Effect of monovalent and bivalent live attenuated vaccines against QX-like IBV infection in young chickens.

Since 1999, QX-like (GI-19) avian infectious bronchitis viruses have been the predominant strains in China till now. Vaccination is the most effective way to control the disease, while live attenuated vaccine is widely used. In the current research, we evaluated the effect of several monovalent and bivalent live IBV vaccines in young chickens against the QX-like (GI-19) IBV infection. The results showed that monovalent 4/91 and bivalent Ma5+LDT3 vaccines could provide efficient protection in day-old chickens that reduced morbidity and mortality, ameliorated histopathology lesions, and reduced viral loads were observed. These data suggest that vaccination through nasal route with monovalent 4/91 or bivalent Ma5+LDT3 in day-old chickens could serve a safe and effective vaccination strategy for controlling QX-like (GI-19) infectious bronchitis virus.

Decreased antibody response to influenza vaccine with an enhanced antibody response to subsequent SARS‐CoV‐2 vaccination in patients with chronic hepatitis B virus infection

Introduction Influenza or SARS‐CoV‐2 vaccination is especially recommended for people with underlying diseases. For the large number of patients with chronic hepatitis B virus infection (CHB), studies on their immune responses to these vaccines are still lacking. Methods A total of 57 CHB patients and 19 healthy controls (HCs) receiving inactivated influenza vaccination were prospectively followed up. Influenza‐specific immunoglobulin G (IgG) antibodies (anti‐H1N1, anti‐H3N2, and anti‐B IgG), antibody‐secreting cells (ASCs), and circulating T follicular helper cells were assessed simultaneously. Eight CHB patients subsequently got inactivated SARS‐CoV‐2 vaccination during 1‐year follow‐up, and levels of serum antibodies against SARS‐CoV‐2 were further analyzed. Results On day 28 after influenza vaccination, three influenza antibodies levels appeared to be lower in CHB patients than in HCs. And anti‐H1N1 IgG level was significantly decreased in cirrhotic patients (p < .05). Anti‐H1N1 IgG levels (day 28) were positively correlated with ASC frequencies (day 7) (p < .05), and negatively correlated with cirrhosis and hepatitis B surface antigen levels (p < .05). Anti‐SARS‐CoV‐2 antibodies were higher in patients with influenza vaccination history than in patients without the history (p < .05). Moreover, positive correlations existed between influenza vaccination history and anti‐SARS‐CoV‐2 antibody levels (p < .01). Conclusions CHB patients, especially those with cirrhosis, appeared to have a decreased antibody response to inactivated influenza vaccine. A history of inactivated influenza vaccination within 1 year before inactivated SARS‐CoV‐2 vaccination might induce stronger anti‐SARS‐CoV‐2 antibody response. Antibody response to an inactivated influenza vaccine appears to be reduced in patients with CHB, especially in those with cirrhosis. A history of inactivated influenza vaccination within 1 year before inactivated SARS‐CoV‐2 vaccination might result in a stronger anti‐SARS‐CoV‐2 antibody response

Performance comparison of reusable versus disposable colonoscopes:a non-inferiority Trial (preprint)

Objective We herein compared the performance of reusable and disposable colonoscopes in patients scheduled to undergo colonoscopy with a view of preventing patient cross-infection, protecting the safety of clinical medical staff, reducing the risk of infection, and minimizing the decontamination process, particularly during the coronavirus disease 2019 pandemic. Methods We randomly divided patients meeting the enrollment criteria into reusable and disposable colonoscopy groups; the success rate of photographing customary anatomical sites with a non-inferiority margin of -8% was the primary endpoint. Secondary endpoints were the adenoma detection rate, operation time, endoscopic image quality score, endoscopic mucosal resection (EMR) success rate, and adverse events. Results We recruited patients who were treated using reusable or disposable (n = 45, each) colonoscopes. Both groups had 100% success rate for capturing images of customary anatomical sites, with no between-group differences. The lower limit of 95% CI was - 7.8654%, which was greater than the non-inferiority threshold of -8%. The disposable group had a significantly lower average image quality score (26.09 ±1.33 vs. 27.44±0.59, P < 0.001) than the reusable group. The groups did not significantly differ in maneuverability, safety, or device failure/defect rate. The en-bloc EMR success rate was 100% in both groups. EMR took significantly longer in the disposable group (466.18 s±180.56 s vs . 206.32 s±109.54 s, P < 0.001). The incidence of EMR-related bleeding and perforation did not significantly differ between the groups. Conclusions Disposable colonoscope endoscopy is safe and feasible for endoscopy examinations and EMR.

