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1.
Int J Environ Res Public Health ; 19(10)2022 05 16.
Article in English | MEDLINE | ID: covidwho-1875630

ABSTRACT

Under the background of tightening resource constraints and a deteriorating ecological environment, innovation is aimed at saving energy, reducing consumption, abating pollution and achieving sustainable economic growth. This has gradually become an important way to improve industrial structure, competitiveness and environmental performance worldwide. In this study, we use the super-efficiency SBM model to calculate the innovation efficiency of 283 cities in China from 2009 to 2019. Then, based on the dynamic threshold regression model, we explore the impact of innovation efficiency on ecological footprint in innovative cities or non-innovative cities under different economic development levels. The main conclusions that can be drawn are as follows. (1) Within the research period, the influence of innovation efficiency on ecological footprint in China shows a negative double threshold feature, that is, increasing regional innovation efficiency has an inhibitory effect on ecological footprint. (2) For innovative cities, innovation efficiency has a strong inhibitory effect on ecological footprint, and it becomes stronger and stronger with the growth of night light data; but this inhibitory effect is gradually decreasing with improvement of economic development level in non-innovative cities. (3) Under the threshold of different levels of economic development, the number of scientific human resources, scientific financial resources, scientific information resources and scientific papers has a positive effect on ecological footprint, while the number of patent applications has a negative effect on ecological footprint.


Subject(s)
Conservation of Natural Resources , Economic Development , China , Cities , Efficiency , Humans
2.
J Med Microbiol ; 71(5)2022 May.
Article in English | MEDLINE | ID: covidwho-1874076

ABSTRACT

Introduction. Coronavirus disease 2019 (COVID-19) has caused a serious threat to public health worldwide, and there is currently no effective therapeutic strategy for treating COVID-19.Hypothesis/Gap Statement. We propose that sophocarpine (SOP) might have potential therapeutic effects on COVID-19 through inhibiting the cytokine storm and the nuclear factor NF-κB signalling pathway.Aim. The objective was to elucidate the potential mechanism of SOP against COVID-19 through a network pharmacology analysis and its experimental validation.Methodology. The BATMAN-TCM database was used to identify the therapeutic targets of SOP, while the GeneCards and DisGeNET databases were used to identify the targets related to COVID-19. A protein-protein interaction (PPI) network was constructed from the STRING and analysed using Cytoscape software. Gene ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and disease ontology (DO) enrichment analyses of the co-targets were performed using Metascape. Autodock 4.2.6 and Pymol software were applied for molecular docking. Levels of the proinflammatory cytokines IL-6, TNFα and IL-1ß were measured by ELISA, while mRNA expression levels of intercellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor A (VEGFA) and IFN gamma (IFNG) were detected by real-time quantitative reverse transcription PCR. The protein levels of the molecules involved in the NF-κB signalling pathway were validated by western blot analysis.Results. A total of 65 co-targets of SOP and COVID-19 were determined. GO and KEGG enrichment analyses suggested that SOP affected COVID-19 by regulating the IL-17 signalling pathway, TNF signalling pathway and other signalling pathways. The PPI network and molecular docking showed that p65, ICAM-1 and VEGFA were key targets of SOP against COVID-19 and the underlying mechanism was validated in A549 cells in vitro. SOP attenuated the LPS-induced production of TNF-α and IL-6 and downregulated the LPS-induced mRNA expression of ICAM-1, VEGFA and IFNG. Mechanistically, SOP pretreatment inhibited the phosphorylation of p65 and facilitated the activation of Nrf2.Conclusions. SOP has a potential therapeutic effect on COVID-19 through multiple pathways and targets, and inhibits the production of pro-inflammatory cytokines and molecules involved in the NF-κB signalling pathway.


