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Aim. To find the predictors of coronavirus disease 2019 (COVID-19) in hospitalized patients. Methods. A prevalence study compared the characteristics of COVID-19 patients with non-COVID-19 patients from January 19, 2020, to February 18, 2020, during the COVID-19 outbreak. Laboratory test results and pulmonary chest imaging of confirmed COVID-19 and non-COVID-19 patients were collected by retrieving medical records in our center. Results. 96 COVID-19 patients and 122 non-COVID-19 patients were enrolled in this study. COVID-19 patients were older (53 vs. 39; P P = 0.011); however, differences in gender were not observed between the two groups. Logistic regression analysis showed that exposure history (OR: 23.34, P P = 0.006), alanine aminotransferase (ALT) (OR: 1.03, P = 0.049), lactate dehydrogenase (LDH) (OR: 1.01, P = 0.020), lymphocyte (OR: 0.27, P = 0.007), and bilateral involvement on chest CT imaging (OR: 23.01, P P

Hepatitis E virus (HEV) superinfection is a common excerbating event in patients with chronic hepatitis B, but the impact on the long-term prognosis is not clear. This study investigates the specific role of HEV superinfection in the long-term outcome of hepatitis B virus (HBV) patients with liver cirrhosis.A retrospective, observational cohort study was conducted using clinical, laboratory, and survival data collected from patients suffering from hepatitis B cirrhosis with or without HEV superinfection. Disease progression and mortality rates were analyzed.After a two-year follow-up, HEV superinfection was identified in 27 of 811 patients. The transplantation-free mortality was significantly increased (51.9% vs. 14.3%, p0.001) in HEV superinfection compared to that in hepatitis B cirrhosis patients without HEV superinfection. Logistic regression analysis demonstrated that elderly people were independent host risk factors for hepatitis B cirrhosis patients with HEV superinfection before and after propensity score matching (PSM). Moreover, HEV superinfection was a risk factor for patients with hepatitis B cirrhosis with new acute decompensation (AD) and acute-on-chronic liver failure (ACLF) during hospitalization. A multivariate Cox proportional hazards regression model demonstrated that acute HEV co-infection is associated with two-year mortality (hazard ratio [HR]: 2.49; 95% CI: 1.40-4.43; p= 0.002; and HR: 5.79; 95% CI: 1.87-17.87; p= 0.002) in patients with hepatitis B cirrhosis before and after PSM.Elder patients with hepatitis B cirrhosis are susceptible to HEV superinfection, accelerating disease progression and increasing long-term mortality in hospitalized patients with HBV-related decompensated liver cirrhosis.

We read with great interest the recent article published in Gut in which Yeoh et al demonstrated that gut microbiota composition of recovered patients with COVID-19 remained significantly distinct from uninfected controls.1 Persisting symptoms, also known as ‘long COVID-19’, have been reported in a significant proportion of patients following hospital discharge.2 3 Gut dysbiosis might link to long COVID-19 risks.1 Few studies have focused on the recovery process of gut microbiota following SARS-CoV-2 infection. Here, we conducted a prospective study to longitudinally monitor alterations of gut microbiota in patients with COVID-19 using 16S rDNA sequencing (detailed methods in online supplementary materials). Faecal microbiota was monitored at three timepoints, acute phase (from illness onset to viral clearance), convalescence (from viral clearance to 2 weeks after hospital discharge), postconvalescence (6 months after hospital discharge).### Supplementary data [gutjnl-2021-324090supp001.pdf] The gut microbiota richness, measured by Chao 1 index, was obviously lower (p

BackgroundCoronavirus disease 2019(COVID-19) has spread worldwide. The present study aimed to characterize the clinical features and outcomes of imported COVID-19 patients with high body mass index (BMI) and the independent association of BMI with disease severity.MethodsIn this retrospective cohort study, 455 imported COVID-19 patients were admitted and discharged in Zhejiang province by February 28, 2020. Epidemiological, demographic, clinical, laboratory, radiological, treatment, and outcome data were collected, analyzed and compared between patients with BMI ≥ 24and ResultsA total of 268 patients had BMI P = 0.0040). Hemoglobin, alanine aminotransferase (ALT), CRP, and serum creatinine (Scr) were independent risk factors associated with high BMI.ConclusionsContrasted with the imported COVID-19 patients with BMI

Cryptococcal meningitis (CM) is a common opportunistic infection in HIV-negative patients, with mortality rates as high as those in the HIV-negative population. This requires accurate initial clinical decision-making, warranting the development of a prognostic score. Two groups of patients were investigated separately to develop a novel prognostic model (AAIT) for HIV-negative patients with CM. A retrospective analysis of 201 HIV-negative patients with CM was conducted to develop the CM prognostic score. In addition, the CM cohort (n = 21) was recruited longitudinally to verify the new prognostic score. Meanwhile, the association between the prognostic score and 1-year mortality of CM was expounded. AAIT (age, albumin, combined bacterial infection, and total triiodothyronine) is a novel prognostic score based on age, albumin level, combined bacterial infection, and total triiodothyronine (TT3) level, which were significantly higher in nonsurvivors than in survivors (0.68 [-0.70 to 1.55] vs - 1.72 [-3.75 to -0.73], P

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection swept through Wuhan and spread across China and overseas beginning in December 2019. To identify predictors associated with disease progression, we evaluated clinical risk factors for exacerbation of SARS-CoV-2 infection. Methods A retrospective analysis was used for PCR-confirmed COVID-19 (coronavirus disease 2019)-diagnosed hospitalized cases between January 19, 2020, and February 19, 2020, in Zhejiang, China. We systematically analysed the clinical characteristics of the patients and predictors of clinical deterioration. Results One hundred patients with COVID-19, with a median age of 54 years, were included. Among them, 49 patients (49%) had severe and critical disease. Age ([36–58] vs [51–70], P = 0.0001); sex (49% vs 77.6%, P = 0.0031); Body Mass Index (BMI) ([21.53–25.51] vs [23.28–27.01], P = 0.0339); hypertension (17.6% vs 57.1%, P P = 0.0001); IL-10 ([2.16–5.82] vs [4.35–9.63], P P = 0.0001); B lymphocyte count ([91–213] vs [54.5–163.5], P = 0.0001); white blood cell count ([3.9–7.6] vs [5.5–13.6], P = 0.0002); D2 dimer ([172–836] vs [408–953], P = 0.005), PCT ([0.03–0.07] vs [0.04–0.15], P = 0.0039); CRP ([3.8–27.9] vs [17.3–58.9], P P = 0.0484); artificial liver therapy (2% vs 16.3%, P = 0.0148); and glucocorticoid therapy (64.7% vs 98%, P Conclusion Deterioration among COVID-19-infected patients occurred rapidly after hospital admission. In our cohort, we found that multiple factors were associated with the severity of COVID19. Early detection and monitoring of these indicators may reduce the progression of the disease. Removing these factors may halt the progression of the disease. In addition, Oxygen support, early treatment with low doses of glucocorticoids and artificial liver therapy, when necessary, may help reduce mortality in critically ill patients.

