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1.
Cell Death Differ ; 2022 Jan 08.
Article in English | MEDLINE | ID: covidwho-1612182

ABSTRACT

A recent mutation analysis suggested that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a key determinant of the viral pathogenicity. Here, by transcriptome analysis, we demonstrated that the inflammasome-related NOD-like receptor signaling was activated in SARS-CoV-2-infected lung epithelial cells and Coronavirus Disease 2019 (COVID-19) patients' lung tissues. The induction of inflammasomes/pyroptosis in patients with severe COVID-19 was confirmed by serological markers. Overexpression of NSP6 triggered NLRP3/ASC-dependent caspase-1 activation, interleukin-1ß/18 maturation, and pyroptosis of lung epithelial cells. Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1α,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis. NSP6 directly interacted with ATP6AP1, a vacuolar ATPase proton pump component, and inhibited its cleavage-mediated activation. L37F NSP6 variant, which was associated with asymptomatic COVID-19, exhibited reduced binding to ATP6AP1 and weakened ability to impair lysosome acidification to induce pyroptosis. Consistently, infection of cultured lung epithelial cells with live SARS-CoV-2 resulted in autophagic flux stagnation, inflammasome activation, and pyroptosis. Overall, this work supports that NSP6 of SARS-CoV-2 could induce inflammatory cell death in lung epithelial cells, through which pharmacological rectification of autophagic flux might be therapeutically exploited.

2.
Front Immunol ; 12: 790469, 2021.
Article in English | MEDLINE | ID: covidwho-1581320

ABSTRACT

Background: Neutralizing monoclonal antibodies (mAbs) to SARS-CoV-2 are clinically efficacious when administered early, decreasing hospitalization and mortality in patients with mild or moderate COVID-19. We investigated the effects of receiving mAbs (bamlanivimab alone and bamlanivimab and etesevimab together) after SARS-CoV-2 infection on the endogenous immune response. Methods: Longitudinal serum samples were collected from patients with mild or moderate COVID-19 in the BLAZE-1 trial who received placebo (n=153), bamlanivimab alone [700 mg (n=100), 2800 mg (n=106), or 7000 mg (n=98)], or bamlanivimab (2800 mg) and etesevimab (2800 mg) together (n=111). A multiplex Luminex serology assay measured antibody titers against SARS-CoV-2 antigens, including SARS-CoV-2 protein variants that evade bamlanivimab or etesevimab binding, and SARS-CoV-2 pseudovirus neutralization assays were performed. Results: The antibody response in patients who received placebo or mAbs had a broad specificity. Titer change from baseline against a receptor-binding domain mutant (Spike-RBD E484Q), as well as N-terminal domain (Spike-NTD) and nucleocapsid protein (NCP) epitopes were 1.4 to 4.1 fold lower at day 15-85 in mAb recipients compared with placebo. Neutralizing activity of day 29 sera from bamlanivimab monotherapy cohorts against both spike E484Q and beta variant (B.1.351) were slightly reduced compared with placebo (by a factor of 3.1, p=0.001, and 2.9, p=0.002, respectively). Early viral load correlated with the subsequent antibody titers of the native, unmodified humoral response (p<0.0001 at Day 15, 29, 60 and 85 for full-length spike). Conclusions: Patients with mild or moderate COVID-19 treated with mAbs develop a wide breadth of antigenic responses to SARS-CoV-2. Small reductions in titers and neutralizing activity, potentially due to a decrease in viral load following mAb treatment, suggest minimal impact of mAb treatment on the endogenous immune response.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/immunology , COVID-19/drug therapy , COVID-19/immunology , Adult , Antibodies, Neutralizing/immunology , Antiviral Agents/therapeutic use , Drug Combinations , Female , Humans , Male , Middle Aged , SARS-CoV-2
3.
Preprint | EuropePMC | ID: ppcovidwho-296542