Subject(s)
COVID-19 , Intercellular Adhesion Molecule-1 , Alkaloids , COVID-19/drug therapy , Cytokines/metabolism , Humans , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism , Interleukin-6 , Lipopolysaccharides , Molecular Docking Simulation , NF-kappa B/metabolism , RNA, Messenger , Tumor Necrosis Factor-alpha , Vascular Endothelial Growth Factor A
3.
Emerg Microbes Infect ; 11(1): 1572-1585, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1873822

ABSTRACT

Cryptococcal meningoencephalitis (CM) is emerging as an infection in HIV/AIDS patients shifted from primarily ART-naive to ART-experienced individuals, as well as patients with COVID-19 and immunocompetent hosts. This fungal infection is mainly caused by the opportunistic human pathogen Cryptococcus neoformans. Brain or central nervous system (CNS) dissemination is the deadliest process for this disease; however, mechanisms underlying this process have yet to be elucidated. Moreover, illustrations of clinically relevant responses in cryptococcosis are currently limited due to the low availability of clinical samples. In this study, to explore the clinically relevant responses during C. neoformans infection, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feature of HIV/AIDS patients, was a centric pathway regulated in both infection models. Notably, assays of clinical immune cells confirmed an enhanced macrophage "Trojan Horse" in patients with HIV/AIDS, which could be shut down by cytoskeleton inhibitors. Furthermore, myocilin, encoded by MYOC, was found to be a novel enhancer for the macrophage "Trojan Horse," and an enhanced fungal burden was achieved in the brains of MYOC-transgenic mice. Taken together, the findings from this study reveal fundamental roles of the cytoskeleton and MYOC in fungal CNS dissemination, which not only helps to understand the high prevalence of CM in HIV/AIDS but also facilitates the development of novel therapeutics for meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.


Subject(s)
COVID-19 , Cryptococcosis , Cryptococcus neoformans , HIV Infections , Meningoencephalitis , MicroRNAs , Animals , Brain/pathology , Cryptococcosis/microbiology , Cryptococcus neoformans/genetics , Disease Models, Animal , Humans , Macaca , Meningoencephalitis/microbiology , Mice , MicroRNAs/genetics , Transcriptome
4.
Cell Rep ; 39(11): 110955, 2022 Jun 14.
Article in English | MEDLINE | ID: covidwho-1866959

ABSTRACT

Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven inflammation is the leading cause of acute cardiac injury associated with coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In this study, using a quantitative spatial proteomics strategy that combines comparative anatomy, laser-capture microdissection, and histological examination, we establish a region-resolved proteome map of the myocardia and microvessels with obvious inflammatory cells from hearts of patients with COVID-19. A series of molecular dysfunctions of myocardia and microvessels is observed in different cardiac regions. The myocardia and microvessels of the left atrial are the most susceptible to virus infection and inflammatory storm, suggesting more attention should be paid to the lesion and treatment of these two parts. These results can guide in improving clinical treatments for cardiovascular diseases associated with COVID-19.


Subject(s)
COVID-19 , Heart Injuries , COVID-19/complications , Humans , Inflammation , Proteome , SARS-CoV-2
5.
Alpha Psychiatry ; 23(3):113-120, 2022.
Article in English | Academic Search Complete | ID: covidwho-1865619

ABSTRACT

Background: This study aimed to explore the underlying mechanisms of the relationship between stress response and behavioral response and to develop a moderated mediation model with stress management and risk cognition. Methods: We developed 4 novel questionnaires, namely, stress response questionnaire, behavioral response questionnaire, stress management questionnaire, and risk cognition questionnaire. A total of 5896 university students in China were investigated during the peak period of the coronavirus disease 2019. Results: The results showed that stress response had a significant negative predictive effect on behavioral response (r = -0.489, P < .001). Moreover, stress management had a partial mediating effect between stress response and behavioral response. Risk cognition plays a moderating effect on the mediation model (β = -0.109, P = .030), and the effect of high-risk cognition is more significant. Conclusion: During the coronavirus disease 2019 period, improving the risk awareness of university students will help to enhance the buffering effect of stress management on behavioral response and indirectly reduce their behavioral response. [ FROM AUTHOR] Copyright of Alpha Psychiatry is the property of Anatolian Journal of Psychiatry and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

