A parsimonious approach for recognizing SARS-CoV-2 and host interactions.

Effective countermeasures against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demand a better understanding of the pathogen-host interactions. However, such information about the targets, responses, and effects in the host due to the virus is limited, especially so in the case of newly emerged pathogens. The peptide domains that form the interfaces of host and pathogen interacting proteins being evolutionarily conserved, it may be hypothesized that such interactions can be inferred from the similarities in the nucleotide sequences between the host and the pathogen. This communication reports the results of a study based on a parsimonious approach for the identification of the host-virus interactions, where sequence complementarity between the human and SARS-Cov-2 genomes was used to predict several interactions between the host and SARS-CoV-2 at different levels of biological organization. In particular, the findings are suggestive of a direct effect of SARS-CoV-2 on cardiac health. The existing literature on host responses to SARS-CoV-2 and other viruses attest to many of these predicted interactions, supporting the utility of the proposed approach for the identification of host interactions with other novel pathogens.

Vitamin D supplementation prior to or during COVID-19 associated with better 3-month survival in geriatric patients: Extension phase of the GERIA-COVID study.

BACKGROUND: The objective of this extension phase of the quasi-experimental GERIA-COVID study was to determine whether vitamin D3 supplementation taken prior to or during COVID-19 was associated with better 3-month survival in geriatric patients hospitalized for COVID-19. METHODS: Intervention group was defined as all participants supplemented with vitamin D3 prior to or during COVID-19 (n = 67). Supplements were either bolus vitamin D3 (ie, 50,000 IU per month, or 80,000 IU or 100,000 IU or 200,000 IU every 2-3 months), or daily supplementation with 800 IU. Comparator group involved those without vitamin D supplements (n = 28). Outcome was 3-month mortality. Covariables were age, sex, functional abilities, history of malignancies, cardiomyopathy, undernutrition, number of acute health issues, antibiotics use, systemic corticosteroids use, and 25(OH)D concentration. RESULTS: 76.1 % (n = 51) of participants survived at 3 months in Intervention group, compared to only 53.6 % (n = 15) in Comparator group (P = 0.03). The fully-adjusted hazard ratio for 3-month mortality was HR = 0.23 [95 %CI: 0.09;0.58](P = 0.002) in Intervention group compared to Comparator group. Intervention group had also longer survival time (log-rank P = 0.008). CONCLUSIONS: Vitamin D3 supplementation was associated with better 3-month survival in older COVID-19 patients.

CardiOvaScular Mechanisms In Covid-19: methodology of a prospective observational multimodality imaging study (COSMIC-19 study).

BACKGROUND: 8-28% of patients infected with COVID-19 have evidence of cardiac injury, and this is associated with an adverse prognosis. The cardiovascular mechanisms of injury are poorly understood and speculative. We aim to use multimodality cardiac imaging including cardiac magnetic resonance (CMR) imaging, computed tomography coronary angiography (CTCA) and positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG-PET/CT) to identify the cardiac pathophysiological mechanisms related to COVID-19 infections. METHODS: This is a single-centre exploratory observational study aiming to recruit 50 patients with COVID-19 infection who will undergo cardiac biomarker sampling. Of these, 30 patients will undergo combined CTCA and 18F-FDG-PET/CT, followed by CMR. Prevalence of obstructive and non-obstructive atherosclerotic coronary disease will be assessed using CTCA. CMR will be used to identify and characterise myocardial disease including presence of cardiac dysfunction, myocardial fibrosis, myocardial oedema and myocardial infarction. 18F-FDG-PET/CT will identify vascular and cardiac inflammation. Primary endpoint will be the presence of cardiovascular pathology and the association with troponin levels. DISCUSSION: The results of the study will identify the presence and modality of cardiac injury associated COVID-19 infection, and the utility of multi-modality imaging in diagnosing such injury. This will further inform clinical decision making during the pandemic. TRIAL REGISTRATION: This study has been retrospectively registered at the ISRCTN registry (ID ISRCTN12154994) on 14th August 2020. Accessible at https://www.isrctn.com/ISRCTN12154994.

COVID-19 and Cardiovascular Disease: From Bench to Bedside.

A pandemic of historic impact, coronavirus disease 2019 (COVID-19) has potential consequences on the cardiovascular health of millions of people who survive infection worldwide. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can infect the heart, vascular tissues, and circulating cells through ACE2 (angiotensin-converting enzyme 2), the host cell receptor for the viral spike protein. Acute cardiac injury is a common extrapulmonary manifestation of COVID-19 with potential chronic consequences. This update provides a review of the clinical manifestations of cardiovascular involvement, potential direct SARS-CoV-2 and indirect immune response mechanisms impacting the cardiovascular system, and implications for the management of patients after recovery from acute COVID-19 infection.

