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1.
Frontiers in genetics ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1877027

ABSTRACT

Observational studies have found a relationship between directly measured short leukocyte telomere length (LTL) and severe coronavirus disease 19 (COVID-19). We investigated the causal association between genetically predicted LTL and COVID-19 susceptibility or severity. A previous genome-wide association study (GWAS) of 78,592 European-ancestry participants identified single nucleotidepolymorphisms (SNPs) that can be utilized to genetically predict LTL. Summary-level data for COVID-19 outcomes were analyzed from the COVID-19 Host Genetics Initiative. A two-sample bidirectional Mendelian randomization (MR) study was designed to evaluate these causal relationships. Using an inverse-weighted MR analysis and population-based controls, genetically predicted LTL did not reveal any significant association with COVID-19 susceptibility (odds ratio (OR): 0.94;95% CI: 0.85–1.04;p = 0.202) or severity (OR: 0.85;95% CI: 0.70–1.03;p = 0.099). Similar results were found for five other definitions of cases/controls and/or COVID-19 outcomes. Six additional MR methods and sensitivity analyses were conducted after removing variants with potential horizontal pleiotropy and including variants at a liberal significance level, which produced similar results. Using SNPs identified for the prediction of LTL from another GWAS study, we found a non-significant association for COVID-19 susceptibility or severity with narrower CIs toward the null hypothesis. No proof of genetically predicted COVID-19 phenotypes remained causally associated with genetically predicted LTL, and the null association was consistent with a lack of significant genetic correlation. Genetic evidence does not support shorter LTL as a causal risk factor for COVID-19 susceptibility or severity.

2.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1876857

ABSTRACT

Safe and effective vaccines and therapeutics based on the understanding of antiviral immunity are urgently needed to end the COVID-19 pandemic. However, the understanding of these immune responses, especially cellular immune responses to SARS-CoV-2 infection, is limited. Here, we conducted a cohort study of COVID-19 patients who were followed and had blood collected to characterize the longitudinal dynamics of their cellular immune responses. Compared with healthy controls, the percentage of activation of SARS-CoV-2 S/N-specific T cells in recovered patients was significantly higher. And the activation percentage of S/N-specific CD8+ T cells in recovered patients was significantly higher than that of CD4+ T cells. Notably, SARS-CoV-2 specific T-cell responses were strongly biased toward the expression of Th1 cytokines, included the cytokines IFNγ, TNFα and IL2. Moreover, the secreted IFNγ and IL2 level in severe patients was higher than that in mild patients. Additionally, the number of IFNγ-secreting S-specific T cells in recovered patients were higher than that of N-specific T cells. Overall, the SARS-CoV-2 S/N-specific T-cell responses in recovered patients were strong, and virus-specific immunity was present until 14-16 weeks after symptom onset. Our work provides a basis for understanding the immune responses and pathogenesis of COVID-19. It also has implications for vaccine development and optimization and speeding up the licensing of the next generation of COVID-19 vaccines.

3.
Small ; : e2200854, 2022 May 22.
Article in English | MEDLINE | ID: covidwho-1858927

ABSTRACT

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 is profoundly influencing the global healthcare system and people's daily lives. The high resource consumption of coronavirus disease 2019 (COVID-19) is resulting in insufficient surveillance of coinfection or resurgence of other critical respiratory epidemics, which is of public concern. To facilitate evaluation of the current coinfection situation, a microfluidic system (MAPnavi) is developed for the rapid (<40 min) and sensitive diagnosis of multiple respiratory viruses from swab samples in a fully sealed and automated manner, in which a nested-recombinase polymerase amplification and the CRISPR-based amplification system is first proposed to ensure the sensitivity and specificity. This novel system has a remarkably low limit of detection (50-200 copies mL-1 ) and is successfully applied to detect 171 clinical samples (98.5% positive predictive agreement; 100% negative predictive agreement), and the results identify 45.6% coinfection among clinical samples from patients with COVID-19. This approach has the potential to shift diagnostic and surveillance efforts from targeted testing for a high-priority virus to comprehensive testing of multiple virus sets and to greatly benefit the implementation of decentralized testing.

