Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a new coronavirus causing Coronavirus Disease 2019 (COVID-19), is a major topic of global human health concern. The Delta and Omicron variants have caused alarming responses worldwide due to their high transmission rates and a number of mutations. During a one-year follow-up (from June 2020 to June 2021), we included 114 patients with SARS-CoV-2 infection to study the long-term dynamics and the correlative factors of neutralizing antibodies (NAbs) in convalescent patients. The blood samples were collected at two detection time points (at 6 and 12 months after discharge). We evaluated the NAbs response of discharged patients by performing a micro-neutralization assay using a SARS-CoV-2 wild type. In addition, a total of 62 serum samples from discharged COVID-19 patients with Alpha, Beta, Delta, and Omicron variants of infection were enrolled to perform cross-neutralization tests using the original SARS-CoV-2 strain and VOCs variants (including Alpha, Beta, Gamma, Delta, and Omicron variants) and to assess the ability of NAbs against the SARS-CoV-2 variants. NAbs seroconversion occurred in 91.46% of patients (n = 82) in the first timepoint and in 89.29% of patients (n = 84) in the second detection point, and three kinds of NAbs kinetics curves were perceived. The NAbs levels in young patients had higher values than those in elder patients. The kinetics of disease duration was accompanied by an opposite trend in NAbs levels. Despite a declining NAbs response, NAbs activity was still detectable in a substantial proportion of recovered patients one year after discharge. Compared to the wild strain, the Omicron strain could lead to a 23.44-, 3.42-, 8.03-, and 2.57-fold reduction in neutralization capacity in “SAlpha”, “SBeta”, “SDelta”, and “SOmicron”, respectively, and the NAbs levels against the Omicron strain were significantly lower than those of the Beta and Delta variants. Remarkably, the NAbs activity of convalescent serum with Omicron strain infection was most obviously detectable against six SARS-CoV-2 strains in our study. The role of the vaccination history in NAbs levels further confirmed the previous study that reported vaccine-induced NAbs as the convincing protection mechanism against SARS-CoV-2. In conclusion, our findings highlighted the dynamics of the long-term immune responses after the disappearance of symptoms and revealed that NAbs levels varied among all types of convalescent patients with COVID-19 and that NAbs remained detectable for one year, which is reassuring in terms of protection against reinfection. Moreover, a moderate correlation between the duration of disease and Nabs titers was observed, whereas age was negatively correlated with Nabs titers. On the other hand, compared with other VOCs, the Omicron variant was able to escape the defenses of the immune system more significantly, and the convalescent serum infected with the Omicron variant played a critical part in protection against different SARS-CoV-2 variants. Recovery serum from individuals vaccinated with inactivated vaccine preceding infection with the Omicron strain had a high efficacy against the original strain and the VOCs variants, whereas the convalescent serum of persons vaccinated by inactivated vaccine prior to infection with the Delta variant was only potent against the wild-type strain.

目的 对感染性腹泻样本进行检测鉴定,并对轮状病毒A组进行病毒分离,研究2019年广东省部分地区感染性腹泻病原学及轮状病毒分子流行病学特征.方法 2019年1月1日至2020年1月12日,采集广东省广州市、东莞市和江门市临床感染性腹泻患者粪便样本,进行多重RT-PCR扩增和微球杂交技术检测鉴定,并对轮状病毒A组阳性样本进行分离后,采用半巢式PCR试验对阳性细胞培养物进行G/P基因分型.结果 共纳入706例合格病例,病原体总检出率43.06％,病毒检出率18.13％高于细菌检出率8.36％高于寄生虫检出率1.27％.病毒病原谱以轮状病毒A组G9P[8]和诺如病毒GII型感染为主,细菌病原谱以沙门菌和艰难梭菌为主,寄生虫以蓝氏贾第鞭毛虫为首.不同季度、不同年龄组病原谱构成各不相同.轮状病毒A组主要受累群体为≤5岁儿童,主要时间分布于1-4月,基因型呈现多样性,包括G2P[4]、G3P[8]和G9P[8].结论 2019年广东省部分地区感染性腹泻病毒类病原体高于细菌类高于寄生虫类,轮状病毒A组G9P[8]、诺如GII型、沙门菌和蓝氏贾第鞭毛虫是最主要的病原体,且G9P[8]型A组轮状病毒毒株在轮状病毒感染中占主导趋势.在防控病毒性和细菌性腹泻的同时,应警惕寄生虫所致腹泻并重视混合感染的病原学监测.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus and its variants, has posed unprecedented challenges worldwide. Existing vaccines have limited effectiveness against SARS-CoV-2 variants. Therefore, novel vaccines to match mutated viral lineages by providing long-term protective immunity are urgently needed. We designed a recombinant adeno-associated virus 5 (rAAV5)-based vaccine (rAAV-COVID-19) by using the SARS-CoV-2 spike protein receptor binding domain (RBD-plus) sequence with both single-stranded (ssAAV5) and self-complementary (scAAV5) delivery vectors and found that it provides excellent protection from SARS-CoV-2 infection. A single-dose vaccination in mice induced a robust immune response; induced neutralizing antibody (NA) titers were maintained at a peak level of over 1:1024 more than a year post-injection and were accompanied by functional T-cell responses. Importantly, both ssAAV-and scAAV-based RBD-plus vaccines produced high levels of serum NAs against the circulating SARS-CoV-2 variants, including Alpha, Beta, Gamma and Delta. A SARS-CoV-2 virus challenge showed that the ssAAV5-RBD-plus vaccine protected both young and old mice from SARS-CoV-2 infection in the upper and lower respiratory tracts. Whole genome sequencing demonstrated that AAV vector DNA sequences were not found in the genomes of vaccinated mice one year after vaccination, demonstrating vaccine safety. These results suggest that the rAAV5-based vaccine is safe and effective against SARS-CoV-2 and several variants as it provides long-term protective immunity. This novel vaccine has a significant potential for development into a human prophylactic vaccination to help end the global pandemic.

