SARS-CoV-2 neurotropism-induced anxiety and depression-like behaviors require Microglia activation (preprint)

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with a wide range of long COVID neurological symptoms. However, the mechanisms governing SARS-CoV-2 neurotropism and its effects on long-term behavioral changes remain poorly understood. Using a highly virulent mouse-adapted SARS-CoV-2 strain, denoted as SARS2-N501YMA30, we demonstrated that intranasal inoculation of SARS2-N501YMA30 results in viral dissemination to multiple brain regions, including the amygdala and hippocampus. Behavioral assays show a significant increase in anxiety- and depression-like behaviors 14 days following viral infection. Moreover, we observed microglia activation following SARS2-N501YMA30 infection, along with an augmentation in microglia-dependent neuronal activity in the amygdala. Pharmacological inhibition of microglial activity subsequent to viral spike inoculation mitigates microglia-dependent neuronal hyperactivity. Furthermore, transcriptomic analysis of infected brains revealed the upregulation of inflammatory and cytokine-related pathways, implicating microglia-driven neuroinflammation in the pathogenesis of neuronal hyperactivity and behavioral abnormality. Overall, these data provide critical insights into the neurological consequences of SARS-CoV-2 infection and underscore microglia as a potential therapeutic target for ameliorating virus-induced neurobehavioral abnormalities.

Effects of COVID-19 infection in patients with autoimmune pulmonary alveolar proteinosis: a single-center study (preprint)

Background:Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare interstitial lung disease. COVID-19 is associated with worse prognosis in previous lung diseases patients. But the prognosis of aPAP patients after infection with COVID-19 is unclear. In December 2022, China experienced a large-scale outbreak of Omicron variant of the SARS-CoV-2. In this study, we aim to explore the clinical outcomes of aPAP patients infected with COVID-19. Results: A total of 39 aPAP patients were included in this study. 30.77% patients had a decrease in oxygen saturation after COVID-19 infection. We compared the two groups of patients with or without decreased oxygen saturation after COVID-19 infection and found that patients who had previous oxygen therapy (decreased oxygen saturation vs. non decreased oxygen saturation: 6/12 vs. 4/27, P = 0.043), with lower baseline arterial oxygen partial pressure (74.50 ± 13.61 mmHg vs. 86.49 ± 11.92 mmHg, P = 0.009), lower baseline DLCO/VA% [77.0 (74.3, 93.6) % vs. 89.5 (78.2, 97.4) %, P = 0.036], shorter baseline 6MWD [464 (406, 538) m vs. 532 (470, 575) m, P = 0.028], higher disease severity score (P = 0.017), were more likely to have decreased oxygen saturation after COVID-19 infection. Conclusion: aPAP patients with poor baseline respiration have a higher probability of hypoxia after COVID-19 infection, but fatal events were rare.

Short-Term Effects of Air Pollution on the Risk of Influenza in Jinan, China during 2020-2021: A Time-Series Analysis

Background: Air pollution leads to many adverse diseases, especially respiratory diseases and cardiac symptoms. However, it has not been studied the association between air pollution and influenza cases in Jinan City, especially during the outbreak of COVID-19;Methods: The data were obtained from China's Disease Information System, and influenza cases during 2020-2021 in Jinan City were collected from it. We used the generalized additive Poisson model to measure the association between air pollutants and the daily influenza cases after adjusting for possible influence variables;Results: There were 4767 influenza cases. PM2.5 and PM10 on lag 0, lag 3, and lag 4 were significantly associated with an increased risk of influenza;gaseous pollutants (NO2 and SO2) led to higher risk than particulate matter pollutants (PM2.5 and PM10). There were no significant differences for sex subgroup analyses. Except for O3, the incidence risk of males and females was highest on lag 3 and lag 4. For the study of different age groups, influenza cases aged over 59 years had a slightly larger relative risk when exposed to all air pollutants (except O3) than the younger group;Conclusions: The overall number of influenza cases decreased in 2020-2021. PM2.5, SO2, CO, and NO2 were significantly associated with the risk of influenza during 2020-2021. Countermeasures should be developed according to the characteristics of influenza risk to prevent and control it.