Hong Zhao,* Huilan Tu,* Xia Yu,* Junwei Su, Xuan Zhang, Kaijin Xu, Yu Shi, Yunqing Qiu, Jifang Sheng State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jifang Sheng; Yunqing Qiu, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China, Tel +86 571 8723 6491, Fax +86 571 8723 6491, Email jifang_sheng@zju.edu.cn; qiuyq@zju.edu.cnAim: To analyze the possible risk factors of delayed virus clearance in hospitalized patients with coronavirus disease 2019 (COVID-19).Methods: Retrospective analysis of patients with COVID-19 admitted to the isolation wards from our hospital from 19th Jan 2020 to 18th March 2020. We were collected patient’s data including demographic, epidemiologic, and clinical information, as well as laboratory and radiologic findings. The possible confounding risk factors for prolonged viral RNA shedding of COVID-19 during hospitalization were explored by univariate analysis and any variables with a p value less than 0.05 after univariate analysis were included in a subsequent multivariate logistic regression model analysis.Results: The 104 patients included 30 mild patients and 74 severe or critically ill patients. The median duration of viral RNA positivity in sputum was 11 days, and the longest duration of viral RNA positivity was 49 days after admission. Multivariate analysis shown that the used with darunavir/cobicistat treatment (odds ratio [OR]: 4.25, 95% confidence interval [CI]: 1.25– 14.42, p = 0.020), duration of fever (OR: 1.15, 95% CI: 1.03– 1.30, p = 0.015) and time to radiological improvement (OR: 1.14, 95% CI: 1.01– 1.30, p = 0.033) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients. Then adjusted in the multivariate binary logistic regression analysis model in severe COVID-19 and found that critical COVID-19 patients (OR: 13.25, 95% CI: 1.45– 12.07, p = 0.022), lower virus cycle threshold (CT) values of RT-PCR (OR: 0.96, 95% CI: 0.93– 0.99, p = 0.004) and used with darunavir/cobicistat treatment (OR: 8.44, 95% CI: 2.21– 32.28, p = 0.022) were associated with delayed clearance of SARS-CoV-2 in sputum from COVID-19 patients.Conclude: Clearance of viral RNA in sputum was delayed in severe COVID-19 patients, especially with lower virus CT value. And antivirals with darunavir/cobicistat has little advantage in eliminating SARS-CoV-2.Keywords: COVID-19, SARS-CoV-2, clearance, critical disease, viral load

Highlights • The detection rate of hock-a-loogie saliva was higher than nasopharyngeal swabs. • Hock-a-loogie saliva sample had a higher viral load than throat swab. • Hock-a-loogie saliva sampling for SARS-CoV-2 detection is reliable., To clarify the effect of different respiratory sample types on SARS-CoV-2 detection, we collected throat swabs, nasal swabs and hock-a-loogie saliva or sputum, and compared their detection rates and viral loads. The detection rates of sputum (95.65%, 22/23) and hock-a-loogie saliva (88.09%, 37/42) were significantly higher than those in throat swabs (41.54%, 27/65) and nasal swabs (72.31%, 47/65) (P

This retrospective cohort study aimed to investigate the correlation of the neutrophil-to-lymphocyte ratio (NLR) with critical illness in older patients with COVID-19, and evaluate the prognostic power of the NLR at admission. We enrolled 232 patients with COVID-19, aged ≥60 y, in Zhejiang province from January 17 to March 3, 2020. Primary outcomes were evaluated until April 13. Cox regression was performed for prognostic factors. Twenty-nine (12.5%) patients progressed to critical illness. Age, shortness of breath, comorbidities including hypertension, heart disease, and chronic obstructive pulmonary disease, higher NLR, lower albumin levels, and multiple mottling and ground-glass opacity were associated with progression. In the multivariate analysis, older age (hazard ratio [HR] 1.121, confidence interval [CI] 1.070-1.174, P

Background Despite the ongoing spread of coronavirus disease 2019 (COVID-19), knowledge about factors affecting prolonged viral excretion is limited. Methods In this study, we retrospectively collected data from 99 hospitalized patients with coronavirus disease 2019 (COVID-19) between 19 January and 17 February 2020 in Zhejiang Province, China. We classified them into 2 groups based on whether the virus test results eventually became negative. Cox proportional hazards regression was used to evaluate factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding. Results Among 99 patients, 61 patients had SARS-CoV-2 clearance (virus-negative group), but 38 patients had sustained positive results (virus-positive group). The median duration of SARS-CoV-2 excretion was 15 (interquartile range, 12–19) days among the virus-negative patients. The shedding time was significantly increased if the fecal SARS-CoV-2 RNA test result was positive. Male sex (hazard ratio [HR], 0.58 [95% confidence interval {CI}, .35–.98]), immunoglobulin use (HR, 0.42 [95% CI, .24–.76]), APACHE II score (HR, 0.89 [95% CI, .84–.96]), and lymphocyte count (HR, 1.81 [95% CI, 1.05–3.1]) were independent factors associated with a prolonged duration of SARS-CoV-2 shedding. Antiviral therapy and corticosteroid treatment were not independent factors. Conclusions SARS-CoV-2 RNA clearance time was associated with sex, disease severity, and lymphocyte function. The current antiviral protocol and low-to-moderate dosage of corticosteroid had little effect on the duration of viral excretion.

