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1.
Mol Med ; 28(1): 57, 2022 05 16.
Article in English | MEDLINE | ID: covidwho-1846786

ABSTRACT

BACKGROUND: Severe COVID-19 is characterized by pro-inflammatory cytokine release syndrome (cytokine storm) which causes high morbidity and mortality. Recent observational and clinical studies suggest famotidine, a histamine 2 receptor (H2R) antagonist widely used to treat gastroesophageal reflux disease, attenuates the clinical course of COVID-19. Because evidence is lacking for a direct antiviral activity of famotidine, a proposed mechanism of action is blocking the effects of histamine released by mast cells. Here we hypothesized that famotidine activates the inflammatory reflex, a brain-integrated vagus nerve mechanism which inhibits inflammation via alpha 7 nicotinic acetylcholine receptor (α7nAChR) signal transduction, to prevent cytokine storm. METHODS: The potential anti-inflammatory effects of famotidine and other H2R antagonists were assessed in mice exposed to lipopolysaccharide (LPS)-induced cytokine storm. As the inflammatory reflex is integrated and can be stimulated in the brain, and H2R antagonists penetrate the blood brain barrier poorly, famotidine was administered by intracerebroventricular (ICV) or intraperitoneal (IP) routes. RESULTS: Famotidine administered IP significantly reduced serum and splenic LPS-stimulated tumor necrosis factor (TNF) and IL-6 concentrations, significantly improving survival. The effects of ICV famotidine were significantly more potent as compared to the peripheral route. Mice lacking mast cells by genetic deletion also responded to famotidine, indicating the anti-inflammatory effects are not mast cell-dependent. Either bilateral sub-diaphragmatic vagotomy or genetic knock-out of α7nAChR abolished the anti-inflammatory effects of famotidine, indicating the inflammatory reflex as famotidine's mechanism of action. While the structurally similar H2R antagonist tiotidine displayed equivalent anti-inflammatory activity, the H2R antagonists cimetidine or ranitidine were ineffective even at very high dosages. CONCLUSIONS: These observations reveal a previously unidentified vagus nerve-dependent anti-inflammatory effect of famotidine in the setting of cytokine storm which is not replicated by high dosages of other H2R antagonists in clinical use. Because famotidine is more potent when administered intrathecally, these findings are also consistent with a primarily central nervous system mechanism of action.


Subject(s)
COVID-19 , Famotidine , Animals , Anti-Inflammatory Agents , Cytokine Release Syndrome , Famotidine/pharmacology , Histamine , Histamine H2 Antagonists , Lipopolysaccharides , Mice , Reflex , Vagus Nerve , alpha7 Nicotinic Acetylcholine Receptor
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-333131

ABSTRACT

Background: Severe COVID-19 is characterized by pro-inflammatory cytokine release syndrome (cytokine storm) which causes high morbidity and mortality. Recent observational and clinical studies suggest famotidine, a histamine 2 receptor (H2R) antagonist widely used to treat gastroesophageal reflux disease , attenuates the clinical course of COVID-19. Because evidence is lacking for a direct antiviral activity of famotidine, a proposed mechanism of action is blocking the effects of histamine released by mast cells. Here we hypothesized that famotidine activates the inflammatory reflex, a brain-integrated vagus nerve mechanism which inhibits inflammation via alpha 7 nicotinic acetylcholine receptor ( α7nAChR ) signal transduction, to prevent cytokine storm. Methods: . The potential anti-inflammatory effects of famotidine and other H2R antagonists was assessed in mice exposed to lipopolysaccharide (LPS)-induced cytokine storm. As the inflammatory reflex is integrated and can be stimulated in the brain, and H2R antagonists penetrate the blood brain barrier poorly, famotidine was administered by intracerebroventricular (ICV) or intraperitoneal (IP) routes. Results: . Famotidine administered IP significantly reduced serum and splenic LPS-stimulated tumor necrosis factor α and interleukin-6 concentrations, significantly improving survival. The effects of ICV famotidine were significantly more potent as compared to the peripheral route. Mice lacking mast cells by genetic deletion also responded to famotidine, indicating the anti-inflammatory effects are not mast cell dependent. Either bilateral sub-diaphragmatic vagotomy or genetic knock-out of α7nAChR abolished the anti-inflammatory effects of famotidine, indicating the inflammatory reflex as famotidine’s mechanism of action. While the structurally similar H2R antagonist tiotidine displayed equivalent anti-inflammatory activity, the H2R antagonists cimetidine or ranitidine were ineffective even at very high dosages. Conclusions: . These observations reveal a previously unidentified vagus nerve-dependent anti-inflammatory effect of famotidine in the setting of cytokine storm which is not replicated by high dosages of other H2R antagonists in clinical use. Because famotidine is more potent when administered intrathecally, these findings are also consistent with a primarily central nervous system mechanism of action.