Analysis of factors influencing the quality of life and anxiety among quarantined individuals in different places during the COVID-19 pandemic (preprint)

Background Since March 2022, Shanghai, China, has been affected by a severe outbreak of COVID-19, which has caused tens of thousands of people to become ill. To prevent and control this disease, Shanghai has implemented strict isolation measures, including arrangements for isolation of individuals in close contact, at isolation shelters in Tongling City, Anhui Province. Isolation may have significantly affected the quality of life and psychological status of such individuals. Therefore, the purpose of this study was to evaluate the quality of life and anxiety of people isolated in different shelters during the COVID-19 pandemic and to analyze the influencing factors.Methods This is a cross-sectional study. An online survey was conducted from April 20 to May 10, 2022. A total of 279 people in close contact with an isolation shelter in Tongling City, Anhui Province, participated in the survey. The quality of life was assessed using the Quality of Life Scale (SF-12), and anxiety status was assessed using the SAS. The study used descriptive analysis, t-tests, analysis of variance, and generalized linear regression analysis to test the factors influencing quality of life and anxiety during the COVID-19 pandemic, as well as the correlation between the two.Results The survey results showed that isolation days and marital status affected psychological and physical aspects, respectively. Age above 40 years was an independent risk factor for PCS, education was a protective factor for psychological status, and low quality of life directly led to an increase in anxiety levels.Conclusion During the pandemic, with infected individuals in close contact were isolated at shelters in other places. Reduction in the quality of life can lead to an increase in the anxiety levels of the population. We should pay attention to the age and education levels of individuals in isolation and take response measures to improve the health status of the isolated population.

Performance prediction and optimization for healthcare enterprises in the context of the COVID-19 pandemic: an intelligent DEA-SVM model

The coronavirus disease (COVID-19) pandemic has caused significant changes in the external environment of enterprises, resulting in tremendous negative impacts. Accordingly, the irregular fluctuation of business data poses a critical challenge to traditional approaches. Therefore, to combat the effects of the COVID-19 pandemic, an effective model is required to proactively predict an enterprise’s performance and simultaneously generate scientific performance optimization solutions. Consequently, at the intersection of artificial intelligence algorithms, operations research, and management science, an intelligent DEA-SVM model, which has a theoretical contribution, is developed in this study. The capabilities of this model are verified through sufficient numerical experiments. On the one hand, this model outperforms traditional algorithms in prediction accuracy. On the other hand, effective performance optimization solutions for low-performance enterprises are obtained from the input–output perspective. Moreover, the application value of this model is reflected in its successful implementation in the healthcare industry. Thus, it is a user-friendly tool for realizing the stable operation of enterprises in the context of the COVID-19 pandemic.

The impact of the COVID-19 pandemic on the mental health and academic performance of medical postgraduates

Background The Coronavirus disease 2019 (COVID-19) has presented a major challenge to the health, economic, and social sectors of the entire world. This study aimed to investigate the mental health and academic performance of medical postgraduates during the COVID-19 pandemic in China. Methods A cross-sectional online survey was conducted from March 20 to April 20, 2022 at the Zhejiang University School of Medicine in China. The questionnaire consisted of three parts: general information, mental health and academic performance. Mental health outcomes were assessed according to the Generalized Anxiety Scale (GAD-7) and the Patient Health Questionnaire-9 Scale (PHQ-9). Results A total of 153 valid questionnaires were obtained. Of the medical postgraduates in this study, (1) 41.8% had no anxiety symptoms. In addition, 51.0% had mild anxiety symptoms during the COVID-19 pandemic. None of the participants had a severe anxiety or depression disorder;(2) Females experienced significantly more symptoms in mental health measure scores than the males (P < 0.01);(3) 78.4% believed that the COVID-19 pandemic had varying degrees of impact on their academics. Doctoral postgraduates showed greater academic stress, and they were more worried about not meeting graduation standards than the master's postgraduates (P < 0.05). There were no significant differences between the surgical postgraduates and internal postgraduates in either mental health or academic performance. Conclusions Our study found that the COVID-19 pandemic has had a mild impact on the mental health and academic performance of medical postgraduates in China. Females experienced significantly more symptoms on mental health measure scores than the males. Doctoral postgraduates showed greater academic stress than the master's postgraduates. There is uncertainty regarding how long this COVID-19 situation will persist and increasing recognition that there may be periods of recurrence in the future. We need more active curricular innovation and transformation to maintain and improve medical postgraduates' mental health and academic performance.

