A spike-targeting bispecific T cell engager strategy provides dual layer protection against SARS-CoV-2 infection in vivo.

Neutralizing antibodies exert a potent inhibitory effect on viral entry; however, they are less effective in therapeutic models than in prophylactic models, presumably because of their limited efficacy in eliminating virus-producing cells via Fc-mediated cytotoxicity. Herein, we present a SARS-CoV-2 spike-targeting bispecific T-cell engager (S-BiTE) strategy for controlling SARS-CoV-2 infection. This approach blocks the entry of free virus into permissive cells by competing with membrane receptors and eliminates virus-infected cells via powerful T cell-mediated cytotoxicity. S-BiTE is effective against both the original and Delta variant of SARS-CoV2 with similar efficacy, suggesting its potential application against immune-escaping variants. In addition, in humanized mouse model with live SARS-COV-2 infection, S-BiTE treated mice showed significantly less viral load than neutralization only treated group. The S-BiTE strategy may have broad applications in combating other coronavirus infections.

Effects of psychosocial function in pediatric-onset inflammatory bowel disease during the coronavirus disease 2019 pandemic.

Background and Aims: Research on the effect of the coronavirus disease 2019 (COVID-19) pandemic on psychosocial function in patients with pediatric-onset inflammatory bowel disease (PIBD) is limited. This study aimed to evaluate the psychological status of patients with PIBD before and during the pandemic, and the relationship between mental health and disease activity. Methods: This study was a retrospective cohort study. Statistical analyses were performed to assess the relationship between demographic, clinical data and psychological data (questionnaires) of PIBD patients before and during the epidemic. The anxiety and depression emotional status of the guardians during the pandemic were evaluated. Results: In the PIBD follow-up cohort, 42 patients(male 61.9%) were included. Female with PIBD had lower pediatric quality of life inventory(PedsQL) scores (P = 0.007) and higher spence children's anxiety scale(SCAS) scores (P = 0.038) than male. The pandemic did not have a substantial impact on PedsQL, pittsburgh sleep quality index(PSQI), SCAS, or children's depression inventory(CDI) in patients with PIBD. The self-rating anxiety scale(SAS) score, anxiety rate, self-rating depression scale(SDS) score, and depression rate of PIBD guardians were significantly higher than those of healthy controls (SAS, P = 0.008; SDS, P = 0.001). Conclusions: Female children with PIBD were more vulnerable to decreased QOL and increased anxiety than male children. The anxiety and depression status of PIBD guardians were significantly higher than those of healthy controls during the COVID-19 pandemic. But the COVID-19 pandemic did not significantly affect quality of life(QOL), sleep, anxiety, or depressive mood of patients with PIBD in our study.

virusMED: an atlas of hotspots of viral proteins.

Metal binding sites, antigen epitopes and drug binding sites are the hotspots in viral proteins that control how viruses interact with their hosts. virusMED (virus Metal binding sites, Epitopes and Drug binding sites) is a rich internet application based on a database of atomic interactions around hotspots in 7041 experimentally determined viral protein structures. 25306 hotspots from 805 virus strains from 75 virus families were characterized, including influenza, HIV-1 and SARS-CoV-2 viruses. Just as Google Maps organizes and annotates points of interest, virusMED presents the positions of individual hotspots on each viral protein and creates an atlas upon which newly characterized functional sites can be placed as they are being discovered. virusMED contains an extensive set of annotation tags about the virus species and strains, viral hosts, viral proteins, metal ions, specific antibodies and FDA-approved drugs, which permits rapid screening of hotspots on viral proteins tailored to a particular research problem. The virusMED portal (https://virusmed.biocloud.top) can serve as a window to a valuable resource for many areas of virus research and play a critical role in the rational design of new preventative and therapeutic agents targeting viral infections.

Engineering mesenchymal stromal cells with neutralizing and anti-inflammatory capability against SARS-CoV-2 infection.

The emergence of the novel human severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the pandemic of coronavirus disease 2019 (COVID-19), which has markedly affected global health and the economy. Both uncontrolled viral replication and a proinflammatory cytokine storm can cause severe tissue damage in patients with COVID-19. SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as its entry receptor. In this study, we generated ACE2 extracellular domain-Fc and single-chain variable fragment-interleukin 6 (IL-6) single-chain variable fragment against IL-6 receptor (scFv-IL6R)-Fc fusion proteins to differentially neutralize viruses and ameliorate the cytokine storm. The human ACE2 (hACE2)1-740-Fc fusion protein showed a potent inhibitory effect on pseudo-typed SARS-CoV-2 entry and a good safety profile in mice. In addition, scFv-IL6R-Fc strongly blocked IL-6 signal activation. We also established a mesenchymal stromal cell (MSC)-based hACE21-740-Fc and scFv-IL6R-Fc delivery system, which could serve as a potential therapy strategy for urgent clinical needs of patients with COVID-19.

The effect of sociodemographic factors on COVID-19 incidence of 342 cities in China: a geographically weighted regression model analysis.

BACKGROUND: Since December 2019, the coronavirus disease 2019 (COVID-19) has spread quickly among the population and brought a severe global impact. However, considerable geographical disparities in the distribution of COVID-19 incidence existed among different cities. In this study, we aimed to explore the effect of sociodemographic factors on COVID-19 incidence of 342 cities in China from a geographic perspective. METHODS: Official surveillance data about the COVID-19 and sociodemographic information in China's 342 cities were collected. Local geographically weighted Poisson regression (GWPR) model and traditional generalized linear models (GLM) Poisson regression model were compared for optimal analysis. RESULTS: Compared to that of the GLM Poisson regression model, a significantly lower corrected Akaike Information Criteria (AICc) was reported in the GWPR model (61953.0 in GLM vs. 43218.9 in GWPR). Spatial auto-correlation of residuals was not found in the GWPR model (global Moran's I = - 0.005, p = 0.468), inferring the capture of the spatial auto-correlation by the GWPR model. Cities with a higher gross domestic product (GDP), limited health resources, and shorter distance to Wuhan, were at a higher risk for COVID-19. Furthermore, with the exception of some southeastern cities, as population density increased, the incidence of COVID-19 decreased. CONCLUSIONS: There are potential effects of the sociodemographic factors on the COVID-19 incidence. Moreover, our findings and methodology could guide other countries by helping them understand the local transmission of COVID-19 and developing a tailored country-specific intervention strategy.

Epidemic characteristics of close contacts of coronavirus disease 2019 in Xi'an

Objective To explore the epidemic characteristics of close contacts of corona virus disease 2019(COVID-19) in Xi'an so as to provide reference for further prevention and control of the epidemic. Methods Data of the close contacts of COVID-19 in Xi'an was collected. We analyzed the distribution of close contacts in the population and isolation measures of close contacts and confirmed cases among different exposure conditions. Results By 0: 00 February 28, the cumulative number of confirmed cases and close contacts in Xi'an had been 120 and 5 241, respectively.Medical workers accounted for 7.92% of the close contacts. Across different age groups, the proportion of the youth group was the highest (56%). Indifferent areas of Xi'an, Yanta District had the largest number of close contacts(913) while Huyi District had the lowest number (29). The main contact route was contact within the family (1 875). The majority of the confirmed cases were infected within the family (35), followed by shopping places (26). Conclusion By 0: 00 February 28, close contacts of COVID-19 in Xi'an had mostly been found in Yanta District. The young constituted the main group, and close contacts within the family had a high risk of infection. In view of the above characteristics, it is necessary to improve the screening of people having close contact with COVID-19 in key areas and populations.