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1.
Stem Cells Int ; 2022: 7695078, 2022.
Article in English | MEDLINE | ID: covidwho-2009238

ABSTRACT

Extracellular vesicles (EVs) play an essential part in multiple pathophysiological processes including tissue injury and regeneration because of their inherent characteristics of small size, low immunogenicity and toxicity, and capability of carrying a variety of bioactive molecules and mediating intercellular communication. Nevertheless, accumulating studies have shown that the application of EVs faces many challenges such as insufficient therapeutic efficacy, a lack of targeting capability, low yield, and rapid clearance from the body. It is known that EVs can be engineered, modified, and designed to encapsulate therapeutic cargos like proteins, peptides, nucleic acids, and drugs to improve their therapeutic efficacy. Targeted peptides, antibodies, aptamers, magnetic nanoparticles, and proteins are introduced to modify various cell-derived EVs for increasing targeting ability. In addition, extracellular vesicle mimetics (EMs) and self-assembly EV-mimicking nanocomplex are applied to improve production and simplify EV purification process. The combination of EVs with biomaterials like hydrogel, and scaffolds dressing endows EVs with long-term therapeutic efficacy and synergistically enhanced regenerative outcome. Thus, we will summarize recent developments of EV modification strategies for more extraordinary regenerative effect in various tissue injury repair. Subsequently, opportunities and challenges of promoting the clinical application of engineered EVs will be discussed.

2.
Journal of Affective Disorders ; 317:79-83, 2022.
Article in English | ScienceDirect | ID: covidwho-2004179

ABSTRACT

Background Pregnant women themselves are at higher risk for psychological symptoms. The impact of ongoing COVID-19 may increase the risk. However, it is uncertain whether COVID-19 affects pregnant women's psychological symptoms directly or indirectly being mediated. Methods This survey was conducted in four obstetrics and gynecology hospitals in Beijing from February 28, 2020, to April 26, 2020. Pregnant women who visited the antenatal-care clinic were mobilized to finish the online questionnaires, including the Generalized Anxiety Disorder 7-Item Scale, Patient Health Questionnaire-9, Connor-Davidson resilience scale, and Insomnia Severity Index. Results A total of 828 pregnant women were included in the analysis. The estimated self-reported rates of anxiety, depression, insomnia, and any of the three were 12.2 %, 24.3 %, 13.3 %, and 33.1 %, respectively. Mediating effect analysis showed that pregnant women's response to COVID-19 was not directly associated with psychological symptoms but indirectly through the mediating effect of maternal concerns, which accounted for 32.35 % of the total effect. Stratified analysis by psychological resilience showed that women's attitude toward COVID-19 (OR, 2.68, 95 % CI: 1.16–6.18) was associated with a higher risk of psychological symptoms in those with poor psychological resilience. Limitations The study was a non-probability sampling survey, and the causal relationship between maternal concerns and psychological symptoms could not be determined due to the study's design. Conclusions Under public health emergencies such as COVID-19, routine antenatal care should still be prioritized, and concerns related to childbirth-related caused by such emergencies should also be addressed, especially for those with weak psychological resilience.

3.
Rheumatology (Oxford) ; 2022 Jul 22.
Article in English | MEDLINE | ID: covidwho-1997074

ABSTRACT

OBJECTIVE: To explore whether inactivated COVID-19 vaccine influences the profile of prothrombotic autoantibodies and induces thrombotic events in primary antiphospholipid syndrome (APS) patients. METHODS: We enrolled 39 primary APS patients who received two doses of inactivated SARS-CoV-2 vaccine (BBIBPCorV, Sinopharm, Beijing, China) voluntarily in this prospective cohort. Prothrombotic autoantibodies were determined before vaccination and four weeks after the 2nd dose of vaccination. Thrombotic disorders were evaluated via hospital site visits and assessments. RESULTS: There was no significant difference in the presence of all eleven autoantibodies detected before and four weeks after vaccination: for aCL, IgG (14 vs. 16, P= 0.64), IgM (13 vs. 19, P= 0.34), IgA (2 vs. 3, P= 0.64); anti-ß2GP1, IgG (12 vs. 12, P= 1.00), IgM (5 vs. 8, P= 0.36), IgA (4 vs. 3, P= 0.69); aPS/PT IgG (13 vs. 16, P= 0.48), IgM (17 vs. 22, P= 0.26); LAC (22 vs. 28, P= 0.16); aPF4-heparin (0 vs. 0, P= 1.00), and antinuclear antibody (ANA) (23 vs. 26, P= 0.48). Notably, the distribution of aPL profile in pre- and post- vaccination cohort was not affected by SARS-CoV-2 vaccination: for patients with low-risk aPL profile (11 vs. 10, P= 0.799) and patients with high-risk aPL profile (28 vs. 29, P= 0.799), respectively. Furthermore, no case exhibited symptoms of the thrombotic disorder during a minimum follow-up period of 12 weeks. There was no adjustment to the ongoing treatment regimens following SARS-CoV-2 vaccination. CONCLUSIONS: Inactivated SARS-CoV-2 vaccine does not influence the profile of antiphospholipid antibodies and anti-PF4-heparin antibodies nor induces thrombotic events in primary APS patients.