Third dose of anti-SARS-CoV-2 inactivated vaccine for patients with RA: Focusing on immunogenicity and effects of RA drugs

Objectives To evaluate the immunogenicity of the third dose of inactivated SARS-CoV-2 vaccine in rheumatoid arthritis (RA) patients and explore the effect of RA drugs on vaccine immunogenicity. Methods We recruited RA patients (n = 222) and healthy controls (HC, n = 177) who had been injected with a third dose of inactivated SARS-CoV-2 vaccine, and their neutralizing antibody (NAb) titer levels were assessed. Results RA patients and HC were age- and gender-matched, and the mean interval between 3rd vaccination and sampling was comparable. The NAb titers were significantly lower in RA patients after the third immunization compared with HC. The positive rate of NAb in HC group was 90.4%, while that in RA patients was 80.18%, and the difference was significant. Furthermore, comparison of NAb titers between RA treatment subgroups and HC showed that the patients in the conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) group exhibited no significant change in NAb titers, while in those receiving the treatment of biological DMARDs (bDMARDs), Janus Kinase (JAK) inhibitors, and prednisone, the NAb titers were significantly lower. Spearman correlation analysis revealed that NAb responses to SARS-CoV-2 in HC did differ significantly according to the interval between 3rd vaccination and sampling, but this finding was not observed in RA patients. In addition, NAb titers were not significantly correlated with RA-related laboratory indicators, including RF-IgA, RF-IgG, RF-IgM, anti-CCP antibody;C-RP;ESR;NEUT% and LYMPH%. Conclusion Serum antibody responses to the third dose of vaccine in RA patients were weaker than HC. Our study will help to evaluate the efficacy and safety of booster vaccination in RA patients and provide further guidance for adjusting vaccination strategies.

Analysis of the Cognitive Load of Employees Working from Home and the Construction of the Telecommuting Experience Balance Model

Adapting to working from home caused physical and psychological difficulties, leading to work–family imbalance and lower employee performance during the COVID-19 pandemic. This study intends to identify the relationship between variables affecting telecommuting experience and improve employees' perceived organizational support by constructing a balanced model of telecommuting experience. An online questionnaire survey was conducted with 142 employees from different organizations telecommuting during the epidemic in Xi'an. The NASA-TLX scale was used to quantitatively evaluate the cognitive load of employees working from home, and the Analytic Hierarchy Process method was applied to map negative experience factors with cognitive load to obtain the weight value of each factor. Finally, a balanced model of telecommuting experience was constructed through a system map. The results show that mental demand was the key factor affecting employees' telecommuting experience. A good telecollaboration system could effectively manage work tasks and reduce the psychological load of employees. Frustration and temporal demand also significantly affected employees' telecommuting experience, mainly due to work–family conflict. Adopting flexible work hours and organizing online sharing activities could reshape employees' social relationships with their families and colleagues, effectively improving the telecommuting experience. The empirical study validated the effectiveness of the telecommuting experience balance model.