3.
Res Sq ; 2022 Apr 11.
Article in English | MEDLINE | ID: covidwho-1786501

ABSTRACT

Background. Severe COVID-19 is characterized by pro-inflammatory cytokine release syndrome (cytokine storm) which causes high morbidity and mortality. Recent observational and clinical studies suggest famotidine, a histamine 2 receptor (H2R) antagonist widely used to treat gastroesophageal reflux disease , attenuates the clinical course of COVID-19. Because evidence is lacking for a direct antiviral activity of famotidine, a proposed mechanism of action is blocking the effects of histamine released by mast cells. Here we hypothesized that famotidine activates the inflammatory reflex, a brain-integrated vagus nerve mechanism which inhibits inflammation via alpha 7 nicotinic acetylcholine receptor ( α7nAChR ) signal transduction, to prevent cytokine storm. Methods. The potential anti-inflammatory effects of famotidine and other H2R antagonists was assessed in mice exposed to lipopolysaccharide (LPS)-induced cytokine storm. As the inflammatory reflex is integrated and can be stimulated in the brain, and H2R antagonists penetrate the blood brain barrier poorly, famotidine was administered by intracerebroventricular (ICV) or intraperitoneal (IP) routes. Results. Famotidine administered IP significantly reduced serum and splenic LPS-stimulated tumor necrosis factor α and interleukin-6 concentrations, significantly improving survival. The effects of ICV famotidine were significantly more potent as compared to the peripheral route. Mice lacking mast cells by genetic deletion also responded to famotidine, indicating the anti-inflammatory effects are not mast cell dependent. Either bilateral sub-diaphragmatic vagotomy or genetic knock-out of α7nAChR abolished the anti-inflammatory effects of famotidine, indicating the inflammatory reflex as famotidine's mechanism of action. While the structurally similar H2R antagonist tiotidine displayed equivalent anti-inflammatory activity, the H2R antagonists cimetidine or ranitidine were ineffective even at very high dosages. Conclusions. These observations reveal a previously unidentified vagus nerve-dependent anti-inflammatory effect of famotidine in the setting of cytokine storm which is not replicated by high dosages of other H2R antagonists in clinical use. Because famotidine is more potent when administered intrathecally, these findings are also consistent with a primarily central nervous system mechanism of action.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318922