ABSTRACT

As the COVID-19 pandemic evolves, and vaccine rollout progresses, the availability and demand for monoclonal antibodies for the prevention and treatment of SARS-CoV-2 infection are also accelerating. This longitudinal serological study evaluated the magnitude and potency of the endogenous antibody response to COVID-19 vaccination in participants who first received a COVID-19 monoclonal antibody in a prevention study. Over the course of six months, serum samples were collected from the prevention population (nursing home residents and staff) enrolled in the BLAZE-2 clinical trial who had received either bamlanivimab (4200 mg) or placebo. In an unplanned component of this trial, a subset of these participants was subsequently fully vaccinated with two doses of either SpikeVax (Moderna) or Comirnaty (BioNTech/Pfizer) COVID-19 mRNA vaccines, as part of the US vaccination program. This post-hoc analysis assessed the immune response to vaccination for the subset of participants (N=135) without prior SARS-CoV-2 infection. Antibody titers and potency were assessed using three assays against SARS-CoV-2 proteins that bamlanivimab does not significantly bind to, thereby reflecting the endogenous antibody response. All bamlanivimab and placebo participants mounted a robust immune response to full COVID-19 vaccination, irrespective of age, risk-category and vaccine type, with any observed differences unlikely to be clinically meaningful. These findings are pertinent for informing public health policy with results that suggest a complementary role for COVID-19 monoclonal antibodies (mAbs) with COVID-19 vaccines and that the benefit of receiving COVID-19 vaccination at the earliest opportunity outweighs the minimal effect on the endogenous immune response due to prior prophylactic COVID-19 mAb infusion.

5.
Open forum infectious diseases ; 8(Suppl 1):S88-S88, 2021.
Article in English | EuropePMC | ID: covidwho-1565007

ABSTRACT

Background Although studies show most COVID-19 survivors have post-infection immunity against SARS-CoV-2 that could prevent re-infection, there is still a need to identify the breadth of antibody (Ab) responses associated with clinical phenotypes. We characterized Ab profiles at the estimated peak of Ab diversity among adults with recovered SARS-CoV-2 infections and determined their relationships with clinical factors. Methods From April-June 2020, 41 health system employees with PCR-confirmed symptomatic COVID-19 infection enrolled 8-10 weeks after symptom onset. Symptom questionnaires including baseline demographics, COVID-19 symptoms, disease severity, and disease duration were collected and plasma samples were assayed using a custom Luminex Multiplex platform (Figure 1) to measure the antibody response against 20 COVID-19 related antigens (Figure 2). Differences in Ab profile titers among different groups were tested using nonparametric t test and Benjamini-Hochberg adjustment for multiplicity. Associations were considered significant at FDR< 0.05. Figure 1: Description of the Luminex Serology Assay Figure 2: List of the COVID-19 Related Antigens and Controls Measured Results Mean age was 48 years (range 27-68), with 51% female, 37% White, 32% Black, 29% Asian, and 17% LatinX. Ab profiles (Figure 3) showed 100% cross-reactivity with related alpha and beta coronavirus, and 95% with SARS-CoV-1. 78% had Abs against SARS-CoV-2 nucleocapsid protein (NCP). However, 29% of patients had no immune response against the four spike protein epitopes. These participants also reported fewer symptoms, including no cases of anosmia/ageusia, suggesting mild illness. Anosmia/ageusia, fever, and cough associated significantly with higher Ab titers (Figure 4). Conclusion Broad immune responses to various SARS-CoV-2 and related antigens were found among a heterogeneous patient population. However, less than 3 months after symptom onset, protective Ab responses to SARS-CoV-2 spike proteins were not detected in nearly one-third of recovered patients, primarily with mild infection. Intact sense of smell and taste demonstrated the greatest association with loss of seroprotective SARS-CoV-2 Ab responses, which may be clinically useful to predict post-infection immunity. Next steps include comparing the magnitude of Ab responses following full series completion with mRNA vaccination among this cohort. Disclosures Robert Bencshop, PhD, Eli Lilly (Employee) Josh Poorbaugh, PhD, Eli Lilly (Employee) Ajay Nirula, MD/PhD, Eli Lilly (Employee, Shareholder) Lin Zhang, PhD, Eli Lilly and Company (Employee, Shareholder) Stephanie Beasley, BA, Eli Lilly (Employee)