Antibiotic use in township hospitals during the COVID-19 pandemic in Shandong, China (preprint)

Background The overuse of antibiotics in primary healthcare settings (PHSs) has caused a serious public health problem in China. The Coronavirus Disease-19 (COVID-19) pandemic outbreak has brought about dramatic changes in the supply of and demand for medical services in PHSs, possibly resulting in unprecedented changes in antibiotic use.Objective This study aims to assess the immediate and long-term impacts of the COVID-19 pandemic on the changes in antibiotic consumption in PHSs.Method From January 2019 to December 2021, the data on antibiotic consumption were collected from selected township hospitals in Shandong, China. Antibiotic consumption was quantified by using the defined daily doses (DDDs) and the WHO Access, Watch, Reserve category. A Segmented regression model was established to analyze the immediate and long-term impacts of the COVID-19 pandemic on antibiotic use by using the interrupted time series analysis.Results The total antibiotic consumption on all PHSs decreased from 170.36 (DDDs in ten thousand) in 2019 to 128.86 (DDDs in ten thousand) in 2020/2021 with a 24.36% reduction under the COVID-19 pandemic. Over the entire study period, the use of penicillins (J01C) and cephalosporins (J01D) accounted for more than 50% of total antibiotic consumption. The average annual consumption of Watch category antibiotics in 2020/2021 down by 37.74% compared to that in 2019. According to the interrupted time series analysis, the total antibiotic consumption decreased significantly immediately after the COVID-19 pandemic outbreak (coef. =-2.712, p = 0.045) and then increased significantly month-over-month in the long-term (coef. =0.205, p = 0.005). Additionally, the consumption of Access category antibiotics increased significantly in PHSs in the log-term (coef. =0.136, p = 0.018), while the consumption of Watch category antibiotics declined sharply immediately (coef. =-1.222, p < 0.001) after the pandemic but increased slightly over the long-term (coef. =0.073, p = 0.001).Conclusion The extensive use of penicillin and cephalosporins should be of great concern. After the outbreak of COVID-19 pandemic, the total antibiotic consumption decreased generally and the use pattern was improved to some extent in the PHSs in Shandong, China. This provides an opportunity to improve the abuse of antibiotic in PHSs in China.

Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development

COVID-19 caused by SARS-CoV-2 has raised a health crisis worldwide. The high morbidity and mortality associated with COVID-19 and the lack of effective drugs or vaccines for SARS-CoV-2 emphasize the urgent need for standard treatment and prophylaxis of COVID-19. The receptor-binding domain (RBD) of the glycosylated spike protein (S protein) is capable of binding to human angiotensin-converting enzyme 2 (hACE2) and initiating membrane fusion and virus entry. Hence, it is rational to inhibit the RBD activity of the S protein by blocking the RBD interaction with hACE2, which makes the glycosylated S protein a potential target for designing and developing antiviral agents. In this study, the molecular features of the S protein of SARS-CoV-2 are highlighted, such as the structures, functions, and interactions of the S protein and ACE2. Additionally, computational tools developed for the treatment of COVID-19 are provided, for example, algorithms, databases, and relevant programs. Finally, recent advances in the novel development of antivirals against the S protein are summarized, including screening of natural products, drug repurposing and rational design. This study is expected to provide novel insights for the efficient discovery of promising drug candidates against the S protein and contribute to the development of broad-spectrum anti-coronavirus drugs to fight against SARS-CoV-2.

Association between Anxiety and Disease Pathophysiology in Participants of Longitudinal Observational Studies in Aging during the COVID-19 Lockdown (preprint)

The burden imposed by the COVID-19 pandemic deferentially interferes with the outcomes of clinical trials of aging and dementia. We examined the impact of the lockdown on cognitive impairment due to Alzheimer’s Disease (AD), anxiety, and COVID-19-related stress in participants from the Translational Biomarkers In Aging and Dementia (TRIAD) cohort using neuropsychiatric assessments, tau and amyloid PET. We found that, before the lockdown, anxiety was higher in cognitively impaired individuals (CI) and positively associated with brain tau load. However, during the lockdown, anxiety increased only in the cognitively unimpaired (CU) and was positively associated with COVID-19 related stress. Interestingly, we found that in patients, tau load was anti-correlated with higher anxiety during lockdown. Our findings contribute to a framework for interpreting the effects of the pandemic on neuropsychiatric symptoms among clinical trial participants. Collectively, our results suggest that caregivers are more vulnerable to external stressors than patients.

