Abstract Aims Corona virus disease 2019 (COVID-19) has rapidly become the most severe public health issue all over the world. Despite respiratory symptoms, hepatic injury has also been observed in clinical settings. This study aimed to investigate the risk factors involved with hepatic injury in the patients with COVID-19. Methods A total of 85 hospitalized patients who were diagnosed with COVID-19 in Beijing You’an Hospital were retrospectively analyzed. According to liver function, they were divided into ALT normal group (n=52) and ALT elevation group (n=33). Clinical features and laboratory data were compared between the two groups. The independent risk factors for liver injury were analyzed. Results There were 33 patients with hepatic injury in our study, accounting for 38.8% (33/85). The patients in ALT elevation group were older than those in ALT normal group. The levels of lactic acid, CRP, myoglobin, and neutrophils were significantly higher in ALT elevation group. The lymphocytes and albumin were significantly lower in ALT elevation group. The proportion of severe and critical patients in ALT elevation group was significantly higher. Multivariate logistic regression analysis showed CRP ≥20 mg/L and lymphocyte count< 1.1×10^9/L were independently related to hepatic injury. Conclusions Lymphopenia and CRP may serve as the risk factors related to hepatic injury in patients with COVID-19, which might be related to inflammatory cytokine storm in liver injury. Early detection and timely treatment of hepatic injury in patients with COVID-19 are necessary.
Abstract Background: The novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has quickly spread worldwide since its outbreak in December 2019. One of the primary measures for controlling the spread of SARS-CoV-2 infection is an accurate assay for its diagnosis. SARS-CoV-2 real-time PCR kits suffer from some limitations, including false-negative results in the clinic. Therefore, there is an urgent need for the development of a rapid antibody test kit for COVID-19 diagnosis. Methods: The nuclear capsid protein (N) and spike protein 1 (S1) fragments of SARS-CoV-2 were expressed in Escherichia coli, and rapid antibody-based tests for the diagnosis of SARS-CoV-2 infection were developed and compared. To evaluate their clinical applications, the serum from COVID-19 patients, suspected COVID-19 patients, recovering COVID-19 patients, patients with general fever or pulmonary infection, doctors and nurses who worked at the fever clinic, and health professionals was analyzed by the rapid antibody test kits. The serum from patients infected with Mycoplasma pneumoniae and patients with respiratory tract infection was further analyzed to test its cross-reactivity with other respiratory pathogens. Results: A 47 kDa N protein and 67 kDa S1 fragment of SARS-CoV-2 were successfully expressed, purified, and renatured. The rapid antibody test with recombinant N protein showed higher sensitivity and specificity than the rapid IgM antibody test with recombinant S1 protein. Clinical evaluation showed that the rapid antibody test kit with recombinant N protein had 88.56% sensitivity and 97.42% specificity for COVID-19 patients, 53.48% positive rate for suspected COVID-19 patients, 57.14% positive rate for recovering COVID-19 patients, and 3.20%-3.27% cross-reactivity with other respiratory pathogens. The sensitivity of the kit did not significantly differ in COVID-19 patients with different disease courses (p < 0.01). Conclusion: The rapid antibody test kit with recombinant N protein has high specificity and sensitivity, and can be used for the diagnosis of SARS-CoV-2 infection combined with RT-PCR.
To the editor, We read with great interest the recent article in Hepatology by Ahmed et al.1 Impressively, Ahmed and colleagues not only adjusted for cardiovascular disease (CVD) risk factors in baseline but also adjusted for changes in CVD risk factors over time. The associations between hepatic steatosis and incident CVD and all-cause mortality were attenuated when accounting for a change in CVD risk factors over time. However, we have different views on the appropriateness of the adjustment for changes in CVD risk factors over time. On the one hand, CVD risk factors, especially type 2 diabetes,2 are associated with the development of NAFLD, so the time-varying covariates of CVD risk factors may reflect changes in the severity of NAFLD. On the other hand, time-varying covariates of CVD risk factors may be associated with the corresponding treatments received by the patients, and these treatments may have additional effects on hepatic steatosis. For example, statins have been shown to reduce the risk of NAFLD occurrence and fibrosis in a large population study.3 Similarly, a meta-analysis has suggested that thiazolidinedione and glucagon-like peptide-1 receptor agonists were effective in attenuating hepatic fat content.4 As a result, adjusting for changes in CVD risk factors over time may underestimate the association between NAFLD and outcomes defined by the study. In addition, we noted that Ahmed et al1 adjusted for the risk factors of CVD together. However, it seemed that not all included risk factors were associated with NAFLD-related CVD events. A recent meta-analysis5 has shown significant effects of type 2 diabetes and plasma LDL-cholesterol concentrations, rather than body mass index, smoking, or hypertension, on the association between NAFLD and the risk of CVD events. Therefore, an overall discussion of all included CVD risk factors may result in an exaggeration of certain factors. In conclusion, it is important to adjust for CVD risk factors, but whether adjusting for changes in CVD risk factors over time is appropriate and which CVD risk factors should be taken into account may need further discussion.
