Sacral neuromodulation remote programming in patients with refractory lower urinary tract dysfunction: China's experience during the COVID-19 pandemic.

Objectives: Sacral neuromodulation is an effective, minimally invasive treatment for refractory lower urinary tract dysfunction. However, regular postoperative programming is crucial for the maintenance of the curative effects of electronic sacral stimulator devices. The outbreak of coronavirus disease 2019 (COVID-19) limited the ability of practitioners to perform traditional face-to-face programming of these stimulators. Therefore, this study aimed to evaluate the application of remote programming technology for sacral neuromodulation during the COVID-19 pandemic in China. Materials and methods: We retrospectively collected data including baseline and programming information of all patients with lower urinary tract dysfunction who underwent sacral neuromodulation remote programming in China after the outbreak of COVID-19 (i.e., December 2019). The patients also completed a self-designed telephone questionnaire on the subject. Results: A total of 51 patients from 16 centers were included. They underwent 180 total remote programming visits, and 118, 2, 25, and 54 voltage, current, pulse width, and frequency adjustments, respectively, were performed. Additionally, remote switching on and off was performed 8 times; impedance test, 54 times; and stimulation contact replacement, 25 times. The demand for remote programming was the highest during the first 6 months of sacral neuromodulation (average, 2.39 times per person). In total, 36 out of the 51 patients completed the questionnaire survey. Of these, all indicated that they chose remote programming to minimize unnecessary travel because they had been affected by COVID-19. The questionnaire also showed that remote programming could reduce the number of patient visits to the hospital, save time, reduce financial costs, and would be easy for patients to master. All surveyed patients indicated that they were satisfied with remote programming and were willing to recommend it to other patients. Conclusion: Remote programming for sacral neuromodulation is feasible, effective, safe, and highly recommended by patients with refractory lower urinary tract dysfunction. Remote programming technology has great development and application potential in the post-pandemic era.

A tool for nuclear imaging of the SARS-CoV-2 entry receptor: molecular model and preclinical development of ACE2-selective radiopeptides.

PURPOSE: The angiotensin converting enzyme-2 (ACE2)-entry receptor of SARS-CoV-2-and its homologue, the angiotensin-converting enzyme (ACE), play a pivotal role in maintaining cardiovascular homeostasis. Potential changes in ACE2 expression levels and dynamics after SARS-CoV-2 infection have been barely investigated. The aim of this study was to develop an ACE2-targeting imaging agent as a noninvasive imaging tool to determine ACE2 regulation. METHODS: DOTA-DX600, NODAGA-DX600 and HBED-CC-DX600 were obtained through custom synthesis and labeled with gallium-67 (T1/2 = 3.26 d) as a surrogate radioisotope for gallium-68 (T1/2 = 68 min). ACE2- and ACE-transfected HEK cells were used for the in vitro evaluation of these radiopeptides. The in vivo tissue distribution profiles of the radiopeptides were assessed in HEK-ACE2 and HEK-ACE xenografted mice and imaging studies were performed using SPECT/CT. RESULTS: The highest molar activity was obtained for [67Ga]Ga-HBED-CC-DX600 (60 MBq/nmol), whereas the labeling efficiency of the other peptides was considerably lower (20 MBq/nmol). The radiopeptides were stable over 24 h in saline (> 99% intact peptide). All radiopeptides showed uptake in HEK-ACE2 cells (36-43%) with moderate ACE2-binding affinity (KD value: 83-113 nM), but no uptake in HEK-ACE cells (< 0.1%) was observed. Accumulation of the radiopeptides was observed in HEK-ACE2 xenografts (11-16% IA/g) at 3 h after injection, but only background signals were seen in HEK-ACE xenografts (< 0.5% IA/g). Renal retention was still high 3 h after injection of [67Ga]Ga-DOTA-DX600 and [67Ga]Ga-NODAGA-DX600 (~ 24% IA/g), but much lower for [67Ga]Ga-HBED-CC-DX600 (7.2 ± 2.2% IA/g). SPECT/CT imaging studies confirmed the most favorable target-to-nontarget ratio for [67Ga]Ga-HBED-CC-DX600. CONCLUSIONS: This study demonstrated ACE2 selectivity for all radiopeptides. [67Ga]Ga-HBED-CC-DX600 was revealed as the most promising candidate due to its favorable tissue distribution profile. Importantly, the HBED-CC chelator enabled 67Ga-labeling at high molar activity, which would be essential to obtain images with high signal-to-background contrast to detect (patho)physiological ACE2 expression levels in patients.