Cardiac injury is associated with inflammation in geriatric COVID-19 patients.

BACKGROUND: Geriatric patients with coronavirus disease (COVID-19) are at high risk of developing cardiac injury. Identifying the factors that affect high-sensitivity cardiac troponin I may indicate the cause of cardiac injury in elderly patients, and this could hopefully assist in protecting heart function in this patient population. METHODS: One hundred and eighty inpatients who were admitted for COVID-19 were screened. Patients older than 60 years were included in this study, and the clinical characteristics and laboratory results of the cohort were analyzed. The correlation between cardiac injury and clinical/laboratory variables was statistically analyzed, and further logistic regression was performed to determine how these variables influence cardiac injury in geriatric patients. RESULTS: Age (p < 0.001) significantly correlated with cardiac injury, whereas sex (p = 0.372) and coexisting diseases did not. Rising procalcitonin (p = 0.001), interleukin-2 receptor (p < 0.001), interleukin 6 (p = 0.001), interleukin 10 (p < 0.001), tumor necrosis factor α (p = 0.001), high-sensitivity C-reactive protein (p = 0.001), D-dimer (p < 0.001), white blood cells (p < 0.001), neutrophils (p = 0.001), declining lymphocytes (p < 0.001), and natural killer cells (p = 0.005) were associated with cardiac injury and showed predictive ability in the multivariate logistic regression. CONCLUSION: Our results suggest that age and inflammatory factors influence cardiac injury in elderly patients. Interfering with inflammation in this patient population may potentially confer cardiac protection.

Women's perspective on the COVID-19 pandemic: Walking into a post-peak phase.

The pandemic of Novel Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has provoked hundreds of thousands of deaths, resulting in catastrophe for humans. Although some insights have been garnered in studies on women, children and young adults infected with COVID-19, these often remain fragmented in literature. Therefore, we discussed the impact of COVID-19 pandemic on women, children and young patients, particularly those with underlying cardiovascular comorbidities or congenital heart disease. Furthermore, we gathered and distilled the existing body of literature that describes their cardiovascular complications and the recommended actions in favour of those patients toward the post-peak pandemic period. Although many questions still require answers, this article is sought to help the practicing clinician in the understanding and management of the threatening disease in special populations.

Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19).

IMPORTANCE: Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown. OBJECTIVE: To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness. DESIGN, SETTING, AND PARTICIPANTS: In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020. EXPOSURE: Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract. MAIN OUTCOMES AND MEASURES: Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained. Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57). RESULTS: Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years. The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days. Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization. At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%). Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2. A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22). There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping. None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = -0.07; P = .50). High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01). Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation. Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology. CONCLUSIONS AND RELEVANCE: In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

Myocardial injury determination improves risk stratification and predicts mortality in COVID-19 patients.

BACKGROUND: Despite being associated with worse prognosis in patients with COVID-19, systematic determination of myocardial injury is not recommended. The aim of the study was to study the effect of myocardial injury assessment on risk stratification of COVID-19 patients. METHODS: Seven hundred seven consecutive adult patients admitted to a large tertiary hospital with confirmed COVID-19 were included. Demographic data, comorbidities, laboratory results and clinical outcomes were recorded. Charlson comorbidity index (CCI) was calculated in order to quantify the degree of comorbidities. Independent association of cardiac troponin I (cTnI) increase with outcomes was evaluated by multivariate regression analyses and area under curve. In addition, propensity-score matching was performed to assemble a cohort of patients with similar baseline characteristics. RESULTS: In the matched cohort (mean age 66.76 ± 15.7 years, 37.3% females), cTnI increase above the upper limit was present in 20.9% of the population and was associated with worse clinical outcomes, including all-cause mortality within 30 days (45.1% vs. 23.2%; p = 0.005). The addition of cTnI to a multivariate prediction model showed a significant improvement in the area under the time-dependent receiver operating characteristic curve (0.775 vs. 0.756, DC-statistic = 0.019; 95% confidence interval 0.001-0.037). Use of renin-angiotensin-aldosterone system inhibitors was not associated with mortality after adjusting by baseline risk factors. CONCLUSIONS: Myocardial injury is independently associated with adverse outcomes irrespective of baseline comorbidities and its addition to multivariate regression models significantly improves their performance in predicting mortality. The determination of myocardial injury biomarkers on hospital admission and its combination with CCI can classify patients in three risk groups (high, intermediate and low) with a clearly distinct 30-day mortality.

[Cardiac biomarkers and COVID-19 - Phenotypes and Interpretation]. / Kardiale Biomarker und COVID-19-Phänotypen und Interpretation.