SEIR-FMi: A coronavirus disease epidemiological model based on intra-city movement, inter-city movement and medical resource investment.

In this paper, we propose a coronavirus disease (COVID-19) epidemiological model called SEIR-FMi (Susceptible-Exposed-Infectious-Recovery with Flow and Medical investments) to study the effects of intra-city population movement, inter-city population movement, and medical resource investment on the spread of the COVID-19 epidemic. We theoretically derived the reproduction number of the SEIR-FMi model by using the next-generation matrix method and empirically simulate the individual impacts of population movement and medical resource investment on epidemic control. We found that intra- and inter-city population movements will increase the risk of epidemic spread, and the effect of inter-city population movement on low-risk areas is higher than that on high-risk areas. Increasing medical resource investment can not only speed up the recover rate of patients but also reduce the growth rate of infected cases and shorten the spread duration of the epidemic. We collected data on intra-city population movement, inter-city population movement, medical resource investment, and confirmed cases in the cities of Wuhan, Jingzhou, and Xiangyang, Hubei Province, China, from January 15 to March 15, 2020. Using the collected data, we validated that the proposed SEIR-FMi model performs well in simulating the spread of COVID-19 in the three cities. Meanwhile, this study confirms that three non-pharmaceutical interventions, namely community isolation, population mobility control, and medical resource aid, applied during the epidemic period are indispensable in controlling the spread of COVID-19 in the three cities.

Therapeutic targets and functions of curcumol against COVID-19 and colon adenocarcinoma.

Since 2019, the coronavirus disease (COVID-19) has caused 6,319,395 deaths worldwide. Although the COVID-19 vaccine is currently available, the latest variant of the virus, Omicron, spreads more easily than earlier strains, and its mortality rate is still high in patients with chronic diseases, especially cancer patients. So, identifying a novel compound for COVID-19 treatment could help reduce the lethal rate of the viral infection in patients with cancer. This study applied network pharmacology and systematic bioinformatics analysis to determine the possible use of curcumol for treating colon adenocarcinoma (COAD) in patients infected with COVID-19. Our results showed that COVID-19 and COAD in patients shared a cluster of genes commonly deregulated by curcumol. The clinical pathological analyses demonstrated that the expression of gamma-aminobutyric acid receptor subunit delta (GABRD) was associated with the patients' hazard ratio. More importantly, the high expression of GABRD was associated with poor survival rates and the late stages of COAD in patients. The network pharmacology result identified seven-core targets, including solute carrier family 6 member 3, gamma-aminobutyric acid receptor subunit pi, butyrylcholinesterase, cytochrome P450 3A4, 17-beta-hydroxysteroid dehydrogenase type 2, progesterone receptor, and GABRD of curcumol for treating patients with COVID-19 and COAD. The bioinformatic analysis further highlighted their importance in the biological processes and molecular functions in gland development, inflammation, retinol, and steroid metabolism. The findings of this study suggest that curcumol could be an alternative compound for treating patients with COVID-19 and COAD.

How Does Inclusive Leadership Curb Workers’ Emotional Exhaustion? The Mediation of Caring Ethical Climate and Psychological Safety

The COVID-19 pandemic has transformed the politics, economy, and society of the world, which has dealt the most severe blow to the hospitality industry. Meanwhile, the pandemic and government control policies have brought high psychological pressure to hospitality front-line employees, resulting in emotional exhaustion. As a part of burnout syndrome, emotional exhaustion poses a threat to employees’ mental health, career sustainability, and well-being. Therefore, the purpose of this paper was to investigate the curb effectiveness of inclusive leadership on emotional exhaustion and to explore the mediation roles of ethical climate and psychological safety between them. Time-lagged data were collected from 65 teams and 358 hospitality front-line employees working in Chinese hotels in two stages with a one-month gap. This research verified that inclusive leadership has a negative impact on emotional exhaustion both indirectly through the mediation roles of ethical climate and psychological safety. And the ethical climate and psychological safety played partial mediation roles between inclusive leadership and emotional exhaustion. In theory, the findings explored the dual mediation mechanism of the inhibitory effect of inclusive leadership on emotional exhaustion. In practice, we provided the training and correct guidance to develop inclusive leadership for hotel enterprises and to resolve the emotional exhaustion of employees, which can enhance sustainability in careers.

