ABSTRACT
With the prevalence of sequentially-emerged sublineages including BA.1, BA.2 and BA.5, SARS-CoV-2 Omicron infection has transformed into a regional epidemic disease. As a sublineage of BA.5, the BA.5.2.48 outbreak and evolved into multi-subvariants in China without clearly established virological characteristics, especially the pathogenicity. Though reduced airborne transmission and pathogenicity of former Omicron sublineages have been revealed in animal models, the virological characteristics of BA.5.2.48 was unidentified. Here, we evaluated the in vitro and in vivo virological characteristics of two isolates of the prevalent BA.5.2.48 subvariant, DY.2 and DY.1.1 (a subvariant of DY.1). DY.2 replicates more efficiently than DY.1.1 in HelahACE2+ cells and Calu-3 cells. The A570S mutation (of DY.1) in a normal BA.5 spike protein (DY.2) leads to a 20% improvement in the hACE2 binding affinity, which is slightly reduced by a further K147E mutation (of DY.1.1). Compared to the normal BA.5 spike, the double-mutated protein demonstrates efficient cleavage and reduced fusogenicity. BA.5.2.48 demonstrated enhanced airborne transmission capacity in hamsters than BA.2. The pathogenicity of BA.5.2.48 is greater than BA.2, as revealed in K18-hACE2 rodents. Under immune selection pressure, DY.1.1 shows stronger fitness than DY.2 in hamster turbinates. Thus the outbreaking prevalent BA.5.2.48 multisubvariants exhibites divergent virological features.
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Encephalitis, Arbovirus , SeizuresABSTRACT
Purpose To investigate the trends of myopia among primary and junior school students in the post-COVID-19 epidemic period. Method A prospective of cross-sectional study using spot photoscreenings in 123,538 children among primary and junior school students from 2019 to 2021 was conducted to evaluate the development of myopia in Xuzhou, China in the post-COVID-19 epidemic period. Equivalent refraction and the prevalence of myopia were recorded. Results The spherical equivalent refraction of myopia decreased across all grades except grade 1 (0.23 ± 0.56 D in 2019, 0.24 ± 0.63 D in 2020) from 2019 to 2020. However, refraction exhibited a hyperopic shift in 2021 compared to 2020 for grades 1–5 (no significant decreased for grade 4). The prevalence of myopia in all grades increased in 2020 compared to 2019, and the most dramatic changes were observed from grades 2–5 and grades 7–8 (P < 0.05). The changes in myopia prevalence in grades 1–4 were mild, and the reduction in myopia for Grade 5 is significant from 2020 to 2021. Nevertheless, students in grades 6 and 9 exhibited the greatest growth in myopia prevalence (P < 0.01). All grades had higher myopia prevalence in 2021 compared with 2019, except grade 1 (P = 0.25). The prevalence of myopia in girls was higher compared with boys, and the urban myopia prevalence was higher than in rural areas over the 3 years except in 2019 (P = 0.18). Conclusions The prevalence of myopia increased during the COVID-19 epidemic. However, the spherical equivalent refraction of lower grade children drifted to hyperopia and the trends of myopia development remained stable in the post-COVID-19 epidemic period. We should be more concerned about the prevalence of myopia in graduating for the primary or junior grades in the future.
ABSTRACT
Striking number of mutations found in the spike protein of recently emerged SARS-CoV-2 Omicron subvariants BA.1, BA.2, BA.3 and BA.4/5 has raised serious concerns regarding the escape from current antibody therapies and vaccine protection. Here, we conducted comprehensive analysis on the extent of two major Omicron lineages BA.1/BA.1.1 and BA.2 to escape neutralization from the therapeutic antibodies approved by the regulatory authorities and convalescent plasma from SARS-CoV-2 patients infected during initial wave of pandemic in early 2020. We showed that Omicron BA.1/BA.1.1 were the most resistant in both magnitude and breadth against antibodies and convalescent plasma, followed by Beta, BA.2, Gamma, Delta and Alpha. While the majority of therapeutic antibodies lost binding and neutralization to Omicron variants, BRII combo (BRII-196 + BRII-198), S309, and AZ combo (COV2-2196 + COV2-2130) maintained neutralization despite of reduction due to either conserved epitope or combinational effect between the two designated antibodies. A single intraperitoneal injection of BRII combo as a prophylactic treatment protected animals from Omicron infection. Treated animals manifested normal body weight, survived infection up to 14 days, undetectable levels of infectious viruses in the lungs, and reduced lung pathology compared to the controls. Analyzing ACE2 from diverse host species showed that Omicron variants acquired ability to use mouse ACE2 for entry. These results demonstrate major antigenic shifts and potentially broadening the host range of two major Omicron lineages BA.1/BA.1.1 and BA.2, posing serious challenges to current antibody therapies and vaccine protection as well as increasing danger of spillover into the wildlife.
