Investigation of Antibody Levels During Three Doses of Sinopharm/BBIBP Vaccine Inoculation.

Levels of neutralizing antibodies (NAb) after vaccine against coronavirus disease 2019 (COVID-19) can be detected using a variety of methods. A critical challenge is how to apply simple and accurate methods to assess vaccine effect. In a population inoculated with three doses of the inactivated Sinopharm/BBIBP vaccine, we assessed the performance of chemiluminescent immunoassay (CLIA) in its implementation to detect severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) specific antibodies, as well as the antibody kinetics of healthcare workers throughout the course of vaccination. The antibody levels of NAb, the receptor-binding-domain (RBD) antibodies and IgG peaked one month after the second and remained at a relatively high level for over three months after the booster injection, while IgM and IgA levels remained consistently low throughout the course of vaccination. The production of high-level neutralizing antibodies is more likely when the inoculation interval between the first two doses is within the range of one to two months, and that between the first and booster dose is within 230 days. CLIA showed excellent consistency and correlation between NAb, RBD, and IgG antibodies with the cytopathic effect (CPE) conventional virus neutralization test (VNT). Receiver operating characteristic (ROC) analysis revealed that the optimal cut-off levels of NAb, RBD and IgG were 61.77 AU/ml, 37.86 AU/ml and 4.64 AU/ml, with sensitivity of 0.833, 0.796 and 0.944, and specificity of 0.768, 0.750 and 0.625, respectively, which can be utilized as reliable indicators of COVID-19 vaccination immunity detection.

Broad and durable antibody response after vaccination with inactivated SARS-CoV-2 in individuals with a history of 2003 SARS-CoV infection.

In vaccinees who were infected with SARS-CoV in 2003, we observed greater antibody responses against spike and nucleoprotein of both SARS-CoV-2 and SARS-CoV after a single dosage of inactivated SARS-CoV-2 vaccine. After receiving the second vaccination, antibodies against RBD of SARS-CoV-2 Wuhan, Beta, Delta, and recently emerged Omicron are significantly higher in SARS-CoV experienced vaccinees than in SARS-CoV naïve vaccinees. Neutralizing activities measured by authentic viruses and pseudoviruses of SARS-CoV, SARS-CoV-2 Wuhan, Beta, and Delta are greater in SARS-CoV experienced vaccinees. In contrast, only weak neutralizing activities against SARS-CoV-2 and variants were detected in SARS-CoV naïve vaccinees. By 6 months after the second vaccination, neutralizing activities were maintained at a relatively higher level in SARS-CoV experienced vaccinees but were undetectable in SARS-CoV naïve vaccinees. These findings suggested a great possibility of developing a universal vaccine by heterologous vaccination using spike antigens from different SARS-related coronaviruses.

Analysis of B Cell Receptor Repertoires Reveals Key Signatures of the Systemic B Cell Response after SARS-CoV-2 Infection.

