OBJECTIVE: This study summarizes and compares clinical and laboratory characteristics of 34 patients admitted to the intensive care unit (ICU) for complications from coronavirus disease 2019 (COVID-19) at the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China from Jan. 22 to Mar. 5, 2020. METHODS: A total of 34 patients were divided into two groups, including those who required noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) with additional extracorporeal membrane oxygenation (ECMO) in 11 patients. Clinical features of COVID-19 patients were described and the parameters of clinical characteristics between the two groups were compared. RESULTS: The rates of the acute cardiac and kidney complications were higher in IMV cases than those in NIV cases. Most patients had lymphocytopenia on admission, with lymphocyte levels dropping progressively on the following days, and the more severe lymphopenia developed in the IMV group. In both groups, T lymphocyte counts were below typical lower limit norms compared to B lymphocytes. On admission, both groups had higher than expected amounts of plasma interleukin-6 (IL-6), which over time declined more in NIV patients. The prothrombin time was increased and the levels of platelet, hemoglobin, blood urea nitrogen (BUN), D-dimer, lactate dehydrogenase (LDH), and IL-6 were higher in IMV cases compared with NIV cases during hospitalization. CONCLUSIONS Data showed that the rates of complications, dynamics of lymphocytopenia, and changes in levels of platelet, hemoglobin, BUN, D-dimer, LDH and IL-6, and prothrombin time in these ICU patients were significantly different between IMV and NIV cases.
Acute Kidney Injury ; virology ; Aged ; Aged, 80 and over ; Betacoronavirus ; Blood Urea Nitrogen ; China ; Coronavirus Infections ; complications ; therapy ; Extracorporeal Membrane Oxygenation ; Female ; Fibrin Fibrinogen Degradation Products ; analysis ; Heart Diseases ; virology ; Hemoglobins ; analysis ; Hospitalization ; Humans ; Intensive Care Units ; Interleukin-6 ; blood ; L-Lactate Dehydrogenase ; blood ; Lymphopenia ; virology ; Male ; Middle Aged ; Noninvasive Ventilation ; Pandemics ; Pneumonia, Viral ; complications ; therapy ; Positive-Pressure Respiration ; Prothrombin Time ; Retrospective Studies

Objective: Present study investigated the mechanism of heart failure associated with coronavirus infection and predicted potential effective therapeutic drugs against heart failure associated with coronavirus infection. Methods: Coronavirus and heart failure were searched in the Gene Expression Omnibus (GEO) and omics data were selected to meet experimental requirements. Differentially expressed genes were analyzed using the Limma package in R language to screen for differentially expressed genes. The two sets of differential genes were introduced into the R language cluster Profiler package for gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) pathway enrichment analysis. Two sets of intersections were taken. A protein interaction network was constructed for all differentially expressed genes using STRING database and core genes were screened. Finally, the apparently accurate treatment prediction platform (EpiMed) independently developed by the team was used to predict the therapeutic drug. Results: The GSE59185 coronavirus data set was searched and screened in the GEO database, and divided into wt group, ΔE group, Δ3 group, Δ5 group according to different subtypes, and compared with control group. After the difference analysis, 191 up-regulated genes and 18 down-regulated genes were defined. The GEO126062 heart failure data set was retrieved and screened from the GEO database. A total of 495 differentially expressed genes were screened, of which 165 were up-regulated and 330 were down-regulated. Correlation analysis of differentially expressed genes between coronavirus and heart failure was performed. After cross processing, there were 20 GO entries, which were mainly enriched in virus response, virus defense response, type Ⅰ interferon response, γ interferon regulation, innate immune response regulation, negative regulation of virus life cycle, replication regulation of viral genome, etc. There were 5 KEGG pathways, mainly interacting with tumor necrosis factor (TNF) signaling pathway, interleukin (IL)-17 signaling pathway, cytokine and receptor interaction, Toll-like receptor signaling pathway, human giant cells viral infection related. All differentially expressed genes were introduced into the STRING online analysis website for protein interaction network analysis, and core genes such as signal transducer and activator of transcription 3, IL-10, IL17, TNF, interferon regulatory factor 9, 2'-5'-oligoadenylate synthetase 1, mitogen-activated protein kinase 3, radical s-adenosyl methionine domain containing 2, c-x-c motif chemokine ligand 10, caspase 3 and other genes were screened. The drugs predicted by EpiMed's apparent precision treatment prediction platform for disease-drug association analysis were mainly TNF-α inhibitors, resveratrol, ritonavir, paeony, retinoic acid, forsythia, and houttuynia cordata. Conclusions: The abnormal activation of multiple inflammatory pathways may be the cause of heart failure in patients after coronavirus infection. Resveratrol, ritonavir, retinoic acid, amaranth, forsythia, houttuynia may have therapeutic effects. Future basic and clinical research is warranted to validate present results and hypothesis.
Betacoronavirus ; COVID-19 ; Computational Biology ; Coronavirus Infections/complications* ; Gene Expression Profiling ; Gene Ontology ; Heart Failure/virology* ; Humans ; Pandemics ; Pneumonia, Viral/complications* ; SARS-CoV-2

