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.
The synthetic dipeptides alanyl-glutamine (Ala-Gln) and glycyl-glutamine (Gly-Gln) are used as Gln substitution to provide energy source in the gastrointestinal tract due to their high solubility and stability. This study aimed to investigate the effects of Gln, Ala-Gln and Gly-Gln on mitochondrial respiration and protein turnover of enterocytes. Intestinal porcine epithelial cells (IPEC-J2) were cultured for 2 days in Dulbecco's modified Eagle's-F12 Ham medium (DMEM-F12) containing 2.5 mM Gln, Ala-Gln or Gly-Gln. Results from 5-ethynyl-2'-deoxyuridine incorporation and flow cytometry analysis indicated that there were no differences in proliferation between free Gln and Ala-Gln-treated cells, whereas Gly-Gln treatment inhibited the cell growth compared with Gln treatment. Significantly lower mRNA expressions of Sp1 and PepT1 were also observed in Gly-Gln-treated cells than that of Ala-Gln treatment. Ala-Gln treatment increased the basal respiration and ATP production, compared with free Gln and Gly-Gln treatments. There were no differences in protein turnover between free Gln and Ala-Gln-treated cells, but Gly-Gln treatment reduced protein synthesis and increased protein degradation. Ala-Gln treatment stimulated mTOR activation whereas Gly-Gln decreased mTOR phosphorylation and increased the UB protein expression compared with free Gln treatment. These results indicate that Ala-Gln has the very similar functional profile to free Gln in porcine enterocytes in vitro and can be substituted Gln as energy and protein sources in the gastrointestinal tract.
Changing characteristics and spatial differentiation of spring precipitation in Southwest China during 1961-2012 *Liu Hong-Lan(刘洪兰) a) † , Zhang Qiang(张 强) b) , Zhang Jun-Guo(张俊国) c) , Hu Wen-Chao(胡文超) d) , Guo Jun-Qin(郭俊琴) e) , and Wang Sheng(王 胜) f) a) Zhangye Meteorological Bureau, Zhangye 734000,
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