Different Profiles of Antibodies and Cytokines Were Found Between Severe and Moderate COVID-19 Patients
Yaolin GuoTianyi LiXinyi XiaBin SuHanping LiYingmei FengJingwan HanXiaolin WangLei JiaZuoyi BaoJingyun LiYongjian LiuLin Li
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Objectives Our objective was to determine the antibody and cytokine profiles in different COVID-19 patients. Methods COVID-19 patients with different clinical classifications were enrolled in this study. The level of IgG antibodies, IgA, IgM, IgE, and IgG subclasses targeting N and S proteins were tested using ELISA. Neutralizing antibody titers were determined by using a toxin neutralization assay (TNA) with live SARS-CoV-2. The concentrations of 8 cytokines, including IL-2, IL-4, IL-6, IL-10, CCL2, CXCL10, IFN-γ, and TNF-α, were measured using the Protein Sample Ella-Simple ELISA system. The differences in antibodies and cytokines between severe and moderate patients were compared by t-tests or Mann-Whitney tests. Results A total of 79 COVID-19 patients, including 49 moderate patients and 30 severe patients, were enrolled. Compared with those in moderate patients, neutralizing antibody and IgG-S antibody titers in severe patients were significantly higher. The concentration of IgG-N antibody was significantly higher than that of IgG-S antibody in COVID-19 patients. There was a significant difference in the distribution of IgG subclass antibodies between moderate patients and severe patients. The positive ratio of anti-S protein IgG3 is significantly more than anti-N protein IgG3, while the anti-S protein IgG4 positive rate is significantly less than the anti-N protein IgG4 positive rate. IL-2 was lower in COVID-19 patients than in healthy individuals, while IL-4, IL-6, CCL2, IFN-γ, and TNF-α were higher in COVID-19 patients than in healthy individuals. IL-6 was significantly higher in severe patients than in moderate patients. The antibody level of anti-S protein was positively correlated with the titer of neutralizing antibody, but there was no relationship between cytokines and neutralizing antibody. Conclusions Our findings show the severe COVID-19 patients’ antibody levels were stronger than those of moderate patients, and a cytokine storm is associated with COVID-19 severity. There was a difference in immunoglobulin type between anti-S protein antibodies and anti-N protein antibodies in COVID-19 patients. And clarified the value of the profile in critical prevention.Keywords:
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Antibody titer
Proinflammatory cytokine
This study on the dynamic change of chicken antibody after inject IgY aims to provide a guidance for clinical use of yolk antibody.50 highland gray cocks whose maternal antibody attenuated to almost disappear randomly assigned into 2 groups.The experiment group were injected with 2 mL IgY including ND-Ab,AVI-Ab H5 and AVI-Ab H9 while the control group with 2 mL Sodium Chloride.The chicken serum antibody titer was measured by hemagglutination inhibition test at different time.Results: the ND-Ab titer was significantly higher than that of control group in 1-8 day(P0.01),AVI-Ab H5 titer was significantly higher than the control group in 1-11 day(P0.01),and AVI-Ab H9 titer was significantly higher than the control group in 1-14 day(P0.01).The serum antibody titers increased significantly just 1d post injection while the high antibody titers continued 5-6 days and then reduced gradually.The half life period of IgY in the serum was about 5days.It can be concluded that injecting the egg yolk antibody can significantly improve chicken serum antibody titer.
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Yolk
Antibody response
Hemagglutination assay
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Objective To analyze the distribution and persistence of neutralizing antibody titer against human cytomegalovirus(HCMV) in plasma donors in Sichuan Province,China.Methods A total of 2 002 serum samples of health plasma donors were collected from 8 plasma stations in Sichuan Province and determined for neutralizing antibody titer by developed method,based on which the samples from 44 donors were traced for one year,and those from one donor for 4 years.Results The neutralizing antibody titers against HCMV in plasma donors in Sichuan Province were mainly distributed in 1 ∶ 16 ～ 1 ∶ 64,while the positive rate(not less than 1 ∶ 8) was 98.35%,of which 8.04% were not less than 1 ∶ 192.The neutralizing antibody titers of 44 plasma donors were stable within the past one year.However,the neutralizing antibody titers of the donors traced for 4 years were maintained at high levels.Conclusion The natural infection rate of HCMV was high in plasma donors in Sichuan Province.The HCMV neutralizing antibody titers were high and persistent in partial donors.It provided a basis for preparation of HCMV-specific IgG.
