[Preparation and immungenicity of recombinant protein containing intramolecular adjuvant in SARS-CoV-2 RBD domain].

A fusion protein containing a tetanus toxin peptide, a tuftsin peptide and a SARS-CoV-2S protein receptor-binding domain (RBD) was prepared to investigate the effect of intramolecular adjuvant on humoral and cellular immunity of RBD protein. The tetanus toxin peptide, tuftsin peptide and S protein RBD region were connected by a flexible polypeptide, and a recombinant vector was constructed after codon optimization. The recombinant S-TT-tuftsin protein was prepared by prokaryotic expression and purification. BALB/c mice were immunized after mixed with aluminum adjuvant, and the humoral and cellular immune effects were evaluated. The recombinant S-TT-tuftsin protein was expressed as an inclusion body, and was purified by ion exchange chromatography and renaturated by gradient dialysis. The renaturated protein was identified by Dot blotting and reacted with serum of descendants immunized with SARS-CoV-2 subunit vaccine. The results showed that the antibody level reached a plateau after 35 days of immunization, and the serum antibody ELISA titer of mice immunized with recombinant protein containing intramolecular adjuvant was up to 1:66 240, which was significantly higher than that of mice immunized with S-RBD protein (P < 0.05). At the same time, the recombinant protein containing intramolecular adjuvant stimulated mice to produce a stronger lymphocyte proliferation ability. The stimulation index was 4.71±0.15, which was significantly different from that of the S-RBD protein (1.83±0.09) (P < 0.000 1). Intramolecular adjuvant tetanus toxin peptide and tuftsin peptide significantly enhanced the humoral and cellular immune effect of the SARS-CoV-2 S protein RBD domain, which provideda theoretical basis for the development of subunit vaccines for SARS-CoV-2 and other viruses.

Mental burden among Chinese undergraduate medical students: A prospective longitudinal study before, during, and after the COVID-19 outbreak.

Background: Increasing evidence indicated a clear association between COVID-19 pandemic and mental health. This study aimed to assess the dynamic change of mental burden during and after the COVID-19 outbreak and related predictive factors among Chinese undergraduate medical students. Methods: This longitudinal survey was conducted among Chinese undergraduate medical students before, during, and after the COVID-19 outbreak. We focused on COVID-19 related mental burdens including psychological distress, stress reaction, and insomnia symptoms, and defined the sum score of the three specific mental burden indexes as the overall mental burden index. The prevalence of specific and overall mental burdens and their changing patterns at two phases of the pandemic (during vs. after the COVID-19 outbreak) were measured. In addition, multinomial logistic regressions were used to assess the associations between the psychosocial status before the pandemic and specific and overall mental burden changing patterns. Results: Our findings showed that the prevalence of overall mental burden increased (from 27.46 to 37.28%) after the COVID-19 outbreak among the 863 Chinese undergraduate medical students who participated in the surveys at baseline, during, and after the COVID-19 outbreak. Specifically, the prevalence of stress reaction symptoms decreased (from 10.90 to 3.60%), while the rates of psychological distress (from 28.06 to 37.95%) and insomnia symptoms (from 12.54 to 20.71%) increased. Participants, with obsessive-compulsive symptoms, somatic symptoms, internet addiction, childhood adversity, stressful life events, and being neurotic were found to have a higher risk of developing mental burden in at least one survey (during or after the COVID-19 outbreak). Healthy family function and being extravert were found to positively impact mental burden. Conclusion: Psychological distress, stress reaction and insomnia symptoms have been prevalent among Chinese undergraduate medical students during the COVID-19 outbreak, and the prevalence of overall mental burden increased after the COVID-19 outbreak. Some students, especially those with the risk factors noted above, exhibited persistent or progression symptoms. Continued mental health care was in demand for them even after the COVID-19 outbreak.

Psychological distress among health professional students during the COVID-19 outbreak.

BACKGROUND: Due to the drastic surge of COVID-19 patients, many countries are considering or already graduating health professional students early to aid professional resources. We aimed to assess outbreak-related psychological distress and symptoms of acute stress reaction (ASR) in health professional students and to characterize individuals with potential need for interventions. METHODS: We conducted a prospective cohort study of 1442 health professional students at Sichuan University, China. At baseline (October 2019), participants were assessed for childhood adversity, stressful life events, internet addiction, and family functioning. Using multivariable logistic regression, we examined associations of the above exposures with subsequent psychological distress and ASR in response to the outbreak. RESULTS: Three hundred and eighty-four (26.63%) participants demonstrated clinically significant psychological distress, while 160 (11.10%) met the criterion for a probable ASR. Individuals who scored high on both childhood adversity and stressful life event experiences during the past year were at increased risks of both distress (ORs 2.00-2.66) and probable ASR (ORs 2.23-3.10), respectively. Moreover, internet addiction was associated with elevated risks of distress (OR 2.05, 95% CI 1.60-2.64) and probable ASR (OR 2.15, 95% CI 1.50-3.10). By contrast, good family functioning was associated with decreased risks of distress (OR 0.43, 95% CI 0.33-0.55) and probable ASR (OR 0.48, 95% CI 0.33-0.69). All associations were independent of baseline psychological distress. CONCLUSIONS: Our findings suggest that COVID-19 related psychological distress and high symptoms burden of ASR are common among health professional students. Extended family and professional support should be considered for vulnerable individuals during these unprecedented times.

