Clinical and antibody characteristics reveal diverse signatures of severe and non-severe SARS-CoV-2 patients.

BACKGROUND: COVID-19 pandemic continues, clarifying signatures in clinical characters and antibody responses between severe and non-severe COVID-19 cases would benefit the prognosis and treatment. METHODS: In this study, 119 serum samples from 37 severe or non-severe COVID-19 patients from the First People's Hospital of Yueyang were collected between January 25 and February 18 2020. The clinical features, antibody responses targeting SARS-CoV-2 spike protein (S) and its different domains, SARS-CoV-2-specific Ig isotypes, IgG subclasses, ACE2 competitive antibodies, binding titers with FcγIIa and FcγIIb receptors, and 14 cytokines were comprehensively investigated. The differences between severe and non-severe groups were analyzed using Mann-Whitney U test or Fisher's exact test. RESULTS: Severe group including 9 patients represented lower lymphocyte count, higher neutrophil count, higher level of LDH, total bile acid (TBA) (P < 1 × 10-4), r-glutaminase (P = 0.011), adenosine deaminase (P < 1 × 10-4), procalcitonin (P = 0.004), C-reactive protein (P < 1 × 10-4) and D-dimer (P = 0.049) compared to non-severe group (28 patients). Significantly, higher-level Igs targeting S, different S domains (RBD, RBM, NTD, and CTD), FcγRIIa and FcγRIIb binding capability were observed in a severe group than that of a non-severe group, of which IgG1 and IgG3 were the main IgG subclasses. RBD-IgG were strongly correlated with S-IgG both in severe and non-severe group. Additionally, CTD-IgG was strongly correlated with S-IgG in a non-severe group. Positive RBD-ACE2 binding inhibition was strongly associated with high titers of antibody (S-IgG1, S-IgG3, NTD-IgG, RBD-IgA, NTD-IgA, and CTD-IgA) especially RBD-IgG and CTD-IgG in the severe group, while in the non-severe group, S-IgG3, RBD-IgG, NTD-IgG, and NTD-IgM were correlated with ACE2 blocking rate. S-IgG1, NTD-IgM and S-IgM were negatively associated with illness day in a severe group, while S-IgG3, RBD-IgA, CTD-IgA in the severe group (r = 0.363, P = 0.011) and S-IgG1, NTD-IgA, CTD-IgA in the non-severe group were positively associated with illness day. Moreover, GRO-α, IL-6, IL-8, IP-10, MCP-1, MCP-3, MIG, and BAFF were also significantly elevated in the severe group. CONCLUSION: Antibody detection provides important clinical information in the COVID-19 process. The different signatures in Ig isotypes, IgG subclasses, antibody specificity between the COVID-19 severe and non-severe group will contribute to future therapeutic and preventive measures development.

Single Nucleotide Polymorphisms of Paclitaxel-induced Peripheral Sensory Neuropathy in Chinese Han Population.

Objective To study the single nucleotide polymorphisms (SNPs)that predict a patient's risk of grade 2-3 paclitaxel-induced peripheral sensory neuropathy (PSN) in Chinese Han populations.Methods Totally 216 patients received paclitaxel in Peking Union Medical College Hospital from May 2014 to December 2016 were enrolled.DNA was isolated from peripheral blood.Genotyping for eight candidate SNPs was performed on Sequenom-MassARRARYiPLEX platform.Patients were followed up and PSN was assessed by trained physicians according to National Cancer Institute-Common Terminology Criteria for Adverse Events v4.03.Results A total of 209 patients entered the final analysis.Among the candidate SNPs,only rs4141404:A>C(LIMK2) was significantly associated with grade 2/3 PSN (OR:4.32,95%CI:2.37-7.89,P<0.0001).In multivariate logistic regression analysis,both rs4141404:A>C(LIMK2) and history of receiving platinum compound (OR:2.70,95%CI:1.32-5.51,P=0.007) were associated with grade 2/3 PSN.Conclusion rs4141404:A>C(LIMK2) may be the markers of risk of grade 2/3 PSN.

Consequences of cps mutation of Klebsiella pneumoniae on 1,3-propanediol fermentation.

The filtration in 1,3-propanediol (1,3-PD) downstream process is influenced by the large amounts of capsular polysaccharides (CPS) produced by Klebsiella pneumoniae CGMCC 1.6366. The morphological and fermentation properties were investigated with the CPS-deficient mutant K. pneumoniae CGMCC 1.6366 CPS. Similar biomass was obtained with CGMCC 1.6366, and the mutant strain in batch cultures indicating the cell growth was slightly inhibited by CPS defection. The viscosity of fermentation broth by mutant strain decreased by 27.45%. The flux with ceramic membrane filter was enhanced from 168.12 to 303.6 l h(-1) m(-2), exhibiting the great importance for downstream processing of 1,3-PD fermentation. The products spectrum of mutant isolate changed remarkably regarding to the concentration of fermentation products. The synthesis of important 1,3-PD and 2,3-butanediol was enhanced from 9.73 and 4.06 g l(-1) to 10.37 and 4.77 g l(-1) in batch cultures. The noncapsuled K. pneumoniae provided higher 1,3-PD yield of 0.54 mol mol(-1) than that of encapsuled wild parent in batch cultures. The fed-batch fermentation of mutant strain resulted in 1,3-PD concentration, yield, and productivity of 78.13 g l(-1), 0.53 mol mol(-1), and 1.95 g l(-1) h(-1), respectively.