Antibody dynamics to SARS-CoV-2 in asymptomatic COVID-19 infections

Background

The missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic.

Measure

Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty-three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS-CoV-2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset.

Results

A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS-CoV-2. Different from strong and persistent N-specific antibodies, S1-specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months.

Conclusion

Our findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health, and immunization strategies.

     

股骨粗隆间骨折合并同侧股骨干骨折的手术治疗

目的探讨股骨粗隆间骨折合并同侧股骨干骨折的手术治疗方法及疗效。方法回顾分析我院自1998年1月至2005年12月收治股骨粗隆间骨折合并同侧股骨干骨折患者18例，全部病例均采用手术切开复位内固定，股骨粗隆间骨折应用动力髋内固定，股骨干骨折采用记忆合金环抱器内固定。结果术后随访2～8年，平均4．2年。全部病例均获骨性愈合，疗效满意。结论股骨粗隆间骨折合并同侧股骨干骨折在下肢骨折中相对较少，但处理较为复杂和困难，治疗有一定难度，使用动力髋与记忆合金环抱器同时进行内固定，方法简单，固定牢靠，患肢可早期进行功能锻炼，这种方法是治疗单侧肢体多处骨折较好的方法之一。     

椎间盘部分切除对腰椎应力分布影响的有限元分析

腰椎间盘突出症是骨科常见病之一。椎间盘切除术被广泛应用于本症的治疗。本文采用有限元素分析法观察了椎间盘部分切除前后腰椎应力分布的改变。本研究观察到,在正常情况下,椎体上下缘的中央部位承受较大的应力;椎间盘部分切除术后,椎体上下缘的侧方承采应力大于中央部分。这些结果表明,椎间盘部分切除术后可引起腰椎应力分布紊乱,出现应力集中,引起骨质增生,从而影响手术的远期疗效。     

110例癫痫患者24hAEEG临床应用报告

目的对１１０例癫痫患者的２４ｈ动态脑电图（ＡＥＥＧ）的应用价值进行了初步探讨。方法使用英国的ＯｘｆｏｒｄＭｅｄｉｌｏｇ９２００型８导磁带记录仪进行２４ｈ描记后作离线回放分析，并与普通ＥＥＧ相比较。结果１１０例中ＡＥＥＧ异常６２例（５６．４％），９８例中ＥＥＧ发现异常３２例（３２．７％）。ＥＥＧ正常而ＡＥＥＧ异常３０例，ＥＥＧ异常而ＡＥＥＧ正常９例。结论ＡＥＥＧ明显优于ＥＥＧ，但有时ＡＥＥＧ也不能捕获到间歇期的发作波。分析ＡＥＥＧ记录必需注意将睡眠Ⅰ、Ⅱ期出现的高幅顶尖波、纺锤波与痫样波区分开来，以免导致错误诊断。ＡＥＥＧ对颞叶和额叶底面的致痫灶反应较差，需补做特殊电极的ＥＥＧ，如蝶骨电极。     

Inactivation of Exonuclease 1 in mice results in DNA mismatch repair defects,increased cancer susceptibility,and male and female sterility

Exonuclease 1 (Exo1) is a 5'-3' exonuclease that interacts with MutS and MutL homologs and has been implicated in the excision step of DNA mismatch repair. To investigate the role of Exo1 in mammalian mismatch repair and assess its importance for tumorigenesis and meiosis, we generated an Exo1 mutant mouse line. Analysis of Exo1(-/-) cells for mismatch repair activity in vitro showed that Exo1 is required for the repair of base:base and single-base insertion/deletion mismatches in both 5' and 3' nick-directed repair. The repair defect in Exo1(-/-) cells also caused elevated microsatellite instability at a mononucleotide repeat marker and a significant increase in mutation rate at the Hprt locus. Exo1(-/-) animals displayed reduced survival and increased susceptibility to the development of lymphomas. In addition, Exo1(-/-) male and female mice were sterile because of a meiotic defect. Meiosis in Exo1(-/-) animals proceeded through prophase I; however, the chromosomes exhibited dynamic loss of chiasmata during metaphase I, resulting in meiotic failure and apoptosis. Our results show that mammalian Exo1 functions in mutation avoidance and is essential for male and female meiosis.     

<Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> Ats1p interacts with Nap1p,a cytoplasmic protein that controls bud morphogenesis

Saccharomyces cerevisiae ATS1 (-tubulin suppressor 1) was originally identified as a high-copy suppressor of class two -tubulin mutations and was proposed to have a regulatory role in coordinating the microtubule state with the cell cycle. Here, we show that Ats1p interacts with Nap1p, a cytoplasmic protein that regulates the activity of the Cdc28p/Clb2p complex. Loss of Nap1p results in a delayed switch from polar to isotropic bud growth. The delayed switch results in elongated buds. Nap1p and Ats1p interact in two-hybrid and co-immunoprecipitation assays. Both nap1 and ats1 cells have a Clb2p-dependent elongated bud morphology. Deletion of ATS1 partially suppresses the elongated bud morphology and benomyl resistance of nap1 mutants. Our results suggest Ats1p might regulate coordination of the microtubule state with the cell cycle through an interaction with Nap1p.Communicated by S. Hohmann     

乙/丙型肝炎病毒双重感染患者前C区终止变异低频率

目的了解乙型肝炎病毒（ＨＢＶ）与丙型肝炎病毒（ＨＣＶ）双重感染患者前Ｃ区基因变异，及其可能的临床意义。方法用聚合酶链反应（ＰＣＲ）与限制片段长度多态性（ＲＦＬＰ）来分析２５例ＨＢＶＤＮＡ和ＨＣＶＲＮＡ均阳性（Ａ组）和３１例ＨＢｓＡｇ和ＨＢＶＤＮＡ阳性但抗－ＨＣＶ和ＨＣＶＲＮＡ均阴性（Ｂ组）的慢性肝病患者前Ｃ区密码２８终止变异（终２８）。结果ＨＢＶ和ＨＣＶ双重感染患者（Ａ组）血清ＨＢＶＤＮＡ第１次ＰＣＲ阳性率（１６％）明显低于单独ＨＢＶ感染组（６５％）（Ｐ＜０．００１）；前Ｃ终２８检出率（２８％）亦明显低于单独ＨＢＶ感染（６８％）（Ｐ＜０．００１）。结论提示双重感染患者ＨＢＶ前Ｃ终止变异低频率可能与ＨＢＶ低水平复制有关     

Integrated medical informatics with small group teaching in medical education

National Taiwan University College of Medicine (NTUCM) introduced small groups of teaching and basic-clinical integrated courses for medical students in 1992. By using computer network and multimedia techniques, this study tried to overcome barriers to learning in small group teaching. The Department of Medical Informatics of NTUCM established campus networking and computer classrooms and provided Internet and intranet network services including mail, netnews, bulletin board systems (BBS), world wide web (WWW), gopher, ftp and local file servers. To implement an interactive learning environment, the authors first tried mail lists, newsgroups and BBS. Next an integrated learning system prototype on the WWW was developed to provide functions including online syllabus, discussion boards simulated to BBS, online talk, interactive case studies, virtual classroom with video on demand (VOD) and Internet medical resources. The results showed that after the medical students completed the required course of medical informatics and had good network access using a network to communicate with each other became a daily practice. In the future, the system will extend to the tutoring of clinical practice and continuing medical education. The authors expect a national medical education network and more international cooperation and exchange.     

双胎妊娠44例临床分析

本文对我院1990～1995年间44例双胎妊娠的分娩方式进行了分析。指出双胎妊娠由于胎位异常、产力异常及妊娠并发症多等因素,难产及手术产率均较单胎明显增高。在25例经阴道分娩的双胎中,阴道手术产率为64％,本组双胎剖宫产率为43.22％。本文认为双胎妊娠的分娩方式应掌握以下原则:当第一胎儿为臀泣、第二胎位为头位,尤其是胎儿较大、羊水较少时,应考虑剖宫产。而单纯的第二胎儿臀位可以经阴道分娩,不必常规剖宫产。     

CD1d-restricted natural killer T cells are potent targets for human immunodeficiency virus infection

Invariant human natural killer T cells (NKT) express a restricted T-cell receptor (TCR) Valpha24Vbeta11 repertoire. These cells share both phenotypic and functional similarities between NK and T cells. Given the emerging role of NKT cells as critical cells in bridging the gap between innate and adaptive immunity, we examined their susceptibility to productive human immunodeficiency virus (HIV) infection by T-tropic, M-tropic, and primary isolates of HIV. We generated three human NKT cell clones (CA5, CA29, and CA31). Phenotypic characterization of these Valpha24+ Vbeta11+ clones indicated that they were predominately positive for CD4, CD161, HLA-DR, CD38, CD45RO, and CD95 expression. The NKT cell clones expressed significantly more surface CCR5 molecules/cell and lower CXCR4 molecules/cell than phytohaemagglutinin-stimulated peripheral blood mononuclear cells (PBMC). Consistent with the surface expression of CCR5 and CXCR4, the NKT clones were also selectively susceptible to HIV M-tropic, T-tropic, and primary isolate infection, as evaluated by both HIV p24 enzyme-linked immunosorbent assay and intracellular staining of HIV proteins. The amount of p24 production was dependent on the NKT clone studied and the HIV strain used. Clones CA29 and CA31 were also susceptible to HIV IIIB infection. The virions produced by these clones were able to productively infect PHA-stimulated PBMCs with the same kinetics as for primary infection of CD4+ blast. Collectively, this data demonstrates that NKT cells can be a target for productive HIV infection but with a lag in the time to peak p24 production.