How National Culture Influences the Speed of COVID-19 Spread: Three Cross-Cultural Studies

The COVID-19 pandemic has affected 222 countries and territories around the globe. Notably, the speed of COVID-19 spread varies significantly across countries. This cross-cultural research proposes and empirically examines how national culture influences the speed of COVID-19 spread in three studies. Study 1 examines the effects of Hofstede's national cultural dimensions on the speed of COVID-19 spread in 60 countries. Drawing on the GLOBE study (House et al., 2004), Study 2 investigates how GLOBE cultural dimensions relate to the speed of the pandemic's spread in 55 countries. Study 3 examines the effect of cultural tightness in 31 countries. We find that five national cultural dimensions – power distance, uncertainty avoidance, humane orientation, in-group collectivism, and cultural tightness – are significantly related to the speed of COVID-19 spread in the initial stages, but not in the later stages, of the pandemic. Study 1 shows that the coronavirus spreads faster in countries with small power distance and strong uncertainty avoidance. Study 2 supports these findings and further reveals that countries with low humane orientation and high in-group collectivism report a faster spread of the disease. Lastly, Study 3 shows that COVID-19 spreads slower in countries with high cultural tightness.

Fiscal Pressure and Public–Private Partnership Investment: Based on Evidence from Prefecture-Level Cities in China

Public–private partnership (PPP) policy is essential to alleviating the local government debt burden and improving resource allocation efficiency. This paper empirically examines the impact of fiscal pressure on PPP investment in Chinese prefecture-level cities from 2014 to 2019 using the ordinary least-squares (OLS) module. Moreover, we also investigate how fiscal pressure influences PPP investment and test the influenced mechanism from other perspectives. The results show the following. (1) Fiscal pressure on the government has a significant positive effect on PPP investment at the prefectural level. (2) The marketization process is the mediated effect of the relationship between fiscal pressure and PPP investment. Fiscal pressure will stimulate the regional marketization process, thus promoting PPP investment. (3) Fiscal pressure has a significant positive effect on PPP investment in the middle region, while the effect is not significant in the eastern and western regions. Meanwhile, the effect is not significant in central cities, but there is a significant positive effect in ordinary cities. (4) The effect of fiscal pressure on PPP investment is not significant in the private reward mode of government payment, but there is a significant positive effect in the mode of user payment and feasibly insufficient subsidies. Our studies could also provide practical suggestions for sustainable development of PPP policy and solving the fiscal pressure of the current economic recession under the COVID-19 pandemic.

How National Culture Influences the Speed of COVID-19 Spread: Three Cross-Cultural Studies

The COVID-19 pandemic has affected 222 countries and territories around the globe. Notably, the speed of COVID-19 spread varies significantly across countries. This cross-cultural research proposes and empirically examines how national culture influences the speed of COVID-19 spread in three studies. Study 1 examines the effects of Hofstede’s national cultural dimensions on the speed of COVID-19 spread in 60 countries. Drawing on the GLOBE study (House et al., 2004), Study 2 investigates how GLOBE cultural dimensions relate to the speed of the pandemic’s spread in 55 countries. Study 3 examines the effect of cultural tightness in 31 countries. We find that five national cultural dimensions – power distance, uncertainty avoidance, humane orientation, in-group collectivism, and cultural tightness – are significantly related to the speed of COVID-19 spread in the initial stages, but not in the later stages, of the pandemic. Study 1 shows that the coronavirus spreads faster in countries with small power distance and strong uncertainty avoidance. Study 2 supports these findings and further reveals that countries with low humane orientation and high in-group collectivism report a faster spread of the disease. Lastly, Study 3 shows that COVID-19 spreads slower in countries with high cultural tightness.

Transcriptional regulation and small compound targeting of ACE2 in lung epithelial cells.