Background The outbreak of coronavirus disease 2019 (COVID-19) is now becoming an enormous threat to public health. The clinical spectrum of COVID-19 is extensive, of which critical cases are with rapid disease progression and high mortality. The aim of our study is to summarize the characteristics of different subtypes and explore risk factors of illness severity for early identification and prompt treatment. Methods In this retrospective study, we collected data of patients confirmed COVID-19 in Zhejiang Province from 17 January to 12 February 2020. According to the definition of clinical classification, we divided confirmed cases into four types, and summarize epidemiological and clinical characteristics, laboratory and radiograph findings, treatments, and outcomes, respectively. Moreover, we used univariate and multivariate ordinal logistic regression models to explore risk factors for the severity of illness in patients with COVID-19. Results A total of 788 patients were enrolled in our study, of whom 52 cases (6.6%) were mild type, 658 cases (83.5%) were common type, 61 cases (7.2%) were severe type, and 17 cases (2.2%) were critical type. Multivariate ordinal logistic regression demonstrated increasing odds of the severity of illness in patients with COVID-19 associated with male (odds ratio [OR] = 1.7, 95% confidence interval [CI]: 1.2–2.6 P = 0.008), fever (OR = 3.6, 95% CI: 2.1–6.3, P OR = 1.7, 95% CI: 1.0–2.9, P = 0.041), hemoptysis (OR = 3.4, 95% CI: 1.1–10.3, P = 0.032), gastrointestinal symptoms (OR = 1.9, 95% CI: 1.0–3.5, P = 0.047), hypertension (OR = 2.6, 95% CI: 1.2–5.6, P = 0.013). With the increase of age-grading, risk for the severity of illness was gradually higher (≤ 18 years [OR = 1.0], 19–40 years [OR = 12.7, 95% CI: 4.5–36.0, P OR = 14.8, 95% CI: 5.2–42.1, P OR = 56.5, 95% CI: 17.1–186.5, P < 0.001]). Conclusions Clinicians should pay close attention to these features in patients with COVID-19 including older age, male, fever, cough, hemoptysis, gastrointestinal symptoms and hypertension to identify the severity of illness as early as possible.

The viral RNA shedding time (VST) for severe acute respiratory syndrome coronavirus 2 has not been well characterized. Clinical data were collected and compared between patients with short and long VSTs (in the lower and upper quartiles, respectively). The probability of recurrent positive reverse-transcription polymerase chain reaction results decreased sharply to 4.8% after 3 consecutive negative results. A series of ≥3 consecutive negative results was suitable as a criterion for the end of viral RNA shedding. The VST for shedding from the respiratory tract was significantly shorter in patients with normal B-cell counts on admission than in those with decreased B-cell counts (median [interquartile range], 11 [9–13] vs 16 [12–20] days, respectively; P = .001).

Highlights • COVID-19 has a great threat to world health. • We investigated clinical features of patients with abnormal imaging findings. • Those with abnormal images have more obvious clinical and laboratory features. • Combing clinical data with imaging scores can predict severe/critical type., Purpose To investigate the epidemiological and clinical characteristics of COVID-19 patients with abnormal imaging findings. Methods Patients confirmed with SARS-CoV-2 infection in Zhejiang province from January 17 to February 8 who had undergone CT or X-ray were enrolled. Epidemiological and clinical data were analyzed among those with abnormal or normal imaging findings. Results Excluding 72 patients with normal images, 230 of 573 patients showed abnormalities affecting more than two lung lobes. The median radiographic score was 2.0, and there was a negative correlation between that score and the oxygenation index (ρ = −0.657, P < 0.001). Patients with abnormal images were older (46.65 ± 13.82), with a higher rate of coexisting condition (28.8%), a lower rate of exposure history, and longer time between onset and confirmation (5 days) than non-pneumonia patients (all P < 0.05). A higher rate of fever, cough, expectoration and headache, a lower level of lymphocytes, albumin, and serum sodium levels and a higher total bilirubin, creatine kinase, lactate dehydrogenase, and C-reactive protein levels and a lower oxygenation index were observed in pneumonia patients (all P < 0.05). Muscle ache, shortness of breath, nausea and vomiting, lower lymphocytes levels, and higher serum creatinine and radiographic score at admission were predictive factors for the severe/critical subtype. Conclusion Patients with abnormal images have more obvious clinical manifestations and laboratory changes. Combing clinical features and radiographic scores can effectively predict severe/critical types.

Background An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. Methods In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan. Results The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13–22) days as measured from illness onset. When comparing patients with early ( Conclusions Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.

No abstract available Keywords: COVID-2019; Disease severity; Host susceptibility; Risk factors.

Hepatitis B virus (HBV) has been classified into ten genotypes (A-J). Genotype B (HBV/B) is divided into nine subgenotypes (B1-B9), each with specific geographical predominance. Some reference sequence of HBV/B subgenotypes are currently in use, but these sequences have defects, being insufficient to represent the reference of individual subgenotype. The aim of this study was to establish a more representative reference of HBV/B subgenotypes in different regions. Full genomic sequences of HBV/B were obtained from GenBank and compartmentalized into genomic subtypes. The homology between our established HBV/B subgenotype references was evaluated at the nucleotide level. We established reference strains for B1-Japan, B2-China, B3-Indonesia, B4-Vietnam, B6-North America, B7-Indonesia and B9-Southeast Asia. Fractional significant mutation sites of the strains that were established were observed in the BCP/Pre-C regions. We calculated the genetic divergence time from the most recent common ancestor of HBV/B pedigree. The reference sequences established in the study provide reference standards for studies on molecular characterization, virology and pathogenesis of HBV/B.

Background: The aim of this study was to investigate the impact of proton pump inhibitor (PPI) therapy on complications and prognosis in cirrhosis patients with and without acute-on-chronic liver failure (ACLF).Materials and Methods: Cirrhosis patients with acute decompensation (AD) (n = 489) admitted in our center were enrolled in this prospective observational cohort study. According to treatment received, patients were identified as users or nonusers of PPI. Clinical and laboratory data, complications during hospitalization, and overall survival were recorded in all the patients.Results: Of the 489 patients, 299 (61.1%) patients received PPI therapy. The logistic regression analysis showed that age, albumin, history of previous hepatic encephalopathy (HE), and the chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score were independent risk factors for HE in patients with decompensated cirrhosis [odds ratio (OR) = 1.07, 95% CI: 1.03–1.12, p = 0.001; OR = 1.13, 95% CI: 1.04–1.24, p = 0.006; OR = 242.52, 95% CI: 40.17–1464.11, p < 0.001; and OR = 2.89, 95% CI: 2.11–3.96, p < 0.001, respectively]. Previous severe liver injury and previous bacterial infections were independent risk factors for spontaneous bacterial peritonitis (SBP) in patients with decompensated cirrhosis (OR = 3.43, 95% CI: 1.16–10.17, p = 0.026 and OR = 6.47, 95% CI: 2.29–18.29, p < 0.001, respectively). The multivariate Cox proportional hazards regression model showed that the type and dose of the PPI used were not related to 28-day and 90-day mortality in cirrhosis patients with AD or ACLF.Conclusion: PPI use does not appear to increase mortality or the risk of HE and SBP in the hospitalized cirrhosis patients with and without ACLF.