ABSTRACT

Objects: To investigate the impact of COVID-19 epidemic on adult myasthenia gravis (MG) patients, in order to provide better medical advice for special patient population during the quarantine period. Methods: Adult MG patients were randomly recruited to participate. The survey consisted of self-designed questionnaires and the revised 15-item Myasthenia Gravis Quality of Life Questionnaire (MGQOL15r). Participation was strictly voluntary and remained anonymous. Results: A total of 214 adult MG patients (84 males and 130 females) gave valid replies. There were 49.53% patients reported they had the fear of COVID-19 outbreak at different levels. And female patients had a significant higher level of fear to COVID outbreak (p=0.009). It was found that the adult MG patients are more likely to be influenced by the COVID-19 epidemic compared to the general population. During the COVID-19 outbreak, 36.45% patients reported they got an improvement of MG disease severity. 57.01% patients reported they felt no change. 6.54% patients reported their condition got worse. The average of MGQOL15r score was 7.38±6.22. The higher level of the fear of COVID-19 outbreak, the higher score of MGQOL15r (p=0.029), the poorer quality of life. 96.73% patients hoped the specialist physicians could provide online consult. In addition, 64.95% patients would go to the tertiary hospital without hesitation if the Outpatients Department was opened even during the COVID-19 epidemic. Conclusions: The COVID-19 epidemic has significant impact on the quality of life and psychological status in the adult MG patients. Compared to the general population, the adult MG patients are more likely to be influenced by the COVID-19 epidemic. Hence, it is important for health care organizations to provide professional therapeutic advice and psychosocial support in time.*, Contributed to this work equally.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317496

ABSTRACT

Background: More evidence in understanding the heterogeneity of COVID-19-associated acute respiratory distress syndrome (ARDS) and in improving strategy to increase the survival from the critical patients intubated is always needed. The study aimed to comprehensively explore the features of COVID-19-associated ARDS and the features and outcomes between the early and late intubation groups. Methods: : This retrospective cohort included 65 adult COVID-19 inpatients with ARDS at two hospitals in Hubei, China. The ARDS in these patients was diagnosed according to the Berlin criteria. We defined intubation within 7 days of ARDS diagnosis as ‘early’ intubation and that performed from the eighth day as ‘late’ intubation based on literatures. The outcomes were invasive mechanical ventilation and in-hospital death. The log-binomial regression models were used to explore the risk factors and the Kaplan-Meier statistic was used to estimate the risk of mortality. Results: : The median number of days from symptom onset to ARDS diagnosis was 11.0 (IQR, 8.0–13.0). Up to 84.1% COVID-19-related ARDS patients demonstrated multiple organ injuries. The mortality rates were 41.9% and 85.7% in moderate and severe ARDS. The early intubation and the late intubation had the differences in days from symptom onset/hospital admission/ARDS diagnosis to intubation (P = 0.023, P = 0.011, P < 0.001). Compared with the early-intubation group, the late-intubation group showed less severity at admission (median oxygenation index 159.0 95% CI 134.0-203.0 vs. 133.9 95% CI 98.3-183.2), but required more aggressive therapies (ICU 80% vs. 70%, CRRT 50% vs. 10%, prone-position 50% vs. 30%, and ECMO 50% vs. 10%) and had higher risk to die at hospital (RR, 3.18;95% CI 1.98-5.12). Conclusion: The ARDS caused by COVID-19 was not typical ARDS due to prolonged onset time, multiple organ injuries, and higher mortalities. The late-intubation group showed less severity at admission but higher risk of in-hospital death than the early-intubation group.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325385

ABSTRACT

Background: Novel coronavirus disease 2019 (COVID-19) is a global public health emergency. Here, we developed and validated a practical model based on the data from a multi-center cohort in China for early identification and prediction of which patients will be admitted to the intensive care unit (ICU). Methods: Data of 1087 patients with laboratory-confirmed COVID-19 were collected from 49 sites between January 2 and February 28, 2020, in Sichuan and Wuhan. Patients were randomly categorized into the training and validation cohorts (7:3). The least absolute shrinkage and selection operator and logistic regression analyzes were used to develop the nomogram. The performance of the nomogram was evaluated for the C-index, calibration, discrimination, and clinical usefulness. Further, the nomogram was externally validated in a different cohort. Results: The individualized prediction nomogram included 6 predictors: age, respiratory rate, systolic blood pressure, smoking status, fever, and chronic kidney disease. The model demonstrated a high discriminative ability in the training cohort (C-index = 0.829), which was confirmed in the external validation cohort (C-index = 0.776). In addition, the calibration plots confirmed good concordance for predicting the risk of ICU admission. Decision curve analysis revealed that the prediction nomogram was clinically useful. Conclusion: We established an early prediction model incorporating clinical characteristics that could be quickly obtained on hospital admission, even in community health centers. This model can be conveniently used to predict the individual risk for ICU admission of patients with COVID-19 and optimize the use of limited resources.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324771

