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Recent studies have characterized the single-cell immune landscape of host immune response of coronavirus disease 2019 (COVID-19), specifically focus on the severe condition. However, the immune response in mild or even asymptomatic patients remains unclear. Here, we performed longitudinal single-cell transcriptome sequencing and T cell/B cell receptor sequencing on 3 healthy donors and 10 COVID-19 patients with asymptomatic, moderate, and severe conditions. We found asymptomatic patients displayed distinct innate immune responses, including increased CD56briCD16- NK subset, which was nearly missing in severe condition and enrichment of a new Th2-like cell type/state expressing a ciliated cell marker. Unlike that in moderate condition, asymptomatic patients lacked clonal expansion of effector CD8+ T cells but had a robust effector CD4+ T cell clonal expansion, coincide with previously detected SARS-CoV-2-reactive CD4+ T cells in unexposed individuals. Moreover, NK and effector T cells in asymptomatic patients have upregulated cytokine related genes, such as IFNG and XCL2. Our data suggest early innate immune response and type I immunity may contribute to the asymptomatic phenotype in COVID-19 disease, which could in turn deepen our understanding of severe COVID-19 and guide early prediction and therapeutics.
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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes a tremendous threat to global health. Although vaccines against the virus are under development, the antigen epitopes on the virus and their immunogenicity are poorly understood. Here, we simulated the three-dimensional structures of SARS-CoV-2 proteins with high performance computer, predicted the B cell epitopes on spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches, and then validated the epitope immunogenicity by immunizing mice. Almost all 33 predicted epitopes effectively induced antibody production, six of which were immunodominant epitopes in patients identified via the binding of epitopes with the sera from domestic and imported COVID-19 patients, and 23 were conserved within SARS-CoV-2, SARS-CoV and bat coronavirus RaTG13. We also found that the immunodominant epitopes of domestic SARS-CoV-2 were different from that of the imported, which may be caused by the mutations on S (G614D) and N proteins. Importantly, we validated that eight epitopes on S protein elicited neutralizing antibodies that blocked the cell entry of both D614 and G614 pseudo-virus of SARS-CoV-2, three and nine epitopes induced D614 or G614 neutralizing antibodies, respectively. Our present study shed light on the immunodominance, neutralization, and conserved epitopes on SARS-CoV-2 which are potently used for the diagnosis, virus classification and the vaccine design tackling inefficiency, virus mutation and different species of coronaviruses.
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Objective:To evaluate the relationship between 1233A/T polymorphism of proteasome subunit α type 6 (PSMA6) gene and cerebral infarction in Chinese Han population. Methods:From January, 2012 to April, 2015, 211 cerebral infarction patients (case group) and 201 healthy controls (control group) were selected in the study. The single nucleotide polymorphism of 1233A/T of PSMA6 gene was identified by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), and genotypes and allele frequency distributions in two groups were analyzed. Results:The frequencies of CC, CT+TT genetype and the C allele all revealed no significant difference between two groups (χ2 < 0.053, P > 0.05). After stratified by gender, the difference among all genetypes and C allele were still not significant between two groups in either male or female (χ2 < 2.735, P > 0.05). Conclusion:The 1233A/T of PSMA6 gene might not be associated with cerebral infarction.
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Objective To understand the drug resistance of Mycobacterium tuberculosis(MTB)and susceptibility of multidrug-resistant MTB(MDR-MTB)to linezolid in Hebei Province, so as to guiding clinical treatment of MDR tuberculosis.Methods The isolated strains and clinical information of patients with tuberculosis in 6 hospitals of 5 cities in Hebei Province between January and December 2016 were collected, susceptibility of MTB to antituberculous drugs isoniazid(INH), rifampicin(RFP), streptomycin(SM), ethambutol(EMB), ofloxacin(OFX), and kanamycin(KM)were detected, 100 strains of MDR-MTB were selected by stratified random sampling method, susceptibility to linezolid was detected.Results Drug resistance rate and MDR rate of the initially treated cases were 26.6％(200/753)and 13.5％(102/753)respectively, drug resistance rate and MDR rate of the retreatment cases were 59.7％(132/221)and 53.4(118/221)respectively, drug resistance rate and MDR rate of the retreatment cases were both statistically higher than initially treated cases(χ2=83.7, P＜0.01;χ2=93.5, P＜0.01).Resistance rates of MTB to first-line antituberculous drugs INH, RFP, SM, and EMB were 25.8％, 23.7％, 16.7％, and 7.1％ respectively, to second-line antituberculous drugs OFX and KM were 4.7％(37/782)and 4.0％(31/782)respectively; susceptibility of MDR-MTB to linezolid was 80.8％ (59/73).Conclusion Drug resistance rate and MDR rate of the retreated tuberculosis patients are higher than initially treated patients, linezolid has good in vitro antimicrobial activity against MDR-MTB.
