First patient management of COVID-19 in Changsha, China: a case report.

BACKGROUND: In December 2019, the novel coronavirus disease 2019 (COVID-19) emerged in Wuhan, Hubei Province, China. It rapidly spread and many cases were identified in multiple countries, posing a global health problem. Here, we report the first patient cured of COVID-19 infection in Changsha, China, and the symptoms, diagnosis, treatment, and management of this patient are all described in this report. CASE PRESENTATION: A 57-year-old woman developed cough and fever after returning to Changsha from Wuhan on January 9, 2020. She tested positive for COVID-19 infection, a diagnosis which was supported by chest CT. The patient was treated with lopinavir and ritonavir tablets and interferon alfa-2b injection. A low dose of glucocorticoids was used for a short period to control bilateral lung immune response, and this patient avoided being crushed by cytokine storms that might have occurred. The clinical condition of this patient improved, and a COVID-19 assay conducted on January 25, 2020 generated negative results. This patient recovered and was discharged on January 30, 2020. CONCLUSIONS: Currently, there are numerous reports on COVID-19 infections focusing on the disease's epidemiological and clinical characteristics. This case describes the symptoms, diagnosis, treatment, and management of a patient cured of COVID-19 infection, which may serve as reference for future cases, while further studies are needed.

Clinical characteristics of coronavirus disease 2019 patients complicated with liver injury. / 2019å† çŠ¶ç— æ¯’ç— æ‚£è€ åˆå¹¶è‚æŸä¼¤çš„ä¸´åºŠç‰¹ç‚¹.

OBJECTIVES: To analyze the clinical characteristics in patients of coronavirus disease 2019 (COVID-19) complicated with liver injury, to explore the relationship between COVID-19 clinical classification and liver injury, and to elucidate whether COVID-19 complicated with hepatitis B virus can aggravate liver injury. METHODS: The abnormal liver function in 110 patients in the First Hospital of Changsha, who were confirmed COVID-19 and admitted to the designated hospital from January 17, 2020 to February 20, 2020, wereretrospectively analyzed. The detection indexes included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBIL). RESULTS: A total of 49.1% of the COVID-19 patients had liver injury. There were significant difference in the ALT, AST, ALB (all P<0.05), but there was no significant difference in the TBIL (P>0.05) between the severe (critical) patients and the general (light) patients. There was also no significant difference in the liver function injury between the HBsAg-positive COVID-19 patients and HBsAg-negative COVID-19 patients (P>0.05). Acute liver injury was not found to be a direct cause of death in the patients. CONCLUSIONS: In the COVID-19 patients, the incidence of liver injury is high with the increase of ALT and AST and the decrease of ALB. Severe and critical patients have obvious liver injury, and those patients complicated with hepatitis B virus infection don't show aggravated liver injury.

Potential of digital chest radiography-based deep learning in screening and diagnosing pneumoconiosis: An observational study.

The diagnosis of pneumoconiosis is complex and subjective, leading to inevitable variability in readings. This is especially true for inexperienced doctors. To improve accuracy, a computer-assisted diagnosis system is used for more effective pneumoconiosis diagnoses. Three models (Resnet50, Resnet101, and DenseNet) were used for pneumoconiosis classification based on 1250 chest X-ray images. Three experienced and highly qualified physicians read the collected digital radiography images and classified them from category 0 to category III in a double-blinded manner. The results of the 3 physicians in agreement were considered the relative gold standards. Subsequently, 3 models were used to train and test these images and their performance was evaluated using multi-class classification metrics. We used kappa values and accuracy to evaluate the consistency and reliability of the optimal model with clinical typing. The results showed that ResNet101 was the optimal model among the 3 convolutional neural networks. The AUC of ResNet101 was 1.0, 0.9, 0.89, and 0.94 for detecting pneumoconiosis categories 0, I, II, and III, respectively. The micro-average and macro-average mean AUC values were 0.93 and 0.94, respectively. The accuracy and Kappa values of ResNet101 were 0.72 and 0.7111 for quadruple classification and 0.98 and 0.955 for dichotomous classification, respectively, compared with the relative standard classification of the clinic. This study develops a deep learning based model for screening and staging of pneumoconiosis is using chest radiographs. The ResNet101 model performed relatively better in classifying pneumoconiosis than radiologists. The dichotomous classification displayed outstanding performance, thereby indicating the feasibility of deep learning techniques in pneumoconiosis screening.