ABSTRACT

Background: The novel coronavirus disease 2019 (Covid-19) has been a worldwide pandemic with more than 300,000 deaths. Corticosteroids have been used in some patients with severe Covid-19 in order to control the systemic inflammation or cytokine storm, however, their effects and safety have not yet been elucidated. Methods Patients with confirmed Covid-19 were retrospectively included from both the epicentre and out of the epicentre. Patients were classified into two groups according to the use of systemic corticosteroids, and the mortality and the rate of virus clearance were compared between the two groups. In addition, independent factors associated with death after corticosteroids treatment were also identified. Results A total of 775 patients were included in our final analysis, of which 238 (30.7%) patients received systemic corticosteroids treatment. Compared with patients without corticosteroids treatment, patients with corticosteroids treatment had significantly higher mortality (19.3% vs. 3.7%, P < 0.001) and lower rate of virus clearance (43.2% vs. 66.7%, P < 0.001) although along with increase of SpO 2 /FiO 2 and blood lymphocytes in patients with severe Covid-19. Corticosteroids treatment was associated with longer hospital length of stays and delayed virus clearance time. In patients with corticosteroids treatment, blood lymphocytes (odds ratio (OR) 0.792, 95% confidence interval (CI) 0.672–0.932, P = 0.005) and creatine kinase (CK) (OR 1.006, 95%CI 1.000-1.012, P = 0.038) were independent risk factors associated with death, with a sensitivity of 90.91% and 44.44% and a specificity of 70.75% and 94.05%, respectively. Conclusions In patients with Covid-19, corticosteroids treatment is associated with increased mortality and reduced rate of virus clearance.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323518

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces new-onset diabetes and severe metabolic complications of pre-existing diabetes. The pathogenic mechanism underlying this is incompletely understood. Here, we provided evidence linking circulating GP73 with the exaggerated gluconeogenesis triggered by SARS-CoV-2 infection. We found that SARS-CoV-2 infection or glucotoxic conditions increased GP73 production and secretion. Secreted GP73 then trafficked to the liver and kidney to stimulate gluconeogenesis through the cAMP/PKA pathway. By using global phosphoproteomics, we found a drastic remodeling of the PKA kinase hub exerted by GP73. Notably, plasma GP73 levels were elevated and positively correlated with blood glucose in patients with COVID19 and diabetes. Neutralization of circulating GP73 in serum of individuals infected with SARS-CoV-2 or with diabetes reduced excessive gluconeogenesis in cultured hepatocytes, and lowered blood glucose levels in animal models of diabetes. Ablation of GP73 from whole animals has a profound glucose-lowering effect secondary to reduced gluconeogenesis. Thus, GP73 is a key glucogenic hormone contributing to SARS-CoV-2-induced glucose abnormality.

9.
Nat Metab ; 4(1): 29-43, 2022 01.
Article in English | MEDLINE | ID: covidwho-1612214

ABSTRACT

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.


Subject(s)
COVID-19/complications , COVID-19/virology , Glucose/metabolism , Hyperglycemia/etiology , Hyperglycemia/metabolism , Membrane Proteins/metabolism , SARS-CoV-2 , Animals , Biomarkers , Cyclic AMP-Dependent Protein Kinases/metabolism , Diet, High-Fat , Disease Models, Animal , Fasting , Gene Expression , Gluconeogenesis/drug effects , Gluconeogenesis/genetics , Host-Pathogen Interactions , Humans , Hyperglycemia/blood , Liver/metabolism , Liver/pathology , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/blood , Membrane Proteins/genetics , Mice , Mice, Knockout , Organ Specificity/genetics
10.
J Clin Lab Anal ; 36(1): e24152, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1565196