Empathy of Marine Aquaculture on Aquatic Products Consumption

The prolonged COVID-19 has caused a global lockdown and greatly impacts the supply chain and consumers’ consumption behavior of aquatic products. Specifically, consumers’ increasing awareness of environmental protection drives the marine aquaculture enterprises to supply green products and establish empathy with consumers in a bid to achieve sustainable consumption. This paper conducts a study on the international green marketing paths of marine aquatic products through PLS-SEM analysis of the 407 valid samples collected from the questionnaire survey. The findings indicate that empathy marketing has a significant positive effect on consumers’ purchase intention;subjective norm has a significant positive effect on consumers’ purchase intention. Additionally, perceived behavior control has a significant mediating effect between consumers’ subjective norm and purchase intention;the consumption environment has a significant positive moderating effect on individual consumption intention. The study suggests that sustainable development can be further propelled by means of coordinating the consumers’ awareness of ecological environment protection and their enhanced consumption intention.

Forecasting of Automobile Sales Based on Support Vector Regression Optimized by the Grey Wolf Optimizer Algorithm

With the development of the Internet and big data, more and more consumer behavior data are used in different forecasting problems, which greatly improve the performance of prediction. As the main travel tool, the sales of automobiles will change with the variations of the market and the external environment. Accurate prediction of automobile sales can not only help the dealers adjust their marketing plans dynamically but can also help the economy and the transportation sector make policy decisions. The automobile is a product with high value and high involvement, and its purchase decision can be affected by its own attributes, economy, policy and other factors. Furthermore, the sample data have the characteristics of various sources, great complexity and large volatility. Therefore, this paper uses the Support Vector Regression (SVR) model, which has global optimization, a simple structure, and strong generalization abilities and is suitable for multi-dimensional, small sample data to predict the monthly sales of automobiles. In addition, the parameters are optimized by the Grey Wolf Optimizer (GWO) algorithm to improve the prediction accuracy. First, the grey correlation analysis method is used to analyze and determine the factors that affect automobile sales. Second, it is used to build the GWO-SVR automobile sales prediction model. Third, the experimental analysis is carried out by using the data from Suteng and Kaluola in the Chinese car segment, and the proposed model is compared with the other four commonly used methods. The results show that the GWO-SVR model has the best performance of mean absolute percentage error (MAPE) and root mean square error (RMSE). Finally, some management implications are put forward for reference.

Assessment of the Performance of TROPOMI NO2 and SO2 Data Products in the North China Plain: Comparison, Correction and Application

The TROPOspheric Monitoring Instrument (TROPOMI) aboard the Sentinel-5 Precursor satellite has been used to detect the atmospheric environment since 2017, and it is of great significance to investigate the accuracy of its products. In this work, we present comparisons between TROPOMI tropospheric NO2 and total SO2 products against ground-based MAX-DOAS at a single site (Xianghe) and OMI products over a seriously polluted region (North China Plain, NCP) in China. The results show that both NO2 and SO2 data from three datasets exhibit a similar tendency and seasonality. In addition, TROPOMI tropospheric NO2 columns are generally underestimated compared with collocated MAX-DOAS and OMI data by about 30–60%. In contrast to NO2, the monthly average SO2 retrieved from TROPOMI is larger than MAX-DOAS and OMI, with a mean bias of 2.41 (153.8%) and 2.17 ×1016 molec cm−2 (120.7%), respectively. All the results demonstrated that the TROPOMI NO2 as well as the SO2 algorithms need to be further improved. Thus, to ensure reliable analysis in NCP area, a correction method has been proposed and applied to TROPOMI Level 3 data. The revised datasets agree reasonably well with OMI observations (R > 0.95 for NO2, and R > 0.85 for SO2) over the NCP region and have smaller mean biases with MAX-DOAS. In the application during COVID-19 pandemic, it showed that the NO2 column in January-April 2020 decreased by almost 25–45% compared to the same period in 2019 due to the lockdown for COVID-19, and there was an apparent rebound of nearly 15–50% during 2021. In contrast, a marginal change of the corresponding SO2 is revealed in the NCP region. It signifies that short-term control measures are expected to have more effects on NO2 reduction than SO2;conversely, we need to recognize that although the COVID-19 lockdown measures improved air quality in the short term, the pollution status will rebound to its previous level once industrial and human activities return to normal.