Angiotensin-converting enzyme 2 (ACE2) is the receptor of COVID-19 pathogen SARS-CoV-2, but the transcription factors (TFs) that regulate the expression of the gene encoding ACE2 (ACE2) have not been systematically dissected. In this study we evaluated TFs that control ACE2 expression, and screened for small molecule compounds that could modulate ACE2 expression to block SARS-CoV-2 from entry into lung epithelial cells. By searching the online datasets we found that 24 TFs might be ACE2 regulators with signal transducer and activator of transcription 3 (Stat3) as the most significant one. In human normal lung tissues, the expression of ACE2 was positively correlated with phosphorylated Stat3 (p-Stat3). We demonstrated that Stat3 bound ACE2 promoter, and controlled its expression in 16HBE cells stimulated with interleukin 6 (IL-6). To screen for medicinal compounds that could modulate ACE2 expression, we conducted luciferase assay using HLF cells transfected with ACE2 promoter-luciferase constructs. Among the 64 compounds tested, 6-O-angeloylplenolin (6-OAP), a sesquiterpene lactone in Chinese medicinal herb Centipeda minima (CM), represented the most potent ACE2 repressor. 6-OAP (2.5 µM) inhibited the interaction between Stat3 protein and ACE2 promoter, thus suppressed ACE2 transcription. 6-OAP (1.25-5 µM) and its parental medicinal herb CM (0.125%-0.5%) dose-dependently downregulated ACE2 in 16HBE and Beas-2B cells; similar results were observed in the lung tissues of mice following administration of 6-OAP or CM for one month. In addition, 6-OAP/CM dose-dependently reduced IL-6 production and downregulated chemokines including CXCL13 and CX3CL1 in 16HBE cells. Moreover, we found that 6-OAP/CM inhibited the entry of SARS-CoV-2 S protein pseudovirus into target cells. These results suggest that 6-OAP/CM are ACE2 inhibitors that may potentially protect lung epithelial cells from SARS-CoV-2 infection.

Epidemiological Characteristics of COVID-19 Deaths In China: An Analysis of Environmental Factors (preprint)

Background: As of April 2020, most of the confirmed cases outside Hubei province have been cured or confirmed dead in China. We aimed to understand environmental factors leading to COVID-19-related mortality in non-Hubei region. Methods: : We collected spatial-temporal and environmental data of 99 cases of COVID-19-related deaths outside of Hubei province in Mainland China between January 22, 2020 and April 6, 2020. A descriptive analysis, including a spatial-temporal distribution of daily reported diagnosed cases and related deaths, was conducted. We analyzed the possible environmental factors that affect the provincial-level case fatality rate (CFR) of COVID-19 outside Hubei, China. Results: Among the 99 reported deaths, 59 (59.6%) were male and 40 (40.4%) were female. The mean age at death was 71.30 (SD 12.98) years and 74 deaths were among those 65 years or older. The CFR was negatively correlated with temperature (r=-0.679, P <0.001) and humidity (r=-0.607, P =0.002), while latitude was positively correlated with the CFR (r=0.636, P =0.001). There were no statistically significant associations between CFR and the social environment factors. Conclusion: Higher CFR of COVID-19 was associated with lower temperature, lower humidity, and higher latitude. Continual analysis of daily reported diagnoses and mortality data can help healthcare professionals and policy makers understand the trends within a country in order to better prepare nationwide prevention and care guidelines, along with adequately appropriate funds accordingly.

Structural basis of main proteases of coronavirus bound to drug candidate PF-07321332 (preprint)

The high mutation rate of COVID-19 and the prevalence of multiple variants strongly support the need for pharmacological options to complement vaccine strategies. One region that appears highly conserved among different genus of coronaviruses is the substrate binding site of the main protease (Mpro or 3CLpro), making it an attractive target for the development of broad-spectrum drugs for multiple coronaviruses. PF-07321332 developed by Pfizer is the first orally administered inhibitor targeting the main protease of SARS-CoV-2, which also has shown potency against other coronaviruses. Here we report three crystal structures of main protease of SARS-CoV-2, SARS-CoV and MERS-CoV bound to the inhibitor PF-07321332. The structures reveal a ligand-binding site that is conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, providing insights into the mechanism of inhibition of viral replication. The long and narrow cavity in the cleft between domains I and II of main protease harbors multiple inhibitor binding sites, where PF-07321332 occupies subsites S1, S2 and S4 and appears more restricted compared with other inhibitors. A detailed analysis of these structures illuminated key structural determinants essential for inhibition and elucidated the binding mode of action of main proteases from different coronaviruses. Given the importance of main protease for the treatment of SARS-CoV-2 infection, insights derived from this study should accelerate the design of safer and more effective antivirals.