ABSTRACT

The ongoing COVID-19 pandemic constitutes a new challenge for public health. Prevention and control of infection have become urgent and serious issues. To meet the clinical demand for higher accuracy of COVID-19 detection, the development of fast and efficient methods represents an important step. The most common methods of COVID-19 diagnosis, relying on real-time fluorescent quantitative PCR(RT-qPCR), computed tomography, and new-generation sequencing technologies, have a series of advantages, especially for early diagnosis and screening. In addition, joint efforts of researchers all over the world have led to the development of other rapid detection methods with high sensitivity, ease of use, cost-effectiveness, or allowing multiplex analysis based on technologies such as dPCR, ELISA, fluorescence immunochromatography assay, and the microfluidic detection chip method. The main goal of this review was to provide a critical discussion on the development and application of these different analytical methods, which based on etiology, serology, and molecular biology, as well as to compare their respective advantages and disadvantages. In addition to these methods, hematology and biochemistry, as well as auxiliary analysis based on pathological anatomy, ultrasonography, and cytokine detection, will help understand COVID-19 pathogenesis. Together, these technologies may promote and open new windows to unravel issues surrounding symptomatic and asymptomatic COVID-19 infections and improve clinical strategies toward reducing mortality.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnostic imaging , Polymerase Chain Reaction/methods , COVID-19/pathology , Chromatography, Affinity/methods , Cytokines/blood , Enzyme-Linked Immunosorbent Assay , Four-Dimensional Computed Tomography , Gold Colloid , Humans , Mass Spectrometry/methods , Nasopharynx/virology , SARS-CoV-2/genetics
11.
Cells ; 10(12)2021 11 26.
Article in English | MEDLINE | ID: covidwho-1551567

ABSTRACT

High mobility group box 1 protein (HMGB1), a highly conserved nuclear DNA-binding protein, is a "damage-associated molecular pattern" molecule (DAMP) implicated in both stimulating and inhibiting innate immunity. As reviewed here, HMGB1 is an oxidation-reduction sensitive DAMP bearing three cysteines, and the post-translational modification of these residues establishes its proinflammatory and anti-inflammatory activities by binding to different extracellular cell surface receptors. The redox-sensitive signaling mechanisms of HMGB1 also occupy an important niche in innate immunity because HMGB1 may carry other DAMPs and pathogen-associated molecular pattern molecules (PAMPs). HMGB1 with DAMP/PAMP cofactors bind to the receptor for advanced glycation end products (RAGE) which internalizes the HMGB1 complexes by endocytosis for incorporation in lysosomal compartments. Intra-lysosomal HMGB1 disrupts lysosomal membranes thereby releasing the HMGB1-transported molecules to stimulate cytosolic sensors that mediate inflammation. This HMGB1-DAMP/PAMP cofactor pathway slowed the development of HMGB1-binding antagonists for diagnostic or therapeutic use. However, recent discoveries that HMGB1 released from neurons mediates inflammation via the TLR4 receptor system, and that cancer cells express fully oxidized HMGB1 as an immunosuppressive mechanism, offer new paths to targeting HMGB1 for inflammation, pain, and cancer.


Subject(s)
Disulfides/metabolism , HMGB1 Protein/metabolism , Inflammation/metabolism , Protein Processing, Post-Translational , Animals , COVID-19/metabolism , Humans , Sensory Receptor Cells/metabolism
12.
Mult Scler Relat Disord ; 58: 103394, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1510133

ABSTRACT

Neuromyelitis optica spectrum disorders (NMOSDs) are uncommon antibody-mediated autoimmune diseases of the central nervous system (CNS), mainly occurring in optic nerves and spinal cord, which can cause visual impairment, paralysis, and occasionally bulbar dysfunction. Such neurological deficits can adversely affect pulmonary functions and increase complicated infection risk. Besides, most NMOSD patients undergo immunosuppressive therapy. All these factors make NMOSD patients the potential high-risk group under the current pandemic of coronavirus disease 2019 (COVID-19). Meanwhile, COVID-19 infection has already been demonstrated as a risk factor for NMOSD relapses. This review discusses the basic immunology of vaccination and common problems, including immunogenicity, safety, and efficacy of vaccination on NMOSD patients. Additionally, we offered vaccination recommendations, health care and treatment advice for NMOSD patients under the background of COVID-19.