6.
Preprint in English | EuropePMC | ID: ppcovidwho-295406

ABSTRACT

Backgroud : Both Chlamydia psittaci and COVID-19 virus can cause lung inflammation, which manifests extremely similarly in clinical symptoms and imaging. Especially during the epidemic of COVID-19, psittacosis pneumonia is easily misdiagnosed as COVID-19 pneumonia. The identification of the chest imaging between the two diseases is of special significance when the epidemiological contact history is unclear, and the etiology and nucleic acid test results are not available. This study conducts to compare the imaging characteristics on chest high-resolution CTs (HRCT) between patients with psittaci pneumonia and COVID-19 pneumonia. Methods: : A retrospective analysis of the imaging characteristics on chest HRCTs of 10 psittaci pneumonia patients and 13 COVID-19 pneumonia patients. The similarities and differences in HRCT images of patients with psittaci pneumonia and COVID-19 pneumonia were analyzed. Results: : HRCT showed that among the 10 psittaci pneumonia patients, 8 cases (80.00%) had single lobe involvement, and 2 cases (20.00%) had multiple lobe involvement. Among the 13 COVID-19 pneumonia patients, 2 cases had single lobe involvement (15.38%), and 11 cases had multiple lobe involvement (84.62%). The types of lesions in 10 psittaci pneumonia patients included simple consolidation in 5 cases (50.00%), and ground-glass opacity (GGO) with consolidation in 5 cases (50.00%). The types of lesions in 13 COVID-19 pneumonia patients included simple GGO in 6 cases (46.15%), GGO with consolidation in 4 cases (30.77%), GGO with paving stone sign in 2 cases (15.38%), and simple consolidation in 1 case (7.69%). Lymphadenopathy was observed in 1 psittaci pneumonia patient (10.00%) and 1 COVID-19 pneumonia patient (7.69%). Among the 10 psittaci pneumonia patients, 8 cases (80.00%) had bronchial inflation, and 6 patients (60.00%) had pleural effusion. Among the 13 COVID-19 pneumonia patients, 5 patients (38.46%) showed signs of bronchial inflation, while no pleural effusion was observed in 13 patients. Conclusion: : Chest HRCTs can distinguish COVID-19 pneumonia from psittaci pneumonia, and can provide early diagnoses of these two diseases.

7.
Public Health Nurs ; 2021 Dec 03.
Article in English | MEDLINE | ID: covidwho-1550848

ABSTRACT

OBJECTIVE: We aimed to describe how the prevention and controlling strategies have been experienced by COVID-19 patients in China, especially those who had passed through the suspected, diagnosed, hospitalized, and recovery stages of the disease. DESIGN: A descriptive qualitative study followed the Standards for Reporting Qualitative Research guidelines. SAMPLES: COVID-19 patients were recruited from a COVID-19-designated facility in Shanghai, China, from April to June 2020, by the purposive sampling method. METHODS: Semi-structured, in-depth interviews by cell phone were used and transcriptions were analyzed using inductive qualitative content analysis method. RESULTS: We recruited 26 COVID-19 patients. Three theme categories emerged from the data analysis. The first was "Consciously adhere to COVID-19-related controlling strategies." The second category was "Positive experiences of the COVID-19-related controlling strategies." These patients experienced a quick and adequate medical response, confident in the medical system, or received help from community workers. The third category was "Negative experiences of the COVID-19-related controlling strategies." These patients experienced psychological distress, stigma, privacy exposures, and inconveniences from the controlling strategies. CONCLUSIONS: It is urgent to develop a culturally sensitive intervention to eliminate the psychological distress and stigma of patients with COVID-19 and to protect their privacy during and after the pandemic.