Association of lncRNA PVT1 Gene Polymorphisms with the Risk of Essential Hypertension in Chinese Population.

Vascular dysfunction and hyperlipidemia are essential risk factors contributing to essential hypertension (EH). The plasmacytoma variant translocation 1 (PVT1) is involved in modulating angiogenesis in tumor tissues and plays an important role in fat differentiation in the progress of obesity. Therefore, we selected two tagSNPs of PVT1 (rs10956390 and rs80177647) to investigate whether they are contributing to the risk of hypertension in Chinese patients. In total, 524 adult patients with EH and 439 matched healthy controls were enrolled for two central of China. Results. PVT1 rs10956390 and rs80177647 polymorphisms were genotyped by using TaqMan assay. PVT1 rs10956390 TT genotype was associated with a decreased risk of EH (OR = 0.561, 95% CI = 0.372-0.846, P = 0.006), while rs80177647 TA genotype was associated with an increased risk (OR = 2.236, 95% CI = 1.515-3.301, P < 0.001). Rs10956390 T allele was associated with lower triglyceride levels in the plasma both from healthy and EH donors. What is more, there is an association between rs10956390 polymorphism and HDL-C level, as well as LDL-C. Conclusion. PVT1 rs10956390 and rs80177647 polymorphisms may contribute to the risk of EH in Chinese population by regulating blood lipid levels.

SOCS3 Gene Polymorphism and Hypertension Susceptibility in Chinese Population: A Two-Center Case-Control Study.

Endothelial inflammation and vascular damage are essential risk factors contributing to hypertension. Suppressor of cytokine signaling 3 (SOCS3) is involved in the regulation of multiple inflammatory pathways. A large number of studies have shown that the anti-inflammatory effect of SOCS3 in hypertension, obesity, and allergic reactions has brought more insights into the inhibition of inflammation. Therefore, we selected a tagSNP of SOCS3 (rs8064821) to investigate whether they are contributing to the risk of hypertension in the Chinese population. In total, 532 patients with hypertension and 569 healthy controls were enrolled for two central of China. SOCS3 rs8064821 C>A polymorphism was genotyped using TaqMan assay. SOCS3 rs8064821 CA genotype was associated with an increased risk of hypertension (OR = 1.821, 95%CI = 1.276-2.600, P = 0.001). Rs8064821 A allele was associated with higher SOCS3 mRNA level in PBMCs from healthy donors. SOCS3 rs8064821 C>A polymorphism may contribute to the risk of hypertension in the Chinese population by regulating the expression of SOCS3.

MicroRNA-455-5p Contributes to Cholangiocarcinoma Growth and Mediates Galangin's Anti-Tumor Effects.

Fully understanding the mechanism of how Cholangiocarcinoma (CCA) development and discovering promising therapeutic drugs are important to improve patients' survival time. This study identifies that microRNA-455-5p (miR-455-5p) targets protein phosphatase 1 regulatory subunit 12A (PPP1R12A), an effect that represses mitogen-activated protein kinase (MAPK) and PI3K/AKT pathway activation, thereby controlling CCA cells survival and metastasis. Moreover, miR-455-5p expression is reduced in CCA tissues and negative correlation with PPP1R12A and PPP1R12A knockdown phenotypic mimics miR-455-5p' effects on CCA cells. Furthermore, we demonstrate that galangin inhibits CCA growth both in vitro and in vivo, which is associated with increased miR-455-5p and repressed PPP1R12A expression. In support, overexpression of miR-455-5p abrogates those galangin-mediated anti-CCA effects. These findings establish an essential role of miR-455-5p in CCA development and galangin may provide a potential therapeutic adjuvant agent for anti-CCA treatment.

Dynamic Changes in the Immune Response Correlate with Disease Severity and Outcomes During Infection with SARS-CoV-2.