Dynamic changes in liver function parameters in patients with coronavirus disease 2019: a multicentre, retrospective study.

BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.

The Characteristics of Spike Glycoprotein Gene of Swine Acute Diarrhea Syndrome Coronavirus Strain CH/FJWT/2018 Isolated in China.

Swine acute diarrhea syndrome (SADS) is a highly contagious infectious disease characterized by acute vomiting and watery diarrhea in neonatal piglets. The causative agent for SADS is the swine acute diarrhea syndrome coronavirus (SADS-CoV), an alphacoronavirus in the family Coronaviridae. Currently, SADS-CoV was identified only in Guangdong and Fujian provinces of China, not in any other regions or countries in the world. To explore the genetic diversity of SADS-CoV isolates, herein we comparatively analyzed 44 full-length genomes of viruses isolated in Guangdong and Fujian provinces during 2017-2019. The spike glycoprotein gene of SADS-CoV strain CH/FJWT/2018 isolated in Fujian province is distinct from that of other viral isolates in either spike glycoprotein gene-based phylogenetic analysis or whole genome-based gene similarity analysis. Moreover, at least 7 predicted linear B cell epitopes in the spike glycoprotein of CH/FJWT/2018 would be affected by amino acid variations when compared with a representative virus isolated in Guangdong province. The spike glycoprotein of coronaviruses determines viral host range and tissue tropism during virus infection via specific interactions with the cellular receptor and also plays critical roles in eliciting the production of neutralizing antibodies. Since SADS-CoVs have a broad cell tropism, the results in this report further emphasize that the spike glycoprotein gene is a pivotal target in the surveillance of SADS-CoV.

Association between tachyarrhythmia and mortality in a cohort of critically ill patients with coronavirus disease 2019 (COVID-19).

BACKGROUND: Cardiovascular involvement manifesting as arrhythmias has been confirmed in patients with coronavirus disease 2019 (COVID-19), so we aimed to explore the association between primary tachyarrhythmia and death in critically ill patients with COVID-19 in this retrospective study. METHODS: A total of 79 critically ill patients with COVID-19 were included. Demographic characteristics, clinical data (past history, vital signs, therapeutic management, and outcomes), and results of laboratory findings and cardiac investigations were collected. All statistical analyses were performed using SPSS 23.0 software (IBM, Armonk, NY, USA). RESULTS: The median age was 65±12 years, and 53 patients (67%) were male. A total of 57 (72%) patients died, and compared with survivors, these patients were older and had significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score and fewer lymphocytes as well as higher heart rate (P<0.05). Autopsy findings did not suggest severe myocarditis. A total of 19 (24%) patients had tachyarrhythmias, including 10 (13%) with atrial fibrillation (AF) and 9 (11%) with ventricular tachycardia or fibrillation. The incidence of tachyarrhythmias in non-survivor was much higher than in survivors (P=0.04). In a Cox regression model, older patients with ventricular tachyarrhythmias (VTAs) age were at a higher risk of death, with hazard ratio (HR) of 3.302 [95% confidence interval (CI), 1.524-7.154, P=0.002] and 1.045 (95% CI, 1.020-1.071, P=0.000), respectively. The use of beta-blockers [HR, 0.219 (95% CI, 0.066-0.722); P=0.013] was associated with a lower risk of death. CONCLUSIONS: Critically ill patients with COVID-19 had a poor prognosis. VTA and older age were independent prognostic factors of death. Beta-blockers might be an effective therapy to improve survival.

Exploring the impact of the COVID-19 epidemic on the medical emergency calls and calls for cardiovascular diseases in Hangzhou, China.

AIMS: We aimed to evaluate the impact of the COVID-19 epidemic on emergency and cardiovascular disease-related calls in Hangzhou, China. METHODS: We conducted a single-center retrospective study, collecting data on emergency calls to the Hangzhou Emergency Center (HEC) during the COVID-19 epidemic (January 20, 2020, to March 15, 2020). Data were compared with the same period in 2019. RESULTS: Compared to 2019, the number of emergency calls has dropped by 21.63%, ambulance calls by 29.02%, rescue calls by 22.57%, and cardiovascular disease-related emergency calls by 32.86%. The numbers of emergency, ambulance, and rescue calls in 2020 were significantly lower than in 2019. CONCLUSIONS: During the COVID-19 epidemic in Hangzhou, the numbers of emergency and cardiovascular disease-related calls have decreased significantly. These results point to a severe social problem that requires the attention of the medical community and the government.

