Spatial and temporal variation of economic resilience and its drivers: Evidence from Chinese cities

Based on panel data of 282 cities in China from 2005-2019, this paper constructs an economic resilience evaluation index system in three dimensions and applies the entropy value method to measure it. The two-stage nested Thiel index, kernel density estimation and geographic detector methods are also used to explore the characteristics of their spatial and temporal divergence and their driving factors. We find that the economic resilience of Chinese cities has increased rapidly over the sample period, but with significant spatial variation, with the intra-provincial variation being the main source of the overall variation. Without considering the spatial conditions, the economic resilience of cities has a strong stability. In the case of spatial conditions, spatial factors have a significant impact on cities with low economic resilience, but not on cities with high economic resilience. Differences in technological innovation capabilities are a key driver of spatial divergence in the economic resilience of Chinese cities. The interaction of any two factors enhances their respective effects on the spatial differentiation of economic resilience in Chinese cities. Based on the above findings, cities should actively explore targeted and differentiated ways to improve economic resilience based on their comparative advantages, accelerate the construction of a collaborative improvement mechanism for urban economic resilience, and support the collaborative improvement of urban economic resilience in China. Our findings provide a useful reference for promoting the concerted improvement of economic resilience in Chinese cities.

Sequelae of long COVID, known and unknown: A review of updated information.

Over three years have passed since the COVID-19 pandemic started. The dangerousness and impact of COVID-19 should definitely not be ignored or underestimated. Other than the symptoms of acute infection, the long-term symptoms associated with SARS-CoV-2 infection, which are referred to here as "sequelae of long COVID (LC)", are also a conspicuous global public health concern. Although such sequelae were well-documented, the understanding of and insights regarding LC-related sequelae remain inadequate due to the limitations of previous studies (the follow-up, methodological flaws, heterogeneity among studies, etc.). Notably, robust evidence regarding diagnosis and treatment of certain LC sequelae remain insufficient and has been a stumbling block to better management of these patients. This awkward situation motivated us to conduct this review. Here, we comprehensively reviewed the updated information, particularly focusing on clinical issues. We attempt to provide the latest information regarding LC-related sequelae by systematically reviewing the involvement of main organ systems. We also propose paths for future exploration based on available knowledge and the authors' clinical experience. We believe that these take-home messages will be helpful to gain insights into LC and ultimately benefit clinical practice in treating LC-related sequelae.

Cross-Sectional Association of Patient Language and Patient-Provider Language Concordance with Video Telemedicine Use Among Patients with Limited English Proficiency.

BACKGROUND: Telemedicine's dramatic increase during the COVID-19 pandemic elevates the importance of addressing patient-care gaps in telemedicine, especially for patients with limited English proficiency. OBJECTIVE: To examine the associations of patient language and patient-provider language concordance with telemedicine visit type (video versus telephone visit). DESIGN: Cross-sectional automated data study of patient-scheduled primary care telemedicine appointments from March 16, 2020, to October 31, 2020. SETTING: Northern California integrated healthcare delivery system. PARTICIPANTS: All 22,427 completed primary care telemedicine visits scheduled by 13,764 patients with limited English proficiency via the patient portal. MEASUREMENTS: Cross-sectional association of electronic health record-documented patient language (Spanish as referent) and patient-provider language concordance with patients' choice of a video (versus telephone) visit, accounting for patient sociodemographics, technology access, and technology familiarity factors. RESULTS: Of all patient-scheduled visits, 34.5% (n = 7747) were video visits. The top three patient languages were Spanish (42.4%), Cantonese (16.9%), and Mandarin (10.3%). Adjusting for sociodemographic and technology access and familiarity factors and compared to patients speaking Spanish, video visit use was higher among patients speaking Cantonese (OR = 1.34, 95% CI: 1.18-1.52), Mandarin (OR = 1.33, 95% CI: 1.16-1.52), or Vietnamese (OR = 1.27, 95% CI: 1.09-1.47), but lower among patients speaking Punjabi (OR = 0.75, 95% CI: 0.75, 0.62-0.91). Language concordance was associated with lower video visit use (OR = 0.86, 95% CI: 0.80-0.93) and moderated associations of speaking Spanish, Cantonese, and Korean with video visit use. In addition, for all language groups, those with prior video visit use were more likely to re-use video visits compared to those with no prior use (p < .05 for all languages except Hindi with p = 0.06). CONCLUSIONS: Among linguistically diverse patients with limited English proficiency, video telemedicine use differed by specific language. Disaggregating patient subpopulation data is necessary for identifying those at greatest risk of being negatively impacted by the digital divide.