Tenofovir disoproxil fumarate (TDF) is a first-line treatment for chronic hepatitis B virus (HBV) infection for its high potency and a low rate of drug resistance. This study investigated the efficacy and safety of TDF in Chinese patients with chronic hepatitis B (CHB) infection after treatment failure with multiple nucleos(t)ide analogues (NAs).Patients included were aged 18-65 years, with treatment failure with multiple NAs (serum HBV DNA 200 IU/mL after more than two different NA treatments). The primary endpoint was proportion of patients with serum HBV DNA 20 IU/mL at Week 144 of TDF monotherapy. Secondary endpoints and safety were also assessed.Overall, 213 patients were enrolled. At Week 144, mean HBV DNA decreased significantly from baseline (4.4 vs 1.4 logTenofovir disoproxil fumarate monotherapy is efficacious in CHB patients with multiple NAs treatment failure with no new safety findings.

Understanding the immunological characteristics of monocytes-including the characteristics associated with fibrosis-in severe coronavirus disease 2019 (COVID-19) is crucial for understanding the pathogenic mechanism of the disease and preventing disease severity. In this study, we performed single-cell transcriptomic sequencing of peripheral blood samples collected from six healthy controls and 14 COVID-19 samples including severe, moderate, and convalescent samples from three severely/critically ill and four moderately ill patients. We found that the monocytes were strongly remodeled in the severely/critically ill patients with COVID-19, with an increased proportion of monocytes and seriously reduced diversity. In addition, we discovered two novel severe-disease-specific monocyte subsets: Mono 0 and Mono 5. These subsets expressed amphiregulin (AREG), epiregulin (EREG), and cytokine interleukin-18 (IL-18) gene, exhibited an enriched erythroblastic leukemia viral oncogene homolog (ErbB) signaling pathway, and appeared to exhibit pro-fibrogenic and pro-inflammation characteristics. We also found metabolic changes in Mono 0 and Mono 5, including increased glycolysis/gluconeogenesis and an increased hypoxia inducible factor-1 (HIF-1) signaling pathway. Notably, one pre-severe sample displayed a monocyte atlas similar to that of the severe/critical samples. In conclusion, our study discovered two novel severe-disease-specific monocyte subsets as potential predictors and therapeutic targets for severe COVID-19. Overall, this study provides potential predictors for severe disease and therapeutic targets for COVID-19 and thus provides a resource for further studies on COVID-19.

Background The high case fatality rate of influenza A(H7N9)-infected patients has been a major clinical concern. Methods To identify the common causes of death due to H7N9 as well as identify risk factors associated with the high inpatient mortality, we retrospectively collected clinical treatment information from 350 hospitalized human cases of H7N9 virus in mainland China during 2013–2017, of which 109 (31.1%) had died, and systematically analyzed the patients’ clinical characteristics and risk factors for death. Results The median age at time of infection was 57 years, whereas the median age at time of death was 61 years, significantly older than those who survived. In contrast to previous studies, we found nosocomial infections comprising Acinetobacter baumannii and Klebsiella most commonly associated with secondary bacterial infections, which was likely due to the high utilization of supportive therapies, including mechanical ventilation (52.6%), extracorporeal membrane oxygenation (14%), continuous renal replacement therapy (19.1%), and artificial liver therapy (9.7%). Age, time from illness onset to antiviral therapy initiation, and secondary bacterial infection were independent risk factors for death. Age >65 years, secondary bacterial infections, and initiation of neuraminidase-inhibitor therapy after 5 days from symptom onset were associated with increased risk of death. Conclusions Death among H7N9 virus–infected patients occurred rapidly after hospital admission, especially among older patients, followed by severe hypoxemia and multisystem organ failure. Our results show that early neuraminidase-inhibitor therapy and reduction of secondary bacterial infections can help reduce mortality. Characterization of 350 hospitalized avian influenza A(H7N9)-infected patients in China shows that age >65 years, secondary bacterial infections, and initiation of neuraminidase-inhibitor therapy after 5 days from symptom onset were associated with increased risk of death.

Objective Acute decompensation (AD) in liver cirrhosis has high mortality. We assessed prognostic scoring models and established prediction models for different etiologies of AD. Methods This retrospective analysis included 732 patients hospitalized with acute decompensated cirrhosis without acute-on-chronic liver failure. We performed logistic regression analysis of risk factors for mortality associated with different etiologies, to establish predictive models. Results Patients with different etiologies, scored using different scoring systems and various impact factors, exhibited differences with respect to mortality. MELD, CLIF-C-AD, MELD-Na, and AARC-ACLF scores exhibited adequate predictive ability for mortality. Area under the receiver operating characteristic curve for 28-day mortality for MELD, CLIF-C-AD, MELD-Na, AARC-ACLF, and the newly developed AD scores was 0.663, 0.673, 0.657, 0.662, and 0.773, respectively, in the hepatitis B virus group (HBV-AD score =−5.51 + 0.07*WBC count (109/L) +0.7*AD sum+0.4*AARC-ACLF score); 0.731, 0.737, 0.735, 0.689, and 0.778, respectively, in the alcoholic liver disease group (ALD-AD score =−4.55 +0.08* WBC count (109/L) +1.34* AD sum); and 0.765, 0.767, 0.814, 0.720, and 0.814, respectively, in the Others group (OTHERS-AD score =−2.14 + 1.24*MELD-Na score +4.49*AD sum). Conclusions The newly developed scoring models for short-term mortality were superior to the other scoring systems in predicting prognosis of acute decompensated cirrhosis in hospitalized patients.

strongABSTRACT/strongMicrobial infection is an important cause of acute-on-chronic liver failure (ACLF), which is a syndrome that results in multiple organ dysfunction or failure and is accompanied by an increased short-term risk of mortality. Early detection and treatment of microbial infection can effectively reduce the mortality of patients with ACLF. However, antimicrobial resistance has recently increased due to the increased use of antimicrobial agents. Therefore, it is important to choose appropriate antibiotics and antifungal agents for early prevention or treatment of patients with microbial infection and ACLF to reduce the occurrence of drug resistance and to reduce patient mortality. This review summarizes the current status in the understanding of the epidemiology, pathogenesis, early diagnosis, treatment, and strategies for prevention of microbial infection in patients with ACLF.