Myocardial Injury on Admission as a Risk in Critically Ill COVID-19 Patients: A Retrospective in-ICU Study.

OBJECTIVE: The aim of this study was to investigate the incidence, clinical presentation, cardiovascular (CV) complications, and mortality risk of myocardial injury on admission in critically ill intensive care unit (ICU) inpatients with COVID-19. DESIGN: A single-center, retrospective, observational study. SETTING: A newly built ICU in Tongji hospital (Sino-French new city campus), Huazhong University of Science and Technology, Wuhan, China. PARTICIPANTS: Seventy-seven critical COVID-19 patients. INTERVENTIONS: Patients were divided into a myocardial injury group and nonmyocardial injury group according to the on-admission levels of high-sensitivity cardiac troponin I. MEASUREMENTS AND MAIN RESULTS: Demographic data, clinical characteristics, laboratory tests, treatment, and clinical outcome were evaluated, stratified by the presence of myocardial injury on admission. Compared with nonmyocardial injury patients, patients with myocardial injury were older (68.4 ± 10.1 v 62.1 ± 13.5 years; p = 0.02), had higher prevalence of underlying CV disease (34.1% v 11.1%; p = 0.02), and in-ICU CV complications (41.5% v 13.9%; p = 0.008), higher Acute Physiology and Chronic Health Evaluation II scores (20.3 ± 7.3 v 14.4 ± 7.4; p = 0.001), and Sequential Organ Failure Assessment scores (7, interquartile range (IQR) 5-10 v 5, IQR 3-6; p < 0.001). Myocardial injury on admission increased the risk of 28-day mortality (hazard ratio [HR], 2.200; 95% confidence interval [CI] 1.29 to 3.74; p = 0.004). Age ≥75 years was another risk factor for mortality (HR, 2.882; 95% CI 1.51-5.50; p = 0.002). CONCLUSION: Critically ill patients with COVID-19 had a high risk of CV complications. Myocardial injury on admission may be a common comorbidity and is associated with severity and a high risk of mortality in this population.

Clinical characteristics and survival analysis in critical and non-critical patients with COVID-19 in Wuhan, China: a single-center retrospective case control study.

Since the outbreak of COVID-19 in China at the end of 2019, the world has experienced a large-scale epidemic caused by the SARS-CoV-2. The epidemiological and clinical course of COVID-19 patients has been reported, but there have been few analyses about the characteristics, predictive risk factors, and outcomes of critical patients. In this single-center retrospective case-control study, 90 adult inpatients hospitalized at Tongji Hospital (Wuhan, China) were included. Demographic, clinical, laboratory tests, and treatment data were obtained and compared between critical and non-critical patients. We found that compared with non-critical patients, the critical patients had higher SOFA score and qSOFA scores. Critical patients had lower lymphocyte and platelet count, elevated D-dimer, decreased fibrinogen, and elevated high-sensitivity C-reactive protein (hsCRP), and interleukin-6(IL-6). More critical patients received treatment including antibiotics, anticoagulation, corticosteroid, and oxygen therapy than non-critical ones. Multivariable regression showed higher qSOFA score and elevation of IL-6 were related to critical patients. Antibiotic usage and anticoagulation were associated with decreased in-hospital mortality. And critical grouping contributed greatly to in-hospital death. Critical COVID-19 patients have a more severe clinical course. qSOFA score and elevation of IL-6 are risk factors for critical condition. Non-critical grouping, positive antibiotic application, and anticoagulation may be beneficial for patient survival.

Swollen heart in COVID-19 patients who progress to critical illness: a perspective from echo-cardiologists.

