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Elucidation the kinetics of neutralizing antibody response in the coronavirus disease 2019 (COVID-19) convalescents is crucial for the future control of the COVID-19 pandemic and vaccination strategies. Here we tested 411 sequential plasma samples collected up to 480 days post symptoms onset (d.a.o) from 214 convalescents of COVID-19 across clinical spectrum without re-exposure history after recovery and vaccination of SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. COVID-19 convalescents free of re-exposure and vaccination could maintain relatively stable anti-RBD IgG and MN titers during 400[~]480 d.a.o after the peak at around 120 d.a.o and the subsequent decrease. Undetectable neutralizing activity started to occur in mild and asymptomatic infections during 330 to 480 d.a.o with an overall rate of 14.29% and up to 50% for the asymptomatic infections. Significant decline in MN titers was found in 91.67% COVID-19 convalescents with [≥] 50% decrease in MN titers when comparing the available peak and current MN titers ([≥] 300 d.a.o). Antibody-dependent immunity could also provide protection against most of circulating variants after one year, while significantly decreased neutralizing activities against the Beta, Delta and Lambda variants were found in most of individuals. In summary, our results indicated that neutralizing antibody responses could last at least 480 days in most COVID-19 convalescents despite of the obvious decline of neutralizing activity, while the up to 50% undetectable neutralizing activity in the asymptomatic infections is of great concern.
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BackgroundSARS-CoV-2 could infect people at all ages, and the viral shedding and immunological features of children COVID-19 patients were analyzed. MethodsEpidemiological information and clinical data were collected from 35 children patients. Viral RNAs in respiratory and fecal samples were detected. Plasma of 11 patients were collected and measured for 48 cytokines. Results40% (14/35) of the children COVID-19 patients showed asymptomatic infections, while pneumonia shown by CT scan occurred in most of the cases (32/35, 91.43%). Elevated LDH, AST, CRP, neutropenia, leukopenia, lymphopenia and thrombocytopenia occurred in some cases, and CD4 and CD8 counts were normal. A total of 22 cytokines were significantly higher than the healthy control, and IP-10, IFN-2 of them in children were significantly lower than the adult patients. Meanwhile, MCP-3, HGF, MIP-1, and IL-1ra were similar or lower than healthy control, while significantly lower than adult patients. Viral RNAs were detected as early as the first day after illness onset (d.a.o) in both the respiratory and fecal samples. Viral RNAs decreased as the disease progression and mostly became negative in respiratory samples within 18 d.a.o, while maintained relatively stable during the disease progression and still detectable in some cases during 36~42 d.a.o. ConclusionCOVID-19 in children was mild, and asymptomatic infection was common. Immune responses were relatively normal in children COVID-19 patients. Cytokine storm also occurred in children patients, while much weaker than adult patients. Positive rate of viral RNAs in fecal samples was high, and profile of viral shedding were different between respiratory and gastrointestinal tract.
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The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report biomarkers that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, providing novel therapeutic targets and strategy.
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BackgroundThe novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated. MethodsA total of 173 patients with confirmed SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during the hospitalization period were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2 using immunoassays. The dynamics of antibodies with the progress and severity of disease was analyzed. ResultsAmong 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1% (161/173), 82.7% (143/173) and 64.7% (112/173), respectively. Twelve patients who had not seroconverted were those only blood samples at the early stage of illness were collected. The seroconversion sequentially appeared for Ab, IgM and then IgG, with a median time of 11, 12 and 14 days, respectively. The presence of antibodies was < 40% among patients in the first 7 days of illness, and then rapidly increased to 100.0%, 94.3% and 79.8% for Ab, IgM and IgG respectively since day 15 after onset. In contrast, the positive rate of RNA decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15 to 39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 patients (p < 0.001), even in early phase of 1-week since onset (p = 0.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (p = 0.006). ConclusionsThe antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.