4.
Sustainability ; 14(9):5325, 2022.
Article in English | MDPI | ID: covidwho-1820367

ABSTRACT

This paper investigates how investors respond to the COVID-19 pandemic, particularly regarding their intention to invest in sustainability-related investment (SRI) funds. We conduct two experiments online with participants who have experience with stock and fund investments. The first one includes 292 participants, which aims to explore investors' attitudes and investment intention of different sustainability-related components, and the second one includes 432 participants, which aims to examine how the COVID-19 pandemic affects individuals' attitudes and investment intention. Our results show that investors tend to invest in SRI funds when the threat of the COVID-19 pandemic is salient. Specifically, we find that although investors perceive environmental issues to be more important than economic and social issues, their investment intention of economic-focused SRI funds significantly increases in response to the COVID-19 pandemic threat. These findings suggest that fund managers can focus on particular types of investors when designing SRI funds, such as active investors with a preference for technical analysis and young female investors with a high level of income and education.

5.
Journal of Shandong University ; 59(1):115-121, 2021.
Article in Chinese | GIM | ID: covidwho-1780232

ABSTRACT

Objective: Taking the undergraduate education and preventive medicine for example, this paper examines and evaluates the student engagement and learning outcome in online learning during the period of "suspending classes without stopping learning", and to explore the influencing factors.

6.
Front Neurol ; 13: 838222, 2022.
Article in English | MEDLINE | ID: covidwho-1775722

ABSTRACT

Corona Virus Disease 2019 (COVID-19), the novel coronavirus disease, is now a global pandemic. Vaccination can significantly reduce the mortality rate caused by the severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). There are currently several effective vaccines that have been introduced. Inactivated COVID-19 vaccine is one of these options and is generally considered safe. Neurofascin (NF) plays an important role in keeping the functionality of the node of Ranvier. We report here a rare case of anti-NF186+ chronic inflammatory demyelinating polyneuropathy (CIDP) in a 23-year-old male patient who was vaccinated with inactivated COVID-19 vaccine prior to the onset. This report adds a new possible rare side effect of a COVID-19 vaccine and provides a case for the clinical effectiveness of rituximab (RTX) in patients with anti-NF186+ CIDP.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318614

ABSTRACT

Excessive inflammatory responses induced upon SARS-CoV-2 infection interlocks with severe symptoms and acute lung injury in patients with Severe Coronavirus Disease 2019 (COVID-19). Revealing the mechanism underlying the control of SARS-CoV-2-triggered immune-inflammatory responses would help us to understand the pathological process and guide clinical treatment. However, the effect of the NLRP3 inflammasome on regulating SARS-CoV-2-induced inflammatory responses has not been reported. Here, we revealed a distinct mechanism by which SARS-CoV-2 nucleocapsid (N) protein promotes the NLRP3 inflammasome activation to induce hyperinflammation. We demonstrated that N protein facilitates the maturation of proinflammatory cytokines IL-1β and IL-6 and induces proinflammatory responses in cultured cells and mice tissues. In team of molecular mechanism, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates the assemble of the inflammasome complex. More importantly, N protein aggravates lung injury, accelerated death in sepsis and acute inflammation mouse models, and promotes IL-1β and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production were blocked by Ac-YVAD-cmk, an inhibitor of the NLRP3 inflammasome. Therefore, this study revealed a distinct mechanism by which SARS-CoV-2 N protein promotes the NLRP3 inflammasome activation and induces excessive inflammatory responses.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318608