A comprehensive study of the B cell response against SARS-CoV-2 could be significant for understanding the immune response and developing therapeutical antibodies and vaccines. To define the dynamics and characteristics of the antibody repertoire following SARS-CoV-2 infection, we analyzed the mRNA transcripts of immunoglobulin heavy chain (IgH) repertoires of 24 peripheral blood samples collected between 3 and 111 days after symptom onset from 10 COVID-19 patients. Massive clonal expansion of naive B cells with limited somatic hypermutation (SHM) was observed in the second week after symptom onset. The proportion of low-SHM IgG clones strongly correlated with spike-specific IgG antibody titers, highlighting the significant activation of naive B cells in response to a novel virus infection. The antibody isotype switching landscape showed a transient IgA surge in the first week after symptom onset, followed by a sustained IgG elevation that lasted for at least 3 months. SARS-CoV-2 infection elicited poly-germ line reactive antibody responses. Interestingly, 17 different IGHV germ line genes recombined with IGHJ6 showed significant clonal expansion. By comparing the IgH repertoires that we sequenced with the 774 reported SARS-CoV-2-reactive monoclonal antibodies (MAbs), 13 shared spike-specific IgH clusters were found. These shared spike-specific IgH clusters are derived from the same lineage of several recently published neutralizing MAbs, including CC12.1, CC12.3, C102, REGN10977, and 4A8. Furthermore, identical spike-specific IgH sequences were found in different COVID-19 patients, suggesting a highly convergent antibody response to SARS-CoV-2. Our analysis based on sequencing antibody repertoires from different individuals revealed key signatures of the systemic B cell response induced by SARS-CoV-2 infection. IMPORTANCE Although the canonical delineation of serum antibody responses following SARS-CoV-2 infection has been well established, the dynamics of antibody repertoire at the mRNA transcriptional level has not been well understood, especially the correlation between serum antibody titers and the antibody mRNA transcripts. In this study, we analyzed the IgH transcripts and characterized the B cell clonal expansion and differentiation, isotype switching, and somatic hypermutation in COVID-19 patients. This study provided insights at the repertoire level for the B cell response after SARS-CoV-2 infection.

Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients.

Monoclonal antibodies (mAbs) encoded by IGHV3-53 (VH3-53) targeting the spike receptor-binding domain (RBD) have been isolated from different COVID-19 patients. However, the existence and prevalence of shared VH3-53-encoded antibodies in the antibody repertoires is not clear. Using antibody repertoire sequencing, we found that the usage of VH3-53 increased after SARS-CoV-2 infection. A highly shared VH3-53-J6 clonotype was identified in 9 out of 13 COVID-19 patients. This clonotype was derived from convergent gene rearrangements with few somatic hypermutations and was evolutionary conserved. We synthesized 34 repertoire-deduced novel VH3-53-J6 heavy chains and paired with a common IGKV1-9 light chain to produce recombinant mAbs. Most of these recombinant mAbs (23/34) possess RBD binding and virus-neutralizing activities, and recognize ACE2 binding site via the same molecular interface. Our computational analysis, validated by laboratory experiments, revealed that VH3-53 antibodies targeting RBD are commonly present in COVID-19 patients' antibody repertoires, indicating many people have germline-like precursor sequences to rapidly generate SARS-CoV-2 neutralizing antibodies. Moreover, antigen-specific mAbs can be digitally obtained through antibody repertoire sequencing and computational analysis.

Epidemiological and clinical characteristics of 70 cases of coronavirus disease and concomitant hepatitis B virus infection: A multicentre descriptive study.

The interaction between existing chronic liver diseases caused by hepatitis B virus (HBV) infection and COVID-19 has not been studied. We analysed 70 COVID-19 cases combined with HBV infection (CHI) to determine the epidemiological, clinical characteristics, treatment and outcome. We investigated clinical presentation, imaging and laboratory parameters of COVID-19 patients of seven hospitals from Jan 20 to March 20, 2020. Multivariate analysis was used to analyse risk factors for progression of patients with COVID-19 combined with HBV infection. Compared with COVID-19 without HBV infection (WHI) group, patients with dual infection had a higher proportion of severe/critically ill disease (32.86% vs. 15.27%, P = .000), higher levels of alanine aminotransferase (ALT), aspartate transaminase (AST) and activated partial thromboplastin (APTT) [50(28-69)vs 21(14-30), P = .000; 40(25-54) vs 23(18-30), P = .000; 34.0(27.2-38.7) vs 37.2(31.1-41.4), P = .031]. The utilization rates of Arbidol and immunoglobulin were significantly higher than those in the co-infected group [48.57% vs. 35.64%, P < .05; 21.43% vs. 8.18%, P < .001], while the utilization rate of chloroquine phosphate was lower (1.43% vs 14.00%, P < .05) in the co-infected patients group. Age and c-reactive protein (CRP) level were independent risk factors for recovery of patients with COVID-19 combined with HBV infection. The original characteristics of COVID-19 cases combined with HBV infection were higher rate of liver injury, coagulation disorders, severe/critical tendency and increased susceptibility. The elderly and patients with higher level of CRP were more likely to experience a severe outcome of COVID-19.

