mRNA vaccine-induced SARS-CoV-2-specific T cells recognize B.1.1.7 and B.1.351 variants but differ in longevity and homing properties depending on prior infection status

While mRNA vaccines are proving highly efficacious against SARS-CoV-2, it is important to determine how booster doses and prior infection influence the immune defense they elicit, and whether they protect against variants. Focusing on the T cell response, we conducted a longitudinal study of infection-naive and COVID-19 convalescent donors before vaccination and after their first and second vaccine doses, using a high-parameter CyTOF analysis to phenotype their SARS-CoV-2-specific T cells. Vaccine-elicited spike-specific T cells responded similarly to stimulation by spike epitopes from the ancestral, B.1.1.7 and B.1.351 variant strains, both in terms of cell numbers and phenotypes. In infection-naive individuals, the second dose boosted the quantity and altered the phenotypic properties of SARS-CoV-2-specific T cells, while in convalescents the second dose changed neither. Spike-specific T cells from convalescent vaccinees differed strikingly from those of infection-naive vaccinees, with phenotypic features suggesting superior long-term persistence and ability to home to the respiratory tract including the nasopharynx. These results provide reassurance that vaccine-elicited T cells respond robustly to emerging viral variants, confirm that convalescents may not need a second vaccine dose, and suggest that vaccinated convalescents may have more persistent nasopharynx-homing SARS-CoV-2-specific T cells compared to their infection-naive counterparts.

Distinctive features of SARS-CoV-2-specific T cells predict recovery from severe COVID-19

Although T cells are likely players in SARS-CoV-2 immunity, little is known about the phenotypic features of SARS-CoV-2-specific T cells associated with recovery from severe COVID-19. We analyzed T cells from longitudinal specimens of 34 COVID-19 patients with severities ranging from mild (outpatient) to critical culminating in death. Relative to patients that succumbed, individuals that recovered from severe COVID-19 harbored elevated and increasing numbers of SARS-CoV-2-specific T cells capable of homeostatic proliferation. In contrast, fatal COVID-19 displayed elevated numbers of SARS-CoV-2-specific regulatory T cells and a time-dependent escalation in activated bystander CXCR4+ T cells. Together with the demonstration of increased proportions of inflammatory CXCR4+ T cells in the lungs of severe COVID-19 patients, these results support a model whereby lung-homing T cells activated through bystander effects contribute to immunopathology, while a robust, non-suppressive SARS-CoV-2-specific T cell response limits pathogenesis and promotes recovery from severe COVID-19. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=197 SRC="FIGDIR/small/21250054v2_ufig1.gif" ALT="Figure 1"> View larger version (73K): org.highwire.dtl.DTLVardef@c82ec8org.highwire.dtl.DTLVardef@778d7forg.highwire.dtl.DTLVardef@ea9130org.highwire.dtl.DTLVardef@1e21805_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIDysfunctional spike-specific T cells are characteristic of severe COVID-19 C_LIO_LISpike-specific CD127+ Th1 cells are increased in survivors of severe COVID-19 C_LIO_LISpike-specific Tregs and IL6+ CD8+ T cells are increased in fatal COVID-19 C_LIO_LIEscalation of activated lung-homing CXCR4+ T cells associates with fatal COVID-19 C_LI BRIEF SUMMARYBy conducting CyTOF on total and SARS-CoV-2-specific T cells from longitudinal specimens spanning the entire spectrum of COVID-19 diseases, Neidleman et al. demonstrate that spike-specific Th1 cells capable of IL7-dependent homeostatic proliferation predict survival from severe COVID-19, while Tregs and IL6+ CD8+ T cells recognizing spike predict fatal outcome. Fatal COVID-19 is characterized by escalating activation of bystander CXCR4+ T cells in the lungs. Boosting SARS-CoV-2-specific CD4+ T effector responses while diminishing CXCR4-mediated homing may help recovery from severe disease.

SARS-CoV-2-specific T cells exhibit unique features characterized by robust helper function, lack of terminal differentiation, and high proliferative potential

Convalescing COVID-19 patients mount robust T cell responses against SARS-CoV-2, suggesting an important role for T cells in viral clearance. To date, the phenotypes of SARS-CoV-2-specific T cells remain poorly defined. Using 38-parameter CyTOF, we phenotyped longitudinal specimens of SARS-CoV-2-specific CD4+ and CD8+ T cells from nine individuals who recovered from mild COVID-19. SARS-CoV-2-specific CD4+ T cells were exclusively Th1 cells, and predominantly Tcm with phenotypic features of robust helper function. SARS-CoV-2-specific CD8+ T cells were predominantly Temra cells in a state of less terminal differentiation than most Temra cells. Subsets of SARS-CoV-2-specific T cells express CD127, can homeostatically proliferate, and can persist for over two months. Our results suggest that long-lived and robust T cell immunity is generated following natural SARS-CoV-2 infection, and support an important role for SARS-CoV-2-specific T cells in host control of COVID-19.