Multivariate morphological brain signatures enable individualized prediction of dispositional need for closure

Need for closure (NFC) reflects stable individual differences in the desire for a quick, definite, and stable answer to a question. A large body of research has documented the association between NFC and various cognitive, emotional and social processes. Despite considerable interest in psychology, little effort has been made to uncover the neural substrates of individual variations in NFC. Herein, we took a data-driven approach to predict NFC trait combining machine learning framework and the whole-brain grey matter volume (GMV) features, which represent a reliable brain imaging measure and have been commonly employed to explore neural basis underlying individual differences of cognition and behaviors. Brain regions contributing to the prediction were then subjected to functional connectivity and decoding analyses for a quantitative inference on their psychophysiological functions. Our results indicated that multivariate patterns of GMV derived from multiple regions across distributed brain systems predicted NFC at individual level. The contributing regions are distributed across the emotional processing network (e.g., striatum), cognitive control network (e.g., lateral prefrontal cortex), social cognition network (e.g., temporoparietal junction) and perceptual processing network (e.g., occipital cortex). The current study provided the first evidence that dispositional NFC is embodied in multiple large-scale brain networks, helping to delineate a more complete picture about the neuropsychological processes that support individual differences in NFC. Beyond these findings, the current interdisciplinary approach to constructing and interpreting neuroimaging-based prediction model of personality traits would be informative to a wide range of future studies on personality. Supplementary Information The online version contains supplementary material available at 10.1007/s11682-021-00574-w.

Recurrence of Lymphedema and Related Characteristics in Discharged Breast Cancer Patients During The COVID-19 Pandemic: A Multicenter, Cross-Sectional Survey (preprint)

Background: To evaluate recurrence of lymphedema and its influencing factors in discharged breast cancer patients with treated lymphedema during the COVID-19 pandemic and to propose feasible improvements. Methods: A multicenter, cross-sectional, hospital-based survey of discharged breast cancer patients was conducted during the COVID-19 pandemic in eight first-class hospitals in Wuhan city, China. Norman Questionnaire was used for assessing lymphedema, and multivariable binary logistic regression was performed to risk factors of moderate or severe lymphedema. Difference in living characteristics, anxiety and depression between no or mild group and moderate or severe group were compared. Preference in management of lymphedema were collected. Results: 202 valid patients were included. 191 participants reported recurred lymphedema (prevalence: 94.6%, 95%CI 90.5% to 97.3%). 134 of them was mild and 57 were moderate/severe. In the 191 patients, the main symptom was swelling (140, 69.3%) and pain (56, 27.7%). Multivariable regression showed that age (odds ratio, 1.06, 95%CI: 1.02-1.10), radical surgery (OR=4.35, 95%CI: 1.54-12.50) and fully complete radiotherapy (OR=2.62, 95%CI: 1.17-5.87, P=0.019) was associated with the risk of moderate or severe lymphedema. No significant difference in lifestyles was observed but moderate or severe group experienced higher rate of anxiety and depression. patients preferred treatment in hospital and self-care at home equally. Conclusion: The high recurrence rate of lymphedema in breast cancer patients with during COVID-19 should draw our great attention, continuous efforts should be made to identify patient at risk of lymphedema and distribute feasible guidance and education for self-management for these patients.