Objective: To explore the predictive value of neutrophil/lymphocyte ratio (NLR) on myocardial injury in severe COVID-19 patients. Methods: In this single-center retrospective cohort study, we collected and analyzed data form 133 severe COVID-19 patients admitted to Renmin Hospital of Wuhan University (Eastern District) from January 30 to February 18, 2020. Patients were divided into myocardial injury group (n=29) and non-myocardial injury group (n=104) according the presence or absence of myocardial injury. The general information of patients was collected by electronic medical record database system. All patients were followed up for 30 days, the organ injury and/or dysfunction were monitored, the in-hospital death was compared between the two groups, and the disease progression was reevaluated and classified at 14 days after initial hospitalization. Logistic regression analysis was performed to identify risk factors of myocardial injury in severe COVID-19 patients. The ROC of NLR was calculated, and the AUC was determined to estimate the optimal cut-off value of NLR for predicting myocardial injury in severe cases of COVID-19. Results: There was statistical significance in age, respiratory frequency, systolic blood pressure, symptoms of dyspnea, previous chronic obstructive pulmonary disease, coronary heart disease history, white blood cells, neutrophils, lymphocytes, platelets, C-reactive protein, platelet counting, aspartate transaminase, albumin, total bilirubin, direct bilirubin, urea, estimated glomerular filtration rate, total cholesterol, low-density lipoprotein cholesterol, D-dimer, CD3⁺, CD4⁺, partial pressure of oxygen, partial pressure of CO₂, blood oxygen saturation, other organ injury, clinical outcome and prognosis between patients with myocardial injury and without myocardial injury (all P<0.05). Multivariate logistic regression analysis showed that NLR was a risk factor for myocardial injury (OR=1.066，95%CI 1.021-1.111，P=0.033). ROC curve showed that NLR predicting AUC of myocardial injury in severe COVID-19 patients was 0.774 (95%CI 0.694-0.842), the optimal cut-off value of NLR was 5.768, with a sensitivity of 82.8%, and specificity of 69.5%. Conclusion: NLR may be used to predict myocardial injury in severe COVID-19 patients.
Betacoronavirus ; COVID-19 ; Coronavirus Infections/pathology* ; Heart Diseases/virology* ; Humans ; Lymphocytes/cytology* ; Myocardium/pathology* ; Neutrophils/cytology* ; Pandemics ; Pneumonia, Viral/pathology* ; Prognosis ; ROC Curve ; Retrospective Studies ; SARS-CoV-2

