportion of females (73.2 vs. 51.7%; p = 0.065) with comparable age and prevalence of cardiovascular risk factors. There were no significant differences in the transthoracic echocardiogram and pulmonary function test. Patients who complained of persistent dyspnea had a significant decline in predicted peak VO2 consumption (77.8 (64-92.5) vs. 99 (88-105); p < 0.00; p < 0.001), total distance in the six-minute walking test (535 (467-600) vs. 611 (550-650) meters; p = 0.001), and quality of life (KCCQ-23 60.1 ± 18.6 vs. 82.8 ± 11.3; p < 0.001). Additionally, abnormalities in CPET were suggestive of an impaired ventilatory efficiency (VE/VCO2 slope 32 (28.1-37.4) vs. 29.4 (26.9-31.4); p = 0.022) and high PETCO2 (34.5 (32-39) vs. 38 (36-40); p = 0.025). INTERPRETATION: In this study, >50% of COVID-19 survivors present a symptomatic functional impairment irrespective of age or prior hospitalization. Our findings suggest a potential ventilation/perfusion mismatch or hyperventilation syndrome.
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BACKGROUND: Hypertension is a prevalent condition among SARS-CoV-2 infected patients. Whether renin-angiotensin-aldosterone system (RAAS) inhibitors are beneficial or harmful is controversial. METHODS: We have performed a national retrospective, nonexperimental comparative study from two tertiary hospitals to evaluate the impact of chronic use of RAAS inhibitors in hypertensive COVID-19 patients. A meta-analysis was performed to strengthen our findings. RESULTS: Of 849 patients, 422 (49.7%) patients were hypertensive and 310 (73.5%) were taking RAAS inhibitors at baseline. Hypertensive patients were older, had more comorbidities, and a greater incidence of respiratory failure (-0.151 [95% CI -0.218, -0.084]). Overall mortality in hypertensive patients was 28.4%, but smaller among those with prescribed RAAS inhibitors before (-0.167 [95% CI -0.220, -0.114]) and during hospitalization (0.090 [-0.008,0.188]). Similar findings were observed after two propensity score matches that evaluated the benefit of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers among hypertensive patients. Multivariate logistic regression analysis of hypertensive patients found that age, diabetes mellitus, C-reactive protein, and renal failure were independently associated with all-cause mortality. On the contrary, ACEIs decreased the risk of death (OR 0.444 [95% CI 0.224-0.881]). Meta-analysis suggested a protective benefit of RAAS inhibitors (OR 0.6 [95% CI 0.42-0.8]) among hypertensive COVID-19. CONCLUSION: Our data suggest that RAAS inhibitors may play a protective role in hypertensive COVID-19 patients. This finding was supported by a meta-analysis of the current evidence. Maintaining these medications during hospital stay may not negatively affect COVID-19 outcomes.
Subject(s)
COVID-19 , Hypertension , Aldosterone/pharmacology , Aldosterone/therapeutic use , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensins/pharmacology , Angiotensins/therapeutic use , Antihypertensive Agents/therapeutic use , Humans , Hypertension/complications , Hypertension/drug therapy , Mineralocorticoid Receptor Antagonists/therapeutic use , Registries , Renin/pharmacology , Renin/therapeutic use , Renin-Angiotensin System , Retrospective Studies , SARS-CoV-2ABSTRACT
Deterioration is sometimes unexpected in SARS-CoV2 infection. The aim of our study is to establish laboratory predictors of mortality in COVID-19 disease which can help to identify high risk patients. All patients admitted to hospital due to Covid-19 disease were included. Laboratory biomarkers that contributed with significant predictive value for predicting mortality to the clinical model were included. Cut-off points were established, and finally a risk score was built. 893 patients were included. Median age was 68.2 ± 15.2 years. 87(9.7%) were admitted to Intensive Care Unit (ICU) and 72(8.1%) needed mechanical ventilation support. 171(19.1%) patients died. A Covid-19 Lab score ranging from 0 to 30 points was calculated on the basis of a multivariate logistic regression model in order to predict mortality with a weighted score that included haemoglobin, erythrocytes, leukocytes, neutrophils, lymphocytes, creatinine, C-reactive protein, interleukin-6, procalcitonin, lactate dehydrogenase (LDH), and D-dimer. Three groups were established. Low mortality risk group under 12 points, 12 to 18 were included as moderate risk, and high risk group were those with 19 or more points. Low risk group as reference, moderate and high patients showed mortality OR 4.75(CI95% 2.60-8.68) and 23.86(CI 95% 13.61-41.84), respectively. C-statistic was 0-85(0.82-0.88) and Hosmer-Lemeshow p-value 0.63. Covid-19 Lab score can very easily predict mortality in patients at any moment during admission secondary to SARS-CoV2 infection. It is a simple and dynamic score, and it can be very easily replicated. It could help physicians to identify high risk patients to foresee clinical deterioration.
