Viral Kinetics and Antibody Responses in Patients with COVID-19

BackgroundA 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. MethodsWe 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). ResultsThe 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). ConclusionsNasopharyngeal, 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. Summary boxesO_ST_ABSWhat is already known on this topicC_ST_ABSAs a newly appearing infectious disease, early efforts have focused on virus identification, describing the epidemiologic characteristics, clinical course, prognostics for critically illed cases and mortality. Among COVID-19 cases reported in mainland China (72 314 cases, updated through February 11, 2020), 81% are mild, 14% are severe, and 5% are critical. The estimated overall case fatality rate (CFR) is 2.3%. Some case series reported had shown that SARS-CoV-2 could shed in upper/lower respiratory specimens, stools, blood and urines of patients. However, important knowledge gaps remain, particularly regarding full kinetics of viral shedding and host serologic responses in association with clinical manifestations and host factors. What this study addsThe incubation period has no change after spreading out of Wuhan, and has no sex or age differences, however, children had prolonged incubation period. Due to early recognition and intervention, COVID-19 illness of Chongqing cohort is milder than that of Wuhan patients reported. This prospective cohort study on SARS-CoV-2 infection shows clearly that the viral and serological kinetics were related in duration of infection, disease severity, and clinical manifestations of COVID-19. Our data demonstrate that nasopharyngeal, sputum and stools are major shedding routes for SARS-CoV-2, and stronger NP antibody response is associated with delayed viral clearance and disease severity.

Preparation of budesonide sustained-release dry powder for inhalation and influence of lactose content / 药学学报

Using high pressure homogenization method combined with spray-drying, budesonide-loaded chitosan microparticles were prepared and the in vitro release profile was investigated. The microparticles were then blended with lactose using a vortex mixer, influence of mixing speed, mixing time on drug recovery rate and content homogeneity were investigated. Meanwhile, influence of lactose content on drug recovery rate, content homogeneity, powder flowability and in vitro deposition were studied. It turned out that budesonide was released from the microparicles in a sustained manner, with fine particle fraction as high as 46.0%, but the powder flowability was poor. After blending with 10 times of lactose, the drug recovery rate was 96.5%, with relative standard deviation of drug content 2.5%, and fine particle fraction of the formulation increased to 59.6% with good flowability. It's demonstrated that using a vortex mixer, budesonide sustained-release dry powder for inhalation with good recovery and content homogeneity could be prepared, the formulation had good flowability and was suitable for pulmonary inhaling.

Plasma levels of omentin-1 and visfatin in senile patients with coronary heart disease and heart failure

OBJECTIVE@#To investigate the alteration of plasma levels of omentin-1 and visfatin in elderly patients with coronary heart disease (CHD) and heart failure.@*METHODS@#Plasma omentin-1 and visfatin levels were measured in 90 subjects (29 stable angina pectoris (SAP) cases, 30 unstable angina pectoris (UAP) cases and 31 age- and sex-matched healthy controls (age ≥ 60 years) by enzyme-linked immunosorbent assay methods. According to the New York Heart Association classification, 59 CHDs were divided into three groups: functional I class, 11 cases; functional II/III class, 36 cases; and functional IV class, 12 cases.@*RESULTS@#The plasma level of omentin-1 in CHD patients was significantly lower than that of the control group. Omentin-1in SAP group and UAP group were significantly lower compared to the control group (there was no statistical significance between UAP group and SAP group; P >0.05). The plasma level of visfatin in CHD patients was significantly higher than that of the control group. Similarly, visfatin in SAP group and UAP group were all significantly higher compared to the control group, while there was no statistical significance between UAP group, and SAP group. The plasma omentin-1 level was negatively correlated with SBP (r=-0.264, P<0.05), positively correlated with HDL-c level (r=0.271, P<0.05); the plasma visfatin level was positively correlated with TC (r=0.292,P<0.05), negatively correlated with HDL-c level (r=-0.266,P<0.05). There was a negative correlation between plasma omentin-1 and visfatin levels (r=-0.280, P<0.05). Moreover, multiple linear stepwise regression analysis showed that omentin-1 and visfatin levels might be affected by HDL-c level. Logistic regression analysis showed that visfatin could be an independent risk factor of CHD.@*CONCLUSIONS@#Decreased levels of omentin-1 and increased levels of visfatin may be involved in the occurrence and development of CHD. Omentin-1 and visfatin, independently, may be protective and pro-inflammatory cytokines. Additionally, both omentin-1 and visfatin may be related to lipid metabolism. Visfatin may be an independent risk factor of CHD.