8.
Preprint in English | EuropePMC | ID: ppcovidwho-293368

ABSTRACT

Backgroud : Both Chlamydia psittaci and COVID-19 virus can cause lung inflammation, which manifests extremely similarly in clinical symptoms and imaging. Especially during the epidemic of COVID-19, psittacosis pneumonia is easily misdiagnosed as COVID-19 pneumonia. The identification of the chest imaging between the two diseases is of special significance when the epidemiological contact history is unclear, and the etiology and nucleic acid test results are not available. This study conducts to compare the imaging characteristics on chest high-resolution CTs (HRCT) between patients with psittaci pneumonia and COVID-19 pneumonia. Methods: : A retrospective analysis of the imaging characteristics on chest HRCTs of 10 psittaci pneumonia patients and 13 COVID-19 pneumonia patients. The similarities and differences in HRCT images of patients with psittaci pneumonia and COVID-19 pneumonia were analyzed. Results: : HRCT showed that among the 10 psittaci pneumonia patients, 8 cases (80.00%) had single lobe involvement, and 2 cases (20.00%) had multiple lobe involvement. Among the 13 COVID-19 pneumonia patients, 2 cases had single lobe involvement (15.38%), and 11 cases had multiple lobe involvement (84.62%). The types of lesions in 10 psittaci pneumonia patients included simple consolidation in 5 cases (50.00%), and ground-glass opacity (GGO) with consolidation in 5 cases (50.00%). The types of lesions in 13 COVID-19 pneumonia patients included simple GGO in 6 cases (46.15%), GGO with consolidation in 4 cases (30.77%), GGO with paving stone sign in 2 cases (15.38%), and simple consolidation in 1 case (7.69%). Lymphadenopathy was observed in 1 psittaci pneumonia patient (10.00%) and 1 COVID-19 pneumonia patient (7.69%). Among the 10 psittaci pneumonia patients, 8 cases (80.00%) had bronchial inflation, and 6 patients (60.00%) had pleural effusion. Among the 13 COVID-19 pneumonia patients, 5 patients (38.46%) showed signs of bronchial inflation, while no pleural effusion was observed in 13 patients. Conclusion: : Chest HRCTs can distinguish COVID-19 pneumonia from psittaci pneumonia, and can provide early diagnoses of these two diseases.

9.
Int J Environ Res Public Health ; 18(21)2021 11 02.
Article in English | MEDLINE | ID: covidwho-1502422

ABSTRACT

Online mental health service (OMHS) platforms have contributed significantly to the public's mental health during the COVID-19 pandemic in China. However, it remains unclear why the public used OMHS platforms for psychological help-seeking (PHS) behavior and how PHS behavior varied across different stages of the COVID-19 pandemic. Based on the ecological PHS behavior data from two OMHS platforms, we extracted population, psychological problems, and influential factors of PHS behavior by text mining and time series analysis methods. Seven top-ranked psychological problems (i.e., depression and anxiety, lack of interest, suicidal tendencies, social phobia, feelings of being worried and afraid, suffering, anger) and seven influential factors (i.e., interpersonal relationships, love, family, work, psychotherapy, personal characteristics, marriage) were found. The online PHS behaviors related to different psychological problems and influential factors remained a growing trend before 2020 and have been increasing significantly due to the COVID-19 outbreak. Four main stages were found during the pandemic according to the changes in the online PHS population: sharp growth, significant decline, slight rebound, and slow decline. This study identified large-scale, spontaneous PHS behaviors among the online public during the COVID-19 pandemic and the various psychological problems and influential factors that varied across different stages of the pandemic, suggesting that the government and health practitioners should adopt effective policies and strategies to prevent and intervene in mental health problems for the online public.


Subject(s)
COVID-19 , Pandemics , Anxiety , Data Mining , Depression , Humans , SARS-CoV-2
10.
Comput Biol Med ; 139: 104887, 2021 12.
Article in English | MEDLINE | ID: covidwho-1482517

ABSTRACT

The 2019 novel severe acute respiratory syndrome coronavirus 2-SARS-CoV2, commonly known as COVID-19, is a highly infectious disease that has endangered the health of many people around the world. COVID-19, which infects the lungs, is often diagnosed and managed using X-ray or computed tomography (CT) images. For such images, rapid and accurate classification and diagnosis can be performed using deep learning methods that are trained using existing neural network models. However, at present, there is no standardized method or uniform evaluation metric for image classification, which makes it difficult to compare the strengths and weaknesses of different neural network models. This paper used eleven well-known convolutional neural networks, including VGG-16, ResNet-18, ResNet-50, DenseNet-121, DenseNet-169, Inception-v3, Inception-v4, SqueezeNet, MobileNet, ShuffeNet, and EfficientNet-b0, to classify and distinguish COVID-19 and non-COVID-19 lung images. These eleven models were applied to different batch sizes and epoch cases, and their overall performance was compared and discussed. The results of this study can provide decision support in guiding research on processing and analyzing small medical datasets to understand which model choices can yield better outcomes in lung image classification, diagnosis, disease management and patient care.