6.
J Med Microbiol ; 71(5)2022 May.
Article in English | MEDLINE | ID: covidwho-1853315

ABSTRACT

Introduction. As a novel global epidemic, corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 brought great suffering and disaster to mankind. Recently, although significant progress has been made in vaccines against SARS-CoV-2, there are still no drugs for treating COVID-19. It is well known that traditional Chinese medicine (TCM) has achieved excellent efficacy in the treatment of COVID-19 in China. As a treasure-house of natural drugs, Chinese herbs offer a promising prospect for discovering anti-COVID-19 drugs.Hypothesis/Gap Statement. We proposed that Rhei Radix et Rhizome-Schisandrae Sphenantherae Fructus (RS) may have potential value in the treatment of COVID-19 patients by regulating immune response, protecting the cardiovascular system, inhibiting the production of inflammatory factors, and blocking virus invasion and replication processes.Aim. We aimed to explore the feasibility and molecular mechanisms of RS against COVID-19, to provide a reference for basic research and clinical applications.Methodology. Through literature mining, it is found that a Chinese herbal pair, RS, has potential anti-COVID-19 activity. In this study, we analysed the feasibility of RS against COVID-19 by high-throughput molecular docking and molecular dynamics simulations. Furthermore, we predicted the molecular mechanisms of RS against COVID-19 based on network pharmacology.Results. We proved the feasibility of RS anti-COVID-19 by literature mining, virtual docking and molecular dynamics simulations, and found that angiotensin converting enzyme 2 (ACE2) and 3C-like protease (3 CL pro) were also two critical targets for RS against COVID-19. In addition, we predicted the molecular mechanisms of RS in the treatment of COVID-19, and identified 29 main ingredients, 21 potential targets and 16 signalling pathways. Rhein, eupatin, (-)-catechin, aloe-emodin may be important active ingredients in RS. ALB, ESR1, EGFR, HMOX1, CTSL, and RHOA may be important targets against COVID-19. Platelet activation, renin secretion, ras signalling pathway, chemokine signalling pathway, and human cytomegalovirus infection may be important signalling pathways against COVID-19.Conclusion. RS plays a key role in the treatment of COVID-19, which may be closely related to immune regulation, cardiovascular protection, anti-inflammation, virus invasion and replication processes.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , COVID-19 Vaccines , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Feasibility Studies , Flavonoids , Humans , Molecular Docking Simulation , Rhizome , SARS-CoV-2
7.
Front Microbiol ; 13: 884034, 2022.
Article in English | MEDLINE | ID: covidwho-1847188

ABSTRACT

Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), public health worldwide has been greatly threatened. The development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanisms and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the clinic to treat bacterial infection, significantly restrained the cell entry of Ebola virus, SARS-CoV, and MERS-CoV by specifically inhibiting the activity of cathepsin L (CTSL). Here, we found that the cleavage sites of CTSL on the spike proteins of SARS-CoV-2 were highly conserved among all the variants. The treatment with teicoplanin suppressed the proteolytic activity of CTSL on spike and prevented the cellular infection of different pseudotyped SARS-CoV-2 viruses. Teicoplanin potently prevented the entry of SARS-CoV-2 into the cellular cytoplasm with an IC50 of 2.038 µM for the Wuhan-Hu-1 reference strain and an IC50 of 2.116 µM for the SARS-CoV-2 (D614G) variant. The pre-treatment of teicoplanin also prevented SARS-CoV-2 infection in hACE2 mice. In summary, our data reveal that CTSL is required for both SARS-CoV-2 and SARS-CoV infection and demonstrate the therapeutic potential of teicoplanin for universal anti-CoVs intervention.