Subject(s)
COVID-19 , Neuromyelitis Optica , COVID-19/prevention & control , Humans , Neuromyelitis Optica/complications , SARS-CoV-2 , Spinal Cord , Vaccination/adverse effects
13.
Front Immunol ; 12: 748566, 2021.
Article in English | MEDLINE | ID: covidwho-1463474

ABSTRACT

Coronavirus disease 2019 (COVID-19) remains a major health challenge globally. Previous studies have suggested that changes in the glycosylation of IgG are closely associated with the severity of COVID-19. This study aimed to compare the profiles of IgG N-glycome between COVID-19 patients and healthy controls. A case-control study was conducted, in which 104 COVID-19 patients and 104 age- and sex-matched healthy individuals were recruited. Serum IgG N-glycome composition was analyzed by hydrophilic interaction liquid chromatography with the ultra-high-performance liquid chromatography (HILIC-UPLC) approach. COVID-19 patients have a decreased level of IgG fucosylation, which upregulates antibody-dependent cell cytotoxicity (ADCC) in acute immune responses. In severe cases, a low level of IgG sialylation contributes to the ADCC-regulated enhancement of inflammatory cytokines. The decreases in sialylation and galactosylation play a role in COVID-19 pathogenesis via the activation of the lectin-initiated alternative complement pathway. IgG N-glycosylation underlines the complex clinical phenotypes of SARS-CoV-2 infection.


Subject(s)
COVID-19/metabolism , Immunoglobulin G/metabolism , SARS-CoV-2/physiology , Adult , Antibody-Dependent Cell Cytotoxicity , Case-Control Studies , Chromatography, High Pressure Liquid , Complement Pathway, Mannose-Binding Lectin , Female , Glycosylation , Humans , Male , Middle Aged , Phenotype
14.
Front Immunol ; 12: 733418, 2021.
Article in English | MEDLINE | ID: covidwho-1450812

ABSTRACT

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and abnormal fatigability due to the antibodies against postsynaptic receptors. Despite the individual discrepancy, patients with MG share common muscle weakness, autoimmune dysfunction, and immunosuppressive treatment, which predispose them to infections that can trigger or exacerbate MG. Vaccination, as a mainstay of prophylaxis, is a major management strategy. However, the past years have seen growth in vaccine hesitancy, owing to safety and efficacy concerns. Ironically, vaccines, serving as an essential and effective means of defense, may induce similar immune cross-reactivity to what they are meant to prevent. Herein, we outline the progress in vaccination, review the current status, and postulate the clinical association among MG, vaccination, and immunosuppression. We also address safety and efficacy concerns of vaccination in MG, in relation to COVID-19. Since only a handful of studies have reported vaccination in individuals with MG, we further review the current clinical studies and guidelines in rheumatic diseases. Overall, our reviews offer a reference to guide future vaccine clinical decision-making and improve the management of MG patients.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Myasthenia Gravis/immunology , Myasthenia Gravis/pathology , SARS-CoV-2/immunology , Autoimmunity/immunology , Humans , Immune Tolerance/immunology , Influenza Vaccines/immunology , Risk , Vaccination/adverse effects
15.
Front Immunol ; 12: 714177, 2021.
Article in English | MEDLINE | ID: covidwho-1444042

