Single-cell Transcriptome Analysis Indicates New Potential Regulation Mechanism of ACE2 and NPs signaling among heart failure patients infected with SARS-CoV-2

BackgroundCOVID-19 patients with comorbidities such as hypertension or heart failure (HF) are associated with poor clinical outcomes. Angiotensin-converting enzyme 2 (ACE2), the critical enzyme for SARS-CoV-2 infection, is broadly expressed in many organs including heart. However, the cellular distribution of ACE2 in the human heart, particularly the failing heart is unknown. MethodsWe analyzed single-cell RNA sequencing (scRNA-seq) data in both normal and failing hearts, and characterized the ACE2 gene expression profile in various cell subsets, especially in cardiomyocyte subsets, as well as its interaction with gene networks relating to various defense and immune responses at the single cell level. ResultsThe results demonstrated that ACE2 is present in cardiomyocytes (CMs), endothelial cells, fibroblasts and smooth muscle cells in the heart, while the number of ACE2-postive (ACE2+) CMs and ACE2 gene expression in these CMs are significantly increased in the failing hearts. Interestingly, both brain natriuretic peptides (BNP) and atrial natriuretic peptide (ANP) are significantly up-regulated in the ACE2+ CMs. Further analysis shows that ANP, BNP and ACE2 may form a negative feedback loop with a group of genes associated with the development of heart failure. To our surprise, we found that genes related to virus entry, virus replication and suppression of interferon-gamma (IFN-{gamma}) signaling are all up-regulated in CMs in failing hearts, and the increases were significantly higher in ACE2+ CMs as compared with ACE2 negative (ACE2-) CMs, suggesting that these ACE2+ CMs may be more vulnerable to virus infection. Since ACE2 expression is correlated with BNP expression, we further performed retrospective analysis of the plasma BNP levels and clinic outcome of 91 COVID-19 patients from a single-center. Patients with higher plasma BNP were associated with significantly higher mortality rate and expression levels of inflammatory and infective markers such as procalcitonin and C-reactive protein. ConclusionIn the failing heart, the upregulation of ACE2 and virus infection associated genes, as well as the increased expression of ANP and BNP could facilitate SARS-CoV-2 virus entry and replication in these vulnerable cardiomyocyte subsets. These findings may advance our understanding of the underlying molecular mechanisms of myocarditis associated with COVID-19.

Biochemical analysis between common type and critical type of COVID-19 and clinical value of neutrophil/lymphocyte ratio / 浙江大学学报·医学版

OBJECTIVE@#To identify the key biochemical indicators that affect the clinical type and outcomes of COVID-19 patients and explore the application of neutrophil/lymphocyte ratio (NLR) in COVID-19.@*METHODS@#Ninety-three patients with confirmed diagnosis of COVID-19 admitted in Ezhou Central Hospital from February to April in 2020 were analyzed. Among them, 43 patients were selected from Intensive Care Unit (ICU) with the diagnosis of critical type of COVID-19, and 50 cases of common type were selected from the Department of Respiratory Medicine. The baseline data, blood routine test and biochemical indexes of the patients were collected on the first day of admission. NLRs of the patients were calculated, and COX survival analysis according to the NLR 4-category method was performed. The patients' outcomes were analyzed with receiver operating curves (ROCs). The patients were divided into two groups according to NLR cutoff value for comparison of the biochemical indexes. Based on the patients' outcomes, NLR cutoff value classification and clinical classification, multiple binary logistics regression was performed to screen the key variables and explore their significance in COVID-19.@*RESULTS@#The NLR four-category method was not applicable for prognostic evaluation of the patients. The cut-off value of NLR for predict the prognosis of COVID-19 was 11.26, with a sensitivity of 0.903 and a specificity of 0.839; the laboratory indicators of the patients with NLR < 11.26 were similar to those in patients of the common type; the indicators were also similar between patients with NLR≥11.26 and those with critical type COVID-19. NLR, WBC, NEUT, PCT, DD, BUN, TNI, BNP, and LDH had significant effects on the clinical classification and outcome of the patients ( < 0.05); Cr, Ca, PH, and Lac had greater impact on the outcome of the patients ( < 0.05), while Na, PCO had greater impact on the clinical classification of the patients ( < 0.05).@*CONCLUSIONS@#NLR can be used as an important reference for clinical classification, prognostic assessment, and biochemical abnormalities of COVID-19. Patients of critical type more frequently have bacterial infection with more serious inflammatory reactions, severer heart, lung and kidney damages, and much higher levels of DD and LDH than those of the common type. NLR, NEUT, DD, TNI, BNP, LDH, Ca, PCT, PH, and Lac have obvious influence on the prognosis of COVID-19 and should be observed dynamically.

Biochemical analysis between common type and critical type of COVID-19 and clinical value of neutrophil/lymphocyte ratio / 南方医科大学学报

OBJECTIVE@#To identify the key biochemical indicators that affect the clinical type and outcomes of COVID-19 patients and explore the application of neutrophil/lymphocyte ratio (NLR) in COVID-19.@*METHODS@#Ninety-three patients with confirmed diagnosis of COVID-19 admitted in Ezhou Central Hospital from February to April in 2020 were analyzed. Among them, 43 patients were selected from Intensive Care Unit (ICU) with the diagnosis of critical type of COVID-19, and 50 cases of common type were selected from the Department of Respiratory Medicine. The baseline data, blood routine test and biochemical indexes of the patients were collected on the first day of admission. NLRs of the patients were calculated, and COX survival analysis according to the NLR 4-category method was performed. The patients' outcomes were analyzed with receiver operating curves (ROCs). The patients were divided into two groups according to NLR cutoff value for comparison of the biochemical indexes. Based on the patients' outcomes, NLR cutoff value classification and clinical classification, multiple binary logistics regression was performed to screen the key variables and explore their significance in COVID-19.@*RESULTS@#The NLR four-category method was not applicable for prognostic evaluation of the patients. The cut-off value of NLR for predict the prognosis of COVID-19 was 11.26, with a sensitivity of 0.903 and a specificity of 0.839; the laboratory indicators of the patients with NLR < 11.26 were similar to those in patients of the common type; the indicators were also similar between patients with NLR≥11.26 and those with critical type COVID-19. NLR, WBC, NEUT, PCT, DD, BUN, TNI, BNP, and LDH had significant effects on the clinical classification and outcome of the patients ( < 0.05); Cr, Ca, PH, and Lac had greater impact on the outcome of the patients ( < 0.05), while Na, PCO had greater impact on the clinical classification of the patients ( < 0.05).@*CONCLUSIONS@#NLR can be used as an important reference for clinical classification, prognostic assessment, and biochemical abnormalities of COVID-19. Patients of critical type more frequently have bacterial infection with more serious inflammatory reactions, severer heart, lung and kidney damages, and much higher levels of DD and LDH than those of the common type. NLR, NEUT, DD, TNI, BNP, LDH, Ca, PCT, PH, and Lac have obvious influence on the prognosis of COVID-19 and should be observed dynamically.