8.
Comput Math Methods Med ; 2022: 3009589, 2022.
Article in English | MEDLINE | ID: covidwho-1832669

ABSTRACT

Objective: This study is aimed at investigating the epidemiology and risk factors of acute hemorrhagic conjunctivitis (pinkeye) in Huangshi Port District of Huangshi City. Methods: A total of 593 cases of acute hemorrhagic conjunctivitis from January 2019 to December 2021 were selected as the observation group. The epidemiological characteristics (age of onset, season, occupation, clinical manifestations, and etiological characteristics) were analyzed. A total of 425 healthy subjects (nonacute hemorrhagic conjunctivitis) were selected as the control group. The general data of the two groups were compared, and the risk factors affecting the occurrence of acute hemorrhagic conjunctivitis were analyzed by logistic regression. Results: The onset age of acute hemorrhagic conjunctivitis was mainly concentrated in 0-20-year-old and 60-year-old age groups, and the onset season was mainly concentrated in April to August, with the highest incidence in May. The proportions of middle school students and workers in patients with acute hemorrhagic conjunctivitis were higher than those of other occupations (both P < 0.05). Ocular conjunctival congestion, tingling, and foreign body sensation were the main clinical manifestations of patients with acute hemorrhagic conjunctivitis. Among the 593 conjunctival swab samples collected in this study, the positive rates of HEV70 and CVA24v were higher than those of adenovirus nucleic acid (both P < 0.05). The proportion of people aged ≤40 years old, male, working outdoors, using potable water equipment, contact history of patients with acute conjunctivitis, history of chemical substances entering eyes, combined with immune system diseases, and public toilet utilization rate ≥ 1 times/d in the observation group was higher than that in the control group (all P < 0.05), and the proportion of people washing hands before eating and after toilet was lower than that in the control group (P < 0.05). Multiple logistic regression analysis showed that working place outdoors, use of potable water equipment, contact history of patients with acute conjunctivitis (all P < 0.05), and use of public toilets ≥ once a day were risk factors for the occurrence of acute hemorrhagic conjunctivitis, and washing hands before eating and after toilet was a protective factor (P < 0.05). Conclusion: The onset age of acute hemorrhagic conjunctivitis was mainly concentrated in 0-20-year-old and 60-year-old age; the onset season was mainly concentrated in summer and autumn; adenovirus is the main pathogenic bacteria; ocular conjunctivitis congestion, tingling, and foreign body sensation were the main clinical manifestations; working place outdoors, use of potable water equipment, contact history of patients with acute conjunctivitis (all P < 0.05), and use of public toilets ≥ once a day were risk factors for the occurrence of acute hemorrhagic conjunctivitis, while washing hands before eating and after toilet was a protective factor.


Subject(s)
Conjunctivitis, Acute Hemorrhagic , Conjunctivitis , Drinking Water , Foreign Bodies , Adolescent , Adult , Child , Child, Preschool , Conjunctivitis/epidemiology , Conjunctivitis, Acute Hemorrhagic/epidemiology , Conjunctivitis, Acute Hemorrhagic/microbiology , Factor Analysis, Statistical , Humans , Infant , Infant, Newborn , Male , Risk Factors , Young Adult
9.
Front Pediatr ; 10: 787947, 2022.
Article in English | MEDLINE | ID: covidwho-1809481