Establishment and preliminary mechanism study of the zebrafish strain of KIAA0196: A candidate pathogenic gene for heart development / 中南大学学报(医学版)

To explore the effects of KIAA0196 gene on cardiac development and the establishment of zebrafish strain.
 Methods: Peripheral blood and gDNA from patients were extracted. Copy number variation analysis and target sequencing were conducted to screen candidate genes. The KIAA0196 knockout zebrafish was generated by CRISPR/Cas9 to detect whether KIAA0196 deficiency could affect cardiac development. Finally, the wild-type and mutant zebrafish were anatomized and histologically stained to observe the phenotype of heart defects.
 Results: The KIAA0196 knockout zebrafish strain was successfully constructed using CRISPR/Cas9 technology. After 60 hours fertilization, microscopic examination of KIAA0196 knockout zebrafish (heterozygote + homozygote) showed pericardial effusion, cardiac compression and severely curly tail. Compared with wild-type zebrafish, the hearts of mutant KIAA0196 zebrafish had cardiac defects including smaller atrium and larger ventricle, and the myocardial cells were looser.
 Conclusion: KIAA0196 gene plays an important regulatory role in the development of heart. It might be a candidate gene for congenital heart disease.

Influence of different kinds of ovulation promotion scheme on clinical outcome of patients with IVF-ET/ICSI and POR / 中国医师进修杂志

Objective@#To investigate the influence of routine antagonist and optimization super-long termovulation promotion scheme on clinical outcome of patients with IVF-ET/ICSI and POR.@*Methods@#One hundred and thirty patients with IVF-ET/ICSI and POR were chosen in the period from October 2014 to May 2016 and randomly divided into two groups including control group (65 patients) with routine antagonist scheme and observation group (65 patients) with optimization super-long term scheme for ovulation promotion; and the number and total dose of Gn application, endometrium thickness and P levels in HCG day, the number of ovum retrieved, the incidence of premature LH peak, fertilization rate, quality embryo rate, cycle cancellation rate, implantation rate, clinical pregnancy rate, abortion rate and ectopic pregnancy rate of two groups were compared.@*Results@#The number and total doses of Gn application of observation group were significant higher than those of control group:(12.50 ± 1.78) d vs.(8.16 ± 1.25) d, (4 272.81 ± 547.95) U vs. (1 909.13 ± 341.48) U (P<0.05). The endometrium thickness and P levels in HCG day of observation group were significant lower than those of control group: (12.86 ± 1.39) mm vs. (10.08 ± 1.02) mm, (0.43 ± 0.17) nmol/L vs. (0.60 ± 0.22) nmol/L (P<0.05). There was no significant difference in the number of ovum retrieved, the incidence of premature LH peak and fertilization rate between two groups (P > 0.05). The quality embryo rate and cycle cancellation rate of observation group was significant lower than that of control group (P<0.05). The implantation rate and clinical pregnancy rate of observation group were significant higher than that of control group (P<0.05).There was no significant difference in the abortion rate and ectopic pregnancy rate between two groups (P > 0.05).@*Conclusions@#Compared with routine antagonist scheme, optimization super-long termscheme for ovulation promotion in the treatment of patients with IVF-ET/ICSI and POR can efficiently improve the ovulation effects and increase the long-term pregnancy rate, but has the higher overall treatment cost.

Comparative Study on Water Soluble Extract and Total Flavonoid Content between Jinzhen Suanzao Teabag and Decoction / 中国药房

OBJECTIVE:To compare the quality control index between Jinzhen Suanzao teabag and decoction,and explore the alternative supplement of teabag to decoction. METHODS:The test sample solutions of Jinzhen Suanzao teabag and decoction were prepared by hot-maceration method and water-decoction method. The contents of water soluble extract and total flavonoids were de-termined and compared between 2 kinds of preparation. The leaching rates of teabag were investigated at different soak time(0,5, 10,15,20,25,30 min) to optimize soaking time. RESULTS:The average content of water soluble extract were 50.56% and 44.45%(P<0.05) respectively for the teabag and decoction. The total flavonoids content were 0.64 mg/g and 0.69 mg/g (P<0.05). The dissolution amount of teabag were increasing and leaching rate increased within first 20 min,and reached balance gradu-ally 25 min later. CONCLUSIONS:According to the convenience of use and results of each index,the difference in quality control index is not great between 2 kinds of preparation. Teabag can be as the supplement of decoction.