11.
Gastroenterology ; 2021 Oct 21.
Article in English | MEDLINE | ID: covidwho-1475507

ABSTRACT

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with altered gut microbiota composition. Phylogenetic groups of gut bacteria involved in the metabolism of short chain fatty acids (SCFAs) were depleted in SARS-CoV-2-infected patients. We aimed to characterize a functional profile of the gut microbiome in patients with COVID-19 before and after disease resolution. METHODS: We performed shotgun metagenomic sequencing on fecal samples from 66 antibiotics-naïve patients with COVID-19 and 70 non-COVID-19 controls. Serial fecal samples were collected (at up to 6 times points) during hospitalization and beyond 1 month after discharge. We assessed gut microbial pathways in association with disease severity and blood inflammatory markers. We also determined changes of microbial functions in fecal samples before and after disease resolution and validated these functions using targeted analysis of fecal metabolites. RESULTS: Compared with non-COVID-19 controls, patients with COVID-19 with severe/critical illness showed significant alterations in gut microbiome functionality (P < .001), characterized by impaired capacity of gut microbiome for SCFA and L-isoleucine biosynthesis and enhanced capacity for urea production. Impaired SCFA and L-isoleucine biosynthesis in gut microbiome persisted beyond 30 days after recovery in patients with COVID-19. Targeted analysis of fecal metabolites showed significantly lower fecal concentrations of SCFAs and L-isoleucine in patients with COVID-19 before and after disease resolution. Lack of SCFA and L-isoleucine biosynthesis significantly correlated with disease severity and increased plasma concentrations of CXCL-10, NT- proB-type natriuretic peptide, and C-reactive protein (all P < .05). CONCLUSIONS: Gut microbiome of patients with COVID-19 displayed impaired capacity for SCFA and L-isoleucine biosynthesis that persisted even after disease resolution. These 2 microbial functions correlated with host immune response underscoring the importance of gut microbial functions in SARS-CoV-2 infection pathogenesis and outcome.

12.
J Affect Disord ; 297: 269-275, 2022 01 15.
Article in English | MEDLINE | ID: covidwho-1474675

ABSTRACT

BACKGROUND: The aim of this study was to adapt and modify the HIV/AIDS Stigma Instrument-Patient to develop the COVID-19 Stigma Instrument-Patient (CSI-P) and validate its psychometric characteristics, as well as explore how affected individuals in China experienced COVID-related stigma and its associated variables, including depressive symptomology and quality of life (QOL). METHODS: From September to October 2020, 151 COVID-19 survivors recruited in Shanghai, China, completed a set of measures of demographic characteristics, depression, stigma, and QOL. RESULTS: The 15-item CSI-P-2 achieved a Cronbach's α of 0.67 to 0.91. The six-factor structure was obtained by exploratory factor analysis. The mean score for the CSI-P-2 in Chinese COVID survivors was 8.14 ± 9.98. Regression analysis showed that survivors' age, comorbid diseases, education levels, and loneliness level were the factors influencing their COVID-19 stigma, explaining 37.80% of the total variance (F = 19.25, p < 0.001). Also, stigma's effect on QOL was significant in direct and indirect paths mediated by depressive symptomology. LIMITATIONS: First, this sample might limit the generalization of the findings to other Chinese-speaking regions. Second, future longitudinal or experimental studies are warranted for checking and further refinement of the scale. Finally, future studies are needed on the changing dynamics of stigma in different stages of the pandemic. CONCLUSIONS: The 29-item CSI-P-2 with six domains is an instrument with sound psychometric properties that can be used to measure COVID-19 stigma during the COVID-19 outbreak and, later, for COVID-19 survivors. Future studies should explore how to integrate the significant demographic and psychological characteristics influencing the experience of stigma work on this study into the development of stigma-reducing interventions.