INTRODUCTION: Respiratory virus (RV) infections have been implicated in acute exacerbation cardiopulmunary conditions. This study aimed to determine the prevalence of RV infections in patients admitted to the cardiology unit with acute decompensated heart failure (ADHF) in a tertiary hospitals in Singapore. MATERIALS AND METHODS: This was a single-centre, prospective observational study. A total of 194 adults (aged >21) admitted to the Singapore General Hospital with ADHF were recruited. A nasopharyngeal swab was taken for multiplex polymerase chain reaction (PCR) detection of influenza virus, rhinovirus, parainfluenza virus (HPIV), human coronavirus (HcoV), adenoviurs, human bocavirus (HboV), human metapneumovirus (hMPV), and respiratory syncytial virus (RSV). RESULTS: Twenty-five (13%) had RVs detected by RV multiplex PCR. There comprised 9 rhinoviruses (36%), 4 influenza A viruses (16%), 3 HPIV (12%), 3 HCoV (12%), 2 adenoviruses (8%), 1 human HBoV (4%), 1 hMPV (4%), and 1 RSV (4%). Symptoms-wise, cough was significantly more common in the PCR-positive group (48% vs 24%, = 0.02). There were no statistically significant differences in laboratory investigations (haemoglobin, leukocytes, platelets, creatine kinase, creatine kinase-muscle/brain, troponin T), and radiology findings between RV PCR-positive and -negative groups. The PCR-positive group did not have increased mortality or length of hospital stay. CONCLUSION This study identified a considerable burden of RVs in our ADHF cohort, and highlights the need for prevention of RVs in this group of patients. We also recognised the difficulty with clinical diagnosis of RVs in ADHF patients.
Adult ; Comorbidity ; Diagnosis, Differential ; Female ; Heart Failure ; epidemiology ; physiopathology ; therapy ; Humans ; Length of Stay ; statistics & numerical data ; Male ; Nasopharynx ; virology ; Outcome Assessment (Health Care) ; Prospective Studies ; Respiratory Tract Infections ; epidemiology ; therapy ; virology ; Singapore ; epidemiology ; Survival Analysis ; Symptom Flare Up ; Viruses ; classification ; isolation & purification ; pathogenicity

Group B coxsackieviruses (CVBs) are a group of common human pathogens producing various clinical symptoms. Although the virology of CVB is well known, there is limited information on viral pathogenesis and the relationship between clinical symptoms and viral phenotype, particularly for CVB type 2 (CVB2). In 2004 in Korea, two CVB2 strains were isolated: CB2/04/279 from stool of an acute myocarditis patient with heart failure and CB2/04/243 from an aseptic meningitis patient. In this study, a high degree of homology was observed between the CB2/04/279 and CB2/04/243 full genome sequences. The two Korean CVB2 isolates had 93.1% homology compared to 82.1%–82.5% nucleotide sequence identity with the cardiovirulence-associated reference CVB strain Ohio-1 (CVB/O). CVB2-induced pathogenesis was analyzed, focusing on virus-induced pathology of various tissues in 4-week-old BALB/c inbred male mice. Myocarditis developed and extensive pancreatic inflammation was observed in all mice infected with CB2/04/279 or CVB/O, but not in animals infected with CB2/04/243. This is the first report of the full-genomic sequence and pathogenesis of the CVB2 strain isolated from an acute myocarditis patient in Korea.
Animals ; Base Sequence ; Enterovirus ; Genome ; Heart Failure ; Humans ; Inflammation ; Korea* ; Male ; Meningitis, Aseptic* ; Mice* ; Myocarditis* ; Pathology ; Phenotype ; Virology

OBJECTIVETo analyze the reason and treatment of the complications of 61 cases of extracorporeal membrane oxygenation (ECMO) in order to improve survival rate of ECMO treatment.

METHODSECMO records from January 2007 to December 2014 in Shanghai Chest Hospital were investigated retrospectively focusing on complications. There were included 43 male and 18 female patients, age 3 to 66 years. Indications for ECMO included post-operative low cardiac output, viral myocarditis, bridge to heart transplantation, acute respiratory distress syndrome and myocardial infarction. There were 49 cases of veno-arterial ECMO and 12 cases of veno-venous ECMO.

RESULTSECMO duration was 2 to 61 days. Among 43 patients, 37 patients weaned from ECMO successfully and 28 survived to discharge. Various complications occurred to 56 patients, including oxygenator plasma leakage(4 case times), circuit emboli (7), hemolysis (4), bleeding (34), infection (8), acute kidney injury (35), lower limb ischemia (8) and neurologic complications (6). There were 49 cases times of complications in survivors, while 61 cases times in death group. Bleeding (10 time cases) and acute kidney injury (33 time cases) happened in the death group. Progresses in ECMO technique had influences on complications in some parts. For instance, incidence of lower limb ischemia was 6/7 in cutdown cannulating group, but reduced to 2/42(4.8%) when semi-open technique was applied.

CONCLUSIONSComplications in ECMO are relative to patients' outcome intimately. Appropriate prevention and treatment of complication play a major role in the success of ECMO support. The incidences of certain complications reduce significantly due to progresses of equipment and medical experiences.