INTRODUCTION: The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout China and worldwide. Little is known about the dynamic changes in the patient immune responses to SARS-CoV-2 and how different responses are correlated with disease severity and outcomes. METHODS: Seventy-four patients with confirmed COVID-19 were enrolled in this prospective research. The demographic information, medical history, symptoms, signs and laboratory results were analyzed and compared between severe and non-severe patients. The leukocytes, lymphocyte subsets and inflammatory cytokines were longitudinally collected. RESULTS: Of the 74 patients included, 17 suffered from severe disease. The severe patients tended be older (65.29 ± 12.33 years vs. 45.37 ± 18.66 years) and had a greater degree of underlying disease (41.18% vs. 24.56%), lower baseline lymphocyte counts [0.64 (0.46-0.95) × 109 vs. 1.27 (0.95-1.70) × 109], higher neutrophil-lymphocyte ratios [NLRs; 3.76 (3.15-5.51) vs. 2.07 (1.48-2.93)] and lower baseline eosinophil counts [0 (0-0.01) × 109 vs. 0.03 (0.01-0.06) × 109] than those in non-severe patients. The baseline helper T (Th) cells (335.47 vs. 666.46/µl), suppressor T(Ts) cells (158 vs. 334/µl), B cells (95 vs. 210/µl) and natural killer (NK) cells (52 vs. 122/µl) were significantly decreased in severe cases compared to that in non-severe cases. In addition, the baseline neutrophils were positively correlated with the severity of COVID-19, and the baseline lymphocytes were negatively correlated with the severity of COVID-19. The dynamic change of T cells, Th cells and IFN-γ in the severe cases were parallel to the amelioration of the disease. CONCLUSIONS: Collectively, our study provides novel information on the kinetics of the immune responses in a cohort of COVID-19 patients with different disease severities. Furthermore, our study indicates that both innate and adaptive immune responses correlate with better clinical outcomes.

Case Report: Clinical Features of a COVID-19 Patient With Cirrhosis.

Coronavirus disease 2019 (COVID-19) was first reported in Wuhan, Hubei Province, China in December 2019. At present, COVID-19 has emerged as a global pandemic. The clinical features of this disease are not fully understood, especially the interaction of COVID-19 and preexisting comorbidities and how these together further impair the immune system. In this case study, we report a COVID-19 patient with cirrhosis. A 73-year-old woman with cirrhosis reported a fever and cough on February 6, 2020. CT of the chest indicated an infection in her bilateral lungs. She tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The woman was treated with lopinavir and ritonavir tablets and interferon alpha-2b injection, but there was no obvious effect. Although this patient was basically asymptomatic after 2 days in the hospital, the inflammation of the bilateral lungs was slow to subside as shown in CT of the chest. In addition, the white blood cell count (WBC), absolute neutrophil count, and absolute lymphocyte count remained decreased and the result of real-time reverse transcription polymerase chain reaction (PCR) (rRT-PCR) assay was still positive for SARS-CoV-2 on hospital day 28. After infusion of plasma from a recovered COVID-19 patient four times, the patient tested negative for SARS-CoV-2. She was discharged on March 13, 2020. This patient tested negative for SARS-CoV-2 after infusion of plasma from a recovered COVID-19 patient four times. Cirrhosis could impair the homeostatic role of the liver in the systemic immune response, which may affect the removal of SARS-CoV-2. This could lead to a diminished therapeutic effect of COVID-19. Thus, clinicians should pay more attention to COVID-19 patients with cirrhosis.

Epidemiological and clinical features of 201 COVID-19 patients in Changsha city, Hunan, China.

In December 2019, a cluster of coronavirus Disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China. The present study was conducted to report the clinical characteristics of 201 COVID-19 patients in Changsha, China, a city outside of Wuhan. All of the patients with confirmed COVID-19 were admitted to the First Hospital of Changsha City, the designated hospital for COVID-19 assigned by the Changsha City Government. The clinical and epidemiological characteristics, data of laboratory, radiological picture, treatment, and outcomes records of 201 COVID-19 patients were collected using electronic medical records. This study population consisted of 201 hospitalized patients with laboratory-confirmed COVID-19 in Changsha by April 28, 2020. The median age of the patients was 45 years (IQR 34-59). About half (50.7%) of the patients were male, and most of the infected patients were staff (96 [47.8%]). Concerning the epidemiologic history, the number of patients linked to Wuhan was 92 (45.8%). The most common symptoms were fever (125 [62.2%]), dry cough (118 [58.7%]), fatigue (65 [32.3%]), and pharyngalgia (31 [15.4%]). One hundred and forty-four (71.6%) enrolled patients showed bilateral pneumonia. Fifty-four (26.9%) patients showed unilateral involvement, and three (1.5%) patients showed no abnormal signs or symptoms. The laboratory findings differed significantly between the Intensive Care Unit (ICU) and non-ICU groups. Compared with non-ICU patients, ICU patients had depressed white blood cell (WBC), neutrocytes, lymphocytes, and prolonged prothrombin time (PT). Moreover, higher plasma levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), alanine aminotransferase (ALA), aspartate aminotransferase (AST), creatine kinase (CK), creatine kinase-MB (CK-MB), creatinine (CREA), and lactate dehydrogenase (LDH) were detected in the ICU group. In this single-center study of 201 COVID-19 patients in Changsha, China, 22.4% of patients were admitted to ICU. Based on our findings, we propose that the risk of cellular immune deficiency, hepatic injury, and kidney injury should be monitored. Previous reports focused on the clinical features of patients from Wuhan, China. With the global epidemic of COVID-19, we should pay more attention to the clinical and epidemiological characteristics of patients outside of Wuhan.