4.
J Am Coll Health ; : 1-8, 2022 May 27.
Article in English | MEDLINE | ID: covidwho-1868139

ABSTRACT

Introduction: This study seeks to understand the reality and psychological difficulties faced by university graduates in Wuhan after the COVID-19 epidemic was controlled. Methods: A total of 6,417 graduate students were surveyed through an online questionnaire from late May to early June 2020. The questionnaire asked questions on depression, anxiety, insomnia, and suicidal behavior. In addition, self-administered epidemic-related questionnaires consisting of eight items were collected from university graduates. Results: Participants' positive detection rates for depression, anxiety, insomnia, and suicidal behavior are 13.4%, 8.3%, 4.4%, and 12.1%, respectively. The three biggest challenges faced by graduates are future development, economic difficulties, and employment problems. Conclusion: The detectable rate of depression, anxiety, and insomnia is low, and the detectable rate of suicide symptoms should be given more attention. The biggest problem of this group is their future development, and what they want to solve the most is the economic difficulty.

5.
Nutr Health ; : 2601060221099782, 2022 May 06.
Article in English | MEDLINE | ID: covidwho-1832978

ABSTRACT

Background: The COVID-19 pandemic has negatively impacted the eating behaviours of people especially fruits and vegetable intake. No study has addressed the fruits and vegetables intake during the COVID-19 in Malaysia. Aim: to assess the daily intake of fruits and vegetables among Malaysian adults during the COVID-19 outbreak, perceived changes in intake, as well as factors associated with the changes in intake. Methods: A cross-sectional study was conducted through online platforms and a total of 506 participants were recruited. Semi food-frequency questionnaires were used to assess participants' fruit and vegetable intake. Socio-demographics information, knowledge, attitude and practices (KAP) of fruits and vegetables were collected. All statistical analyses were performed using SPSS. Results: The majority of participants (99.8%) did not achieve the recommended five servings per day, in which they consumed an average of 0.84 servings of fruits and vegetables per day. 46.4% of participants reported no changes in intake compared to before the outbreak. Fruits and vegetables intake was associated with physical activity level, knowledge, and beliefs of foods that may prevent/cure COVID-19. Binary logistic regression identified two significant risk factors of daily fruits and vegetables intake namely, being a non-Chinese (AOR = 1.905, 95% CI = 1.114-3.257) and having good practices scores (AOR = 2.543, 95% CI = 1.611-4.015). Conclusion: The study found a low daily intake of fruits and vegetables. The findings suggested that nutritional interventions are necessary to improve awareness on consuming more fruits and vegetables to improve overall health.

6.
Data Brief ; 42: 108232, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1814313

ABSTRACT

The dataset describes factors affecting international students' acceptance of Online Distance Learning (ODL) mode while pursuing oversea education during COVID-19 pandemic. The recruited respondents comprised of international students who were pursuing undergraduate degree programmes in the institutions of higher learning (IHLs) in Malaysia. Respondents were invited to participate in an online survey via Google Forms. A purposive sampling technique was adopted in this research whereby a total of 207 valid questionnaires were obtained and used for data analysis. Data outputs such as respondents' profile, Partial Least Squares Structural Equation Modelling, and importance-performance matrix analysis were presented. The data can be used as a reference source to identify areas of improvement by educators, academic management, and policy makers of IHLs.