A storm in a teacup -- A biomimetic lung microphysiological system in conjunction with a deep-learning algorithm to monitor lung pathological and inflammatory reactions.

Creating a biomimetic in vitro lung model to recapitulate the infection and inflammatory reactions has been an important but challenging task for biomedical researchers. The 2D based cell culture models - culturing of lung epithelium - have long existed but lack multiple key physiological conditions, such as the involvement of different types of immune cells and the creation of connected lung models to study viral or bacterial infection between different individuals. Pioneers in organ-on-a-chip research have developed lung alveoli-on-a-chip and connected two lung chips with direct tubing and flow. Although this model provides a powerful tool for lung alveolar disease modeling, it still lacks interactions among immune cells, such as macrophages and monocytes, and the mimic of air flow and aerosol transmission between lung-chips is missing. Here, we report the development of an improved human lung physiological system (Lung-MPS) with both alveolar and pulmonary bronchial chambers that permits the integration of multiple immune cells into the system. We observed amplified inflammatory signals through the dynamic interactions among macrophages, epithelium, endothelium, and circulating monocytes. Furthermore, an integrated microdroplet/aerosol transmission system was fabricated and employed to study the propagation of pseudovirus particles containing microdroplets in integrated Lung-MPSs. Finally, a deep-learning algorithm was developed to characterize the activation of cells in this Lung-MPS. This Lung-MPS could provide an improved and more biomimetic sensory system for the study of COVID-19 and other high-risk infectious lung diseases.

Primary care video and telephone telemedicine during the COVID-19 pandemic: treatment and follow-up health care utilization.

OBJECTIVES: Telemedicine use expanded greatly during the COVID-19 pandemic, and broad use of telemedicine is expected to persist beyond the pandemic. More evidence on the efficiency and safety of different telemedicine modalities is needed to inform clinical and policy decisions around telemedicine use. To evaluate the efficiency and safety of telemedicine, we compared treatment and follow-up care between video and telephone visits during the COVID-19 pandemic. STUDY DESIGN: Observational study of patient-scheduled telemedicine visits for primary care. METHODS: We used multivariate logistic regression to compare treatment (medication prescribing, laboratory/imaging orders) and 7-day follow-up care (in-person office visits, emergency department visits, and hospitalizations) between video and telephone visits, adjusted for patient characteristics. RESULTS: Among 734,442 telemedicine visits, 58.4% were telephone visits. Adjusted rates of medication prescribing and laboratory/imaging orders were higher in video visits than telephone visits, with differences of 3.5% (95% CI, 3.3%-3.8%) and 3.9% (95% CI, 3.6%-4.1%), respectively. Adjusted rates of 7-day follow-up in-person office visits, emergency department visits, and hospitalizations were lower after video than telephone visits, with differences of 0.7% (95% CI, 0.5%-0.9%), 0.3% (95% CI, 0.2%-0.3%), and 0.04% (95% CI, 0.02%-0.06%), respectively. CONCLUSIONS: Among telemedicine visits with primary care clinicians, return visits were not common and downstream emergency events were rare. Adjusted rates of treatment measures were higher and adjusted rates of follow-up care were lower for video visits than telephone visits. Although video visits were marginally more efficient than telephone visits, telephone visits may offer an accessible option to address patient primary care needs without raising safety concerns.

The association between video or telephone telemedicine visit type and orders in primary care.

INTRODUCTION: Telemedicine is increasingly relied upon for care delivery in primary care, but the impact of visit type on clinical ordering behavior is uncertain. METHODS: Within Kaiser Permanente Northern California, we identified patients who self-scheduled and completed telemedicine encounters with their personal primary care provider or another available primary care provider in the same medical group, between April 1st, 2020, and October 31st, 2020, while physical distancing restrictions for COVID-19 were in place. We collected patient sociodemographic and clinical characteristics, measures of technology access, and categorized the most common primary encounter diagnoses. We measured proportions of patient-scheduled video versus telephone visits for each of eight diagnosis groups (Skin & Soft Tissue, Musculoskeletal Pain, Back Pain, General Gastrointestinal, Hypertension & Diabetes, Mental Health, Upper Respiratory, and Abdominal Pain), and compared physician orders for medications, antibiotics, lab and imaging studies by visit type within each diagnosis group. RESULTS: There were 273,301 included encounters, with 86,676 (41.5%) video visits and 122,051 (58.5%) telephone visits. Of the diagnosis groups, Skin & Soft Tissue conditions had the highest proportion of video visits (59.7%), while Mental Health conditions had the highest proportion of telephone visits (71.1%). After adjusting for covariates, the overall rates of medication orders (46.6% vs. 44.5%), imaging orders (17.3% vs. 14.9%), lab orders (19.5% vs. 17.2%), and antibiotic orders (7.5% vs. 5.2%) were higher during video visits as compared to telephone visits (p < 0.05). The largest difference within diagnosis groups was for Skin & Soft Tissue conditions, where the rate of medication orders was 9.1% higher than during video visits than telephone visits (45.5% vs. 36.5%, p < 0.05). CONCLUSIONS: We observed statistically significant differences in clinician orders by visit type during telemedicine encounters for common primary care conditions. Our findings suggest that, for certain conditions, visual information conveyed during video visits may promote clinical work-up and treatment.