Novel coronavirus infection in children outside of Wuhan, China.

BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID-19) has spread rapidly, but information about children with COVID-19 is limited. METHODS: This retrospective and the single-center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID-19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019-nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019-nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground-glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT-PCR for 2019-nCoV and were discharged. The median time from exposure to a negative RT-PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.

Clinical characteristics of older and younger patients infected with SARS-CoV-2.

BACKGROUND: SARS-CoV-2 causes high mortality risk in older patients. This study aims to characterize the clinical features of older and younger SARS-CoV-2 infected patients. RESULTS: A total of 239 patients were divided into the younger group (<60 years; n=181) and the older group (≥60 years; n=58). In both groups, fever and cough were common symptoms. However, dyspnea was more frequent in older patients than younger patients (20.7% versus 9.9%, p=0.032). Compared with younger patients, older patients harbored more severe cases (37.9% versus 17.1%, p=0.001) and comorbidities (58.6% versus 21.0%, p<0.001) such as hypertension and diabetes. The baseline values of eosinophils and C-reactive protein were abnormal in older and younger groups. From baseline to day 14, significant decreases of three biomarkers (C-reactive protein, hemoglobin, albumin) and dramatic increases of three biomarkers (lymphocytes, platelets, blood urea nitrogen) were observed in older patients. CONCLUSION: Older and younger patients exhibited differences in dyspnea, comorbidities, and proportions of severe cases. Moreover, the disease progression of SARS-CoV-2 in older patients is observed with the dynamics of laboratory biomarkers, supporting their potential use in disease monitoring. METHODS: We retrieved clinical symptoms, laboratory findings, comorbidities, and hospitalization information of SARS-CoV-2 cases in Changsha.

Treatment strategies of hospitalized patients with coronavirus disease-19.

With the outbreak of coronavirus disease-19 (COVID-19), Changsha faced an increasing burden of treating the Wuhan migrants and their infected patients. This study is a retrospective, single-center case series of the 238 consecutive hospitalized patients with confirmed COVID-19 at the First Hospital of Changsha city, China, from 01/21 to 02/14, 2020; the final date of follow-up was 02/27, 2020. Of 238 patients 43.7% visited Wuhan, 58.4% got in touch with Wuhan people, and 47.5% had contacted with diagnosed patients. 37.8% patients had family members infected. 190 cases had mild / general disease, and 48 cases had severe / critical disease. Compared to mild or general patients, more severe or critical patients visited Wuhan (59.6% vs 40.2%; P=0.02) and contacted with Wuhan people (74.5% vs 55.0%; P=0.02). All patients received antiviral treatment, including Lopinavir / Ritonavir (29.3%), Interferon (14.6%) and their combination (40.6%), Arbidol (6.7%), Xuebijing (7.1%) and Chloroquine phosphate (1.3%). Severe and critical patients received glucocorticoid, Gamma-globulin and oxygen inhalation. Some received mechanic ventilation support. As of 02/27, 161 patients discharged. The median length of hospital stay was 13 days. The 10-, 14-, 20- and 28-day discharge rate was 19.1%, 42.8%, 65.0% and 76.4%, respectively. No hospital-related transmission was observed.

Mortality risk of COVID-19 in elderly males with comorbidities: a multi-country study.