Transcriptomic characteristics and impaired immune function of patients who retest positive for SARS-CoV-2 RNA.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global public health crisis. Some patients who have recovered from COVID-19 subsequently test positive again for SARS-CoV-2 RNA after discharge from hospital. How such retest-positive (RTP) patients become infected again is not known. In this study, 30 RTP patients, 20 convalescent patients, and 20 healthy controls were enrolled for the analysis of immunological characteristics of their peripheral blood mononuclear cells. We found that absolute numbers of CD4+ T cells, CD8+ T cells, and natural killer cells were not substantially decreased in RTP patients, but the expression of activation markers on these cells was significantly reduced. The percentage of granzyme B-producing T cells was also lower in RTP patients than in convalescent patients. Through transcriptome sequencing, we demonstrated that high expression of inhibitor of differentiation 1 (ID1) and low expression of interferon-induced transmembrane protein 10 (IFITM10) were associated with insufficient activation of immune cells and the occurrence of RTP. These findings provide insight into the impaired immune function associated with COVID-19 and the pathogenesis of RTP, which may contribute to a better understanding of the mechanisms underlying RTP.

Clinical Characteristics of Coronavirus Disease 2019 in China.

BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).

Depressive State in the Emergency Department During COVID-19: A National Cross-Sectional Survey in China.

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1-15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31-45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.

Development of an indirect ELISA for detecting swine acute diarrhoea syndrome coronavirus IgG antibodies based on a recombinant spike protein.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV) is a newly identified swine enteropathogenic coronavirus that causes watery diarrhoea in neonatal piglets, leading to significant economic losses to the swine industry. Currently, there are no suitable serological methods to assess the infection of SADS-CoV and effectiveness of vaccines, making an urgent need to exploit effective enzyme-linked immunosorbent assay (ELISA) to compensate for this deficiency. Here, a recombinant plasmid that expresses the spike (S) protein of SADS-CoV fused to the Fc domain of human IgG was constructed to generate recombinant baculovirus and expressed in HEK 293F cells. The S-Fc protein was purified with protein G Resin, which retained reactivity with anti-human Fc and anti-SADS-CoV antibodies. The S-Fc protein was then used to develop an indirect ELISA (S-iELISA) and the reaction conditions of S-iELISA were optimized. As a result, the cut-off value was determined as 0.3711 by analyzing OD450nm values of 40 SADS-CoV-negative sera confirmed by immunofluorescence assay (IFA) and western blot. The coefficient of variation (CV) of 6 SADS-CoV-positive sera within and between runs of S-iELISA were both less than 10%. The cross-reactivity assays demonstrated that S-iELISA was non-cross-reactive with other swine viruses' sera. Furthermore, the overall coincidence rate between IFA and S-iELISA was 97.3% based on testing 111 clinical serum samples. Virus neutralization test with seven different OD450nm values of the sera showed that the OD450nm values tested by S-iELISA are positively correlated with the virus neutralization assay. Finally, a total of 300 pig field serum samples were tested by S-iELISA and commercial kits of other swine enteroviruses showed that the IgG-positive for SADS-CoV, TGEV, PDCoV and PEDV was 81.7, 54, 65.3 and 6%, respectively. The results suggest that this S-iELISA is specific, sensitive, repeatable and can be applied for the detection of the SADS-CoV infection in the swine industry.

Coronary artery calcification and risk of mortality and adverse outcomes in patients with COVID-19: a Chinese multicenter retrospective cohort study.

Background: Coronary artery calcification (CAC) is an independent risk factor of major adverse cardiovascular events; however, the impact of CAC on in-hospital death and adverse clinical outcomes in patients with coronavirus disease 2019 (COVID-19) remains unclear. Objective: To explore the association between CAC and in-hospital mortality and adverse events in patients with COVID-19. Methods: This multicenter retrospective cohort study enrolled 2067 laboratory-confirmed COVID-19 patients with definitive clinical outcomes (death or discharge) admitted from 22 tertiary hospitals in China between January 3, 2020 and April 2, 2020. Demographic, clinical, laboratory results, chest CT findings, and CAC on admission were collected. The primary outcome was in-hospital death and the secondary outcome was composed of in-hospital death, admission to intensive care unit (ICU), and requiring mechanical ventilation. Multivariable Cox regression analysis and Kaplan-Meier plots were used to explore the association between CAC and in-hospital death and adverse clinical outcomes. Results: The mean age was 50 years (SD,16) and 1097 (53.1%) were male. A total of 177 patients showed high CAC level, and compared with patients with low CAC, these patients were older (mean age: 49 vs. 69 years, P < 0.001) and more likely to be male (52.0% vs. 65.0%, P = 0.001). Comorbidities, including cardiovascular disease (CVD) ([33.3%, 59/177] vs. [4.7%, 89/1890], P < 0.001), presented more often among patients with high CAC, compared with patients with low CAC. As for laboratory results, patients with high CAC had higher rates of increased D-dimer, LDH, as well as CK-MB (all P < 0.05). The mean CT severity score in high CAC group was also higher than low CAC group (12.6 vs. 11.1, P = 0.005). In multivariable Cox regression model, patients with high CAC were at a higher risk of in-hospital death (hazard ratio [HR], 1.731; 95% CI 1.010-2.971, P = 0.046) and adverse clinical outcomes (HR, 1.611; 95% CL 1.087-2.387, P = 0.018). Conclusion: High CAC is a risk factor associated with in-hospital death and adverse clinical outcomes in patients with confirmed COVID-19, which highlights the importance of calcium load testing for hospitalized COVID-19 patients and calls for attention to patients with high CAC. Supplementary Information: The online version contains supplementary material available at 10.1007/s42058-021-00072-4.

Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: A multicenter, open-label, randomized trial.

BACKGROUND: The clinical characteristics and treatment of patients who tested positive for COVID-19 after recovery remained elusive. Effective antiviral therapy is important for tackling these patients. We assessed the efficacy and safety of favipiravir for treating these patients. METHODS: This is a multicenter, open-label, randomized controlled trial in SARS-CoV-2 RNA re-positive patients. Patients were randomly assigned in a 2:1 ratio to receive either favipiravir, in addition to standard care, or standard care alone. The primary outcome was time to achieve a consecutive twice (at intervals of more than 24 h) negative RT-PCR result for SARS-CoV-2 RNA in nasopharyngeal swab and sputum sample. RESULTS: Between March 27 and May 9, 2020, 55 patients underwent randomization; 36 were assigned to the favipiravir group and 19 were assigned to the control group. Favipiravir group had a significantly shorter time from start of study treatment to negative nasopharyngeal swab and sputum than control group (median 17 vs. 26 days); hazard ratio 2.1 (95% CI [1.1-4.0], p = 0.038). The proportion of virus shedding in favipiravir group was higher than control group (80.6% [29/36] vs. 52.6% [10/19], p = 0.030, respectively). C-reactive protein decreased significantly after treatment in the favipiravir group (p = 0.016). The adverse events were generally mild and self-limiting. CONCLUSION: Favipiravir was safe and superior to control in shortening the duration of viral shedding in SARS-CoV-2 RNA recurrent positive after discharge. However, a larger scale and randomized, double-blind, placebo-controlled trial is required to confirm our conclusion.

The relationship between SARS-COV-2 RNA positive duration and the risk of recurrent positive.

BACKGROUND: The management of discharge COVID-19 patients with recurrent positive SARS-CoV-2 RNA is challenging. However, there are fewer scientific dissertations about the risk of recurrent positive. The aim of this study was to explore the relationship between SARS-COV-2 RNA positive duration (SPD) and the risk of recurrent positive. METHODS: This case-control multi-center study enrolled participants from 8 Chinese hospital including 411 participants (recurrent positive 241). Using unadjusted and multivariate-adjusted logistic regression analyses, generalized additive model with a smooth curve fitting, we evaluated the associations between SPD and risk of recurrent positive. Besides, subgroup analyses were performed to explore the potential interactions. RESULTS: Among recurrent positive patients, there were 121 females (50.2%), median age was 50 years old [interquartile range (IQR): 38-63]. In non-adjusted model and adjusted model, SPD was associated with an increased risk of recurrent positive (fully-adjusted model: OR = 1.05, 95% CI: 1.02-1.08, P = 0.001); the curve fitting was not significant (P = 0.286). Comparing with SPD < 14 days, the risk of recurrent positive in SPD > 28 days was risen substantially (OR = 3.09, 95% CI: 1.44-6.63, P = 0.004). Interaction and stratified analyses showed greater effect estimates of SPD and risk of recurrent positive in the hypertension, low monocyte count and percentage patients (P for interaction = 0.008, 0.002, 0.036, respectively). CONCLUSION: SPD was associated with a higher risk of recurrent positive and especially SPD > 28 day had a two-fold increase in the relative risk of re-positive as compared with SPD < 14 day. What's more, the risk may be higher among those with hypertension and lower monocyte count or percentage.

Clinical characteristics and risk factors for symptomatic venous thromboembolism in hospitalized COVID-19 patients: A multicenter retrospective study.