Subject(s)
COVID-19 , Quality of Life , China , Depression/epidemiology , Humans , Reproducibility of Results , SARS-CoV-2 , Surveys and Questionnaires
13.
Parkinsonism Relat Disord ; 92: 41-45, 2021 11.
Article in English | MEDLINE | ID: covidwho-1472127

ABSTRACT

BACKGROUND: The initial COVID-19 pandemic shutdown led to the canceling of elective surgeries throughout most of the USA and Canada. OBJECTIVE: This survey was carried out on behalf of the Parkinson Study Group (PSG) to understand the impact of the shutdown on deep brain stimulation (DBS) practices in North America. METHODS: A survey was distributed through RedCap® to the members of the PSG Functional Neurosurgical Working Group. Only one member from each site was asked to respond to the survey. Responses were collected from May 15 to June 6, 2020. RESULTS: Twenty-three sites participated; 19 (83%) sites were from the USA and 4 (17%) from Canada. Twenty-one sites were academic medical centers. COVID-19 associated DBS restrictions were in place from 4 to 16 weeks. One-third of sites halted preoperative evaluations, while two-thirds of the sites offered limited preoperative evaluations. Institutional policy was the main contributor for the reported practice changes, with 87% of the sites additionally reporting patient-driven surgical delays secondary to pandemic concerns. Pre-post DBS associated management changes affected preoperative assessments 96%; electrode placement 87%; new implantable pulse generator (IPG) placement 83%; IPG replacement 65%; immediate postoperative DBS programming 74%; and routine DBS programming 91%. CONCLUSION: The COVID-19 pandemic related shutdown resulted in DBS practice changes in almost all North American sites who responded to this large survey. Information learned could inform development of future contingency plans to reduce patient delays in care under similar circumstances.

14.
Cancer Epidemiol Biomarkers Prev ; 30(10): 1884-1894, 2021 10.
Article in English | MEDLINE | ID: covidwho-1450633

ABSTRACT

BACKGROUND: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. METHODS: We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. RESULTS: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%-18% and 1%-14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events. CONCLUSIONS: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent. IMPACT: This study provides epidemiologic characteristics that can inform clinical care and etiologic studies.


Subject(s)
COVID-19/mortality , Neoplasms/epidemiology , Outcome Assessment, Health Care/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Child , Cohort Studies , Comorbidity , Databases, Factual , Female , Hospitalization/statistics & numerical data , Humans , Influenza, Human/epidemiology , Male , Middle Aged , Pandemics , Prevalence , Risk Factors , SARS-CoV-2 , Spain/epidemiology , United States/epidemiology , Young Adult
15.
Prim Care Diabetes ; 15(6): 899-909, 2021 12.
Article in English | MEDLINE | ID: covidwho-1447044

ABSTRACT

This review comprehensively summarizes epidemiologic evidence of COVID-19 in patients with Type 2 diabetes, explores pathophysiological mechanisms, and integrates recommendations and guidelines for patient management. We found that diabetes was a risk factor for diagnosed infection and poor prognosis of COVID-19. Patients with diabetes may be more susceptible to adverse outcomes associated with SARS-CoV-2 infection due to impaired immune function and possible upregulation of enzymes that mediate viral invasion. The chronic inflammation caused by diabetes, coupled with the acute inflammatory reaction caused by SARS-CoV-2, results in a propensity for inflammatory storm. Patients with diabetes should be aware of their increased risk for COVID-19.