7.
Arthritis Rheumatol ; 2022 Apr 18.
Article in English | MEDLINE | ID: covidwho-1797978
8.
Pathy's Principles and Practice of Geriatric Medicine ; n/a(n/a):530-541, 2022.
Article in English | Wiley | ID: covidwho-1709041

ABSTRACT

Summary The incidence, severity, and mortality of COVID-19 infection appear to impact the elderly more negatively, especially in those who are frail and have multiple comorbidities. This chapter reviews the epidemiology of the COVID-19 pandemic with a focus on the older age group. The transmission of the virus to humans likely occurs through the consumption of an infected animal as a source of food, followed by human-to-human transmission through close contact. The epidemiology of COVID-19 incidence, severity of illness, and mortality appear to have unfavourable outcomes for older people. Managing older people with COVID-19 infection includes symptomatic therapy that focuses on the direct relief of the typical symptoms of COVID-19, drug therapy that focuses on agents directly treating the viral infection load, and general supportive care, which focuses on the relief of atypical symptoms in the acute setting. Ethical issue is the participation of older people in clinical trials.;Objective While endothelial dysfunction has been implicated in the widespread thrombo-inflammatory complications of coronavirus disease-19 (COVID-19), the upstream mediators of endotheliopathy remain for the most part cryptic. Our aim was to identify circulating factors contributing to endothelial cell activation and dysfunction in COVID-19. Methods Human endothelial cells were cultured in the presence of serum or plasma from 244 patients hospitalized with COVID-19 and plasma from 100 patients with non-COVID sepsis. Cell adhesion molecules (E-selectin, VCAM-1, and ICAM-1) were quantified by in-cell ELISA. Results Serum and plasma from patients with COVID-19 increased surface expression of cell adhesion molecules. Furthermore, levels of soluble ICAM-1 and E-selectin were elevated in patient serum and tracked with disease severity. The presence of circulating antiphospholipid antibodies was a strong marker of the ability of COVID-19 serum to activate endothelium. Depletion of total IgG from antiphospholipid antibody-positive serum markedly restrained upregulation of cell adhesion molecules. Conversely, supplementation of control serum with patient IgG was sufficient to trigger endothelial activation. Conclusion These data are the first to suggest that some patients with COVID-19 have potentially diverse antibodies that drive endotheliopathy, adding important context regarding thrombo-inflammatory effects of autoantibodies in severe COVID-19.

9.
Arthritis Rheumatol ; 74(7): 1132-1138, 2022 07.
Article in English | MEDLINE | ID: covidwho-1694821

ABSTRACT

OBJECTIVE: While endothelial dysfunction has been implicated in the widespread thromboinflammatory complications of COVID-19, the upstream mediators of endotheliopathy remain, for the most part, unknown. This study was undertaken to identify circulating factors contributing to endothelial cell activation and dysfunction in COVID-19. METHODS: Human endothelial cells were cultured in the presence of serum or plasma from 244 patients hospitalized with COVID-19 and plasma from 100 patients with non-COVID-19-related sepsis. Cell adhesion molecules (E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 [ICAM-1]) were quantified using in-cell enzyme-linked immunosorbent assay. RESULTS: Serum and plasma from COVID-19 patients increased surface expression of cell adhesion molecules. Furthermore, levels of soluble ICAM-1 and E-selectin were elevated in patient serum and correlated with disease severity. The presence of circulating antiphospholipid antibodies was a strong marker of the ability of COVID-19 serum to activate endothelium. Depletion of total IgG from antiphospholipid antibody-positive serum markedly reduced the up-regulation of cell adhesion molecules. Conversely, supplementation of control serum with patient IgG was sufficient to trigger endothelial activation. CONCLUSION: These data are the first to indicate that some COVID-19 patients have potentially diverse antibodies that drive endotheliopathy, providing important context regarding thromboinflammatory effects of autoantibodies in severe COVID-19.


Subject(s)
Antibodies, Antiphospholipid , COVID-19 , Endothelial Cells , Antibodies, Antiphospholipid/immunology , COVID-19/immunology , Cell Adhesion Molecules/metabolism , E-Selectin , Endothelial Cells/metabolism , Endothelium, Vascular , Humans , Immunoglobulin G/metabolism , Intercellular Adhesion Molecule-1/metabolism , Vascular Cell Adhesion Molecule-1/metabolism
10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-319971