Background Pegylated interferon (PEG-IFN) alfa-2b is recommended for chronic hepatitis B (CHB). We aimed to investigate the sustainability of off-treatment responses among Chinese HBeAg-positive CHB patients treated with PEG-IFN alfa-2b from a randomized trial. Methods Eligible Chinese patients (n = 322) were followed up by one visit after a median of 6 years (LTFU) following their participation in a randomized trial evaluating the efficacy of three PEG-IFN alfa-2b dosing regimens (1.0 or 1.5 μg/kg/wk. 24 weeks or 1.5 μg/kg/wk. 48 weeks). Primary endpoints at the LTFU were sustained SR and CR (SR/CR at the end of original study [EOS] and at the LTFU). SR was defined as HBeAg loss and seroconversion to anti-HBe and CR as HBeAg loss and seroconversion to anti-HBe and HBV-DNA

Background and aim Long-term treatment with tenofovir disoproxil fumarate (TDF) has demonstrated suppression of viral replication outside of China. This study aims to assess efficacy, resistance and safety of TDF for up to 240 weeks in Chinese patients with chronic hepatitis B virus (HBV) infection. Methods Patients (HBeAg-positive or HBeAg-negative) who were randomised to receive TDF 300 mg or adefovir dipivoxil (ADV) 10 mg once daily in the 48-week double-blind phase (N = 498) were eligible to enter the open-label TDF phase (TDF–TDF and ADV–TDF groups) for additional 192 weeks. Results Overall, 457/512 (89.3%) randomised patients completed 240 weeks of treatment. Virological suppression was achieved in 84.5% and 87.9% in HBeAg-positive patients and 89.6% and 89.5% in HBeAg-negative patients in TDF–TDF and ADV–TDF groups, respectively, at week 240. The majority of patients from both groups had normalized alanine transaminase levels. More patients had HBeAg loss (41.7% vs. 36.4%) and HBeAg seroconversion (32.0% vs. 28.3%) in TDF–TDF than in ADV–TDF group, respectively. Only one HBeAg-positive patient in TDF–TDF group had HBsAg loss at week 240. No evidence of resistance to TDF was observed. The incidence of adverse events was similar in both groups (TDF–TDF, 56.4% vs. ADV–TDF, 51.6%). One patient had serum creatinine elevation ≥ 0.5 mg/dL above baseline, and three patients had confirmed grade 3/4 phosphorus abnormalities ( Conclusion In Chinese patients with chronic HBV, long-term treatment with TDF showed sustained viral suppression without development of resistance up to 240 weeks. No new safety concerns were found with TDF in this patient population. Clinical Trial Registration ClinicalTrial.gov Identifier NCT01300234; GSK Clinical Study Register 114648.

Aims: Patients with hepatitis B-related acute-on-chronic liver failure (HB-ACLF) may have an increased circulating microbial burden. This study aimed to assess circulating microbial load and composition and to explore the association between the circulating microbiome and both systemic inflammation and clinical outcome in HB-ACLF. Methods: Plasma from 49 HB-ACLF patients, 15 healthy controls (HCs) and 18 patients with compensated liver cirrhosis (C-LC) was analyzed for chemokines/cytokines and bacterial DNA and further analysed by 16S rDNA pyrosequencing. Linear discriminant analysis effect size (LEfSe) and inferred metagenomics analyses were performed. Results: The circulating bacterial DNA was significantly increased in HB-ACLF patients compared to that in the control groups. The overall microbial diversity was significantly decreased in HB-ACLF patients. HB-ACLF patients were enriched with Moraxellaceae, Sulfurovum, Comamonas, and Burkholderiaceae but were depleted in Actinobacteria, Deinococcus-Thermus, Alphaproteobacteria, Xanthomonadaceae and Enterobacteriaceae compared to controls. Networkanalysis revealed a direct positive correlation between Burkholderiaceae and chemokine IP-10 in HB-ACLF patients. The relative abundance of Prevotellaceae independently predicted 28-day mortality. Inferred functional metagenomics predicted an enrichment of bacteria with genes related to methane, alanine, aspartate, glutamate, pyrimidine, purine and energy metabolism. Conclusions: HB-ACLF patients display increased circulating microbial burden, altered microbiome composition and a shift in microbiome functionality. The dysbiosis in circulating microbiota is associated with systemic inflammation (SI) and clinical outcome in HB-ACLF. Funding Statement: This research was funded by [National Natural Science Foundation of China] grant numbers [81870425, 81500464, 81671949 and 81670567]. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the ethics committee of each participating hospital.

Objectives: The objective of this study was to conduct a multicentre evaluation of the performance of the biochip assay in the rapid identification of mycobacteria in smear-positive sputum specimens. Methods: A total of 1751 sputum specimens were obtained from 7 cities in Zhejiang, China. All of the specimens were used for the discrimination of Mycobacterium species using the biochip assay, and the results were compared to the golden standard method of culture, hsp65, 16S rRNA and rpoB sequence analysis. Results: In the 1751 sputum specimens, 1685 samples were cultured successfully; among these samples, 1361 were Mycobacterium tuberculosis, 323 were NTM and 1 was Nocadia farcinica. Of the 323 NTM, most of them were Mycobacterium intracellulare(52.5%) followed by Mycobacterium abscessus (20.7%), Mycobacterium avium (11.7%), Mycobacterium kansasii (9.6%) and Mycobacterium fortuitum (1.9%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the biochip assay to differentiate TB and NTM from AFB positive specimens were 99.8%, 99.7%, 99.9%, 99.1%, 98.8%, 1, 1, and 99.7%, respectively. The concordance between the biochip assay and mycobacterial culture for the identification of NTM species was 95.4%. Conclusions: The biochip assay is a reliable tool for the rapid identification of most mycobacteria in clinical sputum specimens. This assay can be helpful for physicians in the early diagnosis and treatment of mycobacterium infections. Keywords: Mycobacterium tuberculosis, Nontuberculous mycobacteria, Species identification, Molecular diagnosis, Biochip Assay, Sputum

Sleep disturbance is the most prominent symptom in depressive patients and was formerly regarded as a main secondary manifestation of depression. However, many longitudinal studies have identified insomnia as an independent risk factor for the development of emerging or recurrent depression among young, middle‐aged and older adults. This bidirectional association between sleep disturbance and depression has created a new perspective that sleep problems are no longer an epiphenomenon of depression but a predictive prodromal symptom. In this review, we highlight the treatment of sleep disturbance before, during and after depression, which probably plays an important role in improving outcomes and preventing the recurrence of depression. In clinical practice, pharmacological therapies, including hypnotics and antidepressants, and non‐pharmacological therapies are typically applied. A better understanding of the pathophysiological mechanisms between sleep disturbance and depression can help psychiatrists better manage this comorbidity.

