High-affinity binding to the SARS-CoV-2 spike trimer by a nanostructured, trivalent protein-DNA synthetic antibody (preprint)

Multivalency enables nanostructures to bind molecular targets with high affinity. Although antibodies can be generated against a wide range of antigens, their shape and size cannot be tuned to match a given target. DNA nanotechnology provides an attractive approach for designing customized multivalent scaffolds due to the addressability and programmability of the nanostructure shape and size. Here, we design a nanoscale synthetic antibody ("nano-synbody") based on a three-helix bundle DNA nanostructure with one, two, or three identical arms terminating in a mini-binder protein that targets the SARS-CoV-2 spike protein. The nano-synbody was designed to match the valence and distance between the three receptor binding domains (RBDs) in the spike trimer, in order to enhance affinity. The protein-DNA nano-synbody shows tight binding to the wild-type, Delta, and several Omicron variants of the SARS-CoV-2 spike trimer, with affinity increasing as the number of arms increases from one to three. The effectiveness of the nano-synbody was also verified using a pseudovirus neutralization assay, with the three-arm nanostructure inhibiting two Omicron variants against which the structures with only one or two arms are ineffective. The structure of the three-arm nano-synbody bound to the Omicron variant spike trimer was solved by negative-stain transmission electron microscopy reconstruction, and shows the protein-DNA nanostructure with all three arms attached to the RBD domains, confirming the intended trivalent attachment. The ability to tune the size and shape of the nano-synbody, as well as its potential ability to attach two or more different binding ligands, will enable the high-affinity targeting of a range of proteins not possible with traditional antibodies.

The Effect of Stress, Worries and Resilience on Sleep Quality of Chinese Population During the Normalization of COVID-19 Pandemic Prevention and Control (preprint)

Background: The COVID-19 pandemic has spread worldwide and has attracted considerable attention. This study aims to investigate the sleep quality of the public during the normalization of COVID-19 pandemic prevention and control in China, as well as related factors that affect sleep quality. Methods: : A web-based cross-sectional survey was implemented from Feb 2 nd to Feb 9 th , 2021 in China. A total of 613 subjects from 27 provinces and 4 municipalities participated in this study. Questionnaire including Pittsburgh Sleep Quality Index (PSQI), COVID Stress Scale (CSS), COVID-19 Worry Scale and 14-item Resilience Scale (the RS-14) as well as demographic characteristics and pandemic-related information was used to measure sleep quality, stress, worries and resilience of Chinese population. Hierarchical multiple regression analysis was conducted to explore the associated factors of sleep quality. Results: : The prevalence of poor sleep quality among 613 participants was 41.1% (95%CI=37.2%-45%). Regression analysis indicated that chronic diseases, medical visits, occupation, and negative life events were factors affecting sleep quality. Stress and worries were positively associated with score of sleep quality, while resilience was negatively associated with score of sleep quality. Conclusions: : During the normalization of COVID-19 pandemic prevention and control, Chinese public has poor sleep quality. Effective interventions should be taken to decrease people’s COVID-19 stress and worries. Resilience enhancement is also an important factor to be considered to improve people’s sleep quality.

Scoring Systems for Predicting Mortality for Severe Patients with COVID-19 (preprint)

Background: Coronavirus disease 2019 (COVID-19) has been widely spread and caused tens of thousands of deaths, mainly in patients with severe COVID-19.Methods: Patients with COVID-19 were retrospectively analyzed. Clinical characteristics were compared, and LASSO regression as well as multivariate analysis were used to screen variables and establish prediction model. Findings: A total of 2529 patients with COVID-19 was retrospectively analyzed, and 452 eligible severe COVID-19 were used for finally analysis. In training cohort, the median age was 66·0 years while it was 73·0 years in non-survivors. Patients aged 60-75 years accounted for the largest proportion of infected populations and mortality toll. Anti-SARS-CoV-2 antibodies were monitored up to 54 days, and IgG levels reached the highest during 20-30 days. About 60.2% of severe patients had complications. Acute myocardial injury was the earliest injured organ, whereas the time from acute kidney injury to death was the shortest. Age, diabetes, coronary heart disease (CHD), percentage of lymphocytes (LYM%), procalcitonin (PCT), serum urea, C reactive protein and D-dimer (DD), were identified associated with mortality by LASSO binary logistic regression. Then multivariate analysis was performed to conclude that old age, CHD, LYM%, PCT and DD remained independent risk factors for mortality. Based on the above variables, a scoring system of COVID-19 (CSS) was established and divided into low-risk and high-risk groups. This model displayed good discrimination (AUC=0·919) and calibration (P =0·264). The complications in low-risk and high-risk groups were significantly different. We also found that the use of corticosteroids in low-risk groups increased hospital stays by 4·5 days (P =0·036) and durations of disease by 7·5 days (P =0 · 012) compared with no corticosteroids.Interpretation: Old age, CHD, LYM%, PCT and DD were independently related to mortality. CSS was useful for predicting in-hospital mortality and complications, and it could help clinicians to identify high-risk patients with poor prognosis.Funding Statement: This work was supported by the Key Project for Anti-2019 novel Coronavirus Pneumonia from the Ministry of Science and Technology, China (grant number 2020YFC0845500). Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: This study was conducted according to the principles of Helsinki and approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (No.2020063).