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The novel coronavirus SARS-CoV-2, etiological agent of recently named Coronavirus infected disease (COVID-19) by WHO, has caused more than 2, 000 deaths worldwide since its emergency in Wuhan City, Hubei province, China, in December, 2019. The symptoms of COVID-19 varied from modest, mild to acute respiratory distress syndrome (ARDS), and the latter of which is generally associated with deregulated immune cytokine production; however, we currently know little as to the interplay between the extent of clinical symptoms and the compositions of lung immune microenvironment. Here, we comprehensively characterized the lung immune microenvironment with the bronchoalveolar lavage fluid (BALF) from 3 severe and 3 mild COVID-19 patients and 8 previously reported healthy lung controls through single-cell RNA sequence (scRNA-seq) combined with TCR-seq. Our data shows that monocyte-derived FCN1+ macrophages, whereas notFABP4+ alveolar macrophages that represent a predominant macrophage subset in BALF from patients with mild diseases, overwhelm in the severely damaged lungs from patients with ARDS. These cells are highly inflammatory and enormous chemokine producers implicated in cytokine storm. Furthermore, the formation of tissue resident, highly expanded clonal CD8+ T cells in the lung microenvironment of mild symptom patients suggests a robust adaptive immune response connected to a better control of COVID-19. This study first reported the cellular atlas of lung bronchoalveolar immune microenvironment in COVID-19 patients at the single-cell resolution, and unveiled the potential immune mechanisms underlying disease progression and protection in COVID-19. HighlightsO_LIImmune microenvironment of SARS-CoV-2-infected lungs revealed by scRNA/TCR seq C_LIO_LIIncreased inflammatory FCN1+ macrophages are replacing FABP4+ macrophages in the BALF from severe COVID-19 patients C_LIO_LIHighly expanded and functional competent tissue resident clonal CD8+ T cells in mild COVID-19 patients C_LI
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BackgroundThe outbreak of novel coronavirus pneumonia (NCP) caused by 2019-nCoV spread rapidly, and elucidating the diagnostic accuracy of different respiratory specimens is crucial for the control and treatment of this disease. MethodsRespiratory samples including nasal swabs, throat swabs, sputum and bronchoalveolar lavage fluid (BALF) were collected from Guangdong CDC confirmed NCP patients, and viral RNAs were detected using a CFDA approved detection kit. Results were analyzed in combination with sample collection date and clinical information. FindingsExcept for BALF, the sputum possessed the highest positive rate (74.4%[~]88.9%), followed by nasal swabs (53.6%[~]73.3%) for both severe and mild cases during the first 14 days after illness onset (d.a.o). For samples collected [≥] 15 d.a.o, sputum and nasal swabs still possessed a high positive rate ranging from 42.9%[~]61.1%. The positive rate of throat swabs collected [≥] 8 d.a.o was low, especially in samples from mild cases. Viral RNAs could be detected in all the lower respiratory tract of severe cases, but not the mild cases. CT scan of cases 02, 07 and 13 showed typical viral pneumonia with ground-glass opacity, while no viral RNAs were detected in first three or all the upper respiratory samples. InterpretationSputum is most accurate for laboratory diagnosis of NCP, followed by nasal swabs. Detection of viral RNAs in BLAF is necessary for diagnosis and monitoring of viruses in severe cases. CT scan could serve as an important make up for the diagnosis of NCP. FundingNational Science and Technology Major Project, Sanming Project of Medicine and China Postdoctoral Science Foundation.
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Objective To understand the efficacy of antiretroviral therapy for people living with HIV/AIDS and influencing factors;and provide evidence to improve the treatment of HIV infection and AIDS for the better life of the patients.Methods A cross sectional study was conducted in designated AIDS hospitals in Harbin.A questionnaire was used to collect the information of the patients receiving treatment in these hospitals.The statistical analysis was done with software SAS 9.2 and Excel 2010.Univariate analysis was performed with t test and multivariate analysis was performed with ordinal logistic regression model.Wilcoxon ranks sum test was conducted to compare the CD4+ T lymphocyte counts.Results The number of the patients receiving antiretroviral therapy was in increase in recent years.The HIV infection route was mainly homosexual contact.The CD4 +T lymphocyte count of the patients increased at different levels after ≥6 months treatment (P＜0.01).Household income (P＜0.05),adherence to treatment plan or not (P＜0.05),social relationship (P＜ 0.05),concern of economic cost (P＜0.01) medication compliance (P＜0.01) and initial level of CD4 + T lymphocyte (P＜0.01) were the influencing factors for antiretroviral therapy efficacy.Conclusion In designated hospitals in Harbin,the number of the patients receiving HIV antiretroviral therapy kept to increase and the efficacy of the treatment was obvious.