16.
R Soc Open Sci ; 8(9): 201867, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1429382

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) has spread worldwide and threatened human life. Diagnosis is crucial to contain the spread of SARS-CoV-2 infections and save lives. Diagnostic tests for COVID-19 have varying sensitivity and specificity, and the false-negative results would have substantial consequences to patient treatment and pandemic control. To detect all suspected infections, multiple testing is widely used. However, it may be challenging to build an assertion when the testing results are inconsistent. Considering the situation where there is more than one diagnostic outcome for each subject, we proposed a Bayesian probabilistic framework based on the sensitivity and specificity of each diagnostic method to synthesize a posterior probability of being infected by SARS-CoV-2. We demonstrated that the synthesized posterior outcome outperformed each individual testing outcome. A user-friendly web application was developed to implement our analytic framework with free access via http://www2.ccrb.cuhk.edu.hk/statgene/COVID_19/. The web application enables the real-time display of the integrated outcome incorporating two or more tests and calculated based on Bayesian posterior probability. A simulation-based assessment demonstrated higher accuracy and precision of the Bayesian probabilistic model compared with a single-test outcome. The online tool developed in this study can assist physicians in making clinical evaluations by effectively integrating multiple COVID-19 tests.

17.
Pediatrics ; 148(3)2021 09.
Article in English | MEDLINE | ID: covidwho-1394618

ABSTRACT

OBJECTIVES: To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children and adolescents diagnosed or hospitalized with coronavirus disease 2019 (COVID-19) and to compare them in secondary analyses with patients diagnosed with previous seasonal influenza in 2017-2018. METHODS: International network cohort using real-world data from European primary care records (France, Germany, and Spain), South Korean claims and US claims, and hospital databases. We included children and adolescents diagnosed and/or hospitalized with COVID-19 at age <18 between January and June 2020. We described baseline demographics, comorbidities, symptoms, 30-day in-hospital treatments, and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome, multisystem inflammatory syndrome in children, and death. RESULTS: A total of 242 158 children and adolescents diagnosed and 9769 hospitalized with COVID-19 and 2 084 180 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were more common among those hospitalized with versus diagnosed with COVID-19. Dyspnea, bronchiolitis, anosmia, and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital prevalent treatments for COVID-19 included repurposed medications (<10%) and adjunctive therapies: systemic corticosteroids (6.8%-7.6%), famotidine (9.0%-28.1%), and antithrombotics such as aspirin (2.0%-21.4%), heparin (2.2%-18.1%), and enoxaparin (2.8%-14.8%). Hospitalization was observed in 0.3% to 1.3% of the cohort diagnosed with COVID-19, with undetectable (n < 5 per database) 30-day fatality. Thirty-day outcomes including pneumonia and hypoxemia were more frequent in COVID-19 than influenza. CONCLUSIONS: Despite negligible fatality, complications including hospitalization, hypoxemia, and pneumonia were more frequent in children and adolescents with COVID-19 than with influenza. Dyspnea, anosmia, and gastrointestinal symptoms could help differentiate diagnoses. A wide range of medications was used for the inpatient management of pediatric COVID-19.


Subject(s)
COVID-19 , Adolescent , Age Distribution , COVID-19/complications , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/epidemiology , Child , Child, Preschool , Cohort Studies , Comorbidity , Databases, Factual , Diagnosis, Differential , Female , France/epidemiology , Germany/epidemiology , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Influenza, Human/complications , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Male , Republic of Korea/epidemiology , Spain/epidemiology , Symptom Assessment , Time Factors , Treatment Outcome , United States/epidemiology
18.
Comput Math Methods Med ; 2021: 8924293, 2021.
Article in English | MEDLINE | ID: covidwho-1356985

ABSTRACT

In recent years, with the acceleration of industrialization, urbanization, and aging process, the number of patients with chronic diseases in the world is increasing year by year. In China, the number of chronic diseases has increased tenfold in 10 years. The percentage of the disease burden in the whole society accounts for 79.4%. Chronic diseases have become the top killer for Chinese people's health. However, for chronic diseases, prevention is more important than treatment. It is the best way to keep healthy. Therefore, health intervention is the key to prevent chronic diseases. Especially now, with the spread of COVID-19 pandemic, reducing the times of hospital check-ups and treatments for chronic patients is practically significant for releasing the stress on medical staffs and decreasing the rate of transmission and infection of COVID-19. In this paper, case-based reasoning (CBR) technology is used to assist personalized intervention for chronic diseases, and the key technologies of personalized intervention for chronic diseases based on case-based reasoning are proposed. The case organization, case retrieval, and case retention techniques of CBR technology in chronic disease personalized intervention are designed, and the calculation of interclass dispersion is added to the distribution of feature words, which is used to describe the distribution of feature attributes in different categories of cases. It provides an effective method for the establishment of personalized intervention model for chronic disease.