BACKGROUND: High incidence of asymptomatic venous thromboembolism (VTE) has been observed in severe COVID-19 patients, but the characteristics of symptomatic VTE in general COVID-19 patients have not been described. OBJECTIVES: To comprehensively explore the prevalence and reliable risk prediction for VTE in COVID-19 patients. METHODS/RESULTS: This retrospective study enrolled all COVID-19 patients with a subsequent VTE in 16 centers in China from January 1 to March 31, 2020. A total of 2779 patients were confirmed with COVID-19. In comparison to 23,434 non-COVID-19 medical inpatients, the odds ratios (ORs) for developing symptomatic VTE in severe and non-severe hospitalized COVID-19 patients were 5.94 (95% confidence interval [CI] 3.91-10.09) and 2.79 (95% CI 1.43-5.60), respectively. When 104 VTE cases and 208 non-VTE cases were compared, pulmonary embolism cases had a higher rate for in-hospital death (OR 6.74, 95% CI 2.18-20.81). VTE developed at a median of 21 days (interquartile range 13.25-31) since onset. Independent factors for VTE were advancing age, cancer, longer interval from symptom onset to admission, lower fibrinogen and higher D-dimer on admission, and D-dimer increment (DI) ≥1.5-fold; of these, DI ≥1.5-fold had the most significant association (OR 14.18, 95% CI 6.25-32.18, p = 2.23 × 10-10 ). A novel model consisting of three simple coagulation variables (fibrinogen and D-dimer levels on admission, and DI ≥1.5-fold) showed good prediction for symptomatic VTE (area under the curve 0.865, 95% CI 0.822-0.907, sensitivity 0.930, specificity 0.710). CONCLUSIONS: There is an excess risk of VTE in hospitalized COVID-19 patients. This novel model can aid early identification of patients who are at high risk for VTE.

Risk Factors of Fatal Outcome in Hospitalized Subjects With Coronavirus Disease 2019 From a Nationwide Analysis in China.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. The cumulative number of new confirmed cases and deaths are still increasing out of China. Independent predicted factors associated with fatal outcomes remain uncertain. RESEARCH QUESTION: The goal of the current study was to investigate the potential risk factors associated with fatal outcomes from COVID-19 through a multivariate Cox regression analysis and a nomogram model. STUDY DESIGN AND METHODS: A retrospective cohort of 1,590 hospitalized patients with COVID-19 throughout China was established. The prognostic effects of variables, including clinical features and laboratory findings, were analyzed by using Kaplan-Meier methods and a Cox proportional hazards model. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. RESULTS: In this nationwide cohort, nonsurvivors included a higher incidence of elderly people and subjects with coexisting chronic illness, dyspnea, and laboratory abnormalities on admission compared with survivors. Multivariate Cox regression analysis showed that age ≥ 75 years (hazard ratio [HR], 7.86; 95% CI, 2.44-25.35), age between 65 and 74 years (HR, 3.43; 95% CI, 1.24-9.5), coronary heart disease (HR, 4.28; 95% CI, 1.14-16.13), cerebrovascular disease (HR, 3.1; 95% CI, 1.07-8.94), dyspnea (HR, 3.96; 95% CI, 1.42-11), procalcitonin level > 0.5 ng/mL (HR, 8.72; 95% CI, 3.42-22.28), and aspartate aminotransferase level > 40 U/L (HR, 2.2; 95% CI, 1.1-6.73) were independent risk factors associated with fatal outcome. A nomogram was established based on the results of multivariate analysis. The internal bootstrap resampling approach suggested the nomogram has sufficient discriminatory power with a C-index of 0.91 (95% CI, 0.85-0.97). The calibration plots also showed good consistency between the prediction and the observation. INTERPRETATION: The proposed nomogram accurately predicted clinical outcomes of patients with COVID-19 based on individual characteristics. Earlier identification, more intensive surveillance, and appropriate therapy should be considered in patients at high risk.