The COVID-19 pandemic causes severe morbidity and mortality. This multi-country study aimed to explore risk factors that drive mortality in COVID-19 patients who received neither dexamethasone nor remdesivir. We analyzed a cohort of 568 survivors and 507 non-survivors from China, European regions, and North America. Elderly males ≥70 years accounted for only 25% of survivors, but this rate was significantly higher in non-survivors from China (55%), European regions (63%), and North America (47%). Compared with survivors, non-survivors had more incidences of comorbidities such as cerebrovascular disease and chronic obstructive pulmonary disease (COPD, p-values<0.05). Survival analyses revealed age, male gender, shortness of breath, cerebrovascular disease, and COPD as mortality-associated factors. Survival time from symptom onset was significantly shorter in elderly versus young patients (median: 29 versus 62 days), males versus females (median: 46 versus 59 days), and patients with versus without comorbidities (mean: 41 versus 61 days). Mortality risk was higher in elderly males with comorbidities than in young females without comorbidities (p-value<0.01). Elderly male survivors with comorbidities also had longer hospital stays than other survivors (25 versus 18.5 days, p-value<0.01). Overall, the high mortality risk in elderly males with COVID-19-associated comorbidities supports early prevention and critical care for elderly populations.

SARS-CoV-2 clearance in COVID-19 patients with Novaferon treatment: A randomized, open-label, parallel-group trial.

BACKGROUND: The antiviral effects of Novaferon, a potent antiviral protein drug, on COVID-19 was evaluated in the laboratory, and in a randomized, open-label, parallel-group trial. METHODS: In the laboratory, Novaferon's inhibition of viral replication in cells infected with SARS-CoV-2, and prevention of SARS-CoV-2 entry into healthy cells was determined. Antiviral effects of Novaferon in COVID-19 patients with treatment of Novaferon, Novaferon plus Lopinavir/Ritonavir, or Lopinavir/Ritonavir were evaluated. The primary endpoint was the SARS-CoV-2 clearance rates on day six of treatment, and the secondary endpoint was the time to SARS-CoV-2 clearance. RESULTS: Novaferon inhibited viral replication (EC50=1.02ng/ml), and prevented viral infection (EC50=0.10ng/ml). Results from the 89 enrolled COVID-19 patients showed that both Novaferon and Novaferon plus Lopinavir/Ritonavir groups had significantly higher viral clearance rates on day six than Lopinavir/Ritonavir group (50.0% vs. 24.1%, p=0.0400, and 60.0% vs. 24.1%, p=0.0053). The median time to viral clearance was six days, six days, and nine days for three groups, respectively, a 3-day reduction in both the Novaferon and Novaferon plus Lopinavir/Ritonavir groups compared with the Lopinavir/Ritonavir group. CONCLUSIONS: Novaferon exhibited anti-SARS-CoV-2 effects in vitro and in COVID-19 patients. These data justify further evaluation of Novaferon. TRIAL REGISTRATION NUMBER: Number ChiCTR2000029496 at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/).

Early hepatitis B viral DNA clearance predicts treatment response at week 96.

AIM: To investigate whether hepatitis viral DNA load at 24 wk of treatment predicts response at 96 wk in patients with chronic hepatitis B. METHODS: A total of 172 hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B patients who received initial treatment at 16 tertiary hospitals in Hunan Province, China were enrolled in this study. All patients received conventional doses of lamivudine and adefovir dipivoxil, telbivudine, entecavir dispersible tablets, or entecavir tablets for 96 wk. Patients who used other antiviral drugs or antitumor and immune regulation therapy were excluded. Patients were stratified into three groups according to their viral DNA load at 24 wk: < 10 IU/mL (group 1), 10-103 IU/mL (group 2), and > 103 IU/mL (group 3). Correlations of 24-wk DNA load with HBeAg negative status and HBeAg seroconversion at 96 wk were analyzed. Receiver operating characteristic curve analysis was used to test the predictive value of the HBV DNA load at 24 wk for long-term response. RESULTS: The rates of conversion to HBeAg negative status and HBeAg seroconversion rates were 53.7% and 51.9%, respectively, in group 1; 35.21% and 32.39% in group 2; and 6.38% and 6.38% in group 3. The receiver operating characteristic curves for the three subgroups revealed that the lowest DNA load (< 10 IU/mL) was better correlated with response at 96 wk than a higher DNA load (10-103 IU/mL). Nested PCR was used for amplifying and sequencing viral DNA in patients with a viral DNA load > 200 IU/mL at 96 wk; resistance mutations involving different loci were present in 26 patients, and three of these patients had a viral DNA load 10-103 IU/mL at 96 wk. CONCLUSION: Hepatitis B viral DNA load at 24 wk of antiviral treatment in patients with chronic hepatitis B is a predictor of the viral load and response rate at 96 wk.