ABSTRACT

Objective: The COVID-19 lockdown extended premature rupture of membranes (PROM) expectant time among nulliparas and increased the risk of term neonatal complications. This study investigated the impact of term nulliparas with PROM delays at home on neonatal outcomes during the COVID-19 lockdown period, considering the clinical diagnostic application of maternal C-reactive protein (CRP). Methods: This study collected 505 term nulliparous women who underwent PROM at home from five provinces in a non-designated hospital of China in 2020. We analyzed PROM maternal information at home and neonatal complications in the COVID-19 regional lockdown and compared related information in the national lockdown. Poisson regression models estimated the correlation of PROM management at home, maternal CRP, and neonatal morbidity. We constructed two diagnostic models: the CRP univariate model, and an assessed cut-off value of CRP in the combined model (CRP with PROM waiting time at home). Results: In the regional lockdown, PROM latency at home and the severity of neonatal complications were extended and increased lower than in the nationwide lockdown, but term neonatal morbidity was not reduced in the COVID-19 localized lockdown. Prolonged waiting time at home (≥8.17 h) was associated with increasing maternal CRP values and neonatal morbidity (adjusted risk ratio 2.53, 95% CI, 1.43 to 4.50, p for trend <0.001) in the regional lockdown period. In the combined model, CRP ≥7 mg/L with PROM latency ≥8.17 h at home showed higher diagnostic sensitivity and AUC than only CRP for initial assessing the risk of adverse neonatal complications in COVID-19 regional lockdowns (AUC, 0.714 vs. 0.534; sensitivity, 0.631 vs. 0.156). Conclusion: The impact of the acute COVID-19 national blockade on the PROM newborns' health could continue to the COVID-19 easing period. Maternal CRP reference interval (≥7 mg/L) would effectively assess the risk of term neonatal morbidity when nulliparas underwent prolonged PROM expectant at home (≥8.17 h) during the second COVID-19 lockdown.

10.
Acta Pharmacol Sin ; 2022 Apr 25.
Article in English | MEDLINE | ID: covidwho-1805599

ABSTRACT

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.

11.
Brain Sci ; 12(4)2022 Apr 18.
Article in English | MEDLINE | ID: covidwho-1792814

ABSTRACT

Olfactory dysfunction (OD) is a common symptom in coronavirus disease 2019 (COVID-19) patients. Moreover, many neurological manifestations have been reported in these patients, suggesting central nervous system involvement. The default mode network (DMN) is closely associated with olfactory processing. In this study, we investigated the internetwork and intranetwork connectivity of the DMN and the olfactory network (ON) in 13 healthy controls and 22 patients presenting with COVID-19-related OD using independent component analysis and region of interest functional magnetic resonance imaging (fMRI) analysis. There was a significant correlation between the butanol threshold test (BTT) and the intranetwork connectivity in ON. Meanwhile, the COVID-19 patients with OD showed significantly higher intranetwork connectivity in the DMN, as well as higher internetwork connectivity between ON and DMN. However, no significant difference was found between groups in the intranetwork connectivity within ON. We postulate that higher intranetwork functional connectivities compensate for the deficits in olfactory processing and general well-being in COVID-19 patients. Nevertheless, the compensation process in the ON may not be obvious at this stage. Our results suggest that resting-state fMRI is a potentially valuable tool to evaluate neurosensory dysfunction in COVID-19 patients.

12.
Mathematics ; 10(7):1037, 2022.
Article in English | ProQuest Central | ID: covidwho-1785801

ABSTRACT

Due to the existence and variation of various viruses, an epidemic in which different strains spread at the same time will occur. here, an avian–human epidemic model with two strain viruses are established and analyzed. Both theoretical and simulation results reveal that the mixed infections intensify the epidemic and the dynamics become more complex and sensitive. There are six equilibria. The trivial equilibrium point is a high-order singular point and will undergo the transcritical bifurcations to bifurcate three equilibria. The existence and stability of equilibria mainly depend on five thresholds. A bifurcation portrait for the existence and stability of equilibria is presented. Simulations suggest that the key control measure is to develop the identification technology to eliminate the poultry infected with a high pathogenic virus preferentially, then the infected poultry with a low pathogenic virus in the recruitment and on farms. Controlling contact between human and poultry can effectively restrain the epidemic and controlling contagions in poultry can avoid great infection in humans.

13.
Signal Transduct Target Ther ; 7(1): 114, 2022 04 05.
Article in English | MEDLINE | ID: covidwho-1778593

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.