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Objective To understand the efficacy of antiretroviral therapy for people living with HIV/AIDS and influencing factors;and provide evidence to improve the treatment of HIV infection and AIDS for the better life of the patients.Methods A cross sectional study was conducted in designated AIDS hospitals in Harbin.A questionnaire was used to collect the information of the patients receiving treatment in these hospitals.The statistical analysis was done with software SAS 9.2 and Excel 2010.Univariate analysis was performed with t test and multivariate analysis was performed with ordinal logistic regression model.Wilcoxon ranks sum test was conducted to compare the CD4+ T lymphocyte counts.Results The number of the patients receiving antiretroviral therapy was in increase in recent years.The HIV infection route was mainly homosexual contact.The CD4 +T lymphocyte count of the patients increased at different levels after ≥6 months treatment (P＜0.01).Household income (P＜0.05),adherence to treatment plan or not (P＜0.05),social relationship (P＜ 0.05),concern of economic cost (P＜0.01) medication compliance (P＜0.01) and initial level of CD4 + T lymphocyte (P＜0.01) were the influencing factors for antiretroviral therapy efficacy.Conclusion In designated hospitals in Harbin,the number of the patients receiving HIV antiretroviral therapy kept to increase and the efficacy of the treatment was obvious.
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Objective To compare the dosimetric parameters of volumetric modulated arc therapy(VMAT),fixed field intensity modulated radiation therapy(IMRT)and three-dimensional conformal radiotherapy(3D-CRT)in the radiotherapy for the patients with locally recurrent nasopharyngeal carcinoma, and to analyze their characteristics. Methods Twelve patients with locally recurrent nasopharyngeal carcinoma were treated with VMAT, IMRT and 3D-CRT plan designed by Pinnacle 9.2 and Preciseplan 2.03 treatment planning system.The dosimetric parameters of targeted volumes and organs at risk were compared between three groups. Results The conformation indexes (CI)of VMAT and IMRT plans were similar,and they were both better than 3D-CRT plan,the difference was significant(P0.05).The monitor units(MU)and beam time in 3D-CRT group were better than those in other two groups,and VMRT group was better than IMRT group,the statistical differences were observed between three groups (P0.05).The doses of the spinal cord,optic nerve,optic chiasm and temporal lobe of brain in VMAT and IMRT groups were better than those in 3D-CRT group,there were statistical differences between them(P0.05).Conclusion There are differences of the targeted dose distribution between the three kinds of radiation technology, while VMAT and IMRT plans can cover the targeted areas and reduce the received doses of organs at risk.The CI,MU and beam time of VMAT plan are better than those of IMRT plan. 3D-CRT plan only has advantage in the MU and beam time.
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Objective To study the presence of drug resistant mutations of protease and reverse transcriptase among human immunodeficiency virus (HIV)-1 strains isolated from treatment naive HIV/ acquired immune deficiency syndrome (AIDS) patients in Heilongjiang Province of China and to provide the baseline data for starting antiretroviral therapy in this area. Methods The protease and reverse transcriptase gene sequences were amplified by nested-polymerase chain reaction (PCR) and then sequenced. The results were compared to the subtype B consensus amino acid sequence and analyzed with Stanford HIV-db drug resistance sequence interpretation. Results The results showed that HIV strains from 49 patients were classified as subtype B'. No primary mutations associated with protease inhibitor were detected. Some secondary mutations associated with protease inhibitor were detected, which included V77I(91.5%), L63P(76.6%), I93L(74.5%), E35D(61.7%), R57K (19.1%), R41K(10.6%), A71V(8.5%), M36I(8.5%), L10I(6.4%), D60E(6.4%), L89M (4.2%) and G16E(2. 1%). Only one case had a primary mutation M184I that was associated with resistance to reverse transcriptase inhibitors. However, many secondary mutations associated with resistance to reverse transcriptase inhibitors were found, including I135L/T/R/V(81.8%), V106I(22.7%), V179D/E(11.4%), R211K(9.1%), L214F(4.5%), V189I(4.5%) and V108I(2. 3%).Conclusions The prevalence of genotypic anti-HIV drug resistance is very low in treatment naive HIV/AIDS patients in Heilongjiang Province. However, closely monitoring on drug resistance mutation is very important for preventing the development and prevalence of multi-drug resistant or cross drug resistant HIV.