Toll-Like Receptor Agonist R848 Protects Mice from Lethal SARS-CoV-2 Infections (preprint)

Background: An ideal animal model to study SARS-coronavirus 2 (SARS-CoV-2) pathogenesis and evaluate therapies and vaccines should reproduce SARS-CoV-2 infection and recapitulate lung disease like those seen in humans. The angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, but mice are resistant to the infection because their ACE2 is incompatible with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Methods: We generated a mouse-adapted strain SARS-CoV-2 by serial passages in the lung of BALB/c mice. Complete genome deep sequencing of different generations of viruses was performed to characterize the dynamics of the adaptive mutations in SARS-CoV-2. Indirect immunofluorescence analysis and Biolayer interferometry experiments demonstrated that two mutations in RBD significantly increased its binding affinity towards mouse ACE2. Significantly, TLR7/8 agonist Resiquimod block SARS-CoV-2 in vitro and in vivo. Findings: We adapted a wild-type SARS-CoV-2 by serial passages in the lung of BALB/c mice. The mouse-adapted strain WBP-1 showed increased infectivity in BALB/c mice and led to severe interstitial pneumonia. We characterized the dynamics of the adaptive mutations in SARS-CoV-2 and demonstrated that Q493K and Q498H in RBD significantly increased its binding affinity towards mouse ACE2. Additionally, The TLR7/8 agonist Resiquimod was able to protect mice against WBP-1 challenge, demonstrating this mouse-adapted strain is a useful tool to investigate COVID-19 and develop new therapies. Interpretation: We found for the first time that the Q493K and Q498H mutations in the RBD of WBP-1 enhanced its interactive affinities with mACE2. The mouse-adapted SARS-CoV-2 provides a valuable tool for the evaluation of novel antiviral and vaccine strategies, especially in determining the immunopathological consequences of any intervention. This study also verified the antiviral activity of TLR7/8 agonist Resiquimod against SARS-CoV-2 in vitro and in vivo.Funding Statement: This research was funded by Emergency Science and Technology Project of Hubei Province（2020FCA046）and Independent Science and Technology Innovation Fund of Huazhong Agricultural University in 2020 (2662020PY002).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The animal experiments were approved by the Research Ethics Committee, Huazhong Agricultural University, Hubei, China (HZAUMO-2020-0007). All the animal experiments were conducted in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals from the Research Ethics Committee, Huazhong Agricultural University, Hubei, China.

[Management of a global health crisis: first COVID-19 disease feedback from Overseas and French-speaking countries medical biologists]. / Gestion d'une crise sanitaire mondiale : premiers retours d'expérience de biologistes médicaux d'Outre-mer et de francophonie face au COVID-19.

The French society of clinical biology "Biochemical markers of COVID-19" has set up a working group with the primary aim of reviewing, analyzing and monitoring the evolution of biological prescriptions according to the patient's care path and to look for markers of progression and severity of the disease. This study covers all public and private sectors of medical biology located in metropolitan and overseas France and also extends to the French-speaking world. This article presents the testimonies and data obtained for the "Overseas and French-speaking countries" sub-working group made up of 45 volunteer correspondents, located in 20 regions of the world. In view of the delayed spread of the SARS-CoV-2 virus, the overseas regions and the French-speaking regions have benefited from feedback from the first territories confronted with COVID-19. Thus, the entry of the virus or its spread in epidemic form could be avoided, thanks to the rapid closure of borders. The overseas territories depend very strongly on air and/or sea links with the metropolis or with the neighboring continent. The isolation of these countries is responsible for reagent supply difficulties and has necessitated emergency orders and the establishment of stocks lasting several months, in order to avoid shortages and maintain adequate patient care. In addition, in countries located in tropical or intertropical zones, the diagnosis of COVID-19 is complicated by the presence of various zoonoses (dengue, Zika, malaria, leptospirosis, etc.).