The analysis of the characteristics of imported COVID-19 cases from January to April in 2020: a cross-sectional study.

Background: Since the first case reported in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an outbreak of coronavirus disease 2019 (COVID-19) worldwide. The global case count continued to rise and the WHO declared a Public Health Emergency of International Concern (PHEIC), causing a growing risk of imported COVID-19 infection. This study aimed to provide descriptive and quantitative epidemiological characteristics of imported COVID-19 cases in China. Methods: This cross-sectional study examined all imported COVID-19 cases in Mainland China from 22 January to 21 April 2020. Ratios, Median and percentile were used for descriptive analysis. Spearman's correlation analysis was performed between daily new imported cases in Mainland China and the country of origin. The chi-square test was used to evaluate the difference between home quarantine and compulsory centralized quarantine on native transmission. Results: A total of 1,610 cases of COVID-19 were imported from 49 countries to 27 provincial administrative regions in China; 79.8% were from European countries and the United States of America (the USA). Before 29 March 2020, the imported cases were mainly from the USA (27.7%) and United Kingdom (UK; 42.6%). After 29 March 2020, the daily newly imported cases from Russia rapidly grew. After 12 April 2020, the number of daily newly imported cases gradually decreased and remained at a low level (12±7 cases per day). Airport entry was encouraged, and ground border crossing was limited. Among the 1,610 cases, 54.0% were in the asymptomatic incubation period on arrival in Mainland China. Conclusions: The transmissions by imported COVID-19 were gradually and effectively curbed in Mainland China, despite a disproportionally high number of cases worldwide. Entry screening measures must be implemented universally to all inbound travelers at a point of entry or targeted to specific travel routes or to specific travelers. Compulsory centralized quarantine should be recommended in the prevention of the imported COVID-19 epidemic.

Abnormal myocardial enzymes in the prediction of mortality and hypertension in COVID-19 patients: a retrospective study.

This study aims to determine the differences in myocardial enzymes in COVID-19 patients with and without hypertension. A total of 130 patients with COVID-19 in Yunmeng County People's Hospital were analyzed. The clinical manifestations and laboratory indicators were collected and analyzed. We found that COVID-19 patients with hypertension had higher mortality rate, greater age, and higher rates of basic disease such as diabetes than patients without hypertension. The γ-glutamyl transpeptidase (GGT), blood urea nitrogen (BUN), albumin/globulin (A/G), Ca, Mg, lactate dehydrogenase (LDH), and α-hydroxybutyric-dehydrogenase (α-HBD) levels in COVID-19 patients with hypertension were higher than in COVID-19 patients without hypertension. We found that the predictive effect of the creatine kinase isoenzyme (CK-MB), LDH-L, and α-HBD levels in the COVID-19 patients without hypertension were higher than in COVID-19 patients with hypertension. We used the ROC curve model to predict whether patients would have hypertension, and we found that CK-MB, LDH-L and HBD parameters could distinguish the COVID-19 patients with hypertension and non-hypertension, and could predict the mortality of COVID-19 patients.

Close Contacts, Infected Cases, and the Trends of SARS-CoV-2 Omicron Epidemic in Shenzhen, China.

