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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity and kinetics of the antibody response mounted against this novel virus are not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and non-structural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable of binding the D614G spike mutant and cross-react with the SARS-CoV-1 receptor binding domain. Together, this study reveals that subjects with a more severe SARS-CoV-2 infection exhibit a greater overall antibody response to the spike and nucleocapsid protein and a larger memory B cell response against the spike.
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BackgroundConvalescent plasma therapy for COVID-19 relies on the transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. MethodsMultivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. FindingsMean symptom duration of plasma donors was 11.9{+/-}5.9 days and 7.8% (8/103) had been hospitalized. Antibody titers ranged from 0 to 1:3,892 (anti-receptor binding domain (RBD)) and 0 to 1:3,289 (anti-spike). Multivariable analysis demonstrated that higher anti-RBD and anti-spike titer were associated with increased age, hospitalization for COVID-19, fever, and absence of myalgia (all p<0.05). Fatigue was significantly associated with anti-RBD (p=0.03) but not anti-spike antibody titer (p=0.11). In pairwise comparison among ABO blood types, AB donors had higher anti-RBD titer than O negative donors (p=0.048) and higher anti-spike titer than O negative (p=0.015) or O positive (p=0.037) donors. Eight of the ten recipients were discharged, one remains on ECMO and one died on ECMO. No toxicity was associated with plasma transfusion. After excluding two ECMO patients and adjusting for donor antibody titer, recipient anti-RBD antibody titer increased on average 31% per day during the first three days post-transfusion (p=0.01) and anti-spike antibody titer by 40.3% (p=0.02). InterpretationAdvanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titer to COVID-19. Despite variability in donor titer, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion among COVID-19 patients is needed to determine the clinical efficacy of this therapy. Trial RegistrationNCT04340050 FundingDepartment of Surgery University of Chicago, National Institute of Allergy and Infectious Diseases (NIAID) Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051
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<p><b>OBJECTIVE</b>To detect the expression levels of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) in the peripheral blood of patients with oral squamous cell carcinoma (OSCC) and to discuss their biological and clinical significance.</p><p><b>METHODS</b>PD-1/PD-L1 expression on the surface of T-lymphocytes and the counts of T-lymphocyte subpopulations of peripheral blood in 82 patients with OSCC (OSCC group) and 25 healthy controls (control group) were examined via flow cytometry. The expression levels of soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1) in the serum were observed through enzyme-link immunology method. The data were tested and analyzed with SPSS 17.0 software.</p><p><b>RESULTS</b>The percentage of CD8+ T cells in the OSCC group was significantly higher than that in the control group (P<0.05), whereas the percentages of CD3+ and CD4+ T cells as well as CD4+/CD8+ ratio were significantly lower than those in the control group (P<0.05). The positive rates of PD-1 and PD-L1 in CD3+ and CD4+ T cells in OSCC peripheral blood were remarkably higher than those in the control group (P<0.01). Difference was not observed between the expression levels of sPD-1 in the serum of OSCC group and those in the control group (P>0.05), but the average of sPD-L1 was remarkably higher than that in the control group (P<0.05). sPD-L1 expression was related to clinical stage, tumor cell differentiation, and lymph node status (P<0.05) but not related to sex, age, tumor location, and tumor size.</p><p><b>CONCLUSION</b>T-lymphocyte subpopulations in the peripheral blood of patients with OSCC developed immunosuppression with different degrees. PD-1 and PD-L1 expression levels on the surface of CD3+ and CD4+ T cells significantly increased. Abnormal increase in sPD-L1 expression may be associated with OSCC development.</p>
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Humans , B7-H1 Antigen , Metabolism , Carcinoma, Squamous Cell , Metabolism , Case-Control Studies , Flow Cytometry , Mouth Neoplasms , Metabolism , T-Lymphocyte SubsetsABSTRACT
Objective To study the risk factors of pulmonary embolism and comparison of the effect of different therapy.Methods Risk factors of 182 patients with pulmonary embolism were analyzed retrospectively.The patients were randomly divided into simple drug group and drug joint intervention group.Simple drug group was given heparin and warfarin,or jiont urokinase fibrinolytic therapy.The drug joint intervention group was given the same drug therapy joint vena cava filter implantation and/or catheter broken bolt therapy.After different treatment,the clinical prognosis was compared between the two groups.Results Of 182 patients with pulmonary embolism,the elderly and smoking prevalence rate increased significantly,deep vein thrombosis,cardiovascular disease,cancer,blood system diseases,trauma and surgery,chronic lung disease,fracture and orthopaedic surgery were the main risk factors.The effective rate and mortality between the pure drug therapy group and drug joint intervention group had no significant differences(x2 =0.145,P ＞ 0.05).Conclusion The incidence of pulmonary embolism is closely related to the risk factors.Cancer is one of the important diseases caused by pulmonary embolism.In a timely manner to give the antithrombotic drug treatment has great significance to the prognosis of pulmonary thromboembolism,there was no significant difference compared with the antithrombotic joint intervention.
