Sex differences underlying preexisting cardiovascular disease and cardiovascular injury in COVID-19.
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ABSTRACT:
SUBMITTER: Medzikovic L
PROVIDER: S-EPMC7442559 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical manifestations in disease-ridden patients. Differences in the severity of COVID-19 ranges from asymptomatic infections and mild cases to the severe form, leading to acute respiratory distress syndrome (ARDS) and multiorgan failure with poor survival. MiRNAs can regulate various cellular processes, including proliferation, apoptosis, and differentiation, by binding to the 3′UTR of target mRNAs inducing their degradation, thus serving a fundamental role in post-transcriptional repression. Alterations of miRNA levels in the blood have been described in multiple inflammatory and infectious diseases, including SARS-related coronaviruses. We used microarrays to delineate the miRNAs and snoRNAs signature in the peripheral blood of severe COVID-19 cases (n=9), as compared to mild (n=10) and asymptomatic (n=10) patients, and identified differentially expressed transcripts in severe versus asymptomatic, and others in severe versus mild COVID-19 cases. A cohort of 29 male age-matched patients were selected. All patients were previously diagnosed with COVID-19 using TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Waltham, Massachusetts), or Cobas SARS-CoV-2 Test (Roche Diagnostics, Rotkreuz, Switzerland), with a CT value < 30. Additional criterion for selection was age between 35 and 75 years. Participants were grouped into severe, mild and asymptomatic. Classifying severe cases was based on requirement of high-flow oxygen support and ICU admission (n=9). Whereas mild patients were identified based on symptoms and positive radiographic findings with pulmonary involvement (n=10). Patients with no clinical presentation were labelled as asymptomatic cases (n=10).
2022-03-01 | E-MTAB-10970 | biostudies-arrayexpress
Project description:IntroductionThe coronavirus disease 2019 (COVID-19) pandemic is the largest public health challenge of the twenty-first century. While COVID-19 primarily affects the respiratory system, manifesting as interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also has implications for the cardiovascular system. Moreover, those admitted to hospital with severe COVID-19 are more likely to have cardiovascular comorbidities such as hypertension and diabetes mellitus. The underlying pathophysiology of why COVID-19 onset can further decline cardiac pathologies as well as trigger acute onset of new cardiac complications is not yet well understood.Areas coveredIn this review, the authors extensively review literature focused on the current understanding and approaches of managing patients who have underlying cardiovascular diseases and concomitant COVID-19 infection. Furthermore, the authors explore the possible cardiovascular implications of the suggested COVID-19 therapeutic agents that are used to treat this lethal disease.Expert opinionCurrent evidence is evolving around the many trialed pharmacotherapeutic considerations for the management of coronavirus disease 2019 (COVID-19) in patients with cardiovascular disease. While we await such data, clinicians should advocate for careful consideration of all concomitant medications for those presenting with COVID-19 on a patient-by-patient basis.
| S-EPMC8425433 | biostudies-literature
Project description:BackgroundPreexisting cardiovascular disease (CVD) is perceived as a risk factor for poor outcomes in patients with COVID-19. We sought to determine whether CVD is associated with in-hospital death and cardiovascular events in critically ill patients with COVID-19.MethodsThis study used data from a multicenter cohort of adults with laboratory-confirmed COVID-19 admitted to intensive care units at 68 centers across the United States from March 1 to July 1, 2020. The primary exposure was CVD, defined as preexisting coronary artery disease, congestive heart failure, or atrial fibrillation/flutter. Myocardial injury on intensive care unit admission defined as a troponin I or T level above the 99th percentile upper reference limit of normal was a secondary exposure. The primary outcome was 28-day in-hospital mortality. Secondary outcomes included cardiovascular events (cardiac arrest, new-onset arrhythmias, new-onset heart failure, myocarditis, pericarditis, or stroke) within 14 days.ResultsAmong 5133 patients (3231 male [62.9%]; mean age 61 years [SD, 15]), 1174 (22.9%) had preexisting CVD. A total of 1178 (34.6%) died, and 920 (17.9%) had a cardiovascular event. After adjusting for age, sex, race, body mass index, history of smoking, and comorbidities, preexisting CVD was associated with a 1.15 (95% CI, 0.98-1.34) higher odds of death. No independent association was observed between preexisting CVD and cardiovascular events. Myocardial injury on intensive care unit admission was associated with higher odds of death (adjusted odds ratio, 1.93 [95% CI, 1.61-2.31]) and cardiovascular events (adjusted odds ratio, 1.82 [95% CI, 1.47-2.24]), regardless of the presence of CVD.ConclusionsCVD risk factors, rather than CVD itself, were the major contributors to outcomes in critically ill patients with COVID-19. The occurrence of myocardial injury, regardless of CVD, and its association with outcomes suggests it is likely due to multiorgan injury related to acute inflammation rather than exacerbation of preexisting CVD.RegistrationNCT04343898; https://clinicaltrials.gov/ct2/show/NCT04343898.