Subject(s)
Antibodies, Monoclonal , Antibodies, Viral , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Antibodies, Monoclonal/chemistry , Antibodies, Viral/chemistry , COVID-19 , Cryoelectron Microscopy , Humans , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology
14.
Glob Qual Nurs Res ; 9: 23333936221080969, 2022.
Article in English | MEDLINE | ID: covidwho-1770161

ABSTRACT

Historically, qualitative research has complemented quantitative biologic and epidemiologic studies to provide a more complete understanding of pandemics. The COVID-19 pandemic has generated unique and novel challenges for qualitative researchers, who have embraced creative solutions including virtual focus groups and rapid analyses to continue their work. We present our experience conducting a multilingual global qualitative study of healthcare resilience among teams of pediatric oncology professionals during the COVID-19 pandemic. We provide an in-depth description of our methodology and an analysis of factors we believe contributed to our study's success including our use of technology, engagement of a large multilingual team, global partnerships, and framework-based rapid analysis. We hope these techniques may be useful to qualitative researchers conducting studies during the current pandemic, as well as for all pediatric oncology studies including multiple languages or geographically disparate subjects.

15.
Ann Rheum Dis ; 2022 Mar 11.
Article in English | MEDLINE | ID: covidwho-1741595

ABSTRACT

OBJECTIVES: COVID-19 vaccination often triggers a constellation of transitory inflammatory symptoms. Gout is associated with several comorbidities linked to poor outcomes in COVID-19, and gout flares can be triggered by some vaccinations. We analysed the risk of gout flares in the first 3 months after COVID-19 vaccination with inactivated virus, and whether colchicine can prevent gout flares following post-COVID-19 vaccination. METHODS: A clinical delivery population-based cross-sectional study was conducted in the Gout Clinic at the Affiliated Hospital of Qingdao University between February and October 2021. Study participants were selected using a systematic random sampling technique among follow-up patients with gout. We collected data, including vaccinations and potential risk factors, using a combination of interviews, health QR codes and medical records. Logistic regression was used to adjust for covariates. RESULTS: We enrolled 549 gout participants (median age 39 years, 84.2% vaccinated). For the 462 patients who received COVID-19 vaccine, 203 (43.9%) developed at least one gout flare in the 3 months after vaccination. Most of these flares were experienced within 1 month after the first (99/119 (83.2%)) or second (70/115 (60.9%)) dose of vaccine. Compared with unvaccinated participants, COVID-19 vaccination was associated with higher odds of gout flare within 3 months (adjusted OR 6.02; 95% CI 3.00 to 12.08). Colchicine use was associated with 47% less likelihood of postvaccine gout flare. CONCLUSION: COVID-19 vaccination was associated with increased odds of gout flare, which developed mainly in month 1 after each vaccine dose, and was negatively associated with colchicine prophylaxis.

16.
Signal Transduct Target Ther ; 7(1): 83, 2022 03 11.
Article in English | MEDLINE | ID: covidwho-1740428

ABSTRACT

SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , SARS-CoV-2/metabolism , T-Lymphocytes/metabolism , Animals , Caco-2 Cells , Chlorocebus aethiops , Humans , Vero Cells
17.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328888

ABSTRACT

Background: Medical microbiology and medical immunology are required introductory courses for second-year dentistry students. It is essential to find suitable teaching methods after the outbreak of COVID-19 to implement the call for "stop class, but not stop teaching and not stop learning." Methods We mainly used Rain Classroom for online teaching and QQ Group Classroom to support education during this particular period. Result We assessed the effectiveness of this special period instruction by analyzing anonymous questionnaires and final exam results. The anonymous questionnaire showed that most of the students were satisfied with this online instruction and found it very helpful in answering their questions and solving their problems. The final exam results showed that teaching in 2020 was no worse than teaching in 2019 and better in terms of pass rate. Teaching in 2021 was worse than in 2020, but there was a breakthrough in the highest score. Conclusion These data suggest that online teaching during the epidemic had an impact on teaching effectiveness. Most students are satisfied with online teaching, but some students' grades are affected, which may be related to the fact that some students were not comfortable with blended teaching or online teaching. We share our experiences and reflections on online and blended teaching of medical immunology and medical microbiology courses during the epidemic, hoping that it will be helpful for other teachers to teach.