Acute Disease ; Acute Kidney Injury ; etiology ; Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; Extracorporeal Membrane Oxygenation ; adverse effects ; Female ; Heart Transplantation ; Hemorrhage ; etiology ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; Myocarditis ; virology ; Respiratory Distress Syndrome, Adult ; Retrospective Studies ; Treatment Outcome ; Young Adult

BACKGROUND/AIMS: Infections are major causes of both early and late death after lung transplantation (LT). The development of prophylaxis strategies has altered the epidemiology of post-LT infections; however, recent epidemiological data are limited. We evaluated infections after LT at our institution by time of occurrence, site of infections, and microbiologic etiologies. METHODS: All consecutive patients undergoing lung or heart-lung transplantation between October 2008 and August 2014 at our institution were enrolled. Cases of infections after LT were initially identified from the prospective registry database, which was followed by a detailed review of the patients' medical records. RESULTS: A total of 108 episodes of post-LT infections (56 bacterial, 43 viral, and nine fungal infections) were observed in 34 LT recipients. Within 1 month after LT, the most common bacterial infections were catheter-related bloodstream infections (42%). Pneumonia was the most common site of bacterial infection in the 2- to 6-month period (28%) and after 6 months (47%). Cytomegalovirus was the most common viral infection within 1 month (75%) and in the 2- to 6-month period (80%). Respiratory viruses were the most common viruses after 6 months (48%). Catheter-related candidemia was the most common fungal infection. Invasive pulmonary aspergillosis developed after 6 months. Survival rates at the first and third years were 79% and 73%, respectively. CONCLUSIONS: Although this study was performed in a single center, we provide valuable and recent detailed epidemiology data for post-LT infections. A further multicenter study is required to properly evaluate the epidemiology of post-LT infections in Korea.
Adult ; Bacterial Infections/diagnosis/*microbiology/mortality ; Catheter-Related Infections/microbiology/virology ; Cytomegalovirus Infections/virology ; Female ; Heart-Lung Transplantation/*adverse effects/mortality ; Humans ; Kaplan-Meier Estimate ; Lung Transplantation/*adverse effects/mortality ; Male ; Medical Records ; Middle Aged ; Mycoses/diagnosis/*microbiology/mortality ; Pneumonia, Bacterial/microbiology ; Registries ; Republic of Korea/epidemiology ; Risk Factors ; Time Factors ; Treatment Outcome ; Virus Diseases/diagnosis/mortality/*virology

OBJECTIVETo determine the optimum treatment for viral myocarditis (VMC).

METHODSA total of 126 VMC patients were randomly divided into the control group (42 cases) that was treated with conventional Western medicine, and the intervention group (84 cases) that was treated with a combination of Chinese medicine (CM) and Western medicine intervention termed optimum proposal of integration of disease and syndrome (OPIDS). Before and after 4 weeks of treatment, the integral of CM syndrome, self-rating depression and anxiety scales (SDS and SAS, respectively), echocardiograms (ECGs), heart rate variability and left ventricular systolic function were observed.

RESULTSCompared with the control group, the intervention group showed significant reductions on the SDS and SAS (P <0.05); improvement of premature ventricular beats, atrioventricular blocks, ST-segment abnormalities, and significant T wave changes (P <0.05); greater reductions in standard deviation of NN intervals (SDNN), standard deviation for per 5 min averages NN intervals (SDANN), and root-mean-square of successive difference of NN intervals (rMSSD) (P <0.05); and increases in cardiac output, stroke volume, and ejection fraction, the last of which was statistically significant (P <0.05). Overall, the treatment efficacy rate was significantly better P<0.05) in the intervention group (75.61%) compared with the control group (69.70%).

CONCLUSIONOPIDS is quite effective in treating VMC and improves symptoms such as anxiety and depression, left ventricular systolic dysfunction, premature ventricular contraction, and cardiac autonomic nervous system dysfunction. [

REGISTRATIONChinese clinical trial center (No. ChiCTR-TRC-00000298)].

Adolescent ; Adult ; Anxiety ; complications ; Depression ; complications ; Electrocardiography ; Female ; Heart Rate ; Humans ; Male ; Medicine, Chinese Traditional ; Myocarditis ; diagnostic imaging ; physiopathology ; therapy ; virology ; Syndrome ; Systole ; Ultrasonography ; Ventricular Function ; Young Adult

OBJECTIVETo investigate the correlations among persistent viral infection, heart function and Chinese medicine (CM) difined-syndromes in patients with dilated cardiomyopathy (DCM).