Application of selective cerebral perfusion in aortic arch reconstruction procedure in infants / 中华实用儿科临床杂志

Objective To summarize the cerebral protective effect of selective cerebral perfusion (SCP) technique in aortic arch reconstruction procedure in infants,so as to alleviate brain injury during operation.Methods From Sep.2009 to Sep.2011,17 infants underwent aortic arch reconstruction procedure with SCP in Children's Hospital Affiliated to Fudan University.Median age at operation was (3.5 ±4.2) months(range 1-16 months),median weight was (4.6 ± 1.5) kg(range 3.5-9.5 kg).Seven suffered from interrupted aortic with intracardiac anomaly,and 10 suffered from aortic coarctation with intracardiac anomaly.Temperature of nasopharynx was decreased slowly to 18-20 ℃,temperature of rectum was decreased slowly to 20-22 ℃.Then the arterial cannula was moved upward into innominate artery to perform SCP.The flow rate of SCP was 30-40 mL/(kg · min).Myocardial protection was established with single-dose cold constable's protection fluid (HTK solution).During extracorporeal circulation,all patients underwent conventional ultrafiltration and modified ultrafiltration to achieve a satisfactory hematocrit.Results Mean extracorporeal circulation time was (113.1 ±36.5) minutes(71-190 minutes),mean aortic clamp time was (51.9 ±20.7) minutes (34-107 minutes),and mean SCP time was (24.0 ± 19.7) minutes (4-56 minutes).The spontaneous re-beating rate was 100％.Mean regain consciousness time was 6-8 hours.Mean intubation time in intensive care unit was (164.3 ±63.2) hours(22-305 hours),mean ICU stay time was (252.7 ± 128.3) hours(72-605 hours).One infant died from serious lung infection at the 12th day after operation.There was no neurological complication in all infants.No obvious neurologic complication was observed and no abnormal electroencephalogram was observed in 16 survivals.Conclusion SCP is helpful to alleviate brain injury during operation and it is a feasible and effective technique in aortic arch reconstruction procedure in infants.

Effects of Naoan tablets on brain hemodynamics and cerebral microcirculation of soft membrane in anesthetized dogs and rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of Naoan tablets on brain hemodynamics and cerebral microcirculation of soft membrane.</p><p><b>METHOD</b>Cerebral blood stream flux, resistance of blood vessels, blood pressure and heart rate were used as observation indexes in hemodynamics experiment. Artery caliber and the number of capillaries with recovered blood stream were used as observation indexes in microcirculation experiment.</p><p><b>RESULT</b>Naoan tablets at dose of 0.5 g x kg(-1) and 1.0 g x kg(-1) could enhance cerebral blood stream flux, decrease resistance of blood vessels, and reduce blood pressure. While no effects on heart rate. Naoan tablet at dose of 0.7 g x kg(-1) and 2.1 g x kg(-1) could increase the number of capillaries with recovered blood stream and enlarge the artery caliber of soft membrane in rats.</p><p><b>CONCLUSION</b>Naoan tablets can improve the indexes of hemodynamics and cerebral microcirculation of soft membrane.</p>

Study on Inducing of Cord Blood Derived Endothelial Progenitor Cells into Endothelial Cells / 实用儿科临床杂志

Objective To induce cord blood derived endothelial progenitor cells(EPCs)into endothelial cells,and investigate the feasibility of these cells as the seed cells of tissue engineering cardiovascular replacement.Methods Mononuclear cells were isolated from fresh cord blood by 6%HES and density gradient centrifugation.Isolated cells were cultured in medium supplemented with vascular endothelial growth factor(VEGF).Attached cells were identied by morphology,immunofluorescence staining and flow cytometry.Results The percentage of mononuclear cells isolated from fresh cord blood was(3.4?2.1)?10~7/mL.The morphology of attached cells changed while being cultured and inducted,from small-sized round cells to spindle-like cells,to a typical cobblestone morphology,and the total number of cells was 10~7.After 7 days of culture,immunofluorescence staining showed that the vWF and VEGFR-2 were expressed.Compared with the original,cell markers CD_133 decreased(3.11%?1.05%) to(0.09%?0.02%),P