(1) The overall trends of the number of daily close contacts and infected cases as well as their association during an epidemic of Omicron Variant of SARS-CoV-2 have been poorly described. (2) Methods: This study was to describe the trends during the epidemic of the Omicron variant of SARS-CoV-2 in Shenzhen, China, including the number of close contacts and infected cases as well as their ratios by days and stages (five stages). (3) Results: A total of 1128 infected cases and 80,288 close contacts were identified in Shenzhen from 13 February 2022 to 1 April 2022. Before the citywide lockdown (14 March), the number of daily close contacts and infected cases gradually increased. However, the numbers showed a decrease after the lockdown was imposed. The ratio of daily close contacts to daily infected cases ranged from 20.2:1 to 63.4:1 and reached the lowest during the lockdown period. The growth rate of daily close contacts was consistent with those of infected cases observed 6 days later to some extent. (4) Conclusions: The Omicron variant epidemic was promptly contained by tracing close contacts and taking subsequent quarantine measures.

Effect of Lockdown and Mass Testing for the SARS-CoV-2 Omicron Epidemic on Reducing New Infections in Shenzhen, China.

On 14 March 2022, China's tech hub Shenzhen, a mega-city with more than 18 million inhabitants, imposed a one-week citywide lockdown immediately after it observed a surge in infections. We assessed the effect of this one-week lockdown, coupled with mass testing, on reducing the daily number of new confirmed cases and asymptomatic cases during the Omicron wave, using an interrupted time series analysis approach. Our analysis suggests that the one-week citywide lockdown in Shenzhen was effective at lowering both daily new confirmed cases and asymptomatic cases during the Omicron wave. Early detection ensures timely isolation and treatment of infected patients in designated hospitals, and therefore helps lower the prevalence of confirmed cases and asymptomatic cases. Our findings of the immediate increase in asymptomatic cases after lockdown warrant further verifications in other city epidemic scenarios.

Searching for a safe haven to crude oil: Green bond or precious metals?

In this paper, we explore whether the green bond, a kind of rarely discussed fixed-income asset, acts as a hedge or safe haven to crude oil in extreme market conditions, by comparing the results with precious metals. The green bond has negative correlations with crude oil when the COVID-19 pandemic and the Russia-Ukraine conflict outbreak, and the highest risk reduction effectiveness among all assets, indicating that investors benefit the most from adding the green bond to their portfolios. Applying the model purposed by Baur and McDermott (2010), we further find that the green bond is both a strong safe haven and a strong hedge for the crude oil market, gold is a weak safe haven and a strong hedge, silver only acts as a weak hedge, and other precious metals are neither safe haven nor hedge. Our results reveal that crude oil market investors can hedge the risk during the extreme rise and fall periods by including the green bond in their portfolios.

Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2.

BACKGROUND: The outbreak of SARS-CoV-2 continues to pose a serious threat to human health and social. The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious threat to public health and economic stability worldwide. Given the urgency of the situation, researchers are attempting to repurpose existing drugs for treating COVID-19. METHODS: We first established an anti-coronavirus drug screening platform based on the Homogeneous Time Resolved Fluorescence (HTRF) technology and the interaction between the coronavirus spike protein and its host receptor ACE2. Two compound libraries of 2,864 molecules were screened with this platform. Selected candidate compounds were validated by SARS-CoV-2_S pseudotyped lentivirus and ACE2-overexpressing cell system. Molecular docking was used to analyze the interaction between S protein and compounds. RESULTS: We identified three potential anti-coronavirus compounds: tannic acid (TA), TS-1276 (anthraquinone), and TS-984 (9-Methoxycanthin-6-one). Our in vitro validation experiments indicated that TS-984 strongly inhibits the interaction of the coronavirus S protein and the human cell ACE2 receptor. Additionally, tannic acid showed moderate inhibitory effect on the interaction of S protein and ACE2. CONCLUSION: This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.

[Five patients with novel coronavirus Omicron variant of concern infection].