AIMS: Cardiac complications are common and associated with mortality in critically ill patients with COVID-19; however, the diagnostic and prognostic implications of critical care echocardiography (CCE) have not been studied. METHODS AND RESULTS: A cohort of 43 patients with COVID-19 who were in the intensive care unit (ICU) underwent bedside CCE during their disease course. Demographic, clinical, and survival data were collected. The echocardiographic analyses revealed high frequencies of pericardial effusion (90.7%), increased left ventricular mass index (60.5%), elevated relative wall thickness (76.7%), and reduced left ventricular stroke volume index (LVSVi; 53.5%) and cardiac index (51.2%). Twenty-two (51.2%) patients died in the ICU. In multivariate Cox regression, the strongest predictor of in-ICU death was decreased cardiac index [hazard ratio (HR), 0.67, 95% confidence interval (CI), 0.45-0.98; P = 0.041], after adjusting for male sex, shock status, high-sensitivity cardiac troponin I, and N-terminal pro-B-type natriuretic peptide. Negative associations with mortality were observed for LVSVi (HR, 0.91, 95% CI 0.85-0.96; P = 0.002), tricuspid annular plane systolic excursion (HR, 0.74, 95% CI 0.64-0.84; P < 0.001), and S' (HR, 0.78, 95% CI 0.69-0.88; P < 0.001). Kaplan-Meier analyses indicated that reductions in LVSVi, cardiac index, TAPSE, and S' were associated with a shorter survival time. CONCLUSIONS: Pericardial effusion and increased ventricular mass in COVID-19 might indicate a swollen heart. Both left and right heart dysfunction and a reduced cardiac index may lead to an increased risk of mortality. Clinicians should pay special attention to cardiac haemodynamic disorders in critical patients with COVID-19.

High Inflammatory Burden: A Potential Cause of Myocardial Injury in Critically Ill Patients With COVID-19.

Background: Myocardial injury is a severe complication of novel coronavirus disease (COVID-19), and inflammation has been suggested as a potential cause of myocardial injury. However, the correlation of myocardial injury with inflammation in COVID-19 patients has not been revealed so far. Method: This retrospective single-center cohort study enrolled 64 critically ill patients with COVID-19. Patients were categorized into two groups by the presence of myocardial injury on admission. Demographic data, clinical characteristics, laboratory tests, treatments, and outcomes were analyzed in this study. Result: Of these patients, the mean age was 64.8 ± 12.2 years old, and 34 (53.1%) were diagnosed with myocardial injury. Compared with non-myocardial injury patients, myocardial injury patients were older (67.8 ± 10.3 vs. 61.3 ± 13.3 years; P = 0.033), had more cardiovascular (CV) risk factors such as smoking (16 [47.06%] vs. 7 [23.33%]; P = 0.048) and were more likely to develop CV comorbidities (13 [38.2%] vs. 2 [6.7%]; P = 0.003). Scores on the Acute Physiology and Chronic Health Evaluation II (median [interquartile range (IQR)] 19.0 [13.25-25.0] vs. 13.0 [9.25-18.75]; P = 0.005) and Sequential Organ Failure Assessment systems (7.0 [5.0-10.0] vs. 4.5 [3.0-6.0]; P < 0.001) were significantly higher in the myocardial injury group. In addition, patients with myocardial injury had higher mortality than those without myocardial injury (29 [85.29%] vs. 18 [60.00%]; P = 0.022). Cox regression suggested that myocardial injury was an independent risk factor for high mortality during the time from admission to death (hazard ratio [HR], 2.06 [95% confidence interval (CI), 1.10-3.83]; P = 0.023). Plasma levels of high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-1ß, interleukin-2 receptor (IL-2R), IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) exceeded the normal limits, and levels of hs-CRP, IL-2R, IL-6, IL-8, and TNF-α were statistically higher in the myocardial injury group than in the non-myocardial injury group. Multiple-variate logistic regression showed that plasma levels of hs-CRP (odds ratio [OR] 6.23, [95% CI, 1.93-20.12], P = 0.002), IL-6 (OR 13.63, [95% CI, 3.33-55.71]; P < 0.001) and TNF-α (OR 19.95, [95% CI, 4.93-80.78]; P < 0.001) were positively correlated with the incidence of myocardial injury. Conclusion: Myocardial injury is a common complication that serves as an independent risk factor for a high mortality rate among in-ICU patients with COVID-19. A high inflammatory burden may play a potential role in the occurrence of myocardial injury.

Neurological Manifestations in Critically Ill Patients With COVID-19: A Retrospective Study.

Background: The complications of coronavirus disease 2019 (COVID-19) involved multiple organs or systems, especially in critically ill patients. We aim to investigate the neurological complications in critically ill patients with COVID-19. Methods: This retrospective single-center case series analyzed critically ill patients with COVID-19 at the intensive care unit of Tongji Hospital, Wuhan, China from February 5 to April 2, 2020. Demographic data, clinical and laboratory findings, comorbidities and treatments were collected and analyzed. Results: Among 86 patients with confirmed COVID-19, 54 patients (62.8%) were male, and the mean (SD) age was 66.6 (11.1) years. Overall, 65% patients presented with at least one neurological symptom. Twenty patients (23.3%) had symptoms involving the central nervous system, including delirium, cerebrovascular diseases and hypoxic-ischemic brain injury, while 6 patients (7%) had neuromuscular involvement. Seven of 86 patients exhibited new stroke and 6 (7%) cases were ischemic. A significantly higher prevalence of antiphospholipid antibodies was observed in patients with ischemic stroke than in those without stroke (83.3 vs. 26.9%, p < 0.05). Patients with ischemic stroke were more likely to have a higher myoglobulin level, and a lower hemoglobin level. Conclusions: The clinical spectrum of neurological complications in critically ill patients with COVID-19 was broad. Stroke, delirium and neuromuscular diseases are common neurological complications of COVID-19. Physicians should pay close attention to neurological complications in critically ill patients with COVID-19.