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Objective:To construct the eukaryotic expression vector of interleukin-18 gene and carry out analysis of pVAX1-IL-18 sequence . Methods:The recombinant eukaryotic expression vector pVAX1-IL-18 was constructed by inserting interleukin-18 gene into the eukaryotic expression vector pVAX1 with molecular cloning technique . It was confirmed by restrictive enzymes(BamHⅠ/ EcoRⅠ) digestion and analysis of DNA sequencing . Similar nucleotide sequences encoding IL-18 of pVAX1-IL-18 were looked up by Blast means in NCBI GenBank. Results:Restrictive enzymes digestion analysis and DNA sequencing results revealed that the interleukin-18 gene was cloned into the eukaryotic expression vector pVAX1 successfully .The sequence of encoding IL-18 of pVAX1-IL-18 was exactly the same as the reported sequence of encoding human IL-18 in GenBank . Conclusion: The recombinant eukaryotic expression vector pVAX1-IL-18 has been constructed successfully, which lay the foundation for pVAX1-IL-18 as a genetic adjuvant of DNA vaccine.
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OBJECTIVE To explore the antibiotic activity and changing trend of clinically isolated Pseudomonas aerginosa strains.METHODS The Drug-resistance of 485 clinically isolated to 18 kinds of common antibiotics P.aeruginosa strains was performed by Kirby-Bauer method.The drug sensitiveity test was indged based on the standard of the National Committee for Clinical Laboratory Standards(NCCLS) of the USA from 2004 to 2007.RESULTS Imipenem was sensitire against P.aeruginosa with the total drug-sensitivity rate of 80.8%.The resistance to cefazolin was high(0%).The sensitivity rate of P.aeruginosa was declining year by year.CONCLUSIONS It is very important to select antibiotics correctly according to the results of sensitivity tests.
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Objective To construct the nucleic acid vaccine(DNA vaccine) plasmid of the gag gene of the prevalent HIV-1 strains in China so as to develop a therapeutic AIDS vaccine against the HIV-1 strains, and to investigate the immune responses induced by HIV-1 DNA vaccine in mice. Methods The recombinant expression vector pCI-neo GAG was constructed by inserting HIV gag gene into the eukaryotic expression vector pCI-neo, which was identified by restrictive enzymes (Xba Ⅰ/Sal Ⅰ) digestion analysis and DNA sequencing. Balb/c mice were immunized with pCI-neo GAG or pCI-neo. Their sera were collected for the assay of the titer of anti-HIV antibody and IFN-? level by ELISA, and their splenic cells were isolated for detecting antigen-specific lymphoproliferative responses and specific cytotoxic T lymphocyte(CTL) response by MTT assay and LDH assay, respectively. Results Restrictive enzymes digestion analysis and DNA sequencing results revealed that the recombinant expression vector pCI-neo GAG had been constructed successfully. Both the anti-HIV antibody titer and the IFN-? level of mice immunized with the pCI-neo GAG were higher than those of mice immunized with pCI-neo (P
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The vitamin C content of dateplum persimmon's leaves (Diospyros lotus) collected and processed in some months (May, Jun., Aug., Sept. and Oct.) was determined. It was found that the amount of vitamin C in these products was 2045, 2540, 2650, 2680 and 310 mg per 100 gm respectively. They were all extremely rich in vitamen C and had an average about 2500 mg per 100 gm except that processed in Oct., of which the vitamin C content declined sharply.Observation on the stability of vitamin C in the products packed with several methods and stored in different conditions and durations showed that various environmental factors exerted a considerable influence on vitamin C retention to a certain extent, especially the sunlight and relative humidity which caused seri-ous damage. In general, the vitamin C retention of products packed with various methods were above 75% after two months of storage. Even when the Product was packed by plastic film bag and stored in ordinary condition, the remaining vitamin C was still above 800 mg per 100 gm after six months.After brewing of the product for 5-10 minutes just like making tea, the percentage of vitamin C extracted was about 75% in the first brewing and 11.5% in the second. The total amount of vitamin C extracted in two brews was about 85%.