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Persistence (discontinuity)
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Abstract The World Health Organization (WHO) has highlighted the importance of an international standard (IS) for SARS-CoV-2 neutralizing antibody titer detection, with the aim of calibrating different diagnostic techniques. In this study, IS was applied to calibrate neutralizing antibody titers (IU/mL) and binding antibody titers (BAU/mL) in response to SARS-CoV-2 vaccines. Serum samples were collected from participants receiving the Moderna (n = 20) and Pfizer (n = 20) vaccines at three time points: pre-vaccination, after one dose, and after two doses. We obtained geometric mean titers of 1404.16 and 928.75 IU/mL for neutralizing antibodies after two doses of the Moderna and Pfizer vaccines, respectively. These values provide an important baseline for vaccine development and the implementation of non-inferiority trials. We also compared three commercially available kits from Roche, Abbott, and MeDiPro for the detection of COVID-19 antibodies based on binding affinity to S1 and/or RBD. Our results demonstrated that antibody titers measured by commercial assays are highly correlated with neutralizing antibody titers calibrated by IS.
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Immunoglobulin G subclass measurements are important for the diagnostic work-up of immunodeficiencies and immunoglobulin G4 (IgG4) related diseases. It is currently unknown whether a single sampling is truly representative for an individual's IgG subclass concentrations. This study aimed to investigate whether IgG and IgG subclass concentrations in healthy individuals are stable over time.With a span of median 42 weeks, four samples from each of 54 (34M, 20F) healthy adult volunteers (24-66 years) were analyzed for IgG and IgG1-4 using turbidimetry. Concentrations were compared within and between individuals.IgG and IgG subclass concentrations followed either a normal (IgG, IgG1, and IgG3) or log normal (IgG2 and IgG4) distribution. Immunoglobulin 4 demonstrated by far the widest range of concentrations between individuals (670-fold: 0.004-2.68 g/L). Immunoglobulin G subclass variations within individuals were expressed as pooled standard deviations (PSD). These ranged from 0.056 (IgG4) to 0.955 g/L (IgG) and correlated with mean concentration of IgG or the particular IgG subclass. As a consequence, the relative PSDs (i.e., PSD divided by mean IgG or IgG subclass concentration) fell within a narrow range: 5.82%-10.1%. Based on these numbers, the 95%-upper one-sided confidence limits for intraindividual IgG and IgG subclass variation was calculated to range from 9.82% (IgG2) to 16.9% (IgG4).The study documents that IgG or IgG subclass concentrations within healthy individuals are very stable over at least 42 weeks. The expected variation for IgG4 concentrations at a 95% confidence level does not exceed ±16.9%.
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Knowledge of the SARS-CoV-2 antibody titers induced by tixagevimab–cilgavimab in patients with hematologic diseases remains insufficient. Here, we performed a single-center, prospective study to reveal the changes in antibody titer after administration of tixagevimab–cilgavimab in 78 patients with hematologic diseases. The median peak titer was 155.4 U/mL, and the median AUC was 46556 days·U/mL. First, we compared several characteristics between patients with low titers (peak titer ≤ 155.4 U/mL) and high titers (peak titer > 155.4 U/mL). We extracted 6 factors (patient age, sex, ECOG-PS, serum albumin level, and cross-sectional area and computed tomographic number of the psoas major muscle) as candidates influencing the antibody titers. Multiple regression analysis revealed that antibody titer was closely associated with these 6 factors (contribution rate = 0.76, p = 0.02). Our data support the inability of tixagevimab–cilgavimab to induce sufficient antibody titers against SARS-CoV-2, especially in older, frailer, female patients.
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Antibody response
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Many variants of SARS-CoV-2 have emerged, and decreased neutralizing antibodies after vaccination and breakthrough infections have become a problem. The importance of monitoring titers of neutralizing antibodies is getting higher. We enrolled 146 COVID-19 patients, who were thought to be infected with Wuhan-hu-1 or D614G strains, and examined the time course of neutralizing titers against six concerning strains (Wuhan-hu-1, Alpha, Beta, Gamma, Kappa, and Delta) using newly developed ELISA. The acquisition of neutralizing titer was positively associated with disease severity. Immune evasions were observed approximately 20 to 30% for Alpha, Kappa, and Delta variant, and 40 to 45% for Beta and Gamma variant. The titers against all strains decreased over time, and interestingly, while titers against Wuhan-hu-1 decreased by 23%, those to Delta variant decreased by 70%. Our simple, cost-effective, and non-hazardous system will be applicable to process numerous samples, such as monitoring titers against prevalent strains after infection or vaccination.
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Kappa
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