Construction Safety during Pandemics: Learning from the Xinjia Express Hotel Collapse during COVID-19 in China.

Many construction accidents occur in China each year, leading to a large number of deaths, injures, and property losses. Due to the outbreak of COVID-19, little attention is paid to construction safety, resulting in severe accidents. To prevent construction accidents and learn to how address safety issues in future pandemics, this study proposed an improved STAMP (Systems Theoretic Accident Modeling and Processes) model to analyze the collapse accident of the Xinjia Express Hotel used for COVID-19 quarantine in China. Through the application of the STAMP approach, the causes of the construction accident and the relationship between various causal factors are analyzed from a systematic perspective. The identified causes are divided into five categories: contractors, management of organizations, technical methods, participants, and interactive feedback. Finally, safety recommendations are drawn from this study to improve construction safety and safety management in pandemics.

Research development of mRNA vaccine delivery system based on lipid carrier

Transcriptional messenger RNA(mRNA) has a safe and effective protein expression profile and a good application prospect in the development of new treatment strategies for genetic diseases, expression of functional proteins and antibodies, vaccines or gene editing. With the development of pathogenic biology and immunology, mRNA vaccine has been paid more and more attention because of its high efficiency and stability. At present, the effective means of in vivo delivery is a great challenge for mRNA vaccines. The mRNA vaccine delivery system based on lipid carriers has the characteristics of strong targeting, high entrapment efficiency and good cellular affinity. Some lipid carriers can enable mRNA vaccines to be targeted in a non-invasive manner. This review summarized the research progress of mRNA vaccine delivery system based on lipid vector from three aspects: main challenge of mRNA vaccine delivery, research status of lipid carriers in mRNA vaccine delivery and development progress of mRNA lipid carrier vaccine against SARS-CoV-2, and looks forward to the research direction of gene vaccine delivery system in the future.

Factors Associated with the Expression of ACE2 in Human Lung Tissue: Pathological Evidence from Patients with Normal FEV1 and FEV1/FVC.

BACKGROUND: Whether COVID-19 comorbidities and risk factors such as old age, male gender, smoking, obesity, eosinophils and blood types have direct contact with expression of ACE2 and pro-inflammation cytokines in human lung tissues were still unclear. PATIENTS AND METHODS: Sixty-four patients with normal FEV1 and FEV1/FVC underwent thoracotomy for pulmonary nodules were included. Blinded histological assessments were performed by two pathologists. Clinical features and results of the immunohistochemical staining of ACE2 were collected and analyzed. RESULTS: ACE2 expressed in alveolar macrophages (most obvious), alveolar epithelia and vascular endothelia, but not in small-airway epithelia. ACE2 expressions are positively related to age (r =0.26, P =0.040), weight (r =0.43, P<0.001), as well as BMI (r = 0.38, P =0.002), and male patients show higher expressions of ACE2 in lungs (P <0.05). ACE2 expressions are negatively related to peripheral eosinophils (r = -0.30, P =0.017). There was no correlation between ABO blood types and ACE2 expression in normal lung tissues (P > 0.05). IL-13 and IL-6R expression in lung tissue increased with age (r =0.26, P <0.05, for both). CONCLUSION: Our pathological evidences showed that the alveolar epithelia, vascular endothelia, and alveolar macrophages are susceptible in human lungs for SARS-CoV-2 infection. The risk factors such as high body weight/BMI, old age, male gender, and eosinopenia may be related to ACE2 expression in human lungs, and associated with more chance to develop the severe cases. IL-6R expression in lung tissue also increased with age. Therefore, weight control and smoking cessation are essential to reduce the susceptibility of SARS-CoV-2 infection, especially in obesity, old or male patients. Peripheral eosinophils monitor is also quite necessary to detect severe tendency in COVID-19 patients.