Upper gastrointestinal hemorrhage (UGH) is a life-threatening complication in patients with cirrhosis; however, data regarding the role of UGH in acute-on-chronic liver failure (ACLF) are limited.A prospective, observational cohort study was performed from February 2014 to Mach 2015.UGH was identified in 170 of 492 cirrhotic patients with acute decompensation (AD) at the time of admission. Logistic regression analysis showed that fecal occult blood test positivity was an independent risk factor for UGH in patients with or without ACLF [OR(95%CI): 8.31(4.89-14.10), p 0.001; and 6.29 (1.48-26.76), p = 0.031]. Other independent risk factors were a history of gastrointestinal bleeding [OR(95% CI): 13.43 (7.17-25.15), p 0.001], older age [OR(95% CI): 0.98(0.96-0.99), p = 0.003], greater INR level [OR(95% CI): 0.48(0.28-0.81), p = 0.007] in patients without ACLF. Multivariate Cox proportional hazard model analysis indicated that UGH did not increase mortality at different times in cirrhotic patients with acute decompensation.UGH is a frequent complication in cirrhotic patients with AD, even those with ACLF. Positive fecal occult blood tests and previous GI bleeding were shown to be associated with the risk of UGH. UGH did not significantly increase the risk of mortality in cirrhotic patients with AD or ACLF.

Background Central nervous system (CNS) infection due to Exophiala dermatitidis is rare and fatal, and primarily reported in immunocompromised patients or those with caspase recruitment domain-containing protein 9 deficiency. Herein, we describe a case of an otherwise healthy person (without underlying disease or gene deficiency) diagnosed with Exophiala dermatitidis meningoencephalitis. The patient achieved clinical remission under high-dose antifungal therapy in the first 14 months but died after 2 years of the therapy. Case presentation A 15-year-old student with headache and fever was admitted to our department. Lumbar puncture showed increased cerebrospinal fluid (CSF) pressure, moderately high CSF protein levels and cell counts, and a remarkable decrease in CSF glucose and chloride. Magnetic resonance imaging of the brain revealed multiple lesions and cerebral pia mater enhancement. CSF culture confirmed E. dermatitidis infection. We administered 4-week antifungal therapy of amphotericin B, but his CSF culture remained positive. After receiving the 12-week standard dose of voriconazole (200 mg q12h), the patient's CSF culture became negative, but his condition deteriorated with intracranial lesion enlargement. We administered a high-dose voriconazole therapy (600–800 mg per day) for 12 months, which led to clinical remission. The voriconazole dose was reduced due to adverse effects including hepatic dysfunction and hypokalemia, and the disease progressed with high intracranial pressure and epileptic seizures. Conclusions CNS infection caused by E. dermatitidis is fatal and the most serious form of fungal infection. Initially, high-dose and long-term antifungal therapy could be effective. Gene defect and related antifungal immunodeficiency may be the most important pathogenic and lethal factor.

The aim of this study was to evaluate the safety of an antiviral regimen of protease inhibitors combined with Arbidol (umifenovir) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients. The genomic sequence of SARS-CoV-2 is highly homologous to that of SARS-CoV (Zhou et al., 2020). Previously published basic and clinical research on anti-SARS-CoV treatment found that lopinavir/ritonavir (LPV/r) could improve the prognosis of SARS patients (Chan et al., 2003; Chu et al., 2004). Darunavir (DRV) is another protease inhibitor that blocks the binding of SARS-CoV-2 to human angiotensin-converting enzyme 2 (Omotuyi et al., 2020). The broad-spectrum antiviral drug Arbidol (umifenovir) also shows in vitro anti-SARS-CoV activity (Khamitov et al., 2008).

Coronavirus disease-2019 (COVID-19) is a novel respiratory disease induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It remains poorly understood how the host immune system responds to the infection during disease progression. We applied microarray analysis of the whole genome transcriptome to peripheral blood mononuclear cells (PBMCs) taken from severe and mild COVID-19 patients as well as healthy controls. Functional enrichment analysis of genes associated with COVID-19 severity indicated that disease progression is featured by overactivation of myeloid cells and deficient T cell function. The upregulation of TLR6 and MMP9, which promote the neutrophils-mediated inflammatory response, and the downregulation of SKAP1 and LAG3, which regulate T cells function, were associated with disease severity. Importantly, the regulation of these four genes was absent in patients with influenza A (H1N1). And compared with stimulation with hemagglutinin (HA) of H1N1 virus, the regulation pattern of these genes was unique in PBMCs response to Spike protein of SARS-CoV-2 ex vivo. Our data also suggested that severe SARS-CoV-2 infection largely silenced the response of type I interferons (IFNs) and altered the proportion of immune cells, providing a potential mechanism for the hypercytokinemia. This study indicates that SARS-CoV-2 infection impairs inflammatory and immune signatures in patients, especially those at severe stage. The potential mechanisms underpinning severe COVID-19 progression include overactive myeloid cells, impaired function of T cells, and inadequate induction of type I IFNs signaling.

To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP).This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.cn identifier: CTR20130046). CAP patients received sitafloxacin tablets 100 mg once daily (qd) or 100 mg twice daily (bid) to compare with moxifloxacin tablets 400 mg qd, for 7-10 days. The primary outcome was non-inferiority of sitafloxacin to moxifloxacin in clinical cure rate at test of cure (TOC) visit in per-protocol set (PPS).A total of 343 patients were randomized (sitafloxacin 100 mg qd,Sitafloxacin 100 mg qd or 100 mg bid for 7-10 days is not inferior to moxifloxacin 400 mg qd for 7-10 days in clinical efficacy for adult CAP patients. Sitafloxacin provides a safety profile comparable to moxifloxacin.

Additional file 1: Table S1. Demographic and Epidemiological Characteristics of COVID-19 Patients with BMI ≥ 24. Data are presented as medians (interquartile ranges, IQR), n (%) and mean (SD).GI symptoms* include nausea, vomiting and diarrhea.

Additional file 3: Table S3. Treatments and outcomes of COVID-19 patients with BMI ≥ 24. Data are presented as medians (interquartile ranges, IQR), n (%) and mean (SD). Others* include interferon-α sprays, arbidol, and lopinavir/ritonavir monotherapy.

Additional file 2: Table S2. Radiographic and Laboratory Findings of COVID-19 Patients with BMI ≥ 24. Data are presented as medians (interquartile ranges, IQR), n (%) and mean (SD).