ABSTRACT

Objectives: This study aims to explore and compare a novel deep learning-based quantification with the conventional semi-quantitative computed tomography (CT) scoring for the serial chest CT scans of COVID-19. Materials: and Methods: 95 patients with confirmed COVID-19 and a total of 465 serial chest CT scans were involved, including 61 moderate patients (moderate group, 319 chest CT scans) and 34 severe patients (severe group, 146 chest CT scans). Conventional CT scoring and deep learning-based quantification were performed for all chest CT scans for two study goals: 1. Correlation between these two estimations;2. Exploring the dynamic patterns using these two estimations between moderate and severe groups. Results: : The Spearman’s correlation coefficient between these two estimation methods was 0.920 ( p <0.001). predicted pulmonary involvement (CT score and percent of pulmonary lesions calculated using deep learning-based quantification) increased more rapidly and reached a higher peak on 23 rd days from symptom onset in severe group, which reached a peak on 18 th days in moderate group with faster absorption of the lesions. Conclusions: : The deep learning-based quantification for COVID-19 showed a good correlation with the conventional CT scoring and demonstrated a potential benefit in the estimation of disease severities of COVID-19.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315581

ABSTRACT

Background: A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia were discharged from hospitals in Wuhan, China. We aimed to determine the cumulative percentage of complete radiological resolution at each time point, to explore the relevant affecting factors, and to describe the chest CT findings at different time points after hospital discharge. Methods: : Patients with COVID-19 pneumonia confirmed by RT-PCR who were discharged consecutively from the hospital between 5 February 2020 and 10 March 2020 and who underwent serial chest CT scans on schedule were enrolled. The radiological characteristics of all patients were collected and analysed. The total CT score was the sum of non-GGO involvement determined at discharge. Afterwards, all patients underwent chest CT scans during the 1 st , 2 nd , and 3 rd weeks after discharge. Imaging features and distributions were analysed across different time points. Results: : A total of 149 patients who completed all CT scans were evaluated;there were 67 (45.0%) men and 82 (55.0%) women, with a median age of 43 years old (IQR 36-56). The cumulative percentage of complete radiological resolution was 8.1% (12 patients), 41.6% (62), 50.3% (75), and 53% (79) at discharge and during the 1 st , 2 nd , and 3 rd weeks after discharge, respectively. Patients ≤44 years old showed a significantly higher cumulative percentage of complete radiological resolution than patients >44 years old at the 3-week follow-up. The predominant patterns of abnormalities observed at discharge were ground-glass opacity (GGO) (65 [43.6%]), fibrous stripe (45 [30.2%]), and thickening of the adjacent pleura (16 [10.7%]). Lung lesions showed obvious resolution from 2 to 3 weeks after discharge, especially in terms of GGO and fibrous stripe. “Tinted” sign and bronchovascular bundle distortion as two special features were discovered during the evolution. Conclusion: Lung lesions in COVID-19 pneumonia patients can be absorbed completely during short-term follow-up with no sequelae. Three weeks after discharge might be the optimal time point for early radiological estimation.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315490

ABSTRACT

COVID-19 is affecting every social sector significantly, including human mobility and subsequently road traffic safety. In this study, we analyze the impact of the pandemic on traffic accidents using two cities, namely Los Angeles and New York City in the U.S., as examples. Specifically, we have analyzed traffic accidents associated with various demographic groups, how traffic accidents are distributed in time and space, and the severity level of traffic accidents that both involve and do not involve other transportation modes (e.g., pedestrians and motorists). We have made the following observations: 1) the pandemic has disproportionately affected certain age groups, races, and genders;2) the "hotspots" of traffic accidents have been shifted in both time and space compared to time periods that are prior to the pandemic, demonstrating irregularity;and 3) the number of non-fatal accident cases has decreased but the number of severe and fatal cases of traffic accidents remains the same under the pandemic.