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Objective To analyze the clinical significance of four kinds of microalbuminuria detection in early diagnosis of iodinated contrast agent damage to kidney by studying four elements in the patients' urine:microalbumin (mAlb),immunoglobulin G (IgG),α1-microglobulin (α1-MG) and β2-microglobulin (β2-MG).Methods 106 patients who have received percutaneous coronary interventional therapy were chosen and divided into group A(angiography dose ＜ 100ml,n =51) and group B (angiography dose ≥ 100ml,n =55) according to the amount of contrast agent used.Changes in the amount of mAlb,IgG,α1-MG and β2-MG levels,serum creatinine(Scr),endogenous creatinine clearance rate(eGFR) in the urine of the patients before and after the surgery were observed.Results Postoperative α1-MG and β2-MG levels in the urine of group A higher than before surgery (t =-6.748,-11.173,all P ＜0.0 5).2 4 hours after the surgery,mA1b,IgG,α1-MG and β2-MG levels in group B were elevated than before surgery,and the differences were significant(t =-6.223,-3.518,-11.532,-10.773,all P ＜ 0.05).Two groups had significant differences in terms of mAlb,IgG,α1-MG and β2-MG levels after the surgery (F =27.306,4.704,5.118,19.011,all P ＜ 0.05).Conclusion Four kinds of microalbuminuria detecting are conducive to early diagnosis of iodinated contrast agent damage to kidney and assessing the damage degree.The contrast agent damage to kidney first occurs as the renal tubular damage.When the contrast agent was used at a dosage of more than 100ml,glomerular damage occurred.
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ObjectiveTo explore the protective effect of low molecular dextran combined with salvia miltiorrhiza injection against kidney damage from contrast agent after percutaneous coronary intervention(PCI) and the effect of preventing kidney damage.Methods120 patients who underwent PCI were randomly divided into two groups:the treatment group( low molecular dextran combined with salvia miltiorrhiza treatment) and the control group,each group 60 cases.The control group was given the conventional treatment,and the treatment group was treated with 250ml low molecular dextran and 16ml salvia miltiorrhiza injection for 7d on the basis of conventional treatment.The levels of blood urea nitrogen ( BUN ),serum creatinine ( SCR),β2 microglobulin ( β2-MG),24h urine protein were detected before and 1 d,6d after surgery.ResultsAt one day after application of contrast agent,the levels of BUN,SCR,β2-MG,24h urine protein were increased,and returned to baseline level at 6th day.The levels of BUN,SCR,β2-MG,24h urine protein of the treatment group were significantly lower than those of the control group at 6th day ( P ＜ 0.05 ).ConclusionThe low molecular dextran combined with danshen injection treatment in the perioperative period could effectively reduce the kidney impairment from contrast agent and the incidence of renal insufficiency.