OBJECTIVE: To analyze clinical characteristics of patients with novel coronavirus Omicron variant of concern infection, and to provide practical data and experience for subsequent clinical treatment. METHODS: A retrospective analysis was performed for the clinical data of 5 cases with novel coronavirus Omicron variant of concern infection treated in the First Hospital of Jiaxing from December 18, 2021 to January 28, 2022. The patients' clinical data were recorded, including gender, age, length of hospital stay, vaccination status, clinical symptoms, laboratory indicators [white blood cell count (WBC), lymphocyte count (LYM), eosinophil count (EOS), hypersensitivity C-reactive protein (hs-CRP), novel coronavirus antibody immunoglobulin (IgG and IgM)], chest CT, treatment course and disease outcome. RESULTS: All 5 patients were male, aged 24-37 years old. Four patients were vaccinated with novel coronavirus vaccine (one patient received 3 doses of the vaccine and 3 patients received only the first 2 doses of the vaccine), and no infection was found in chest CT. Laboratory examination showed that WBC, LYM, EOS and hs-CRP levels were normal, and only showed mild symptoms of upper respiratory tract infection. One patient was not vaccinated with novel coronavirus vaccine, and signs of viral pneumonia could be seen in chest CT, laboratory examination showed that WBC and hs-CRP levels increased, suggesting that bacterial infection, fever, cough, sputum and other respiratory symptoms were obvious, and the treatment time was long. All 5 patients were treated with Chinese medicine Lotus antipyretic and Baihu Yinqiao decoction based on routine antiviral therapy. CONCLUSIONS: Patients with novel coronavirus Omicron variant of concern infection vaccinated with the novel coronavirus vaccine have milder clinical symptoms, with less obvious chest CT findings and faster recovery. Chinese medicine Lotus antipyretic and Baihu Yinqiao decoction has obvious therapeutic effect on such patients.

Tourists' perceived restorative qualities and post-visit behavioral intention:the mechanism and boundary condition

Studies have shown that contacting with beautiful natural environments improves people's mood and reduces pressure. Environments that facilitate physical and psychological recovery are called restorative environments. Compared with other types of environments, natural sightseeing resorts have the most prominent restorative value, and have attracted the attention of numerous scholars. Tourists' perceived restorative qualities have gradually become a frontier of environmental psychology and tourism studies. However, studies of tourists' perceived restorative qualities are still in their infancy, with limited results regarding various aspects. For example, the development of a tourist restorative perception scale, and the antecedent factors underlying tourists' perceived restorative qualities. Few studies can be found investigating the relationship between tourists' perceived restorative qualities and their post-visit behavioral intention. Post-visit behavioral intention is of great significance in terms of guiding the management and marketing of tourist destinations. The COVID-19 pandemic has led to a sharp decline in the willingness of potential tourists to travel. As consumption by tourists shifts toward the pursuit of greenness and health during the continuation of the epidenic, further improving their satisfaction, stimulating word-ofmouth promotion, and strengthening tourist loyalty through physical and mental recovery experience to enable tourist destinations to enhance their competitive advantage, then to revitalize, has become an issue worthy of investigation. By maintaining close contact with destination environment, tourists can effectively enhance their physical and mental functions, produce a sense of satisfaction and increase positive behavioral intention. Thus, it is important to explore the mechanism underlying tourists' perceived restorative qualities to aid product innovation and marketing promotion, and promote the sustainable development of tourist destinations. On the basis of previous studies, we used attention restoration theory to analyze the impact of tourists' perceived restorative qualities. On the basis of the Mehrabian-Rusell framework, we developed a theoretical integrated model including four constructs:Tourists' perceived restorative qualities, tourist satisfaction, post-visit behavioral intention and tourist involvement. The model was tested using structural equation modeling. All constructs were measured using selfreported, multiple-item scales adopted from previous studies. Data were collected from Kanas, a well known nature-based tourist destination located in Altay, China. The questionnaires were distributed by a group of five people on 1-7 August 2019. A total of 600 questionnaires were distributed, and 547 completed questionnaires were returned. The results were as follows:(1) Tourists' functional perceived restorative qualities(coherence, novelty) directly and positively affect their emotional perceived restorative qualities(fascination, compatibility, escape);(2) Novelty and escape are key factors affecting post-visit behavioral intention, and fascination and compatibility affect post-visit behavioral intention through satisfaction. Furthermore, novelty, compatibility and satisfaction have a multiple chain-mediating effect on the relationship between coherence and post-visit behavioral intention, while compatibility and satisfaction have a multiple chain-mediating effect on the relationship between novelty and post-visit behavioral intention;(3) The influence of fascination and compatibility on satisfaction is positively regulated by tourist involvement;and(4) The effect of tourists' perceived restorative qualities on their post-visit behavioral intention exhibited a three-stage"environmental stimuli perception-emotion-intention"transmission mechanism.In this study, we analyzes the benefits of tourists' perceived restorative qualities, which provides important references for tourism destination managers in relation to environmental optimization, marketing and brand building. T

Impact of COVID-19 on domestic air transportation in China.