Structure of SARS-CoV-2 main protease in the apo state reveals the inactive conformation (preprint)

Mpro is of considerable interest as a drug target in the treatment of COVID-19 since the proteolytic activity of this viral protease is essential for viral replication. Here we report the first insight of the structure Mpro for SARS-CoV-2 in the inactive conformation under conditions close to the physiological state (pH 7.5) to an overall resolution of 1.9 [A]. The comparisons of Mpro in different states reveal that substrate binding site and the active site are more flexible in the inactive conformation than that in the active conformations. Notably, compared with the active conformation of the apo state structure in pH7.6 of SARS, the SARS-CoV-2 apo state is in the inactive conformation under condition close to physiological state (pH7.5). Two water molecules are present in the oxyanion hole in our apo state structure, whereas in the ligand-bound structure, water molecular is absence in the same region. This structure provides novel and important insights that have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational, structure-based, approaches for the design of specific SARS-CoV-2 ligands as new therapeutic agents.

Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test (preprint)

Background It has been reported that several cases recovered from COVID-19 tested positive for SARS-CoV-2 after discharge (re-detectable positive, RP), however the clinical characteristics, significance and potential cause of RP patients remained elusive. Methods A total of 262 COVID-19 patients were discharged from January 23 to February 25, 2020, and were enrolled for analysis of their clinical parameters. The RP and non-RP (NRP) patients were grouped according to the disease severity during their hospitalization period. The clinical characterization at re-admission to the hospital was analyzed. SARS-CoV-2 RNA and plasma antibody levels were detected using high-sensitive detection methods. Findings Up to March 10, 2020, all of patients were followed up for at least 14 days, and 38/262 of RP patients (14.5%) were present. The RP patients were characterized by being less than 14-years old and having mild and moderate conditions as compared to NRP patients, while no severe patients became RP. Retrospectively, the RP patients displayed fewer symptoms, more sustained remission of CT imaging and earlier RNA negative-conversion but similar plasma antibody levels during their hospitalization period as compared to those NRP patients. When re-admitted to the hospital, these RP patients showed no obvious clinical symptoms or disease progression indicated by normal or improving CT imaging and inflammatory cytokine levels. All 21 close contacts of RP patients were tested negative for SARS-CoV-2 RNA, and no suspicious clinical symptoms were reported. However, 18/24 of RNA-negative samples detected by the commercial kit were tested to be positive for virus RNA using a hyper-sensitive method, suggesting the carrier status of virus possibly existed in patients recovered from COVID-19. Interpretation Our results showed that young and mild COVID-19 patients seem to be RP patients after discharge, who show no obviously clinical symptoms and disease progression upon re-admission. More sensitive RNA detection methods are required to monitor these patients during follow-up. Our findings provide empirical information and evidence for the effective management of COVID-19 patients during their convalescent phase.

COVID-19 in a Designated Infectious Diseases HospitalOutside Hubei Province,China (preprint)

Background A new type of novel coronavirus infection (COVID-19) occurred in Wuhan, Hubei Province. Previous investigations reported patients in Wuhan city often progressed into severe or critical and had a high mortality rate.The clinical characteristics of affected patients outside the epicenter of Hubei province are less well understood. Methods All confirmed COVID-19 case treated in the Third People's Hospital of Shenzhen,from January 11, 2020 to February 6, 2020, were included in this study. We analyzed the epidemiological and clinical features of these cases to better inform patient management in normal hospital settings. Results Among the 298 confirmed cases, 233(81.5%) had been to Hubei while 42(14%) had not clear epidemiological history. Only 192(64%) cases presented with fever as initial symptom. The lymphocyte count decreased in 38% patients after admission. The number (percent) of cases classified as non-severe and severe was 240(80.6%) and 58(19.4%) respectively. Thirty-two patients (10.7%) needed ICU care. Compared to the non-severe cases, severe cases were associated with older age, underlying diseases, as well as higher levels of CRP, IL-6 and ESR. The median (IRQ) duration of positive viral test were 14(10-19). Slower clearance of virus was associated with higher risk of progression to severe clinical condition. As of February 14, 2020, 66(22.1%) patients were discharged and the overall mortality rate remains 0. Conclusions In a designated hospital outside the Hubei Province, COVID-19 patients were mainly characterized by mild symptoms and could be effectively manage by properly using the existing hospital system.