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Food is the core of urban daily life and socio-economic activities but is rarely the focus of urban planning. The spatial layout of food retail outlets is important for optimizing the urban food system, improving land resource allocation, and encouraging healthy food consumption. Based on food retail POI data, this study employed kernel density estimation, road network centrality, spatial autocorrelation analysis, and locational entropy to analyze the spatial characteristics of supermarkets, produce markets, and small stores in an urban center in Beijing, and explored street coupling and supply-demand matching. The results indicated that within the study area: (1) supermarkets had an obvious “core-periphery” distribution, produce markets had a polycentric distribution, and small stores had a relatively uniform distribution;(2) road network centrality indices revealed a differentiated multi-core-edge distribution;(3) streets with high locational entropy values for supermarkets and produce markets were mostly concentrated in the central area, whereas the matching distribution of small stores was relatively balanced. From the perspective of urban planning, policy implications are proposed based on spatial and social equity, urban-rural differences, population structure and distribution status, and a resilient supply chain. The study findings have practical significance for guiding the development of urban food systems in a healthy, just, and sustainable direction, as well as rational urban land planning.
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当前2019冠状病毒病（COVID-19）疫情仍处于胶着状态。浙江大学医学院附属第一医院是国家感染性疾病临床医学中心，浙江省COVID-19患者救治中心。疫情一线的专家集智攻关，以国家卫生健康委员会和国家中医药管理局发布的COVID-19诊治指南为依据，以抗病毒、抗休克、抗低氧血症、抗继发感染、维持水电解质和酸碱平衡、维持微生态平衡的“四抗二平衡”救治策略为核心，总结完善诊治方案，聚焦临床实践的一些具体问题，为COVID-19患者临床诊治提供借鉴。推荐以多学科协作诊治个性化治疗提高COVID-19患者救治质量。建议病原学检测、炎症指标监测和肺部影像学动态观察指导临床诊治。痰液的病毒核酸检测阳性率最高，约10%的急性期患者血液中检测到病毒核酸，50%的患者粪便中检测到病毒核酸，粪便中可分离出活病毒，须警惕粪便是否具有传染性；开展细胞因子等炎症指标监测有助于发现是否出现细胞因子风暴，判断是否需要人工肝血液净化治疗。通过以“四抗二平衡”为核心的综合治疗提高治愈率、降低病死率；早期抗病毒治疗能减少重症、危重症发生，前期使用阿比多尔联合洛匹那韦/利托那韦抗病毒显示出一定效果。休克和低氧血症多为细胞因子风暴所致，人工肝血液净化治疗能迅速清除炎症介质，阻断细胞因子风暴，对维持水电解质酸碱平衡也有很好的作用，可以提高危重型患者的疗效。重型病例疾病早期可适量、短程应用糖皮质激素。氧疗过程中，患者氧合指数小于200 mmHg时应及时转入重症医学科治疗；采用保守氧疗策略，不推荐常规进行无创通气；机械通气患者应严格执行集束化呼吸机相关性肺炎预防管理策略；氧合指数大于150 mmHg时，及早减、停镇静剂并撤机拔管。不推荐预防性使用抗菌药物，对于病程长，体温反复升高和血降钙素原水平升高的患者可酌情使用抗菌药物；要关注COVID-19患者继发真菌感染的诊治。COVID-19患者有肠道微生态紊乱，肠道乳酸杆菌、双歧杆菌等有益菌减少，推荐对所有患者进行营养和胃肠道功能评估，以营养支持和补充大剂量肠道微生态调节剂，纠正肠道微生态失衡，减少细菌移位和继发感染。COVID-19患者普遍存在焦虑和恐惧心理，应建立动态心理危机干预和处理。提倡中西医结合辨证施治；优化重型患者护理促进康复。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染后病毒清除规律仍不明了，出院后仍须居家隔离2周，并定期随访。以上经验和建议在本中心实行，取得较好效果，但COVID-19是一种新的疾病，其诊治方案及策略仍有待进一步探索与完善。
ABSTRACT
Background and Objective: COVID-19 has struck our society as a great calamity, and the need for effective anti-viral drugs is more urgent than ever. Papain-like protease (PLpro) of SARS CoV-2 plays important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses, which is being regarded as a promising druggable target for the treatment of COVID-19. Here, we carried out a combined screening approach to identify novel and highly potent PLpro inhibitors for the treatment of COVID-19. Methods: We used a combined screening approach of structure-based pharmacophore modeling and molecular docking to screen an in-house database containing 35,000 compounds. SARS CoV-2 PLpro inhibition assay was used to carry out the biological evaluation of hit compounds. Molecular dynamics (MD) simulations were conducted to check the stability of the PLpro-hit complexes predicted by molecular docking. Results: We found