The aim of the present study was to explore the effect of hepatitis B virus on T lymphocyte and its subsets in different ALT states, and elucidate the immunological mechanism of ALT basing antiviral therapy for hepatitis B. 363 chronic hepatitis B patients were selected as the study subjects. According to ALT abnormalities, the patients were divided into three study groups. ALT normal group 131 cases, normal≦ ALT < 2 times of upper limit group 110 cases, ALT ≥ 2 times of upper limit group 122 cases. Entecavir was given to the ALT ≥ 2 times of upper limit group patients and followed up for 24 weeks. The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer, the liver function parameters were measured by automatic biochemical analyzer, the hepatitis B virus load were measured by quantitative PCR analyzer, T lymphocytes were detected by flow cytometry, the level of IL-2, IFN-γ, IL-4 and IL-10 were detected by enzyme-linked immunosorbent assay. Detecting the influence of different hepatitis B viru loads in different groups on immunological indexes, and the virological and immunological indexes changes in before and after antiviral therapy patients. In the ALT normal group, different virus load hepatitis B virus had minor effect on T lymphocytes and their subsets (P > 0.05). In the ALT ≥ double upper limit of normal group. with the virus load increased, The total number of T lymphocytes, CD3+ CD4 + T lymphocytes decreased, (P < 0.05)CD3+ CD8 + T lymphocytes increased(P < 0.05). With the virus load increased the cytokines IL-2, IFN-γ which reflect the Th1 lymphocytes increased(P < 0.05), the cytokines IL-4、IL-10 which reflect the Th2 lymphocytes decreased(P < 0.05). Before and after 24 weeks of entecavir treatment, the patient's HBV-DNA decreased significantly(P < 0.05) and the body's immune function improved significantly. (P < 0.05)The influence of hepatitis B virus on immune function is different in different ALT states. Therefore, the scientific significance of ALT grouping in the hepatitis B treatment can be clarified from the immunological point.
The aim of the study was to assess the potential role of preoperative gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) dynamic enhanced MR imaging for diagnosing microvascular invasion (MVI) and pathological grade of hepatocellular carcinoma (HCC).A total of 113 consecutive HCC patients confirmed by histopathology underwent preoperative Gd-EOB-DTPA dynamic enhanced MRI were included. Signal intensity (SI) of peritumoral, normal liver tissue and tumor parenchyma during arterial phase and hepatobiliary phase (HBP) were analyzed. The receiver operating characteristic (ROC) curves were performed to assess the potential diagnostic capability for MVI and pathological grade of HCC. Kaplan-Meier method was performed to estimate the recurrence-free survival rate and compared using the log rank test.SI ratio of peritumoral tissue to normal liver in arterial phase (SIAp/Al) was independently associated with MVI [odds ratio (OR) = 3.115, 95% confidence interval (CI): 1.867-5.198] and pathological grades (OR = 1.437, 95% CI: 1.042-1.981). The area under the curve (AUC) of SIAp/Al was equivalent to the SI of tumor parenchyma on arterial phase (SIAt) in distinguishing low and high pathological grades. However, the AUC of SIAp/Al (0.851) was larger than peritumoral hypointensity on HBP (0.668) for distinguishing MVI. The recurrence-free survival rate of HCC patients with SIAp/Al<1.1 was higher than HCC with SIAp/Al≥1.1(P = .025).The SIAp/Al in preoperative Gd-EOB-DTPA dynamic enhanced MR imaging is a potential diagnosis marker for MVI and pathological grade of HCC noninvasively. The higher SIAp/Al may predict the poor prognosis of HCC after surgery.
Abstract Specific roles of gut microbes in COVID-19 progression are critical. However, the circumstantial mechanism remains elusive. In this study, shotgun metagenomic or metatranscriptomic sequencing were performed on fecal samples collected from 13 COVID-19 patients and controls. We analyzed the structure of gut microbiota, identified the characteristic bacteria and selected biomarkers. Further, GO, KEGG and eggNOG annotation were employed to correlate the taxon alteration and corresponding functions. The gut microbiota of COVID-19 patients was characterized by the enrichment of opportunistic pathogens and depletion of commensals. The abundance of Bacteroides spp. displayed an inverse relationship to COVID-19 severity, whereas Actinomyces oris , Escherichia coli , and Gemmiger formicilis were positively correlated with disease severity. The genes encoding oxidoreductase were significantly enriched in SARS-CoV-2 infection. KEGG annotation indicated that the expression of ABC transporter was up regulated, while the synthesis pathway of butyrate was aberrantly reduced. Furthermore, increased metabolism of lipopolysaccharide, polyketide sugar, sphingolipids and neutral amino acids was found. These results suggested the gut microbiome of COVID-19 patients was correlated with disease severity and in a state of excessive inflammatory response. Healthy gut microbiota may enhance antiviral defenses via butyrate metabolism, whereas the accumulation of opportunistic and inflammatory bacteria may exacerbate the disease progression.
Abstract Since the sudden outbreak of coronavirus disease 2019 (COVID-19), it has rapidly evolved into a momentous global health concern. Due to the lack of constructive information on the pathogenesis of COVID-19 and specific treatment, it highlights the importance of early diagnosis and timely treatment. In this study, 11 key blood indices were extracted through random forest algorithm to build the final assistant discrimination tool from 49 clinical available blood test data which were derived by commercial blood test equipments. The method presented robust outcome to accurately identify COVID-19 from a variety of suspected patients with similar CT information or similar symptoms, with accuracy of 0.9795 and 0.9697 for the cross-validation set and test set, respectively. The tool also demonstrated its outstanding performance on an external validation set that was completely independent of the modeling process, with sensitivity, specificity, and overall accuracy of 0.9512, 0.9697, and 0.9595, respectively. Besides, 24 samples from overseas infected patients with COVID-19 were used to make an in-depth clinical assessment with accuracy of 0.9167. After multiple verification, the reliability and repeatability of the tool has been fully evaluated, and it has the potential to develop into an emerging technology to identify COVID-19 and lower the burden of global public health. The proposed tool is well-suited to carry out preliminary assessment of suspected patients and help them to get timely treatment and quarantine suggestion. The assistant tool is now available online at http://lishuyan.lzu.edu.cn/COVID2019_2/ . Funding This work was supported by the Fundamental Research Funds for the Central Universities (lzujbky-2020-sp11) and the Gansu Provincial COVID-19 Science and Technology Major Project, China.
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