11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-310727

ABSTRACT

It is still nontrivial to develop a new fast COVID-19 screening method with the easier access and lower cost, due to the technical and cost limitations of the current testing methods in the medical resource-poor districts. On the other hand, there are more and more ocular manifestations that have been reported in the COVID-19 patients as growing clinical evidence[1]. This inspired this project. We have conducted the joint clinical research since January 2021 at the ShiJiaZhuang City, Heibei province, China, which approved by the ethics committee of The fifth hospital of ShiJiaZhuang of Hebei Medical University. We undertake several blind tests of COVID-19 patients by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Meantime as an important part of the ongoing globally COVID-19 eye test program by AIMOMICS since February 2020, we propose a new fast screening method of analyzing the eye-region images, captured by common CCD and CMOS cameras. This could reliably make a rapid risk screening of COVID-19 with the sustainable stable high performance in different countries and races. Our model for COVID-19 rapid prescreening have the merits of the lower cost, fully self-performed, non-invasive, importantly real-time, and thus enables the continuous health surveillance. We further implement it as the open accessible APIs, and provide public service to the world. Our pilot experiments show that our model is ready to be usable to all kinds of surveillance scenarios, such as infrared temperature measurement device at airports and stations, or directly pushing to the target people groups smartphones as a packaged application.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324963

ABSTRACT

Background: The Coronavirus Disease 2019 (COVID-19) has been demonstrated as the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. Case Presentation: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as COVID-19 by testing sputum on the first day of admission. He also had an elevated troponin-I (Trop I) level and diffuse myocardial dyskinesia along with decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of Interleukin 6 was 272.40pg/ml. Bedside chest radiograph had typical ground-glass changes of viral pneumonia. The laboratory test results of virus that can cause myocarditis are all negative. The patient conformed to the diagnostic criteria of Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, the Trop I reduced to 0.10 g/L, and Interleukin 6 was 7.63 pg/ml. Meanwhile the LVEF of the patient gradually recovered to 68%. Conclusion: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure, and this is the first case of COVID-19 infection complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.

13.
mBio ; : e0360021, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1662304

ABSTRACT

Pyroptosis, a programmed cell death, functions as an innate immune effector mechanism and plays a crucial role against microbial invasion. Gasdermin D (GSDMD), as the main pyroptosis effector, mediates pyroptosis and promotes releasing proinflammatory molecules into the extracellular environment through pore-forming activity, modifying inflammation and immune responses. While the substantial importance of GSDMD in microbial infection and cancer has been widely investigated, the role of GSDMD in virus infection, including coronaviruses, remains unclear. Enteric coronavirus transmissible gastroenteritis virus (TGEV) and porcine deltacoronavirus (PDCoV) are the major agents for lethal watery diarrhea in neonatal pigs and pose the potential for spillover from pigs to humans. In this study, we found that alphacoronavirus TGEV upregulated and activated GSDMD, resulting in pyroptosis after infection. Furthermore, the fragment of swine GSDMD from amino acids 242 to 279 (242-279 fragment) was required to induce pyroptosis. Notably, GSDMD strongly inhibited both TGEV and PDCoV infection. Mechanistically, the antiviral activity of GSDMD was mediated through promoting the nonclassical release of antiviral beta interferon (IFN-ß) and then enhancing the interferon-stimulated gene (ISG) responses. These findings showed that GSDMD dampens coronavirus infection by an uncovered GSDMD-mediated IFN secretion, which may present a novel target of coronavirus antiviral therapeutics. IMPORTANCE Coronaviruses, primarily targeting respiratory and gastrointestinal epithelia in vivo, have a serious impact on humans and animals. GSDMD, a main executioner of pyroptosis, is highly expressed in epithelial cells and involves viral infection pathogenesis. While the functions and importance of GSDMD as a critical regulator of inflammasome activities in response to intracellular bacterial infection have been extensively investigated, the roles of GSDMD during coronavirus infection remain unclear. We here show that alphacoronavirus TGEV triggered pyroptosis and upregulated GSDMD expression, while GSDMD broadly suppressed the infection of enteric coronavirus TGEV and PDCoV by its pore-forming activity via promoting unconventional release of IFN-ß. Our study highlights the importance of GSDMD as a regulator of innate immunity and may open new avenues for treating coronavirus infection.