Dynamic changes of liver function parameters in patients with coronavirus disease 2019: A multicenter, retrospective study (preprint)

Background: Liver injuries in patients with coronavirus disease 2019 (COVID-19) have been reported, however, the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is obscure.  Methods: In this multicenter, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various timepoints referred to SARS-CoV-2 shedding, and 3 to 7 days before first detection of viral shedding was regarded as reference baseline.Results: Totally, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) cases had self-medications history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal rates of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL), respectively. ALT and AST abnormal rates and levels did not show any significantly dynamic change during the full period of viral shedding (all P > 0.05). GGT abnormal rate (P = 0.008) and level (P = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneously significant increases of ALP abnormal rates and levels were observed. TBIL abnormal rates and levels significantly increased on day 1 and 5 of viral shedding (all P < 0.05). Albumin abnormal decrease rates increased and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all P < 0.05). Thirteen (18.6%) patients had chronic liver diseases, two of them died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver diseases during SARS-CoV-2 shedding.Conclusions: The SARS-CoV-2 does not directly lead to elevations of ALT and AST, but may result in elevations of GGT and TBIL, the albumin decreased extraordinarily even SARS-CoV-2 shedding discontinued.

Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in Patients With Coronavirus Disease 2019.

Currently, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been reported in almost all countries globally. No effective therapy has been documented for COVID-19, and the role of convalescent plasma therapy is unknown. In the current study, 6 patients with COVID-19 and respiratory failure received convalescent plasma a median of 21.5 days after viral shedding was first detected, all tested negative for SARS-CoV-2 RNA within 3 days after infusion, and 5 eventually died. In conclusion, convalescent plasma treatment can end SARS-CoV-2 shedding but cannot reduce the mortality rate in critically ill patients with end-stage COVID-19, and treatment should be initiated earlier.

Clinical course and treatment efficacy of COVID-19 near Hubei Province, China: A multicentre, retrospective study.

Currently, COVID-19 has been reported in nearly all countries globally. To date, little is known about the viral shedding duration, clinical course and treatment efficacy of COVID-19 near Hubei Province, China. This multicentre, retrospective study was performed in 12 hospitals in Henan and Shaanxi Provinces from 20 January to 8 February 2020. Clinical outcomes were followed up until 26 March 2020. The viral shedding duration, full clinical course and treatment efficacy were analysed in different subgroups of patients. A total of 149 COVID-19 patients were enrolled. The median age was 42 years, and 61.1% (91) were males. Of them, 133 (89.3%) had fever, 131 of 144 (91%) had pneumonia, 27 (18.1%) required intensive care unit (ICU) management, 3 (2%) were pregnant, and 3 (2%) died. Two premature newborns were negative for SARS-CoV-2. In total, the median SARS-CoV-2 shedding period and clinical course were 12 (IQR: 9-17; mean: 13.4, 95% CI: 12.5, 14.2) and 20 (IQR: 16-24; mean: 21.2, 95% CI: 20.1, 22.3) days, respectively, and ICU patients had longer median viral shedding periods (21 [17-24] versus 11 [9-15]) and clinical courses (30 [22-33] vs. 19 [15.8-22]) than non-ICU patients (both p < .0001). SARS-CoV-2 clearances occurred at least 2 days before fatality in 3 non-survivors. Current treatment with any anti-viral agent or combination did not present the benefit of shortening viral shedding period and clinical course (all p > .05) in real-life settings. In conclusion, the viral shedding duration and clinical course in Henan and Shaanxi Provinces were shorter than those in Hubei Province, and current anti-viral therapies were ineffective for shortening viral shedding duration and clinical course in real-world settings. These findings expand our knowledge of the SARS-CoV-2 infection and may be helpful for management of the epidemic outbreak of COVID-19 worldwide. Further studies concerning effective anti-viral agents and vaccines are urgently needed.