Clinical characteristics of asymptomatic carriers of novel coronavirus disease 2019: A multi-center study in Jiangsu Province.

Asymptomatic SARS-CoV-2-infected individuals are thought to play major roles in virus transmission. This study aimed to analyze the characteristics of asymptomatic carriers with COVID-19 to control the spread of the virus. We retrospectively investigated the clinical characteristics of 648 consecutive subjects who were enrolled in the study and were divided into asymptomatic carriers, mild cases, ordinary cases, severe or critical cases, and evaluated their impact on disease severity by means of Spearman correlation and multiple regression analyses. Receiver operating characteristic curve analysis was conducted to determine the optimum cutoff levels of laboratory findings for diagnostic predictors of asymptomatic carriers of COVID-19. In our study, a total of 648 subjects on admission with a mean age of 45.61 y including 345 males and 303 females were enrolled in our study. The leukocyte, lymphocyte, eosinophil, platelet, C-reactive protein, interleukin-6, CD3+, CD4+, and CD8 + T lymphocyte levels, and the erythrocyte sedimentation rate differed significantly among the groups (all p ≤ 0.05). Disease severity was negatively associated with the CD3+ (r = -0.340; p < 0.001), CD4+ (r = -0.290; p = 0.001) and CD8+ (r = -0.322; p < 0.001) T lymphocyte levels. The significant diagnostic predictors of asymptomatic carriers of COVID-19 included the blood cell, cytokine, and T lymphocyte subset levels. Inflammation and immune response may play important roles in disease progression. Hence, the laboratory parameters identified should be considered in clinical practice, which provide new insights into the identification of asymptomatic individuals and the prevention of virus transmission.

Clinical Characteristics and Predictors of Disease Progression in Severe Patients with COVID-19 Infection in Jiangsu Province, China: A Descriptive Study.

BACKGROUND: We studied patients with coronavirus disease 2019 (COVID-19) infected by severe acute respiratory syndrome coronavirus 2, a virus that originated in Wuhan, China, and is spreading over the country including Jiangsu Province. We studied the clinical characteristics and therapies of severe cases in Jiangsu Province. METHODS: A multicenter retrospective cohort study was conducted to analyze clinical, laboratory data and treatment of 60 severe cases with COVID-19 infection in Jiangsu Province between January 24, 2020 and April 20, 2020. The improvement and deterioration subgroups were compared to identify predictors of disease progression. RESULTS: A total of 653 infected cases with COVID-19 were reported in Jiangsu Province, of which 60 severe cases were included in this study. Up until April 20, 2020, the mortality of severe patients was 0%. The median age was 57 years. The average body mass index of these patients was 25 kg/m². White blood cell counts decreased in 45.0% of patients, lymphopenia in 63.3%, thrombocytopenia in 13.3% and procalcitonin levels in 88.3% of the patients were less than 0.5 ng/mL. There were no statistically significant differences in immunoglobulin therapy and GCs therapy between the improvement and deterioration subgroups. Logistic regression analysis identified higher levels of troponin T (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.00-1.08; P = 0.04), antiviral therapy with aerosol inhalation of interferon (OR: 6.33; 95% CI: 1.18-33.98; P = 0.03), and the application of non-invasive mechanical ventilation (OR: 1.99; 95%CI: 1.17-3.41; P = 0.01) as predictors of disease progression, whereas higher lymphocyte count (OR: 0.11; 95% CI: 0.02-0.57; P = 0.01) and early prone ventilation were associated with improvement (OR: 0.11; 95% CI: 0.01-0.98; P = 0.04). CONCLUSIONS: COVID-19 infection had a low mortality rate in Jiangsu Province, China. The higher levels of troponin T and lower lymphocyte count were predictors of disease progression. Early prone ventilation may be an effective treatment for severe cases.