14.
Preprint in English | medRxiv | ID: ppmedrxiv-22270417

ABSTRACT

BackgroundThough case fatality rate (CFR) is widely used to reflect COVID-19 fatality risk, its use is limited by large temporal and spatial variation. Hospital mortality rate (HMR) is also used to assess the severity of COVID-19, but HMR data is not directly available except 35 states of USA. Alternative metrics are needed for COVID-19 severity and fatality assessment. MethodsNew metrics and their applications in fatality measurements and risk monitoring are proposed here. We also introduce a new mathematical model to estimate average hospital length of stay for death (Ldead) and discharges (Ldis). Multiple data sources were used for our analysis. FindingsWe propose three new metrics, hospital occupancy mortality rate (HOMR), ratio of total deaths to hospital occupancy (TDHOR) and ratio of hospital occupancy to cases (HOCR), for dynamic assessment of COVID-19 fatality risk. Estimated Ldead and Ldis for 501,079 COVID-19 hospitalizations in US 34 states between Aug 7, 2020 and Mar 1, 2021 were 14.0 and 18.2 days, respectively. We found that TDHOR values of 27 countries are less spatially and temporally variable and more capable of detecting changes in COVID-19 fatality risk. The dramatic changes in COVID-19 CFR observed in 27 countries during early stages of the pandemic were mostly caused by undiagnosed cases. Compared to the first week of November, 2021, the week mean HOCRs (mimics hospitalization-to-case ratio) for Omicron variant decreased 34.08% and 65.16% in the United Kingdom and USA respectively as of Jan 16, 2022. InterpretationThese new and reliable measurements for COVID-19 that could be expanded as a general index to other fatal infectious diseases for disease fatality risk and variant-associated risk monitoring. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed, medRxiv, and bioRxiv for peer-reviewed articles, preprints, and research reports on risk and health care evaluation for COVID-19 using the search terms "hospital occupancy mortality rate", "ratio of total deaths to hospital occupancy", "ratio of hospital occupancy to case" up to Jan 20, 2022. No similar concepts or studies were found. No similar mathematical models based on "hospital occupancy mortality rate" for the estimation of hospital length of stay for deaths and discharges have been identified to date. Added value of the studyOur new metrics, HOMR and TDHOR, mimic HMR for COVID-19 fatality risk assessment but utilize readily available data for many US states and countries around the world. HOCR mimics hospitalization-to-case ratio for COVID-19. We also provide evidence that explains why COVID-19 CFR has such dramatic changes at the beginning of a COVID-19 outbreak. We have additionally provided new metrics for COVID-19 fatality risk dynamic monitoring including Omicron variant and showed that these metrics provided additional information. Implications of all the available evidenceThe results of this study, including average hospital length of stay for deaths and discharges for over 500,000 COVID-19 hospitalizations in the US, can aid county, state, and national leaders in making informed public health decisions related to the ongoing COVID-19 pandemic. This is the first study to provide quantitative evidence to address why CFR has a such a large variation at the beginning of the COVID-19 pandemic in most countries and will hopefully encourage more countries to release hospital occupancy data, which we show is both useful and easy information to collect. The new metrics introduced by our study are effective indicators for monitoring COVID-19 fatality risk, as well as potentially fatal COVID-19 variants, and could also be expanded to other fatal infectious diseases.