that four hit compounds showed excellent inhibitory activities against PLpro with IC50 values ranging from 0.6 to 2.4 μM. Among them, the most promising compound, hit 2 is the best PLpro inhibitor and its inhibitory activity was about 4 times higher than that of the positive control (GRL0617). The study of MD simulations indicated that four hits could bind stably to the active site of PLpro. Further study of interaction analysis indicated that hit 2 could form hydrogen-bond interactions with the key amino acids such as Gln269 and Asp164 in the PLpro-active site. Conclusion: Hit 2 is a novel and highly potent PLpro inhibitor, which will open the way for the development of clinical PLpro inhibitors for the treatment of COVID-19.
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To observe lipid profiles and their alterations in hospitalized patients with COVID-19 pneumonia (NCP) and evaluate the value of lipids for the prediction of the length of hospital stay (LOS), a total of 248 patients aged 18 years or older were enrolled in this retrospective study. At admission, the median levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in all patients were 1.11, 4.00, 0.89, and 2.11 mmol/L, respectively. Compared with common cases (n = 174), severe cases (n = 74) exhibited higher TG and HDL-C, and lower LDL-C. Levels of TC and LDL-C were negatively correlated with LOS. In 68 severe cases, serum lipids were followed up during hospitalization, and the median LOS was 29 days. The average levels of serum lipids were lowest at admission and gradually increased during hospitalization. Compared with the LOS ≤ 29 days group, serum levels of TC, HDL-C, and LDL-C were significantly lower in the LOS > 29 days group at admission; this lower trend was found in the subsequent tests for TC and LDL-C but not for HDL-C or TG. Multiple-variant COX regression showed that levels of TC or LDL-C at admission were independent risk of LOS prolongation. Together, these findings suggest that in patients with NCP, levels of TC and LDL-C at admission were negatively correlated with LOS. In severe cases, the gradual increase in TC, LDL-C, and HDL-C during hospitalization might indicate gradual recovery. TC < 3.75 mmol/L or LDL-C < 1.7 mmol/L at admission may act as an independent predictor of prolonged LOS.
ABSTRACT
Background Recent studies have focused initial clinical and Epidemiologic characteristics on the COVID-19, mainly revealing situation in Wuhan, Hubei. Aim To reveal more data on the epidemiologic and clinical characteristics of COVID-19 patients outside of Wuhan, in Zhejiang, China. Design Retrospective case series. Methods 88 cases of laboratory-confirmed and 3 cases of clinical-confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020. Results Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2 while 3 (3.30%) were clinical-diagnosed COVID-19 cases. The median age of the patients was 50 (36.5-57) years, and female accounted for 59.34%. In this sample 40 (43.96%) patients had contracted the diseases from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, 8 (8.79%) cases had contacted with people from Wuhan, 11 (12.09%) cases were confirmed aircraft transmission. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (IQR, 3-8) days and the median time from first visit to a doctor to confirmed diagnosis was 1 (1-2) days. According to the Chest computed tomography scans, 67.03% cases had bilateral pneumonia. Conclusions Social activity cluster, family cluster and travel by airplane were how COVID-19 patients get transmitted and could be rapidly diagnosed COVID-19 in Zhejiang.