METHODSFifty patients with DCM in the First Affiliated Hospital of Zhejiang Chinese Medical University from October 2009 to December 2011 were selected as the research subjects, and 30 healthy people were simultaneously selected as the normal control group to detect persistent viral infections after admission. The CM syndrome type and grade of heart function were then evaluated. The expression level of Coxsackie adenovirus receptor (CAR) was detected using the flow cytometry (FCM) technique, coxsackie virus RNA (CVB-RNA) using reverse transcription polymerase chain reaction (RTPCR), and the plasma brain natriuretic peptide (BNP) level with a Triage meter plus diagnosis instrument. Finally, the parameters such as left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were measured by ultrasonic cardiogram. Person correlation analysis was used for measured data, Spearman correlation analysis for rating data, and the Chi-square test for numerical data.

RESULTSCVB-RNA was positive in 22 patients (44%) with DCM, while only 6 cases (20%) were CVB-RNA-positive in the normal control group, with a significant difference between the two groups (P<0.01). The expression level of CAR was significantly elevated in the DCM group compared with the normal control group (P<0.01). In CVB-RNA-positive patients (22 cases), the expression level of CAR was significantly higher than in CVB-RNA-negative patients (28 cases; P<0.01). In the DCM patients, there was a positive correlation between the CAR expression and the BNP level (r=0.34, P<0.05), while no significant difference was found between the CAR expression and the LVEF and LVEDd (r=-0.32, 0.30, P>0.05). There was no clear correlation between virus infection and the CM syndrome types in DCM patients (r=-0.22, P>0.05). According to the sequence of syndrome types: phlegm → qi deficiency → blood stasis → hydroretention with asthenic yang (from low to high), a positive correlation was existed between the BNP levels and CM syndrome types (r=0.139, P<0.05).

CONCLUSIONThe expression of CAR on the surface of white cells could be used to detect persistent viral infection. The expression level of CAR and heart function in DCM patients were highly correlated. The expression level of BNP may serve as an objective index for differentiating CM syndromes for patients with DCM.

Adult ; Aged ; Cardiomyopathy, Dilated ; blood ; complications ; physiopathology ; virology ; Coxsackie and Adenovirus Receptor-Like Membrane Protein ; Coxsackievirus Infections ; blood ; complications ; physiopathology ; Female ; Heart Function Tests ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; RNA, Viral ; blood ; Syndrome

OBJECTIVETo explore the apoptotic pathway mediated by endoplasmic reticulum stress in the mouse myocardium with heart failure induced by acute viral myocarditis caused by B-3 Coxsackie virus.

METHODSForty BALB/c male mice were randomly divided into 2 groups (n = 20): the control group and the virus infection group. The BALB/c mouse myocarditis was induced by B-3 Coxsackie virus and the mouse behavior was observed conventionally. All the mice were sacrificed on day 7 and the changes of left ventricular pressure (LVP) and the rate of change of left ventricular pressure (LV dp/dt) were measured. The cardiomyocytic apoptosis was analyzed by TUNEL method and the mRNA expression level of endoplasmic reticulum haperones glucose-regulated protein (GRP)78 and GRP94 was detected by RT-PCR.

RESULTS(1) Compared with those of control group, the parameters of cardiac hemodynamics in the virus infection group were significantly decreased (P < 0.01); (2) Compared with that of control group, myocardial apoptosis was significantly increased in the myocardial cells from mice with heart failure induced by acute viral myocarditis (P < 0.01); (3) The mRNA expression level of GRP78 and GRP94 were increased significantly in the virus infection group compared with the control group.

CONCLUSIONThese findings suggest the endoplasmic reticulum stress may mediate the apoptosis of myocardial cells in the mice myocardium of heart failure induced by acute viral myocarditis caused by B-3 Coxsackie virus.

Animals ; Apoptosis ; Coxsackievirus Infections ; physiopathology ; Endoplasmic Reticulum Stress ; Heart ; physiopathology ; Heart Failure ; physiopathology ; virology ; Heat-Shock Proteins ; metabolism ; Male ; Membrane Glycoproteins ; metabolism ; Mice ; Mice, Inbred BALB C ; Myocarditis ; physiopathology ; virology ; Myocardium ; pathology ; Myocytes, Cardiac ; cytology