Subject(s)
Algorithms , Chronic Disease/prevention & control , Precision Medicine , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/transmission , China/epidemiology , Computational Biology , Humans , Mathematical Concepts , Models, Biological , Pandemics/prevention & control , Problem Solving , SARS-CoV-2
19.
Brief Bioinform ; 22(2): 1466-1475, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343667

ABSTRACT

Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, causing significant mortality. There is a mechanistic relationship between intracellular coronavirus replication and deregulated autophagosome-lysosome system. We performed transcriptome analysis of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and identified the aberrant upregulation of genes in the lysosome pathway. We further determined the capability of two circulating markers, namely microtubule-associated proteins 1A/1B light chain 3B (LC3B) and (p62/SQSTM1) p62, both of which depend on lysosome for degradation, in predicting the emergence of moderate-to-severe disease in COVID-19 patients requiring hospitalization for supplemental oxygen therapy. Logistic regression analyses showed that LC3B was associated with moderate-to-severe COVID-19, independent of age, sex and clinical risk score. A decrease in LC3B concentration <5.5 ng/ml increased the risk of oxygen and ventilatory requirement (adjusted odds ratio: 4.6; 95% CI: 1.1-22.0; P = 0.04). Serum concentrations of p62 in the moderate-to-severe group were significantly lower in patients aged 50 or below. In conclusion, lysosome function is deregulated in PBMCs isolated from COVID-19 patients, and the related biomarker LC3B may serve as a novel tool for stratifying patients with moderate-to-severe COVID-19 from those with asymptomatic or mild disease. COVID-19 patients with a decrease in LC3B concentration <5.5 ng/ml will require early hospital admission for supplemental oxygen therapy and other respiratory support.


Subject(s)
COVID-19/virology , Leukocytes, Mononuclear/metabolism , Lysosomes/metabolism , Microtubule-Associated Proteins/blood , SARS-CoV-2/metabolism , Adult , Autophagy , Biomarkers/blood , COVID-19/blood , Cell Cycle , Cholesterol/metabolism , Female , Humans , Male , Middle Aged , RNA-Binding Proteins/blood , Real-Time Polymerase Chain Reaction , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction
20.
Brief Bioinform ; 22(2): 1291-1296, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343632

ABSTRACT

Patients with spinal muscular atrophy (SMA) are susceptible to the respiratory infections and might be at a heightened risk of poor clinical outcomes upon contracting coronavirus disease 2019 (COVID-19). In the face of the COVID-19 pandemic, the potential associations of SMA with the susceptibility to and prognostication of COVID-19 need to be clarified. We documented an SMA case who contracted COVID-19 but only developed mild-to-moderate clinical and radiological manifestations of pneumonia, which were relieved by a combined antiviral and supportive treatment. We then reviewed a cohort of patients with SMA who had been living in the Hubei province since November 2019, among which the only 1 out of 56 was diagnosed with COVID-19 (1.79%, 1/56). Bioinformatic analysis was carried out to delineate the potential genetic crosstalk between SMN1 (mutation of which leads to SMA) and COVID-19/lung injury-associated pathways. Protein-protein interaction analysis by STRING suggested that loss-of-function of SMN1 might modulate COVID-19 pathogenesis through CFTR, CXCL8, TNF and ACE. Expression quantitative trait loci analysis also revealed a link between SMN1 and ACE2, despite low-confidence protein-protein interactions as suggested by STRING. This bioinformatic analysis could give hint on why SMA might not necessarily lead to poor outcomes in patients with COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Muscular Atrophy, Spinal/complications , Survival of Motor Neuron 1 Protein/metabolism , COVID-19/virology , Disease Susceptibility , Humans , Muscular Atrophy, Spinal/metabolism , Muscular Atrophy, Spinal/prevention & control , Protein Binding , Protein Interaction Maps , Renin-Angiotensin System , SARS-CoV-2/isolation & purification , Signal Transduction , Survival of Motor Neuron 1 Protein/genetics
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