15.
Sustainable Production and Consumption ; 2022.
Article in English | ScienceDirect | ID: covidwho-1627870

ABSTRACT

Past studies related to embodied pollutant accounting reported that free trade has increased the environmental pollution of developing economies, because the developed countries “outsource” their pollutants to developing nations. The COVID-19 pandemic has stimulated the rise of the most serious protectionism after World War II. This study is aimed to discuss whether protectionism improve the environment in developing countries by developing a comprehensive evaluation model, which integrates multi-regional input-output (MRIO), data envelopment analysis (DEA), and scenario analysis. We revealed the role of protectionism from two perspectives: the single impact on pollutant emissions and the comprehensive impact on environmental efficiency. Specifically, the capital inputs, labor inputs, energy consumption, economic output, carbon dioxide, sulfur dioxide and nitrogen oxides emissions related to global trade activities were simulated based on the multi-regional input-output model. And then, sector-level trade environmental efficiency was computed by intergrading the MRIO and DEA using a non-radial directional distance function. Finally, the environmental efficiency of both developing and developed countries under two scenarios with and without trade were estimated. The results confirmed that trade has increased the CO2, SO2 and NOX emissions of developing economies by 12.9%, 9.8% and 12.3%, and has reduced that of developed economies by 6.0%, 29.4% and 21.2%, respectively. However, the results also uncovered that the environmental efficiency of developing and developed economies was dropped by 3% and 5%, respectively, under no-trade scenario. We contend that protectionism is not conducive to the sustainable development of developing countries because it lowers their environmental efficiency, although it may reduce their territorial pollutant emissions. For developed countries, the single impact of protectionism on pollutant emission reduction and the comprehensive impact on environmental efficiency are both negative.

16.
Zhongguo Huanjing Kexue = China Environmental Science ; 41(10):4703, 2021.
Article in English | ProQuest Central | ID: covidwho-1619209

ABSTRACT

Using the method of sewage epidemiology, the occurrence characteristics and changes of two typical psychoactive drugs methamphetamine and ketamine in the domestic sewage of a city in Guangdong Province during and before and after the new crown epidemic in 2020 were studied, and the mobile phone signaling data was used to analyze The total population, structural characteristics and their change laws were combined to analyze the changes in the consumption of the two drugs during the epidemic and before and after the epidemic. The results show that the actual population of the city during the epidemic decreased by about 45% compared with before the epidemic. The total consumption of various drugs has dropped by about 75% compared to before the epidemic. The significant decline in total consumption was largely caused by the actual population decline during the epidemic. In fact, the per capita consumption levels of methamphetamine and ketamine in the city during the epidemic Compared with the pre-epidemic drop of less than 50%. Taking into account the strict control measures during the epidemic, this decline shows that the abuse of these two psychotropic substances is extremely stubborn;after the epidemic, the consumption of the two drugs and their concentrations in the environment have increased significantly. It has basically returned to the level before the epidemic, which further proves the stubbornness of psychotropic substance abuse.

17.
Genes Dis ; 2021 Dec 03.
Article in English | MEDLINE | ID: covidwho-1616497

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Spike protein that mediates coronavirus entry into host cells is a major target for COVID-19 vaccines and antibody therapeutics. However, multiple variants of SARS-CoV-2 have emerged, which may potentially compromise vaccine effectiveness. Using a pseudovirus-based assay, we evaluated SARS-CoV-2 cell entry mediated by the viral Spike B.1.617 and B.1.1.7 variants. We also compared the neutralization ability of monoclonal antibodies from convalescent sera and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine) and ZF2001 (RBD-subunit vaccine) against B.1.617 and B.1.1.7 variants. Our results showed that, compared to D614G and B.1.1.7 variants, B.1.617 shows enhanced viral entry and membrane fusion, as well as more resistant to antibody neutralization. These findings have important implications for understanding viral infectivity and for immunization policy against SARS-CoV-2 variants.