Background. Far upstream element-binding protein 1 (FUBP1) is reported to be involved in cancer development by regulating the transcription of c-myc gene through binding to far upstream element. Highly expressed FUBP1 was negatively correlated with survival rate of patients with hepatocellular carcinoma (HCC) and could promote the proliferation of HCC cells. However, the downstream mechanism of FUBP1 has not yet been clearly explained. This study is aimed at identifying the expression profiles of long noncoding RNA (lncRNA) in HCC cells in response to FUBP1 overexpression and at investigating the possible lncRNAs that participated in cell proliferation process regulated by FUBP1. Methods. The overexpression of FUBP1 was mediated by lentiviral infection on 3 different types of HCC cell lines (MHCC97-H, MHCC97-L, and Huh-7). The expression of target genes was detected by quantitative reverse transcription-PCR (RT-PCR) and western blotting assays. Microarray and quantitative RT-PCR were applied to screen the differentially expressed lncRNAs in HCC cells after FUBP1 overexpression. The Cell Counting Kit-8 assay was used to confirm the growth vitality of HCC cells. Results. The growth vitality of HCC cells was significantly increased after lentivirus infection. A total of 12 lncRNAs had the same expression trend in the 3 HCC cell lines in response to FUBP1 overexpression, including 3 upregulated lncRNAs and 9 downregulated lncRNAs. Coexpression analysis of dysregulated lncRNAs-mRNAs network showed that lnc-LYZ-2 was the lncRNA most relevant to FUBP1. Inhibition of lnc-LYZ-2 could significantly relieve the proproliferation effect of FUBP1 on HCC cells, suggesting that lnc-LYZ-2 was partially involved in proproliferation regulation of FUBP1. Conclusions. Our results indicated that FUBP1 induced the abnormal expression of lncRNAs and the FUBP1-lncRNAs coexpression network in HCC cells, which could provide theoretical and experimental basis for FUBP1-lncRNAs network involved in HCC development.

Stroke is a leading cause of death and disability in humans. The excessive production of reactive oxygen species (ROS) is an important contributor to oxidative stress and secondary brain damage after stroke. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an enzyme complex consisting of membrane subunits and cytoplasmic subunits, regulates neuronal maturation and cerebrovascular homeostasis. However, NADPH oxidase overproduction contributes to neurotoxicity and cerebrovascular disease. NADPH oxidase has been implicated as the principal source of ROS in the brain, and numerous studies have shown that the knockout of NADPH exerts a protective effect in the model of ischemic stroke. In this review, we summarize the mechanism of activation of the NADPH oxidase family members, the pathophysiological effects of NADPH oxidase isoforms in ischemic stroke, and the studies of NADPH oxidase inhibitors to explore potential clinical applications.

Additional file 4: Table S4. Univariable Analysis of Risk Factors associated for the Severe/Critical type COVID-19 patients.

Since the December 2019 outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, the infection has spread locally and globally resulting in a pandemic. As the numbers of confirmed diagnoses and deaths continue to rise, COVID-19 has become the focus of international public health. COVID-19 is highly contagious, and there is no effective treatment yet. New treatment strategies are urgently needed to improve the treatment success rate of severe and critically ill patients. Increasing evidence has shown that a cytokine storm plays an important role in the progression of COVID-19. The artificial-liver blood-purification system (ALS) is expected to improve the outcome of the cytokine storm. In the present study, the levels of cytokines were detected in 12 COVID-19 patients pre- and post-ALS with promising results. The present study shows promising evidence that ALS can block the cytokine storm, rapidly remove the inflammatory mediators, and hopefully, suppress the progression of the disease, thereby providing a new strategy for the clinical treatment of COVID-19.

Background: The aim of this study was to investigate the host factors of patients with COVID-19 that were associated with delayed viral RNA clearance in specimens obtained from the upper respiratory tract. Results: A median of a 32-day period of viral RNA shedding was observed, ranging from 4 days to 111 days. On multivariate analysis, elderly age was independently associated with prolonged viral shedding (OR = 1.02, 95% CI: 1.01–1.04, P = 0.003). An incremental increase in the duration of viral RNA shedding was observed with increasing age (P < 0.05). The median (quartile) duration of viral RNA shedding was 23 (22) days (≤ 40 years), 30 (18) days (41–50 years), 33 (21) days (51–60 years), 34 (17) days (61–70 years) and 34 (17) days (> 70 years). Conclusions: Viral RNA shedding can persist for as long as 111 days in the upper respiratory tract. Increasing age is associated with viral RNA persistence. Method: The demographic and virological data of patients with laboratory-confirmed COVID-19 were retrospectively analyzed. A multivariate logistic regression analysis was performed to identify significant risk factors associated with delayed viral RNA clearance. The duration of viral shedding was compared among age-stratified groups.

The real-time reverse transcription-polymerase chain reaction (RT-PCR) detection of viral RNA from sputum or nasopharyngeal swab had a relatively low positive rate in the early stage of coronavirus disease 2019 (COVID-19). Meanwhile, the manifestations of COVID-19 as seen through computed tomography (CT) imaging show individual characteristics that differ from those of other types of viral pneumonia such as Influenza-A viral pneumonia (IAVP). This study aimed to establish an early screening model to distinguish COVID-19 pneumonia from IAVP and healthy cases through pulmonary CT images using deep learning techniques. A total of 618 CT samples were collected: 219 samples from 110 patients with COVID-19 (mean age 50 years; 63 (57.3%) male patients); 224 samples from 224 patients with IAVP (mean age 61 years; 156 (69.6%) male patients); and 175 samples from 175 healthy cases (mean age 39 years; 97 (55.4%) male patients). All CT samples were contributed from three COVID-19-designated hospitals in Zhejiang Province, China. First, the candidate infection regions were segmented out from the pulmonary CT image set using a 3D deep learning model. These separated images were then categorized into the COVID-19, IAVP, and irrelevant to infection (ITI) groups, together with the corresponding confidence scores, using a location-attention classification model. Finally, the infection type and overall confidence score for each CT case were calculated using the Noisy-or Bayesian function. The experimental result of the benchmark dataset showed that the overall accuracy rate was 86.7% in terms of all the CT cases taken together. The deep learning models established in this study were effective for the early screening of COVID-19 patients and were demonstrated to be a promising supplementary diagnostic method for frontline clinical doctors.