| S-EPMC9575399 | biostudies-literature
Project description:There is increasing evidence that coronavirus disease 2019 (COVID-19) produces more severe symptoms and higher mortality among men than among women1-5. However, whether immune responses against severe acute respiratory syndrome coronavirus (SARS-CoV-2) differ between sexes, and whether such differences correlate with the sex difference in the disease course of COVID-19, is currently unknown. Here we examined sex differences in viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines and blood-cell phenotyping in patients with moderate COVID-19 who had not received immunomodulatory medications. Male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes. By contrast, female patients had more robust T cell activation than male patients during SARS-CoV-2 infection. Notably, we found that a poor T cell response negatively correlated with patients' age and was associated with worse disease outcome in male patients, but not in female patients. By contrast, higher levels of innate immune cytokines were associated with worse disease progression in female patients, but not in male patients. These findings provide a possible explanation for the observed sex biases in COVID-19, and provide an important basis for the development of a sex-based approach to the treatment and care of male and female patients with COVID-19.
| S-EPMC7725931 | biostudies-literature
Project description:ObjectiveTo address the issue of limited national data on the prevalence and distribution of underlying conditions among COVID-19 deaths between sexes and across age groups.Patients and methodsAll adult (≥18 years) deaths recorded in England and Wales (March 1, 2020, to May 12, 2020) were analyzed retrospectively. We compared the prevalence of underlying health conditions between COVID and non-COVID-related deaths during the COVID-19 pandemic and the age-standardized mortality rate (ASMR) of COVID-19 compared with other primary causes of death, stratified by sex and age group.ResultsOf 144,279 adult deaths recorded during the study period, 36,438 (25.3%) were confirmed COVID deaths. Women represented 43.2% (n=15,731) of COVID deaths compared with 51.9% (n=55,980) in non-COVID deaths. Overall, COVID deaths were younger than non-COVID deaths (82 vs 83 years). ASMR of COVID-19 was higher than all other common primary causes of death, across age groups and sexes, except for cancers in women between the ages of 30 and 79 years. A linear relationship was observed between ASMR and age among COVID-19 deaths, with persistently higher rates in men than women across all age groups. The most prevalent reported conditions were hypertension, dementia, chronic lung disease, and diabetes, and these were higher among COVID deaths. Pre-existing ischemic heart disease was similar in COVID (11.4%) and non-COVID (12%) deaths.ConclusionIn a nationwide analysis, COVID-19 infection was associated with higher age-standardized mortality than other primary causes of death, except cancer in women of select age groups. COVID-19 mortality was persistently higher in men and increased with advanced age.
| S-EPMC7377724 | biostudies-literature
Project description:Manuscript describes the daily dynamics of transcriptional responses in whole blood, from acute to convalescent phase, in severe and non-severe COVID-19 patients.
2020-12-31 | E-MTAB-9721 | biostudies-arrayexpress
Project description:BackgroundCOVID-19 infections are associated with accrued inflammatory responses which may result in cardiac injury. Immune response to infection appears different between men and women, suggesting that COVID-19 patients' outcomes may differ according to biological sex. However, the impact of biological sex on the occurrence of cardiac injury during intensive care unit (ICU) stay in COVID-19 patients remain unclear.MethodsIn this multicenter and prospective study, we included consecutive patients admitted to ICU for severe COVID-19 pneumonia, during the first two pandemic waves. Biological, electrocardiogram (ECG) and echocardiographic variables were collected on ICU admission. Cardiac injury was defined by increased troponin above 99th percentile of upper norm value and newly diagnosed ECG and/or echocardiographic abnormalities. The primary endpoint was the proportion of patients with cardiac injury during ICU stay according to biological sex. The impact of biological sex on other subsequent clinical outcomes was also evaluated.ResultsWe included 198 patients with a median age of 66 (56-73) years, 147 (74%) patients were men and 51 (26%) were women. Overall, 119 (60%) patients had cardiac injury during ICU stay and the proportion of patients with cardiac injury during ICU stay was not different between men and women (60% vs. 61%, p = 1.00). Patients with cardiac injury during ICU stay showed more cardiovascular risk factors and chronic cardiac disease and had a higher ICU mortality rate. On ICU admission, they had a more marked lymphopenia (0.70 (0.40-0.80) vs. 0.80 (0.50-1.10) × 109/L, p < 0.01) and inflammation (C-Reactive Protein (155 (88-246) vs. 111 (62-192) mg/L, p = 0.03); D-Dimers (1293 (709-2523) vs. 900 (560-1813) µg/L, p = 0.03)). Plasmatic levels of inflammatory biomarkers on ICU admission correlated with SAPS-2 and SOFA scores but not with the different echocardiographic variables. Multivariate analysis confirmed cardiovascular risk factors (OR = 2.31; 95%CI (1.06-5.02), p = 0.03) and chronic cardiac disease (OR = 8.58; 95%CI (1.01-73.17), p = 0.04) were independently associated with the occurrence of cardiac injury during ICU stay, whereas biological sex (OR = 0.88; 95%CI (0.42-1.84), p = 0.73) was not. Biological sex had no impact on the occurrence during ICU stay of other clinical outcomes.ConclusionsMost critically ill patients with COVID-19 were men and experienced cardiac injury during ICU stay. Nevertheless, biological sex had no impact on the occurrence of cardiac injury during ICU stay or on other clinical outcomes. Clinical trial registration NCT04335162.