ABSTRACT

Background: Coronavirus disease 2019 is an infectious disease. From January 2020 to now, the disease is still a public health event. Aims: : Our aim in the present study was to examine the effects of psychological adaptation on preventive behavior, the mediating effect of risk cognition and the moderating effect of stress coping. Methods: : We took colleges students in China as the survey subject;data were collected during the peak period of the COVID-19. Results: : Psychological adaptation had a significant negative predictive effect on preventive behavior. Risk cognition had a partial mediating effect between psychological adaptation and preventive behavior. Stress coping plays a moderating effect in the first half of the mediating process of psychological adaptation → risk cognition → preventive behavior, and individuals with high stress coping are more vulnerable to the impact of psychological adaptation on risk cognition. Conclusions: : The impact of psychological adaptation on preventive behavior can occur through the mediation variable of risk cognition. Reducing the risk cognition of college students helps to enhance the positive predictive effect of psychological adaptation on preventive behavior. Moreover, stress coping plays a moderating effect of the mediation model. improving the stress coping of colleges and universities students helps to better increase the negative predict effect of psychological adaptation on risk cognition.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319968

ABSTRACT

Background: The outbreak of novel 2019 coronavirus disease (COVID-19) has imposed an enormous physical and psychological pressure on people across the world. This study focused on evaluating the prevalence and influencing factors of anxiety and depression symptoms in surgical nurses during the epidemic in China. MethodA cross-sectional, multicenter quantitative study was conducted in Anhui province (China) from March 3, 2020 to March 19, 2020, with a questionnaire package which consisted of general information questionnaire,Zung's self-rating anxiety scale (SAS), Zung's self-rating Depression Scale (SDS) and social support rating scale (SSRS). A total of 3600 surgical nurses participated in the survey by Wechat and QQ. Data were analysed using multiple linear regression models. ResultsA total of 3492 surgical nurses from 12tertiary hospitals and 12 secondary hospitals in one province of mainland China completed the survey. The prevalence rates of anxiety symptoms and depressive symptoms were 24.83% and 22.39%, respectively. The average level of anxiety and depression of surgical nurses were higher than that of the Chinese norm ( P < 0.05).Levels of social support for surgical nurses were significantly negatively associated with the degree of anxiety (r = -0.630, P < 0.001) and depression (r = -0.578, P < 0.001). Fertility status ( β = 1.469, P = 0.003), hospital ( β = -0.611, P < 0.001), participation in care for COVID-19 patients ( β = 2.229, P < 0.001), likelihood of being infected with COVID-19 ( β = 1.146, P < 0.001), social support ( β = -0.623, P < 0.001) were significantly influencing surgical nurses’ anxiety degree. Similarly, these characteristics were significantly associated with the odds of experiencing depression symptoms in surgical nurses. Divorce and widowed surgical nurses ( β = -2.654, P < 0.001) were significantly more likely to experience depressive symptoms than single nurses. ConclusionIn this survey, we found that the surgical nurses had high anxiety and depression symptoms during the COVID-19 outbreak in China. The findings suggest that targeted psychological interventions to promote the mental health of surgical nurses with psychological problems need to be immediately implemented.

12.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-307686

ABSTRACT

A worldwide effort is ongoing to discover drugs against the Severe Acute Respiratory Syndrome coronavirus type 2 (SARS-CoV-2), which has so far caused >3.5 million fatalities (https://covid19.who.int/). The virus essential RNA-dependent RNA polymerase complex is targeted by several nucleoside/tide analogues whose mechanisms of action and clinical potential are currently evaluated. The guanosine analogue AT-527, a double prodrug of its 5'-triphosphate AT-9010, is currently in phase III clinical trials as a COVID19 treatment. Here we report the cryo-EM structure at 2.98 Å resolution of the SARS-CoV-2 nsp12-nsp7-(nsp8)2 complex with RNA showing AT-9010 bound at three sites of nsp12. At the RdRp active-site, one AT-9010 is incorporated into the RNA product. Its 2'-methyl group prevents correct alignment of a second AT-9010 occupying the incoming NTP pocket. The 2'-F, 2'-methyl 3'-OH ribose scaffold explains the non-obligate RNA chain-termination potency of this NA series for both HCV NS5 and SARS-CoV RTCs. A third AT-9010 molecule 5'-diphosphate binds to a coronavirus-specific pocket in the nsp12 N-terminus NiRAN domain, a SelO pseudo-kinase structural and functional homologue. This unique binding mode impedes NiRAN-mediated UMPylation of SARS-CoV-2 nsp8 and nsp9 proteins. Our results suggest a mechanism of action for AT-527 in line with a therapeutic use for COVID19.

