Background A pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading over the world. However, the viral dynamics, host serologic responses, and their associations with clinical manifestations, have not been well described in prospective cohort. Methods We conducted a prospective cohort and enrolled 67 COVID-19 patients admitting between Jan 26 and Feb 5, 2020. Clinical specimens including nasopharyngeal swab, sputum, blood, urine and stool were tested periodically according to standardized case report form with final follow-up on February 27. The routes and duration of viral shedding, antibody response, and their associations with disease severity and clinical manifestations were systematically evaluated. Coronaviral particles in clinical specimens were observed by transmission electron microscopy (TEM). Results The median duration of SARS-CoV-2 RNA shedding were 12 (3-38), 19 (5-37), and 18 (7-26) days in nasopharyngeal swabs, sputum and stools, respectively. Only 13 urines (5.6%) and 12 plasmas (5.7%) were viral positive. Prolonged viral shedding was observed in severe patients than that of non-severe patients. Cough but not fever, aligned with viral shedding in clinical respiratory specimens, meanwhile the positive stool-RNA appeared to align with the proportion who concurrently had cough and sputum production, but not diarrhea. Typical coronaviral particles could be found directly in sputum by TEM. The anti-nucleocapsid-protein IgM started on day 7 and positive rate peaked on day 28, while that of IgG was on day 10 and day 49 after illness onset. IgM and IgG appear earlier, and their titers are significantly higher in severe patients than non-severe patients (p<0.05). The weak responders for IgG had a significantly higher viral clearance rate than that of strong responders (p= 0.011). Conclusions Nasopharyngeal, sputum and stools rather than blood and urine, were the major shedding routes for SARS-CoV-2, and meanwhile sputum had a prolonged viral shedding. Symptom cough seems to be aligned with viral shedding in clinical respiratory and fecal specimens. Stronger antibody response was associated with delayed viral clearance and disease severity.

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BackgroundProtein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) is an efficient biomarker specific for hepatocellular carcinoma (HCC). Some researchers have proved that levels of PIVKA-II reflect HCC oncogenesis and progression. However, the effectiveness of PIVKA-II based on real-world clnical data has barely been studied.MethodsA total of 14,861 samples were tested in Southwest Hospital in over 2 years’ time. Among them, 4073 samples were PIVKA-II positive. Finally, a total of 2070 patients with at least two image examinations were enrolled in this study. Levels of AFP and PIVKA-II were measured by chemiluminescence enzyme immunoassay (CLEIA) and chemiluminescent microparticle Immunoassay (CMIA), respectively.ResultsA total of 1016 patients with HCC were detected by PIVKA-II in a real-world application. In all these cases, 88.7% cases primarily occurred and patients with advanced HCC covered 61.3%. Levels of PIVKA-II were significantly higher in advanced group (4650.0 mAU/ml, 667.0–33,438.0 mAU/ml) than early-stage group (104.5 mAU/ml, 61.0–348.8 mAU/ml; P < 0.001). Levels of PIVKA-II elevated significantly in recurrence and residual group than recovery group (P < 0.001). A total of 1054 PIVKA-II positive patients were non-HCC cases. Among them, cirrhosis took the largest part (46.3%), followed by hepatitis (20.6%) and benign nodules (15.3%). High-levels of PIVKA-II in at-risk patients is an indicator of HCC development in two-year time.ConclusionsOur data showed that PIVKA-II effectively increases the detection rate of HCC was a valid complement to AFP and image examination in HCC surveillance.

RNA virus population in a host does not consist of a consensus single haplotype but rather an ensemble of related sequences termed quasispecies. The dynamics of quasispecies afford SARS-CoV-2 a great ability on genetic fitness during intrahost evolution.

Prognosis of hepatocellular carcinoma (HCC) remains unsatisfying due to a lack of early detecting methods. Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) has been proved to be an efficient biomarker for HCC. However, the predicting efficacy of PIVKA-II has barely been reported. In the Hepatitis Biobank of Southwest Hospital (HBS) cohort at Southwest Hospital, we did a two-stage nested case-control study. Totally, 45 HCC cases versus 138 matched controls were enrolled to compare levels of α-fetoprotein (AFP) and PIVKA-II in sequential sera at −12, −9, −6, −3 and 0 months before imaging diagnosis. Levels of both PIVKA-II and AFP in HCC cases elevated significantly at all time points compared with controls. In validation stage, the sensitivity and specificity of PIVKA-II at baseline were 58.3% and 92.6%, and AFP were 75.0% and 91.7%. AFP-/PIVKA-II+ patients covered 27.4%, 29.4% and 19.6% at M-12, M-6 and M-0, respectively, while AFP+/PIVKA-II- patients covered 25.5%, 19.6% and 17.7%, respectively. Both PIVKA-II and AFP have the potential for HCC prediction, while PIVKA-II has a better positive rate than AFP before diagnosis.

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Low temperatures (-70°C/80°C) are necessary for storage of serum samples in chronic hepatitis B research after long-term storage.

To investigate the association between long-term changes of serum total bile acid and hepatocellular carcinoma in chronic hepatitis B patients, we did a retrospective cohort study of 2262 chronic hepatitis B patients with regular antiviral treatment using data from the Hepatitis Biobank at Southwest Hospital Program from 2004 to 2014. Patients in the study were classified into 3 groups according to persistence of elevated serum total bile acid during follow-up: none-low, medium, and high persistence of elevated serum total bile acid. The association between persistence of elevated serum total bile acid and hepatocellular carcinoma was estimated using Cox proportional hazard models and Kaplan-Meier analysis including information about patients’ demographic and clinical characteristics. There were 62 hepatocellular carcinoma cases during a total follow-up of 14756.5 person-years in the retrospective study. Compared to patients with none-low persistence of elevated total bile acid, the multivariate adjusted hazard ratios (95% confidence interval) were 2.37 (1.16–4.84), and 2.57 (1.28–5.16) for patients with medium, and high persistence of elevated total bile acid. Our findings identified persistence of elevated serum total bile acid as an independent risk factor of hepatocellular carcinoma in chronic hepatitis B patients.