Transcriptomic Characteristics and Impaired Immune Function of Patients Who Retest Positive for SARS-CoV-2 RNA (preprint)

Background: The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has gradually become a global public health crisis. Some patients who have recovered from COVID-19 subsequently tested positive again for SARS-CoV-2 after discharge (retesting-positive, RTP). However, the underlying mechanism is unknown.Methods: Here, 30 RTP patients, 20 convalescent patients, and 20 healthy controls were enrolled for analysis of the immunological characteristics of their peripheral blood mononuclear cells (PBMCs). Furthermore, we sought to comprehensively characterize the transcriptional changes in the three groups by transcriptome sequencing.Findings: It was found that the absolute numbers of CD4+ T cells, CD8+ T cells, and NK cells were not decreased remarkably, while the expression of activation markers on these cells was significantly decreased in RTP patients. Furthermore, the percentage of granzyme B-producing T cells was also decreased in RTP patients compared with that in convalescent patients. Moreover, the high expression of inhibitor of differentiation-1 (ID1) and the low expression of IFITM10 may be associated with the insufficient activation of immune cells and RTP occurrence.Interpretation: Our findings provide insights into the impaired immune function and pathogenesis of RTP occurrence in COVID-19, which may contribute to the development of immunotherapy for RTP patients.Funding Statement: This work was supported by China National Center for Biotechnology Development (2020YFC0843800 and 2020YFC0846800), Ministry of Science and Technology of China (2020TFC0844100), and China Postdoctoral Science Foundation (2020T130112ZX).Declaration of Interests: The authors declare no potential conflict of interest.Ethics Approval Statement: The studies were approved by the Ethics Committee of the First Affiliated Hospital of the University of Science & Technology of China (2020-XG(H)-005) and Peking University First Hospital (2020-Research-112) for Emerging Infectious Diseases. Experiments were conducted in accordance with the ethical guidelines of the 1975 Declaration of Helsinki, the Principles of Good Clinical Practice, and the guidelines of China’s regulatory requirements.

Designing a Hybrid Biopharmaceutical Laboratory Course to Enhance Content Flexibility and Access

Herein we report the design of an upper-level hybrid laboratory course in the area of applied biopharmaceuticals, which has high scheduling flexibility, and utilizes both virtual and in-person educational elements to enhance students learning experience. This newly developed course applies chemical engineering knowledge, practical and theoretical, in the bioprocess and pharmaceutical industry, including crystallization, chromatography, and mass transport. During the COVID-19 pandemic, we transferred this lab course to a completely virtual mode during midsemester of Spring 2020. Despite the lack of in-person experiments during the second half of the semester, we introduced various additional elements including modeling, simulation, literature review, and added lectures to the virtual version of the course to improve students learning experience. These additional elements introduced during the virtual period enriched the course content and exposed students to more advanced applications of the knowledge in this course, which can be implemented in future hybrid modes. Although the student performance on quizzes and lab reports remained consistent after the transition to online format, the instructors noticed students struggling with data mined from previous groups. The root cause of this was not being able to create and observe their own data in real time, which could be improved by developing better remote data collection methods. Another lesson we learned during this experience is the value of keeping an experimental video archive for all of our laboratory modules, regardless of plans for remote learning.

A web visualization tool using T cell subsets as the predictor to evaluate COVID-19 patient's severity.

Wuhan, China was the epicenter of the 2019 coronavirus outbreak. As a designated hospital for COVID-19, Wuhan Pulmonary Hospital has received over 700 COVID-19 patients. With the COVID-19 becoming a pandemic all over the world, we aim to share our epidemiological and clinical findings with the global community. We studied 340 confirmed COVID-19 patients with clear clinical outcomes from Wuhan Pulmonary Hospital, including 310 discharged cases and 30 death cases. We analyzed their demographic, epidemiological, clinical and laboratory data and implemented our findings into an interactive, free access web application to evaluate COVID-19 patient's severity level. Our results show that baseline T cell subsets results differed significantly between the discharged cases and the death cases in Mann Whitney U test: Total T cells (p < 0.001), Helper T cells (p <0.001), Suppressor T cells (p <0.001), and TH/TSC (Helper/Suppressor ratio, p<0.001). Multivariate logistic regression model with death or discharge as the outcome resulted in the following significant predictors: age (OR 1.05, 95% CI, 1.00 to 1.10), underlying disease status (OR 3.42, 95% CI, 1.30 to 9.95), Helper T cells on the log scale (OR 0.22, 95% CI, 0.12 to 0.40), and TH/TSC on the log scale (OR 4.80, 95% CI, 2.12 to 11.86). The AUC for the logistic regression model is 0.90 (95% CI, 0.84 to 0.95), suggesting the model has a very good predictive power. Our findings suggest that while age and underlying diseases are known risk factors for poor prognosis, patients with a less damaged immune system at the time of hospitalization had higher chance of recovery. Close monitoring of the T cell subsets might provide valuable information of the patient's condition change during the treatment process. Our web visualization application can be used as a supplementary tool for the evaluation.