13.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306021

ABSTRACT

SARS-CoV2, which causes coronavirus disease (COVID-19) is continuing to spread globally and has become a pandemic. People have lost their lives due to the virus and the lack of counter measures in place. Given the increasing caseload and uncertainty of spread, there is an urgent need to develop machine learning techniques to predict the spread of COVID-19. Prediction of the spread can allow counter measures and actions to be implemented to mitigate the spread of COVID-19. In this paper, we propose a deep learning technique, called Deep Sequential Prediction Model (DSPM) and machine learning based Non-parametric Regression Model (NRM) to predict the spread of COVID-19. Our proposed models were trained and tested on novel coronavirus 2019 dataset, which contains 19.53 Million confirmed cases of COVID-19. Our proposed models were evaluated by using Mean Absolute Error and compared with baseline method. Our experimental results, both quantitative and qualitative, demonstrate the superior prediction performance of the proposed models.

14.
Nat Commun ; 13(1): 621, 2022 02 02.
Article in English | MEDLINE | ID: covidwho-1671551

ABSTRACT

The guanosine analog AT-527 represents a promising candidate against Severe Acute Respiratory Syndrome coronavirus type 2 (SARS-CoV-2). AT-527 recently entered phase III clinical trials for the treatment of COVID-19. Once in cells, AT-527 is converted into its triphosphate form, AT-9010, that presumably targets the viral RNA-dependent RNA polymerase (RdRp, nsp12), for incorporation into viral RNA. Here we report a 2.98 Å cryo-EM structure of the SARS-CoV-2 nsp12-nsp7-nsp82-RNA complex, showing AT-9010 bound at three sites of nsp12. In the RdRp active-site, one AT-9010 is incorporated at the 3' end of the RNA product strand. Its modified ribose group (2'-fluoro, 2'-methyl) prevents correct alignment of the incoming NTP, in this case a second AT-9010, causing immediate termination of RNA synthesis. The third AT-9010 is bound to the N-terminal domain of nsp12 - known as the NiRAN. In contrast to native NTPs, AT-9010 is in a flipped orientation in the active-site, with its guanine base unexpectedly occupying a previously unnoticed cavity. AT-9010 outcompetes all native nucleotides for NiRAN binding, inhibiting its nucleotidyltransferase activity. The dual mechanism of action of AT-527 at both RdRp and NiRAN active sites represents a promising research avenue against COVID-19.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Guanosine Monophosphate/analogs & derivatives , Phosphoramides/chemistry , Phosphoramides/pharmacology , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/enzymology , Viral Proteins/antagonists & inhibitors , Viral Proteins/metabolism , COVID-19/virology , Cryoelectron Microscopy , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Guanosine Monophosphate/chemistry , Guanosine Monophosphate/pharmacology , Humans , RNA-Dependent RNA Polymerase/chemistry , RNA-Dependent RNA Polymerase/genetics , RNA-Dependent RNA Polymerase/metabolism , SARS-CoV-2/chemistry , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , Viral Proteins/genetics
15.
Signal Transduct Target Ther ; 6(1): 438, 2021 12 24.
Article in English | MEDLINE | ID: covidwho-1585880

ABSTRACT

Messenger RNA (mRNA) vaccine technology has shown its power in preventing the ongoing COVID-19 pandemic. Two mRNA vaccines targeting the full-length S protein of SARS-CoV-2 have been authorized for emergency use. Recently, we have developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor-binding domain (RBD) of SARS-CoV-2 (termed ARCoV), which confers complete protection in mouse model. Herein, we further characterized the protection efficacy of ARCoV in nonhuman primates and the long-term stability under normal refrigerator temperature. Intramuscular immunization of two doses of ARCoV elicited robust neutralizing antibodies as well as cellular response against SARS-CoV-2 in cynomolgus macaques. More importantly, ARCoV vaccination in macaques significantly protected animals from acute lung lesions caused by SARS-CoV-2, and viral replication in lungs and secretion in nasal swabs were completely cleared in all animals immunized with low or high doses of ARCoV. No evidence of antibody-dependent enhancement of infection was observed throughout the study. Finally, extensive stability assays showed that ARCoV can be stored at 2-8 °C for at least 6 months without decrease of immunogenicity. All these promising results strongly support the ongoing clinical trial.