目的 比较肺炎患者鼻咽拭子(nasopharyngeal swab,NPS)和支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)的病原学差异和诊断价值.方法 收集126例肺炎患者NPS及BALF,阵列qRT-PCR法检测42种病原体,进行多病原联合检测并进行分析.结果 126例患者BALF和NPS的病原阳性率分别为61.11％和46.03％,检出率差异均有统计学意义(x2=5.76,P＜0.05);BALF病毒检出率为33.53％,NPS病毒检出率为30.54％,差异无统计学意义(x2=0.12,P＞0.05),腺病毒(Adenovirus,AdV)检出一致性较好(Kappa=0.57);BALF与NPS的细菌检出率分别为35.71％和20.96％,二者检出率差异具有统计学意义(x2=7.08,P＜0.05),肺炎克雷伯菌(Klebsiella pneumoniae,K.P)的检出一致性较好(Kappa=0.61);BALF 中肺炎支原体(Mycoplasma pneumoniae,MP)检出率(8.73％)高于 NPS 检出率(1.58％),差异具有统计学意义(x2=6.57,P＜0.05).结论 NPS病原学检测可为肺炎诊断提供参考依据,NPS与BALF联合检测可提高病原检出率,增加诊断依据,但不认为NPS可以代替下呼吸道感染情况.推荐细菌性及支原体肺炎患者采集BALF检测病原,而病毒性肺炎患者可采集NPS进行病原检测.

目的 将从世界卫生组织发布的人兽共患病报告,以及PubMed、中国知网、和万方等数据库中检索到的全球自2016-2021年人感染H9N2的相关报道进行整理和汇总,再结合H9N2禽流感病毒的血清学监测结果对其感染人的风险进行评估,从基因学的角度探索H9N2禽流感病毒跨屏障感染人的原因.研究发现人感染H9N2禽流感的病例呈上升趋势,环境中和人群中的血清学监测结果也呈现较高的阳性率;H9N2禽流感病毒基因组中病毒表面结构蛋白血凝素基因突变和聚合酶基因突变对于其感染人具有重要意义.

Background: A lot of recent researches have focused on the duration of the nature immunity elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. An improved understanding of the immunity offered by the antibodies developed against SARS-CoV-2 in recovered patients is critical for the development of diagnostic tests and vaccines. Methods: We enrolled 114 donors, which providing blood samples after discharge for half a year and one year. Neutralizing antibodies (NAbs) were tested using a micro-neutralization assay. Results: In two tests, 82 of 114 recovered patients completed the first test half a year after discharge and NAbs remained detectable in the vast majority of patients (75/82, 91.46%). In the comparison of the two intervals, 50% (27/54) of individuals had increased NAbs titers. when 31.48% (17/54) of patients remained unchanged. Conclusion: Our results suggest that immune ability is acquired in most individuals infected with SARS-CoV-2 and is sustained in a majority of patients for up to a year after recovery.