| S-EPMC10662091 | biostudies-literature
Project description:BackgroundDifferences in proteomic profiles between men and women may provide insights into the biological pathways that contribute to known sex differences in cardiovascular disease (CVD).ObjectivesThis study sought to investigate sex differences in circulating biomarkers representative of biological pathways implicated in the development of CVD among Framingham Heart Study participants.MethodsThe authors measured 71 circulating CVD protein biomarkers in 7,184 participants (54% women, mean age 49 years). Multivariable models were used to evaluate the associations of sex, menopause, and hormone status with biomarkers. Cox models were used to examine whether sex modified the association of biomarkers with incident CVD.ResultsOf 71 biomarkers examined, 61 (86%) differed significantly between men and women, of which 37 were higher in women (including adipokines and inflammatory markers such as leptin and C-reactive protein), and 24 were higher in men (including fibrosis and platelet markers such as MMP-8 (matrix metalloproteinase-8) and TIMP-1 (tissue inhibitor of metalloproteinases 1); false discovery rate q < 0.05 for all). Sex differences in biomarker profiles were most pronounced between pre-menopausal women versus men, with attenuated sex differences among post-menopausal women not taking hormone replacement therapy. Sex modified the association of specific biomarkers with incident CVD, including CD14 and apolipoprotein B (pinteraction <0.05 for all).ConclusionsIn a predominantly Caucasian population, the authors identified widespread sex differences in circulating biomarkers that reflect distinct pathways implicated in CVD, including inflammation, adiposity, fibrosis, and platelet homeostasis. Menopause and hormone status accounted for some, but not all, of the observed sex differences. Further investigation into factors underlying sex-based differences may provide mechanistic insight into CVD development.
| S-EPMC6756178 | biostudies-literature
Project description:Background: The cardiac manifestations of coronavirus disease 2019 (COVID-19) patients with cardiovascular disease (CVD) remain unclear. We aimed to investigate the prognostic value of echocardiographic parameters in patients with COVID-19 infection and underlying CVD. Methods: One hundred fifty-seven consecutive hospitalized COVID-19 patients were enrolled. The left ventricular (LV) and right ventricular (RV) structure and function were assessed using bedside echocardiography. Results: Eighty-nine of the 157 patients (56.7%) had underlying CVD. Compared with patients without CVD, those with CVD had a higher mortality (22.5 vs. 4.4%, p = 0.002) and experienced more clinical events including acute respiratory distress syndrome, acute heart injury, or deep vein thrombosis. CVD patients presented with poorer LV diastolic and RV systolic function compared to those without CVD. RV dysfunction (30.3%) was the most frequent, followed by LV diastolic dysfunction (9.0%) and LV systolic dysfunction (5.6%) in CVD patients. CVD patients with high-sensitivity troponin I (hs-TNI) elevation or requiring mechanical ventilation therapy demonstrated worsening RV function compared with those with normal hs-TNI or non-intubated patients, whereas LV systolic or diastolic function was similar. Impaired RV function was associated with elevated hs-TNI level. RV function and elevated hs-TNI level were independent predictors of higher mortality in COVID-19 patients with CVD. Conclusions: Patients with COVID-19 infection and underlying CVD displayed impaired LV diastolic and RV function, whereas LV systolic function was normal in most patients. Importantly, RV function parameters are predictive of higher mortality.
| S-EPMC8008078 | biostudies-literature
Project description:Many countries have been affected by the worldwide outbreak of COVID-19. Among Western countries, Italy has been particularly hit at the beginning of the pandemic, immediately after China. In Italy and elsewhere, women seem to be less affected than men by severe/fatal COVID-19 infection, regardless of their age. Although women and men are affected differently by this infection, very few studies consider different therapeutic approaches for the two sexes. Understanding the mechanisms underlying these differences may help to find appropriate and sex specific therapies. Here, we consider that other mechanisms are involved to explain this difference, in addition to the protection attributable to oestrogens. Several X-linked genes (such as ACE2) and Y-linked genes (SRY and SOX9) may explain sex differences. Cardiovascular comorbidities are among the major enhancers of virus lethality. In addition, the number of sex-independent, non-genetic factors that can change susceptibility and mortality is enormous, and many other factors should be considered, including gender and cultural habits in different countries.
| S-EPMC7405496 | biostudies-literature