18.
Frontiers in microbiology ; 12, 2021.
Article in English | EuropePMC | ID: covidwho-1609622

ABSTRACT

Coronavirus is an important pathogen with a wide spectrum of infection and potential threats to humans and animals. Its replication occurs in the cytoplasm and is closely related to the endoplasmic reticulum (ER). Studies reported that coronavirus infection causes ER stress, and cells simultaneously initiate unfolded protein response (UPR) to alleviate the disturbance of ER homeostasis. Activation of the three branches of UPR (PERK, IRE1, and ATF6) modulates various signaling pathways, such as innate immune response, microRNA, autophagy, and apoptosis. Therefore, a comprehensive understanding of the relationship between coronavirus and ER stress is helpful to understand the replication and pathogenesis of coronavirus. This paper summarizes the current knowledge of the complex interplay between coronavirus and UPR branches, focuses on the effect of ER stress on coronavirus replication and coronavirus resistance to host innate immunity, and summarizes possible drug targets to regulate the impact of coronavirus infection.

19.
J Econ Behav Organ ; 195: 122-139, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1599409

ABSTRACT

This research examines the intention of undergraduate medical students to withdraw from the medical profession and pursue a career in a different field upon graduation during COVID-19. We leverage the first and most comprehensive nationwide survey for medical education in China, which covered 98,668 enrolled undergraduate students from 90 out of 181 Chinese medical schools in 2020. We focus on these students' self-reported intention to leave the healthcare industry (the "dropout intention") before and after the outbreak of the epidemic. We also designed a randomized experiment to test whether and to what extent medical students dropout intention responded to an information nudge that highlighted the prosociality of health professionals in the fight against the virus. Results from a difference-in-differences model and a student fixed effect model suggest that after the onset of COVID-19, the proportion of Chinese undergraduate medical students with a dropout intention declined from 13.7% to 6.8%. Furthermore, the nudge information reduced the intent-to-drop-out probability by 0.8 additional percentage points for students in their early college years. There was large heterogeneity underneath the treatment effect. Specifically, we find that prior dropout intention and exposures to COVID-19-related information tended to mitigate the nudge effects. Data on students' actual dropout outcomes support our findings.

20.
Preprint in English | medRxiv | ID: ppmedrxiv-21267983

ABSTRACT

RationaleHigh galectin-3 levels predict poor outcomes in patients with COVID-19. Galectin-3 activates monocytes and macrophages which are directly implicated in COVID-19 immunopathology and the cytokine storm. GB0139 is a potent thiodigalactoside galectin-3 inhibitor and may reduce the severe effects of the disease. We report safety and pharmacokinetics and pharmacodynamics of the inhaled galectin-3 inhibitor, GB0139, and assess clinical outcomes and key systemic inflammatory biomarkers in hospitalised patients with COVID-19 (ClinicalTrials.gov/EudraCT identifier: NCT04473053/2020-002230-32). MethodsAdults with COVID-19 requiring oxygen, and with pneumonitis on x-ray, were randomised to receive standard of care (SOC; including dexamethasone; n=21) or SOC plus 10 mg GB0139 twice daily for 48 hours, then once daily for [≤]14 days (n=20). ResultsPatients aged 27-87 years were enrolled from July 2020; the final patient completed the 90-day follow-up in April 2021. GB0139+SOC was well tolerated with no treatment-related serious adverse events reported. Incidences of adverse events were similar between treatment arms (40 with GB0139+SOC vs 35 with SOC). Plasma GB0139 was measurable in all patients after inhaled exposure, with moderate interpatient variability, and demonstrated target engagement with decreased circulating galectin (overall treatment effect post-hoc over days 2-7: p=0{middle dot}0099 vs SOC). Rate of decline in fraction of inspired oxygen (%) requirement was significantly greater in the GB0139+SOC arm with a posterior mean difference of -1{middle dot}51 (95% highest posterior density: -2{middle dot}90, -0{middle dot}189) versus SOC. Plasma levels of biomarkers associated with inflammation, coagulopathy, major organ function and fibrosis showed a downward trend versus SOC. ConclusionsGB0139+SOC was well tolerated and achieved clinically relevant plasma concentrations and target engagement. This, and the reduction in markers associated with inflammatory, coagulation, fibrosis, and reduction in inspired oxygen (%) over SOC alone, indicates the therapeutic potential for inhaled GB0139 in hospitalised patients with COVID-19.

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