ABSTRACT

Sepsis continues to be a major cause of morbidity, mortality, and post-recovery disability in patients with a wide range of non-infectious and infectious inflammatory disorders, including COVID-19. The clinical onset of sepsis is often marked by the explosive release into the extracellular fluids of a multiplicity of host-derived cytokines and other pro-inflammatory hormone-like messengers from endogenous sources ("cytokine storm"). In patients with sepsis, therapies to counter the pro-inflammatory torrent, even when administered early, typically fall short. The major focus of our proposed essay is to promote pre-clinical studies with hCG (human chorionic gonadotropin) as a potential anti-inflammatory therapy for sepsis.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Chorionic Gonadotropin/therapeutic use , Peptides/therapeutic use , Sepsis/drug therapy , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/metabolism , Bacteria/metabolism , Chorionic Gonadotropin/chemistry , Chorionic Gonadotropin/metabolism , Cytokine Release Syndrome/drug therapy , Glycoproteins/chemistry , Glycoproteins/metabolism , Humans , Inflammation , Peptides/chemistry , Peptides/metabolism
16.
Soc Sci Med ; 287: 114371, 2021 10.
Article in English | MEDLINE | ID: covidwho-1386626

ABSTRACT

At the initial stage of COVID-19 outbreak, tracing returnees from Wuhan - the epicenter of the disease - is a major strategy in each province of China to contain its spread. However, scholars are yet to assess the impact of tracing on individuals. Drawing upon a large-scale survey with students from four major universities in Wuhan, we investigate individual experiences with tracing activities at government and community levels and the impacts on students' socio-psychological wellbeing. Findings indicate that tracing is likely to increase the risks of privacy infringement, verbal slur, and warning at residence; and students experience moderate-to-high levels of anxiety and fear. Improved public health measures are therefore necessary to balance the twin goals of containing disease and alleviating unintended consequences of tracing.


Subject(s)
COVID-19 , Anxiety Disorders , China/epidemiology , Humans , SARS-CoV-2 , Students
17.
Mol Ther Methods Clin Dev ; 23: 108-118, 2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1379195

ABSTRACT

Because of the relatively limited understanding of coronavirus disease 2019 (COVID-19) pathogenesis, immunological analysis for vaccine development is needed. Mice and macaques were immunized with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine prepared by two inactivators. Various immunological indexes were tested, and viral challenges were performed on day 7 or 150 after booster immunization in monkeys. This inactivated SARS-CoV-2 vaccine was produced by sequential inactivation with formaldehyde followed by propiolactone. The various antibody responses and specific T cell responses to different viral antigens elicited in immunized animals were maintained for longer than 150 days. This comprehensive immune response could effectively protect vaccinated macaques by inhibiting viral replication in macaques and substantially alleviating immunopathological damage, and no clinical manifestation of immunopathogenicity was observed in immunized individuals during viral challenge. This candidate inactivated vaccine was identified as being effective against SARS-CoV-2 challenge in rhesus macaques.

18.
Int J Gen Med ; 14: 4711-4721, 2021.
Article in English | MEDLINE | ID: covidwho-1378148

ABSTRACT

PURPOSE: We sought to explore the prognostic value of blood urea nitrogen (BUN) to serum albumin ratio (BAR) and further develop a prediction model for critical illness in COVID-19 patients. PATIENTS AND METHODS: This was a retrospective, multicenter, observational study on adult hospitalized COVID-19 patients from three provinces in China between January 14 and March 9, 2020. Primary outcome was critical illness, including admission to the intensive care unit (ICU), need for invasive mechanical ventilation (IMV), or death. Clinical data were collected within 24 hours after admission to hospitals. The predictive performance of BAR was tested by multivariate logistic regression analysis and receiver operating characteristic (ROC) curve and then a nomogram was developed. RESULTS: A total of 1370 patients with COVID-19 were included and 113 (8.2%) patients eventually developed critical illness in the study. Baseline age (OR: 1.031, 95% CI: 1.014, 1.049), respiratory rate (OR: 1.063, 95% CI: 1.009, 1.120), unconsciousness (OR: 40.078, 95% CI: 5.992, 268.061), lymphocyte counts (OR: 0.352, 95% CI: 0.204, 0.607), total bilirubin (OR: 1.030, 95% CI: 1.001, 1.060) and BAR (OR: 1.319, 95% CI: 1.183, 1.471) were independent risk factors for critical illness. The predictive AUC of BAR was 0.821 (95% CI: 0.784, 0.858; P<0.01) and the optimal cut-off value of BAR was 3.7887 mg/g (sensitivity: 0.690, specificity: 0.786; positive predictive value: 0.225, negative predictive value: 0.966; positive likelihood ratio: 3.226, negative likelihood ratio: 0.394). The C index of nomogram including above six predictors was 0.9031125 (95% CI: 0.8720542, 0.9341708). CONCLUSION: Elevated BAR at admission is an independent risk factor for critical illness of COVID-19. The novel predictive nomogram including BAR has superior predictive performance.

