Performances of Clinical Characteristics and Radiological Findings in Identifying COVID- 19 From Suspected Cases (preprint)

Background: To identify effective factors and establish a model to distinguish COVID-19 patients from suspected cases. Methods: : The clinical characteristics, laboratory results and initial chest CT findings of suspected COVID-19 patients in 3 institutions were retrospectively reviewed. Univariate and multivariate logistic regression were performed to identify significant features. A nomogram was constructed, with calibration validated internally and externally. Results: : 239 patients from 2 institutions were enrolled in the primary cohort including 157 COVID-19 and 82 non-COVID-19 patients. 11 features were included for multivariate logistic regression analysis after LASSO selection. We found that the COVID-19 group are more likely to have fever (OR, 4.22), contact history (OR, 284.73), lower WBC count (OR, 0.63), left lower lobe involvement (OR, 9.42), multifocal lesions (OR, 8.98), pleual thickening (OR, 5.59), peripheral distribution (OR, 0.09), and less mediastinal lymphadenopathy (OR, 0.037). The nomogram developed accordingly for clinical practice showed satisfactory internal and external validation. Conclusions: : In conclusion, fever, contact history, decreased WBC count, left lower lobe involvement, pleural thickening, multifocal lesions, peripheral distribution and absence of mediastinal lymphadenopathy are able to distinguish COVID-19 patients from other suspected patients. The corresponding nomogram is a useful tool in clinical practice.

Cerebral Micro-Structural Changes in COVID-19 Patients: An MRI-Based Preliminary Study (preprint)

Background: Increasing evidence supported the possible neuro-invasion potential of SARS-CoV-2. However, no studies were conducted to explore the existence of the structural changes in the neurological system after infection. We aimed to identify the existence of potential brain structural changes related to SARS-CoV-2. Methods: In this prospective study, diffusion tensor imaging (DTI) and 3D high-resolution T1WI sequences were acquired in 48 recovered COVID-19 patients (60.42% male; mean age=47.81 ± 19.51) and 31 age-matched healthy controls (29.03% male; age=43.45 ± 13.6). Registered fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) were quantified for DTI, and a brain score system was introduced. Voxel-based Morphometry (VBM) and DTI metrics were compared using ANCOVA. Independent t-test and Spearman correlation were conducted to assess the relationships among imaging indices, brain scores and clinical information. Findings: COVID-19 patients had higher gray matter volumes (GMV) in hippocampus and Heschl’s gyrus, and higher white matter volumes (WMV) in corona radiata and tapetum. The left paracentral lobule was found to have significantly lower FA, higher MD, AD and RD values when compared with healthy controls. COVID-19 patients also had lower global MD and RD values, as well as lower brain scores of FA-GM, MD-GM, and MD-WM. MD values in the right corona radiata and external capsule were positively related to LDH level (r = 0.428, 0.417). Interpretation: Study findings reveal possible disruption to micro-structural and functional brain integrity in the recovery stages of COVID-19, suggesting neuro-invasion potential of SARS-CoV-2. Funding: This project was supported by Shanghai Natural Science Foundation (Grant No. 18ZR1405700), Youth Program of National Natural Science Foundation of China (Fund No. 81901697), Shanghai Sailing Program (Grant No. 18YF1403000), Shanghai Science and Technology Development (Fund No. 19511121204), Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX01) and ZJ Lab.Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethics Approval Statement: This was a prospective study, which was approved by the local ethics committee (No.20200616017) and written informed consent was obtained from each participant.

Computational analysis on the ACE2-derived peptides for neutralizing the ACE2 binding to the spike protein of SARS-CoV-2 (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19, is spreading globally and has infected more than 3 million people. It has been discovered that SARS-CoV-2 initiates the entry into cells by binding to human angiotensin-converting enzyme 2 (hACE2) through the receptor binding domain (RBD) of its spike glycoprotein. Hence, drugs that can interfere the SARS-CoV-2-RBD binding to hACE2 potentially can inhibit SARS-CoV-2 from entering human cells. Here, based on the N-terminal helix 1 of human ACE2, we designed nine short peptides that have potential to inhibit SARS-CoV-2 binding. Molecular dynamics simulations of peptides in the their free and SARS-CoV-2 RBD-bound forms allow us to identify fragments that are stable in water and have strong binding affinity to the SARS-CoV-2 spike proteins. The important interactions between peptides and RBD are highlighted to provide guidance for the design of peptidomimetics against the SARS-CoV-2.

Computational simulations reveal the binding dynamics between human ACE2 and the receptor binding domain of SARS-CoV-2 spike protein (preprint)

A novel coronavirus (the SARS-CoV-2) has been identified in January 2020 as the causal pathogen for COVID-19 pneumonia, an outbreak started near the end of 2019 in Wuhan, China. The SARS-CoV-2 was found to be closely related to the SARS-CoV, based on the genomic analysis. The Angiotensin converting enzyme 2 protein (ACE2) utilized by the SARS-CoV as a receptor was found to facilitate the infection of SARS-CoV-2 as well, initiated by the binding of the spike protein to the human ACE2. Using homology modeling and molecular dynamics (MD) simulation methods, we report here the detailed structure of the ACE2 in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The predicted model is highly consistent with the experimentally determined complex structures. Plausible binding modes between human ACE2 and the RBD were revealed from all-atom MD simulations. The simulation data further revealed critical residues at the complex interface and provided more details about the interactions between the SARS-CoV-2 RBD and human ACE2. Two mutants mimicking rat ACE2 were modeled to study the mutation effects on RBD binding to ACE2. The simulations showed that the N-terminal helix and the K353 of the human ACE2 alter the binding modes of the CoV2-RBD to the ACE2.

Calibrated Intervention and Containment of the COVID-19 Pandemic (preprint)

Within a short period of time, COVID-19 grew into a world-wide pandemic. Transmission by pre-symptomatic and asymptomatic viral carriers rendered intervention and containment of the disease extremely challenging. Based on reported infection case studies, we construct an epidemiological model that focuses on transmission around the symptom onset. The model is calibrated against incubation period and pairwise transmission statistics during the initial outbreaks of the pandemic outside Wuhan with minimal non-pharmaceutical interventions. Mathematical treatment of the model yields explicit expressions for the size of latent and pre-symptomatic subpopulations during the exponential growth phase, with the local epidemic growth rate as input. We then explore reduction of the basic reproduction number R_0 through specific disease control measures such as contact tracing, testing, social distancing, wearing masks and sheltering in place. When these measures are implemented in combination, their effects on R_0 multiply. We also compare our model behaviour to the first wave of the COVID-19 spreading in various affected regions and highlight generic and less generic features of the pandemic development.