Analysis of Cognition, Protection, Psychological, and Job-search Intentions Among Medical and Nonmedical College Students During COVID-19 Epidemic.

Context: Since December 2019, medical practitioners discovered a novel coronavirus causing an acute respiratory-tract infection in some hospitals in Wuhan, Hubei Province. COVID-19 has spread globally, making it an epidemic worldwide at present. Understanding the mental-health responses of college students to COVID-19 can help a school staff to better guide students seeking education. Objective: The study aimed to explore the differences between nonmedical and medical college students during the COVID-19 epidemic in their cognitive interest about the disease, preventive behaviors, psychological effects, and job-search intentions, hoping to provide more targeted measures for virus-coping education for college students. Design: The research team conducted a cross-sectional study, using an anonymous online questionnaire. Setting: The study took place at Shanghai, China. Participants: Participants were 1648 college students studying different specialties in various provinces of China, 485 nonmedical students and 1163 medical students. Outcome Measures: The survey's questions covered the respondents': (1) general demographic characteristics, (2) cognitive interest and knowledge about COVID-19 and its infectiousness as well as efforts at active learning about infectious diseases and viruses, (3) awareness of precautionary behaviors against COVID-19, (4) effects on mental health, and (5) effects on job-search intentions. The research team used descriptive statistics and Chi-square tests to analyze the survey data. Results: Among nonmedical students: (1) 297 participants (61.2%) were interested in learning about COVID-19, (2) 321 participants (66.2%) took the initiative to learn about the virus, (3) 301 participants (62.1%) took the initiative to learn about infectious disease, and (4) 151 participants (31.1%) watched medical-themed movies or TV series about COVID-19. Among medical students, the corresponding proportions were 772 participants (66.4%), 855 participants (73.5%), 791 participants (68.1%), and 791 participants (68.1%), respectively. Among nonmedical students, 223 participants (46.0%) had N95 masks available, 429 participants (88.5%) had disinfectant supplies available, 271 participants (55.9%) wore goggles in public places, 75 participants (15.5%) chose public transportation, and 77 participants (15.9%) were exposed to public places in the week prior to the survey. Among medical students, the corresponding proportions were 470 participants (40.4%), 935 participants (80.4%), 575 participants (49.4%), 243 participants (20.9%), and 297 participants (25.5%), respectively. Furthermore, COVID-19 had a stronger effect on medical students' psychology and job-search ambitions. Conclusions: The news about COVID-19 piqued the interest of medical students. Nonmedical students had stronger protective behavior than medical students. The COVID-19 outbreak had a significant influence on medical students' lives, studies, and moods. In addition, COVID-19 had a greater impact on the job-search intentions of medical students.

V367F Mutation in SARS-CoV-2 Spike RBD Emerging during the Early Transmission Phase Enhances Viral Infectivity through Increased Human ACE2 Receptor Binding Affinity.

The current pandemic of COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the critical determinant of viral tropism and infectivity. To investigate whether naturally occurring RBD mutations during the early transmission phase have altered the receptor binding affinity and infectivity, we first analyzed in silico the binding dynamics between SARS-CoV-2 RBD mutants and the human angiotensin-converting enzyme 2 (ACE2) receptor. Among 32,123 genomes of SARS-CoV-2 isolates (December 2019 through March 2020), 302 nonsynonymous RBD mutants were identified and clustered into 96 mutant types. The six dominant mutations were analyzed applying molecular dynamics simulations (MDS). The mutant type V367F continuously circulating worldwide displayed higher binding affinity to human ACE2 due to the enhanced structural stabilization of the RBD beta-sheet scaffold. The MDS also indicated that it would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially infectious to humans. The increased infectivity of V367 mutants was further validated by performing receptor-ligand binding enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance, and pseudotyped virus assays. Phylogenetic analysis of the genomes of V367F mutants showed that during the early transmission phase, most V367F mutants clustered more closely with the SARS-CoV-2 prototype strain than the dual-mutation variants (V367F+D614G), which may derivate from recombination. The analysis of critical RBD mutations provides further insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin under negative selection pressure and supports the continuing surveillance of spike mutations to aid in the development of new COVID-19 drugs and vaccines. IMPORTANCE A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused the pandemic of COVID-19. The origin of SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether mutations in the RBD of the circulating SARS-CoV-2 isolates have altered the receptor binding affinity and made them more infectious has been the research hot spot. Given that SARS-CoV-2 is a novel coronavirus, the significance of our research is in identifying and validating the RBD mutant types emerging during the early transmission phase and increasing human angiotensin-converting enzyme 2 (ACE2) receptor binding affinity and infectivity. Our study provides insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin. The continuing surveillance of RBD mutations with increased human ACE2 affinity in human or other animals is critical to the development of new COVID-19 drugs and vaccines against these variants during the sustained COVID-19 pandemic.

Temperature dependence of the SARS-CoV-2 affinity to human ACE2 determines COVID-19 progression and clinical outcome.

The SARS-CoV-2 virus and its homolog SARS-CoV penetrate human cells by binding of viral spike protein and human angiotensin converting enzyme II (ACE2). SARS-CoV causes high fever in almost all patients, while SARS-CoV-2 does not. Moreover, analysis of the clinical data revealed that the higher body temperature is a protective factor in COVID-19 patients, making us to hypothesize a temperature-dependent binding affinity of SARS-CoV-2 to human ACE2 receptor. In this study, our molecular dynamics simulation and protein surface plasmon resonance cohesively proved the SARS-CoV-2-ACE2 binding was less affinitive and stable under 40 °C (~18 nM) than the optimum temperature 37 °C (6.2 nM), while SARS-CoV-ACE2 binding was not (6.4 nM vs. 8.5 nM), which evidenced the temperature-dependent affinity and explained that higher temperature is related to better clinical outcome. The decreased infection at higher temperature was also validated by pseudovirus entry assay using Vero and Caco-2 cells. We also demonstrated the structural basis of the distinct temperature-dependence of the two coronaviruses. Furthermore, the meta-analysis revealed a milder inflammatory response happened in the early stage of COVID-19, which explained the low fever tendency of COVID-19 and indicated the co-evolution of the viral protein structure and the inflammatory response. The temperature dependence of the binding affinity also indicated that higher body temperature at early stages might be beneficial to the COVID-19 patients.