19.
Int J Gen Med ; 14: 4073-4080, 2021.
Article in English | MEDLINE | ID: covidwho-1346355

ABSTRACT

PURPOSE: To analyze the clinical characteristics of patients with coronavirus disease 19 (COVID-19) in Chongqing, and identify the potential hematological markers for reference. PATIENTS AND METHODS: 78 COVID-19-infected patients in Chongqing were recruited and divided into the non-severe and the severe group. The clinical characteristics and hematological features of the patients of the two groups were compared. Receiver-operating characteristic curves (ROC) were calculated to evaluate the diagnostic performance of potential markers, and the dynamic changes of blood routine analyzing items were compared between the non-severe and severe groups. RESULTS: 78 patients (median age of 45 years, 41 females and 37 males) were enrolled. The patients in the severe group exhibited significantly lower lymphocyte (P<0.05) but higher neutrophil to lymphocyte ratio (NLR) (P<0.05) than the patients in the non-severe group. The highest area under the ROC curve (AUC) was lymphocyte (0.74). The patients in the severe group had a lower level of lymphocyte during hospitalization (P<0.01) and lymphocyte-monocyte ratio (LMR) in the progressive and convalescent phases (P<0.05) than the patients in the non-severe group. However, the level of neutrophil of the patients in the severe group was higher in the progressive phase (P<0.05), and so was NLR in the acute, progressive, and convalescent-phase (P<0.05). CONCLUSION: Infected with COVID-19 changed the levels of lymphocyte, neutrophil, LMR, and NLR in the blood, and these analyzing items were significantly different between the non-severe and severe groups. Furthermore, the dynamic changes of lymphocyte and NLR levels may help discriminate the severe group from the non-severe group.

20.
Front Med (Lausanne) ; 8: 593623, 2021.
Article in English | MEDLINE | ID: covidwho-1295651

ABSTRACT

Background and Aims: Gastrointestinal (GI) symptoms are frequently observed in coronavirus disease (COVID-19) symptoms. Previous studies have mainly focused on epidemiology and characteristics in patients with GI symptoms, little is known about the roles of the immune response in susceptibility to and severity of infection. Here, we analyzed COVID-19 cases to determine immune response and clinical characteristics in COVID-19 patients with GI symptoms. Methods: Based on the presence of GI symptoms, 79 patients in Xuzhou were divided into GI and non-GI groups. A retrospective study investigating the clinical characteristics, selected laboratory abnormalities, immune response, treatment, and clinical outcome was performed to compare patients with or without GI symptoms. Results: Approximately 25% of patients reported at least one GI symptom. Our results showed significantly higher rates of fatigue, increased LDH, increased CK, higher percentage increase neutrophil-to-lymphocyte ratio (NLR), lymphopenia, and bilateral pneumonia in patients with GI symptoms. No significant changes in serum amylase (SAA), immunoglobulin (Ig) G, IgM, C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), viral shedding time, liver injury, and kidney injury between the two groups were observed. The clinical type on admission of patients with GI symptoms reported significantly higher rates of critical disease type (20 vs. 3.3%; p = 0.033). However, the survival rate did not differ between the two groups. Conclusions: Increase in total lymphocytes and NLR as well as the elevation of CRP, SAA, PCT, IL-6, CK, and LDH were closely associated with COVID-19 with GI symptoms, implying reliable indicators COVID-19 patients with GI symptoms were more likely to develop into a severe disease.

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