A Radiomics Signature to Quantitatively Analyze COVID-19-Infected Pulmonary Lesions.

Assessing pulmonary lesions using computed tomography (CT) images is of great significance to the severity diagnosis and treatment of coronavirus disease 2019 (COVID-19)-infected patients. Such assessment mainly depends on radiologists' subjective judgment, which is inefficient and presents difficulty for those with low levels of experience, especially in rural areas. This work focuses on developing a radiomics signature to quantitatively analyze whether COVID-19-infected pulmonary lesions are mild (Grade I) or moderate/severe (Grade II). We retrospectively analyzed 1160 COVID-19-infected pulmonary lesions from 16 hospitals. First, texture features were extracted from the pulmonary lesion regions of CT images. Then, feature preselection was performed and a radiomics signature was built using a stepwise logistic regression. The stepwise logistic regression also calculated the correlation between the radiomics signature and the grade of a pulmonary lesion. Finally, a logistic regression model was trained to classify the grades of pulmonary lesions. Given a significance level of α = 0.001, the stepwise logistic regression achieved an R (multiple correlation coefficient) of 0.70, which is much larger than Rα = 0.18 (the critical value of R). In the classification, the logistic regression model achieved an AUC of 0.87 on an independent test set. Overall, the radiomics signature is significantly correlated with the grade of a pulmonary lesion in COVID-19 infection. The classification model is interpretable and can assist radiologists in quickly and efficiently diagnosing pulmonary lesions. This work aims to develop a CT-based radiomics signature to quantitatively analyze whether COVID-19-infected pulmonary lesions are mild (Grade I) or moderate/severe (Grade II). The logistic regression model established based on this radiomics signature can assist radiologists to quickly and efficiently diagnose the grades of pulmonary lesions. The model calculates a radiomics score for a lesion and is interpretable and appropriate for clinical use.

COVID-19 outbreak-related psychological distress among healthcare trainees: a cross-sectional study in China.

OBJECTIVES: The COVID-19 outbreak has caused enormous strain on healthcare systems, and healthcare trainees, which comprise the future healthcare workforce, may be a vulnerable group. It is essential to assess the psychological distress experienced by healthcare trainees during the COVID-19 outbreak. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional study with 4184 healthcare trainees at Sichuan University in China was implemented during 7-13 February 2020. Participants were grouped by training programmes (medicine, medical technology and nursing) and training stages (undergraduate, postgraduate and residency). MAIN OUTCOMES: COVID-19-related psychological distress and acute stress reaction (ASR) were assessed using the Kessler 6-item Psychological Distress Scale and the Impact of Event Scale-Revised, respectively. We estimated the ORs of distress by comparing trainees across programmes and training stages using multivariable logistic regression. RESULTS: Significant psychological distress was found in 1150 (30.90%) participants and probable ASR in 403 (10.74%). Compared with the nursing trainees, the medical trainees (OR 1.54, 95% CI 1.22 to 1.95) reported a higher burden of psychological distress during the outbreak, while the medical technology trainees (OR 1.25, 95% CI 0.97 to 1.62) reported similar symptom scores. Postgraduates (OR 1.55, 95% CI 1.16 to 2.08) in medicine had higher levels of distress than their undergraduate counterparts did, whereas the nursing residents (OR 0.38, 95% CI 0.20 to 0.71) reported a lower burden than did nursing undergraduates. A positive association was found between having active clinical duties during the outbreak and distress (OR 1.17, 95% CI 0.98 to 1.39), particularly among the medical trainees (OR 1.85, 95% CI 1.47 to 2.33) and undergraduates (OR 4.20, 95% CI 1.61 to 11.70). No clear risk patterns of ASR symptoms were observed. CONCLUSIONS: Medical trainees, particularly postgraduates and those with active clinical duties, were at risk for psychological distress during the COVID-19 outbreak. Stress management may be considered for high-risk healthcare trainees.

Analysis on herbal medicines utilized for treatment of COVID-19.

As coronavirus disease 2019 (COVID-19) pandemic poses a substantial global public health threat, traditional Chinese medicine (TCM) was used in 91.50% of the COVID-19 cases in China, showing encouraging results in improving symptom management and reducing the deterioration, mortality, and recurrence rates. A total of 166 modified herbal formulae consisting of 179 single herbal medicines were collected for treating COVID-19 in China. Glycyrrhizae Radix et Rhizome, Scutellariae Radix, and Armeniacae Semen Amarum are the most frequently utilized in clinics, most of which are antipyretic (47, 26.26%), expectorant and cough-suppressing (22, 12.29%), and dampness-resolving (21, 11.73%) from traditional descriptions. A total of 1212 chemical components containing ß-sitosterol, stigmasterol, and quercetin were primarily selected. Additionally, using complex system entropy and unsupervised hierarchical clustering, 8 core herbal combinations and 10 new formulae emerged as potentially useful candidates for COVID-19. Finally, following scaffold analysis, self-organizing mapping (SOM) and cluster analysis, 12 clusters of molecules yielded 8 pharmacophore families of structures that were further screened as pharmacological targets in human metabolic pathways for inhibiting coronavirus. This article aims to make more easily accessible and share historical herbal knowledge used in contemporary treatments in a modern manner to assist researchers contain the global spread of COVID-19.