18.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327774

ABSTRACT

A recent MMWR reported that the effectiveness of a 3rd dose of SARS-CoV-2 mRNA vaccine waned quickly in the Omicron-predominant period. Similarly, a substantial decline of immune responses induced by a 3rd dose of inactivated vaccines was also observed in our study. In response to the fast waning immune response and the great threat of Omicron variant of concern (VOC) to frontline healthcare workers (HCWs), 38 HCWs who were in our previous cohort investigating responses to the first three doses of inactivated vaccines participated in the current study and volunteered to receive a 4th homologous booster. Here, we demonstrated that the 4th dose is safe and capable of recalling waned immune responses 6 months after the 3rd dose. However, a greater suppression on the induction of overall Neutralizing antibodies (NAbs) and NAbs targeting the receptor-binding domain (RBD) was found in participants with stronger immune responses after the 3rd dose. As a result, a stepwise elevation of RBD-NAbs from the 1st to the 3rd vaccination achieved a "turning point". The peak RBD-NAbs level induced by the 4th dose was inferior to the peak of the 3rd dose. Accompanied with reduced induction of RBD-NAbs, the immune system shifted responses to the nucleocapsid protein (NP) and the N-terminal domain (NTD) of the spike protein. Although NTD directed antibodies are capable of neutralization, they only compensated the loss of RBD-NAbs to ancestral SARS-CoV-2 virus but not to the Omicron variant due to a substantial conformational change of Omicron NTD. This longitudinal clinical study monitored the immune response of the same cohort for every doses, shaping a relationship between the trajectory of immune focus and the dynamics of the neutralizing potency against the evolving virus. Our data reveal that immune responses could not be endlessly elevated, while suppression of heightened immune responses focusing on one subunit together with a shift of immune responses to other subunits would occur after repeated vaccination. Thus, an updated vaccine with more diverse epitopes capable of inducing NAbs against VOCs would be a future direction for boosters.