Subject(s)
COVID-19 Vaccines/pharmacology , COVID-19/immunology , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , /pharmacology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Chlorocebus aethiops , Humans , Macaca fascicularis , Vero Cells , /immunology
16.
Non-conventional in English | Social Science Open Access Repository, Grey literature | ID: grc-747788

ABSTRACT

Purpose: This study investigates Chinese college students' satisfaction with using e-learning systems and its influences on their sense of online classroom community in synchronous, asynchronous, or a blend of both synchronous and asynchronous online course format during the COVID-19 pandemic. Methods: A total number of 307 college students were recruited with 270 usable responses from a southeastern university in China. E-learner satisfaction measurement and Classroom Community Scale (both with a 5-point Likert-type scale) were used as the instruments to investigate the research questions. Descriptive statistical analysis and multiple regression analysis were conducted in SPSS. Results: Results of the analysis show that Chinese college students' satisfaction of using the e-learning system regarding the learner interface, learning community, content, and personalization positively impacts their sense of online classroom community no matter in synchronous, asynchronous, or a blend of both synchronous and asynchronous online course format. Implications: A well-developed e-learning system would enhance students' sense of online classroom community. Specifically, the user interface, interaction, content arrangement, and personalization should be focused on when developing the e-learning system.

17.
JCI Insight ; 6(17)2021 09 08.
Article in English | MEDLINE | ID: covidwho-1413722

ABSTRACT

Neutrophil-mediated activation and injury of the endothelium play roles in the pathogenesis of diverse disease states ranging from autoimmunity to cancer to COVID-19. Neutralization of cationic proteins (such as neutrophil extracellular trap-derived [NET-derived] histones) with polyanionic compounds has been suggested as a potential strategy for protecting the endothelium from such insults. Here, we report that the US Food and Drug Administration-approved polyanionic agent defibrotide (a pleiotropic mixture of oligonucleotides) directly engages histones and thereby blocks their pathological effects on endothelium. In vitro, defibrotide counteracted endothelial cell activation and pyroptosis-mediated cell death, whether triggered by purified NETs or recombinant histone H4. In vivo, defibrotide stabilized the endothelium and protected against histone-accelerated inferior vena cava thrombosis in mice. Mechanistically, defibrotide demonstrated direct and tight binding to histone H4 as detected by both electrophoretic mobility shift assay and surface plasmon resonance. Taken together, these data provide insights into the potential role of polyanionic compounds in protecting the endothelium from thromboinflammation with potential implications for myriad NET- and histone-accelerated disease states.


Subject(s)
Fibrinolytic Agents/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Polydeoxyribonucleotides/pharmacology , Thrombosis/drug therapy , Animals , Extracellular Traps/drug effects , Extracellular Traps/metabolism , Fibrinolytic Agents/therapeutic use , Histones/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Male , Mice , Mice, Inbred C57BL , Polydeoxyribonucleotides/therapeutic use , Pyroptosis
18.
JCI Insight ; 6(15)2021 08 09.
Article in English | MEDLINE | ID: covidwho-1282186

ABSTRACT

The release of neutrophil extracellular traps (NETs) by hyperactive neutrophils is recognized to play an important role in the thromboinflammatory milieu inherent to severe presentations of COVID-19. At the same time, a variety of functional autoantibodies have been observed in individuals with severe COVID-19, where they likely contribute to immunopathology. Here, we aimed to determine the extent to which autoantibodies might target NETs in COVID-19 and, if detected, to elucidate their potential functions and clinical associations. We measured anti-NET antibodies in 328 individuals hospitalized with COVID-19 alongside 48 healthy controls. We found high anti-NET activity in the IgG and IgM fractions of 27% and 60% of patients, respectively. There was a strong correlation between anti-NET IgG and anti-NET IgM. Both anti-NET IgG and anti-NET IgM tracked with high levels of circulating NETs, impaired oxygenation efficiency, and high circulating D-dimer. Furthermore, patients who required mechanical ventilation had a greater burden of anti-NET antibodies than did those not requiring oxygen supplementation. Levels of anti-NET IgG (and, to a lesser extent, anti-NET IgM) demonstrated an inverse correlation with the efficiency of NET degradation by COVID-19 sera. Furthermore, purified IgG from COVID-19 sera with high levels of anti-NET antibodies impaired the ability of healthy control serum to degrade NETs. In summary, many individuals hospitalized with COVID-19 have anti-NET antibodies, which likely impair NET clearance and may potentiate SARS-CoV-2-mediated thromboinflammation.


