Immunities Specific to Both of the M Protein Ectodomain and RBD Synergize to Confer Cross-protection against SARS-CoV-2 Infections (preprint)

The effectiveness of the prototypic SARS-CoV-2 vaccine largely decreased overtime against the emerging virus strains, necessitating the universal vaccine development. The most abundant structural membrane (M) protein is highly conserved in amino acid sequence, which arouses our research interests in developing a universal immunogen based on it. Serological analysis showed that IgG responses specific to its N-terminal peptides can be strongly detected in many serum samples from both convalescent patients and vaccinees receiving inactivated vaccines, indicating the potential existence of human B-cell epitopes in reactive peptides. Microneutralization assays showed that the N-terminal peptide S2M2-30-specific hyperimmune serum was capable of cross-neutralizing the authentic viruses including wild-type HKU-001a, B.1.617.2/Delta, and Omicron subvariant BQ.1.1, and synergized with RBD-specific serum in reinforcing antiviral activities. Strong S2M2-30-specific immunities elicited in hACE2-transgenic mice could effectively inhibit B.1.1.7/Alpha (UK) infections. Our results suggest the potentiality of conserved M peptides as vaccine targets for conferring cross-protections against sarbecoviruses.

Mental health status of rural residents in Southwest Anhui province during prevention and control of coronavirus disease 2019

Objective: To explore the mental health status of rural residents in Southwest Anhui province and its influencing factors during the coronavirus disease 2019 (COVID-19) epidemic.

The point-of-care-testing of nucleic acids by chip, cartridge and paper sensors

ABSTRACT Point-of-care nucleic acid testing (POCNAT) has played an important role in the outbreak of infectious diseases (e.g., COVID-19) over recent years. POCNAT aims to realize the rapid, simple and automatic detection of nucleic acid. Thanks to the development of manufacturing technology, electronic information technology, artificial intelligence technology, and biological information technology in recent years, the development of the POCNAT device has led to significant advancement. Instead of the normal nucleic acid detection methods used in the laboratory, some novel experimental carriers have been applied, such as chips, cartridges and papers. The application of these experimental carriers has realized the automation and integration of nucleic acid detection. The entire process of nucleic acid detection is normally divided into three steps (nucleic acid extraction, target amplification and signal detection). All of the reagents required by the process can be pre-stored on these experimental carriers, without unnecessary manual operation. Furthermore, all of the processes are carried out in this experimental carrier, with the assistance of a specific control device. Although they are complicated to manufacture and precise in design, their application provides a significant step forwards in nucleic acid detection and realizes the integration of nucleic acid detection. This technology has great potential in the field of point-of-care molecular diagnostics in the future. This paper focuses on the relevant content of these experimental carriers.

The Cardiac Injury in Hospitalized Patients with Severe COVID-19 in Wuhan, China (preprint)

Background: The Coronavirus disease 2019 (COVID-19) has caused a global pandemic since December 2019, while the date on the relationship between cardiac injury and mortality in patients with COVID-19 is limited.Methods: All consecutive lab-confirmed critically ill COVID-19 patients in intensive care unit of Wuhan Red Cross Hospital from December 30, 2019 to March 18, 2020, were enrolled. Data of patients were collected. The prevalence of cardiac injury and its association with in-hospital mortality was analyzed.Results: Among the 50 ICU patients, 36 patients (72.0%) were complicated with cardiac injury and 14 patients (28.0%) without cardiac injury. Patients with cardiac injury had higher white blood cell counts, values of d-dimer, levels of lactate concentration, APACHE II score and lower PaO2/FiO2 at the time of admission than those without cardiac injury. The in-hospital case fatality ratio was higher in the cardiac injury than non-cardiac injury group (75.0% vs 21.4%;p=0.002).Multivariable-adjusted logistic proportional hazard regression analysis showed that a significantly higher risk of death in patients with cardiac injury than those without cardiac injury (OR, 5.876; 95% CI, 1.039–33.228).Conclusions: Cardiac injury is a common compilation and associated with higher risk of in-hospital death in patients with severe COVID-19. 

SARS-CoV-2 Spike Glycoprotein Receptor Binding Domain is Subject to Negative Selection with Predicted Positive Selection Mutations (preprint)

COVID-19 is a highly contagious disease caused by a novel coronavirus SARS-CoV-2. The interaction between SARS-CoV-2 spike protein and the host cell surface receptor ACE2 is responsible for mediating SARS-CoV-2 infection. By analyzing the spike-hACE2 interacting surface, we predicted many hot spot residues that make major contributions to the binding affinity. Mutations on most of these residues are likely to be deleterious, leading to less infectious virus strains that may suffer from negative selection. Meanwhile, several residues with mostly advantageous mutations have been predicted. It is more probable that mutations on these residues increase the transmission ability of the virus by enhancing spike-hACE2 interaction. So far, only a limited number of mutations has been reported in this region. However, the list of hot spot residues with predicted downstream effects from this study can still serve as a tracking list for SARS-CoV-2 evolution studies. Coincidentally, one advantageous mutation, p.476G>S, started to surge in the last couple of weeks based on the data submitted to the public domain, indicating that virus strains with increased transmission ability may have already spread.

Development and Evaluation of an AI System for COVID-19 (preprint)

Early detection of COVID-19 based on chest CT will enable timely treatment of patients and help control the spread of the disease. With rapid spreading of COVID-19 in many countries, however, CT volumes of suspicious patients are increasing at a speed much faster than the availability of human experts. We proposed an artificial intelligence (AI) system for fast COVID-19 detection and performed extensive statistical analysis of CTs of COVID-19 based on the AI system. We developed and evaluated our system on a large dataset with more than 10 thousand CT volumes from COVID-19, influenza-A/B, non-viral community acquired pneumonia (CAP) and non-pneumonia subjects. In such a difficult multi-class diagnosis task, our deep convolutional neural network-based system is able to achieve an area under the receiver operating characteristic curve (AUC) of 97.17%, a sensitivity of 90.19%, and a specificity of 95.76% for COVID-19 on internal test cohort of 3,203 scans and AUC of 97.77% on the publicly available CC-CCII database with 1,943 test samples. In a reader study involving five radiologists, the AI system outperforms all of radiologists in more challenging tasks at a speed of two orders of magnitude above them. Diagnosis performance of chest x-ray (CXR) is compared. Detailed interpretation of deep network is also performed to relate AI results with CT findings. The code is available at https://github.com/ChenWWWeixiang/diagnosis_covid19.

Nutritional and Metabolic Support and the Treatment Strategy of Severe Corona Virus Disease 2019 (COVID-19) / 中华急诊医学杂志

The digestive tract is a target organ attacked by COVID-19. It is also the earliest affected organ other than the lung and must bear side effects from the anti-virus chemotherapy such as LPV/r. In this article, we aim to provide practical recommendations for a nutritional and metabolic management strategy for severe corona virus disease-19 (COVID-19) patients. These recommendations are based on the newest pathophysiological findings on the risk factors of malnutrition for COVID-19. We also systematically retrieve literatures on nutritional therapy for acute lung injuries from international and Chinese databases according to evidence-based principles. Our suggestions are: 1) Physicians should be mindful of gut injury when they focus on respiratory support, by monitoring and managing the nutritional status; 2) Periodical and dynamic nutritional risk evaluation is needed; 3) For severe patients, the feeding target of calorie and protein should be down-regulated; 4)The using of ω-3 fatty acids products should be in accordance with pharmacological indications; the forms and dosage should be determined individually.