19.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325355

ABSTRACT

Background: Multiple organ damage and abnormal inflammation caused by COVID-19 have previously been reported in hospitalized patients. It remains unclear whether these patients can return to a healthy individual three months after discharge and whether there are related sequelae.Methods: We followed up 95 severe/critical patients and 51 mild/moderate ones who recovered from COVID-19 and were discharged from hospital for 3 months. For comparison, 28 asymptomatic COVID-19 recovered individuals and 42 uninfected healthy donors (HDs) were included. At the visit, patients were interviewed and subjected to quality-of-life evaluation (St. George respiratory questionnaire [SGRQ]), pulmonary function tests, chest CT imaging, laboratory examination, detection of immune cells, and cytokine profiling.Findings: At three months, all recovered patients tested negative for nucleic acid of SARS-CoV-2, and most were positive for serum SARS-COV-2 IgG, but few were still positive for serum IgM. The SGRQ scores for the quality-of-life were higher in recovered patients, especially those who had had severe/critical disease. Laboratory test revealed that CRP, LDH and D-dimer, three prevalent risk factors for COVID-19 prognosis in the acute phase, did not recover to the level of uninfected HDs in the convalescence. Immune cells virtually returned to normal levels in patients who recovered from COVID-19, but some pro-inflammatory cytokines, especially chemokines and factors related to vascular injury and angiogenesis, did not return to the level of HDs, and this was especially true of severe/critical recovered patients. CT of the lungs showed that ground-glass opacity (GGO) still lingered as the main manifestation, followed by strip-like fibrosis. Artificial intelligence (AI) analysis indicated that the lesions were most prominent in the lower lobe of right lung, and were mainly found in recovered severe/critical individuals. Abnormal lung function was mainly manifested as restrictive ventilation dysfunction and lowered diffusion capacity, which was more pronounced in severe/critical COVID-19 recovered patients. Overall, the recovery status of the patients varied with the severity of the disease.Interpretation: Decreased physical quality of life, respiratory sequelae (restrictive ventilatory dysfunction, diffusion capacity disorder, and chest CT abnormalities), vascular injury and aberrant cytokine profiles still existed three months after discharge, and were more frequent and conspicuous in severe/critical COVID-19 rehabilitation patients compared to their mild/moderate and asymptomatic counterparts.Trial Registration: This project was registered on the Clinical Trials website (No. NCT04456101) Funding: This study was supported in part by the National Natural Science Special Foundation of China (82041018, 81800094), National Major Science and Technology Projects of China (CN):2019ZX09301001, Ministry of Science and Technology of the People's Republic of China (CN):2020YFC0844300, and the Fundamental Research Funds for the Central Universities, HUST: 2020kfyXGYJ011.Declaration of Interests: The authors have no conflict of interest or financial relationships to disclose. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.Ethics Approval Statement: The protocol used in this project has been reviewed and approved by the institutional review boards of Medical Ethics Committee of Wuhan Union Hospital (NO.0271-01). All participants or their surrogates signed informed consent.

20.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325094

ABSTRACT

Background: Coronavirus Disease-2019 (COVID-19) has caused considerable morbidity and mortality. Hence, there is an urgency to find effective treatment. Tocilizumab, an inhibitor of IL-6, has been widely proposed as a treatment of severely ill patients without robust evidence supporting its use. Methods: In this multicentre, retrospective, cohort study, we included 5,235 adult patients who were admitted to 3 hospitals in Wuhan, China with confirmed COVID-19 from January 20 to March 18, 2020 . 65 patients in tocilizumab group and 130 patients in non-tocilizumab group were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities. Detailed demographic data, comorbidities, radiological and laboratory parameters, complications and treatments were compared between tocilizumab group and non-tocilizumab group. Furthermore, univariable and multivariable Logistic and Cox regression models were used to explore the risk of complications and in-hospital death associated with tocilizumab. Findings: During the follow-up, patients in non-tocilizumab group were more likely to develop into death (42 [32·31%] vs 14 [21·54%]). After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus the non-tocilizumab group (HR=0·47;95% CI=0·25-0·90;p=0·023). In the multivariable logistic regression model, use of tocilizumab was associated with a lower risk of ARDS (OR=0 · 23;95% CI=0·11-0·45;p<0·0001). Before treatment the patients had heightened inflammation and more dysregulated immune cells, which might aggravate disease progression. However, abnormally elevated IL-6, CRP, fibrinogen and APTT decreased in COVID-19 patients after treatment. And the counts of lymphocytes and immune cells subset in peripheral blood, which decreased in patients, returned to normal after treatment. No obvious complications were observed. Interpretation: Tocilizumab may be of value in improving outcomes in severe patients of COVID-19, which provided a novel strategy for COVID-19-induced cytokine release syndrome (CRS). Our preliminary data could inform bedside decisions until more data from randomized, controlled clinical trials becomes available.Funding Statement: SARS-CoV-2 Pneumonia Emergency Technology Public Relations Project of Tongji Medical College, Huazhong University of Science and Technology (No. 2020kfyXGYJ043) and National Key Research and Development Plan for the Emergency Management of Novel Coronavi rus Pneumonia, China (No. 2020YFC0845100).Declaration of Interests: The authors report no conflicts of interest.Ethics Approval Statement: This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-C20200108) and granted a waiver of informed consent from study participants.

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