Subject(s)
Autoantibodies/immunology , COVID-19/immunology , Extracellular Traps/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Autoantibodies/blood , COVID-19/blood , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged , Neutrophils/immunology , Young Adult
19.
J Leukoc Biol ; 109(1): 67-72, 2021 01.
Article in English | MEDLINE | ID: covidwho-1188010

ABSTRACT

Severe cases of coronavirus disease 2019 (COVID-19) are regularly complicated by respiratory failure. Although it has been suggested that elevated levels of blood neutrophils associate with worsening oxygenation in COVID-19, it is unknown whether neutrophils are drivers of the thrombo-inflammatory storm or simple bystanders. To better understand the potential role of neutrophils in COVID-19, we measured levels of the neutrophil activation marker S100A8/A9 (calprotectin) in hospitalized patients and determined its relationship to severity of illness and respiratory status. Patients with COVID-19 (n = 172) had markedly elevated levels of calprotectin in their blood. Calprotectin tracked with other acute phase reactants including C-reactive protein, ferritin, lactate dehydrogenase, and absolute neutrophil count, but was superior in identifying patients requiring mechanical ventilation. In longitudinal samples, calprotectin rose as oxygenation worsened. When tested on day 1 or 2 of hospitalization (n = 94 patients), calprotectin levels were significantly higher in patients who progressed to severe COVID-19 requiring mechanical ventilation (8039 ± 7031 ng/ml, n = 32) as compared to those who remained free of intubation (3365 ± 3146, P < 0.0001). In summary, serum calprotectin levels track closely with current and future COVID-19 severity, implicating neutrophils as potential perpetuators of inflammation and respiratory compromise in COVID-19.


Subject(s)
COVID-19 , Calgranulin A , Calgranulin B , Neutrophil Activation , Neutrophils , SARS-CoV-2 , COVID-19/blood , COVID-19/immunology , COVID-19/pathology , COVID-19/therapy , Calgranulin A/blood , Calgranulin A/immunology , Calgranulin B/blood , Calgranulin B/immunology , Female , Hospitalization , Humans , Male , Middle Aged , Neutrophils/immunology , Neutrophils/metabolism , Neutrophils/pathology , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Severity of Illness Index , Time Factors
20.
Front Immunol ; 11: 603389, 2020.
Article in English | MEDLINE | ID: covidwho-1069720

ABSTRACT

The catastrophic outbreak of coronavirus disease 2019 (COVID-19) is currently a public emergency. Adult-onset Still's disease (AOSD) is an autoinflammatory disease characterized by life-threatening complications. Systemic hyperinflammation and cytokine storm play a critical role in the pathogenesis of both COVID-19 and AOSD. We aimed to compare the similarities and differences focusing on ferritin and cytokine levels between severe COVID-19 and active AOSD. A literature search was performed using the databases PubMed, EMBASE, and Web of Science to collect the levels of cytokine including IL-1ß, IL-6, IL-18, TNF-α, IL-10, and ferritin in severe COVID-19 patients. After extracting available data of indicators of interest, we acquired these statistics with a single-arm meta-analysis. Furthermore, a comparison was conducted between 52 patients with active AOSD in our center and severe COVID-19 patients from databases. The levels of IL-6 and IL-10 were higher in severe COVID-19 compared with those in active AOSD. There were no significant differences on the cytokine of IL-1ß and TNF-α. Fold changes of IL-18 were defined as the mean expression level ratio of severe COVID-19 to healthy controls in the COVID-19 study and active AOSD to healthy controls in our study, individually. Although the fold change of IL-18 in patients with AOSD was significantly higher than patients with severe COVID-19 (fold change: 594.00 vs 2.17), there was no statistical comparability. In addition, the level of ferritin was higher in active AOSD in comparison with severe COVID-19. Our findings suggest that severe COVID-19 and active AOSD have differences in cytokine panel and ferritin level, indicating the pathogenic role of ferritin in overwhelming inflammation. And it paves the way to make efficacy therapeutic strategy targeting the hyperinflammatory process in COVID-19 according to AOSD management, especially in severe COVID-19.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Inflammation/immunology , Still's Disease, Adult-Onset/immunology , Adult , Aged , COVID-19/epidemiology , Cytokine Release Syndrome/epidemiology , Cytokines/blood , Female , Ferritins/blood , Humans , Male , Middle Aged , Still's Disease, Adult-Onset/epidemiology
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