Current pandemic caused by SARS-CoV-2 inducing viral COVID-19 pneumonia, is categorized in 3 stages. Some biomarkers could be assigned to one of these stages, showing a correlation to mortality in COVID-19 patients. Laboratory findings in COVID-19, especially when serially evaluated, may represent individual disease severity and prognosis. These may help planning and controlling therapeutic interventions. Biomarkers for myocardial injury (high sensitive cardiac troponin, hsTn) or hemodynamic stress (NTproBNP) may occur in COVID-19 pneumonia such as in other pneumonias, correlating with severity and prognosis of the underlying disease. In hospitalized COVID-19 patients' mild increases of hsTn or NTproBNP may be explained by cardiovascular comorbidities and direct or indirect cardiac damage or stress caused by or during COVID-19 pneumonia. In case of suspected NSTE-ACS and COVID-19, indications for echocardiography or reperfusion strategy should be carefully considered against the risk of contamination.

Retrospective Study of Risk Factors for Myocardial Damage in Patients With Critical Coronavirus Disease 2019 in Wuhan.

BACKGROUND The novel severe acute respiratory syndrome coronavirus 2 threatens human health, and the mortality rate is higher in patients who develop myocardial damage. However, the possible risk factors for myocardial damage in patients with coronavirus disease 2019 (COVID-19) are not fully known. METHODS AND RESULTS Critical type patients were selected randomly from 204 confirmed COVID-19 cases occurring in Renmin Hospital of Wuhan University from February 1, 2020 to February 24, 2020. Univariate analyses were used to compare the 2 groups: the myocardial damage group and the non-myocardial damage group. A total of 82 critical patients with COVID-19 were recruited: 34 with myocardial damage and 48 without myocardial damage. A total of 30 patients died in the myocardial damage group, and 20 died in the non-myocardial damage group. In univariate analysis, the proportion of elderly patients (>70 years old, 70.59% versus 37.50%; P=0.003) and patients with cardiovascular disease (41.18% versus 12.50%; P=0.003) was higher among myocardial damage patients than among non-myocardial damage patients. Multivariate analysis showed that age >70 years old (hazard ratio [HR], 2.44; 95% CI, 1.01-5.40), CRP (C-reactive protein) >100 mg/L (HR, 1.92; 95% CI, 0.94-3.92), lactate dehydrogenase >300 U/L (HR, 2.67; 95% CI, 1.03-6.90), and lactic acid >3 mmol/L (HR, 3.25; 95% CI, 1.57-6.75) were independent risk factors for myocardial damage in patients with COVID-19. CONCLUSIONS Old age (>70 years old), CRP >100 mg/L, lactate dehydrogenase >300 U/L, and lactic acid >3 mmol/L are high-risk factors related to myocardial damage in critical patients with COVID-19.

Cardiac and arrhythmic complications in patients with COVID-19.

In December 2019, the world started to face a new pandemic situation, the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Although coronavirus disease (COVID-19) clinical manifestations are mainly respiratory, major cardiac complications are being reported. Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2-receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others. Studies evaluating patients with COVID-19 presenting cardiac injury markers show that it is associated with poorer outcomes, and arrhythmic events are not uncommon. Besides, drugs currently used to treat the COVID-19 are known to prolong the QT interval and can have a proarrhythmic propensity. This review focus on COVID-19 cardiac and arrhythmic manifestations and, in parallel, makes an appraisal of other virus epidemics as SARS-CoV, Middle East respiratory syndrome coronavirus, and H1N1 influenza.

Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms.

Coronavirus disease 2019 (COVID-19) is a pandemic that has affected more than 1.8 million people worldwide, overwhelmed health care systems owing to the high proportion of critical presentations, and resulted in more than 100,000 deaths. Since the first data analyses in China, elevated cardiac troponin has been noted in a substantial proportion of patients, implicating myocardial injury as a possible pathogenic mechanism contributing to severe illness and mortality. Accordingly, high troponin levels are associated with increased mortality in patients with COVID-19. This brief review explores the available evidence regarding the association between COVID-19 and myocardial injury.

[COVID-19 pandemia: Impact on the cariovascular system. Data of 1st April 2020]. / Pandémie COVID-19 : impact sur le systeme cardiovasculaire. Données disponibles au 1er avril 2020.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells with angiotensin receptors, leading to pneumonia linked to COVID-19. The virus has a double impact on the cardiovascular system, the infection will be more intense if the host has cardiovascular co-morbidities and the virus can cause life-threatening cardiovascular lesions. Therapies associated with COVID-19 may have adverse cardiovascular effects. Therefore, special attention should be given to cardiovascular protection during COVID-19 infection.