Introduction In December, 2019, an outbreak of the coronavirus disease 2019 (COVID-19), which was caused by a novel coronavirus, started in Wuhan, China. So far, there is limited clinical evidence on the effect of corticosteroid therapy for this disease. This study aims to investigate the association between corticosteroid therapy and the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance among patients with mild COVID-19. Methods Patients with mild COVID-19 were enrolled from two medical centers in China between January 13, 2020 and February 29, 2020. Baseline characteristics and durations of RNA clearance were compared between the corticosteroid and non-corticosteroid therapy groups. The independent effects of corticosteroid therapy on the duration of RNA clearance were estimated by generalized linear models. Results Of 82 patients with a mild infection, 40 patients were male (48.8%), with a median age of 49 years (interquartile range, IQR 36–61). Among those patients, 36 patients (43.9%) received corticosteroid therapy. The adjusted multivariate models showed that the effects of corticosteroids were non-significant on the durations of onset to first RNA clearance [β 2.48, 95% CI (95% confidence interval) − 0.42 to 5.38, P = 0.0926] and to persistent RNA clearance (β 1.54, 95% CI − 1.41 to 4.48, P = 0.3016), and durations of therapy to first RNA clearance (β 2.16, 95% CI − 0.56 to 4.89, P = 0.1184) and to persistent RNA clearance (β 1.22, 95% CI − 1.52 to 3.95, P = 0.3787). Conclusions Corticosteroid therapy in patients with mild COVID-19 was not associated with the duration of SARS-CoV-2 clearance, suggesting that the use of corticosteroids may not be beneficial for patients with mild COVID-19 and should be prudently recommended in clinical practice. However, further studies are needed to verify the findings. Electronic supplementary material The online version of this article (10.1007/s40121-020-00337-y) contains supplementary material, which is available to authorized users.

Cryptococcal meningitis (CM) is the leading cause of mortality among patients infected with human immunodeficiency virus (HIV). Although treatment strategies for CM are continually being developed, the mortality rate is still high. Therefore, we need to explore more therapeutic strategies that are aimed at hindering its pathogenic mechanism. In the field of CM, several studies have observed rapid iron accumulation and lipid peroxidation within the brain, all of which are hallmarks of ferroptosis, which is a type of programmed cell death that is characterized by iron dependence and lipid peroxidation. In recent years, many studies have confirmed the involvement of ferroptosis in many diseases, including infectious diseases such as Mycobacterium tuberculosis infection and coronavirus disease-2019 (COVID-19). Furthermore, ferroptosis is considered as immunogenic and pro-inflammatory as the ferroptotic cells release damage-associated molecular pattern molecules (DAMPs) and alarmin, both of which regulate immunity and pro-inflammatory activity. Hence, we hypothesize that there might be a relationship between this unique cell death modality and CM. Herein, we review the evidence of ferroptosis in CM and consider the hypothesis that ferroptotic cell death may be involved in the cell death of CM.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is mostly causes lung damages, but also lead to gastroenterology injury. SARS-CoV-2 - associated acute pancreatitis has been reported, however, clearance of SARS-CoV-2 and the pancreatitis was not clear.Case presentation: A 62 year old diabetic female patient suffer from coronavirus diseases (COVID-19) and detection of SARS-CoV-2 turned negative on day 11 and day 12 in sputum. Two days latter, the patient was diagnosed with acute pancreatitis. Through the support treatment, the patient got better and discharged from our hospital 18 days later.Conclusions: Our case provided an initial view of SARS-CoV-2 infection with acute pancreatitis and the acute pancreatitis may occur in COVID-19 patients with clearance of SARS-CoV-2 in lung.

OBJECTIVE This study was to investigate the CT quantification of COVID-19 pneumonia and its impacts on the assessment of disease severity and the prediction of clinical outcomes in the management of COVID-19 patients. MATERIALS AND METHODS Ninety-nine COVID-19 patients who were confirmed by positive nucleic acid test (NAT) of RT-PCR and hospitalized from January 19, 2020 to February 19, 2020 were collected for this retrospective study. All patients underwent arterial blood gas test, routine blood test, chest CT examination, and physical examination on admission. In addition, fellow-up clinical data including the disease severity, clinical treatment, and clinical outcomes were collected for each patient. Lung volume, lesion volume, non-lesion lung volume (NLLV) (lung volume – lesion volume), and fraction of non-lesion lung volume (%NLLV) (non-lesion lung volume / lung volume) were quantified in CT images by using two U-Net models trained for segmentation of lung and COVID-19 lesions in CT images. Furthermore, we calculated 20 histogram textures for lesions volume and non-lesion lung volumes, respectively. To investigate the validity of CT quantification in the management of COVID-19, we built Random Forest (RF) models for the purpose of classification and regression to assess the disease severity (Moderate, Severe, and Critical) and to predict the need and length of ICU stay, the duration of oxygen inhalation, hospitalization, sputum NAT-positive, and patient prognosis. The performance of RF classifiers was evaluated using the area under the receiver operating characteristic (ROC) curves (AUC) and that of RF regressors using the root-mean-square error (RMSE). RESULTS Patients were classified into three groups of disease severity: moderate (n=25), severe (n=47) and critical (n=27), according to the clinical staging. Of which, a total of 32 patients, 1 (1/25) moderate, 6 (6/47) severe and 25 critical (25/27), respectively, were admitted to ICU. The median values of ICU stay were 0, 0, 12 days, the duration of oxygen inhalation 10, 15, and 28 days, the hospitalization 12, 16, and 28 days, and the sputum NAT-positive 8, 9, 13 days, in three severity groups, respectively. The clinical outcomes were complete recovery (n=3), partial recovery with residual pulmonary damage (n=80), prolonged recovery (n=15), and death (n=1). The %NLLV in three severity groups were 92.18±9.89%, 82.94±16.49%, and 66.19±24.15% with p-value

The mutations in the SARS-CoV-2 virus genome during COVID-19 dissemination are unclear. In 788 COVID-19 patients from Zhejiang province, we observed decreased rate of severe/critical cases compared with patients in Wuhan. For mechanisms exploration, we isolated one strain of SARS-CoV-2 (ZJ01) from a mild COVID-19 patient. Thirty-five specific gene mutations were identified. Phylogenetic and relative synonymous codon usage analysis suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 global virus strains based on the base (C or T) at positions 8824 and 28247 while ZJ01 has T at both sites. The prediction of the Furin cleavage site (FCS) and sequence alignment indicated that the FCS may be an important site of coronavirus evolution. ZJ01 mutations identified near the FCS (F1-2) caused changes in the structure and electrostatic distribution of the S surface protein, further affecting the binding capacity of Furin. Single-cell sequencing and ACE2-Furin co-expression results confirmed that the Furin expression was especially higher in glands, liver, kidneys, and colon. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 caused mild flu-like symptoms, further showing its potential in differentiating into mild COVID-19 subtypes.