Subject(s)
COVID-19/diagnosis , Aged , Biomarkers/analysis , COVID-19/mortality , COVID-19/pathology , COVID-19/therapy , Female , Hospitalization , Humans , Male , Multivariate Analysis , Retrospective Studies , Risk Assessment , SARS-CoV-2/physiology , Spain/epidemiology , Treatment OutcomeABSTRACT
BACKGROUND: Cardiovascular risk factors and usage of cardiovascular medication are prevalent among coronavirus disease 2019 (COVID-19) patients. Little is known about the cardiovascular implications of COVID-19. The goal herein, was to evaluate the prognostic impact of having heart disease (HD) and taking cardiovascular medications in a population diagnosed of COVID-19 who required hospitalization. Also, we studied the development of cardiovascular events during hospitalization. METHODS: Consecutive patients with definitive diagnosis of COVID-19 made by a positive real time- -polymerase chain reaction of nasopharyngeal swabs who were admitted to the hospital from March 15 to April 14 were included in a retrospective registry. The association of HD with mortality and with mortality or respiratory failure were the primary and secondary objectives, respectively. RESULTS: A total of 859 patients were included in the present analysis. Cardiovascular risk factors were related to death, particularly diabetes mellitus (hazard ratio in the multivariate analysis: 1.810 [1.159- -2.827], p = 0.009). A total of 113 (13.1%) patients had HD. The presence of HD identified a group of patients with higher mortality (35.4% vs. 18.2%, p < 0.001) but HD was not independently related to prognosis; renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, diuretics and beta-blockers did not worsen prognosis. Statins were independently associated with decreased mortality (0.551 [0.329-0.921], p = 0.023). Cardiovascular events during hospitalization identified a group of patients with poor outcome (mortality 31.8% vs. 19.3% without cardiovascular events, p = 0.007). CONCLUSIONS: The presence of HD is related to higher mortality. Cardiovascular medications taken before admission are not harmful, statins being protective. The development of cardiovascular events during the course of the disease is related to poor outcome.
Subject(s)
COVID-19/epidemiology , Cardiovascular Agents/therapeutic use , Heart Diseases/epidemiology , Pandemics , Aged , Comorbidity , Female , Heart Diseases/drug therapy , Humans , Male , Prognosis , Retrospective Studies , SARS-CoV-2Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hospitals , Humans , SARS-CoV-2Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Heart Diseases/epidemiology , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Aged , Aged, 80 and over , COVID-19 , Cohort Studies , Coronavirus Infections/mortality , Female , Heart Diseases/diagnosis , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Prognosis , SARS-CoV-2 , Survival RateABSTRACT
BACKGROUND: Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory-syndrome coronavirus-2 that interfaces with the renin-angiotensin-aldosterone system (RAAS) through angiotensin-converting enzyme 2. This interaction has been proposed as a potential risk factor in patients treated with RAAS inhibitors. OBJECTIVES: This study analyzed whether RAAS inhibitors modify the risk for COVID-19. METHODS: The RASTAVI (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation) trial is an ongoing randomized clinical trial randomly allocating subjects to ramipril or control groups after successful transcatheter aortic valve replacement at 14 centers in Spain. A non-pre-specified interim analysis was performed to evaluate ramipril's impact on COVID-19 risk in this vulnerable population. RESULTS: As of April 1, 2020, 102 patients (50 in the ramipril group and 52 in the control group) were included in the trial. Mean age was 82.3 ± 6.1 years, 56.9% of the participants were male. Median time of ramipril treatment was 6 months (interquartile range: 2.9 to 11.4 months). Eleven patients (10.8%) have been diagnosed with COVID-19 (6 in control group and 5 receiving ramipril; hazard ratio: 1.150; 95% confidence interval: 0.351 to 3.768). The risk of COVID-19 was increased in older patients (p = 0.019) and those with atrial fibrillation (p = 0.066), lower hematocrit (p = 0.084), and more comorbidities according to Society of Thoracic Surgeons score (p = 0.065). Admission and oxygen supply was required in 4.9% of patients (2 in the ramipril group and 3 in the control group), and 4 of them died (2 in each randomized group). A higher body mass index was the only factor increasing the mortality rate (p = 0.039). CONCLUSIONS: In a high-risk population of older patients with cardiovascular disease, randomization to ramipril had no impact on the incidence or severity of COVID-19. This analysis supports the maintenance of RAAS inhibitor treatment during the COVID-19 crisis. (Renin-Angiotensin System Blockade Benefits in Clinical Evolution and Ventricular Remodeling After Transcatheter Aortic Valve Implantation [RASTAVI]; NCT03201185).