Assessing the impact of the coronavirus disease 2019 (COVID-19) on air transportation is essential for policymakers and airlines to prevent their widespread shutdown. The panel data observed from January 20, 2020, to April 30, 2020, were used to identify the impact of COVID-19 and the relevant control measures adopted on China's domestic air transportation. Hybrid models within negative binomial models were employed to separate the temporal and spatial effects of COVID-19. Temporal effects show that the number of new confirmed cases and the control measures significantly affect the number of operated flights. Spatial effects show that the network effect of COVID-19 cases in destination cities, lockdown, and adjustment to Level I in the early stages have a negative impact on the operated flights. Adjustment to Level II or Level III both has positive temporal and spatial effects. This indicates that the control measures adopted during the early stage of the pandemic positively impact the restoration of the aviation industry and other industries in the later stage.

Development of off-the-shelf hematopoietic stem cell-engineered invariant natural killer T cells for COVID-19 therapeutic intervention.

BACKGROUND: New COVID-19 treatments are desperately needed as case numbers continue to rise and emergent strains threaten vaccine efficacy. Cell therapy has revolutionized cancer treatment and holds much promise in combatting infectious disease, including COVID-19. Invariant natural killer T (iNKT) cells are a rare subset of T cells with potent antiviral and immunoregulatory functions and an excellent safety profile. Current iNKT cell strategies are hindered by the extremely low presence of iNKT cells, and we have developed a platform to overcome this critical limitation. METHODS: We produced allogeneic HSC-engineered iNKT (AlloHSC-iNKT) cells through TCR engineering of human cord blood CD34+ hematopoietic stem cells (HSCs) and differentiation of these HSCs into iNKT cells in an Ex Vivo HSC-Derived iNKT Cell Culture. We then established in vitro SARS-CoV-2 infection assays to assess AlloHSC-iNKT cell antiviral and anti-hyperinflammation functions. Lastly, using in vitro and in vivo preclinical models, we evaluated AlloHSC-iNKT cell safety and immunogenicity for off-the-shelf application. RESULTS: We reliably generated AlloHSC-iNKT cells at high-yield and of high-purity; these resulting cells closely resembled endogenous human iNKT cells in phenotypes and functionalities. In cell culture, AlloHSC-iNKT cells directly killed SARS-CoV-2 infected cells and also selectively eliminated SARS-CoV-2 infection-stimulated inflammatory monocytes. In an in vitro mixed lymphocyte reaction (MLR) assay and an NSG mouse xenograft model, AlloHSC-iNKT cells were resistant to T cell-mediated alloreaction and did not cause GvHD. CONCLUSIONS: Here, we report a method to robustly produce therapeutic levels of AlloHSC-iNKT cells. Preclinical studies showed that these AlloHSC-iNKT cells closely resembled endogenous human iNKT cells, could reduce SARS-CoV-2 virus infection load and mitigate virus infection-induced hyperinflammation, and meanwhile were free of GvHD-risk and resistant to T cell-mediated allorejection. These results support the development of AlloHSC-iNKT cells as a promising off-the-shelf cell product for treating COVID-19; such a cell product has the potential to target the new emerging SARS-CoV-2 variants as well as the future new emerging viruses.

Citrus fruits are rich in flavonoids for immunoregulation and potential targeting ACE2.

The most recent outbreak of 2019 novel coronavirus, named as COVID-19, caused pneumonia epidemic in Wuhan with 2121 deaths cases as of February 20th 2020. Identification of effective antiviral agents to combat the novel coronavirus is urgently needed. Citrus fruit peel or wild citrus are rich in flavonoids, and clinically documented for roles in relief of cough and promotion of digestive health. Therefore, citrus fruits are assumed to possess antivirus activities or enhance the host immunity. A previous study found that hesperetin could act as a high potent inhibitor of SARS-CoV 3CLpro. We determined six flavonoid compounds' content in three citrus species by using LC-MS technique. The content of naringin and naringenin was at higher levels in pummelo. Hesperetin and hesperidin were highly accumulated in mandarin and sweet orange. The subsequent in vitro and in vivo experiments indicated that naringin could inhibit the expression of the proinflammatory cytokines (COX-2, iNOS, IL-1ß and IL-6) induced by LPS in Raw macrophage cell line, and may restrain cytokine through inhibiting HMGB1 expression in a mouse model. The results revealed that naringin may have a potential application for preventing cytokine storm. We simulated molecular docking to predict the binding affinity of those flavonoids to bind Angiotensin-converting enzyme 2 (ACE 2), which is a receptor of the coronavirus. Consideration of the potential anti-coronavirus and anti-inflammatory activity of flavonoids, the citrus fruit or its derived phytochemicals are promising in the use of prevention and treatment of SARS-CoV-2 infection.