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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332871

ABSTRACT

Long COVID, a type of Post-Acute Sequelae of SARS CoV-2 infection (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the pathophysiological mechanisms that drive this inflammation remain unknown. Inflammation during acute Coronavirus Disease 2019 (COVID-19) could be exacerbated by microbial translocation (from the gut and/or lung) to the blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We found higher levels of fungal translocation - measured as beta-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared to those without PASC or SARS-CoV-2 negative controls. The higher beta-glucan correlated with higher levels of markers of inflammation and elevated levels of host metabolites involved in activating N-Methyl-D-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neuro-toxic properties. Mechanistically, beta-glucan can directly induce inflammation by binding to myeloid cells (via the Dectin-1 receptor) and activating Syk/NF-kB signaling. Using an in vitro Dectin-1/NF-kB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-kB signaling compared to plasma from SARS-CoV-2 negative controls. This higher NF-kB signaling was abrogated by the Syk inhibitor Piceatannol. These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330863

ABSTRACT

Two serologically distinct replication-defective chimpanzee-origin adenovirus (Ad) vectors (AdC) called AdC6 and AdC7 expressing the spike (S) or nucleocapsid (N) proteins of an early SARS-CoV-2 isolate were tested individually or as a mixture in a hamster COVID-19 challenge model. The N protein, which was expressed as a fusion protein within herpes simplex virus glycoprotein D (gD) stimulated antibodies and CD8+ T cells. The S protein expressing AdC (AdC-S) vectors induced antibodies including those with neutralizing activity that in part cross-reacted with viral variants. Hamsters vaccinated with the AdC-S vectors were protected against serious disease and showed accelerated recovery upon SARS-CoV-2 challenge. Protection was enhanced if AdC-S vectors were given together with the AdC vaccines that expressed the gDN fusion protein (AdC-gDN). In contrast hamsters that just received the AdC-gDN vaccines showed only marginal lessening of symptoms compared to control animals. These results indicate that immune response to the N protein that is less variable that the S protein may potentiate and prolong protection achieved by the currently used genetic COVID-19 vaccines.

3.
Microbiol Spectr ; 10(1): e0256021, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1700708

ABSTRACT

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring frequent adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting. We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28-day mortality or alter levels of specific antibody responses before and after CIP infusion. In a single-arm phase II study, patients >18 years-old with respiratory symptoms with confirmed COVID-19 infection who were admitted to a non-ICU bed were administered two units of CIP within 72 h of admission. Levels of SARS-CoV-2 detected by PCR in the respiratory tract and circulating anti-SARS-CoV-2 antibody titers were sequentially measured before and after CIP transfusion. Twenty-nine patients were transfused high titer CIP and 48 contemporaneous comparable controls were identified. All classes of antibodies to the three SARS-CoV-2 target proteins were significantly increased at days 7 and 14 post-transfusion compared with baseline (P < 0.01). Anti-nucleocapsid IgA levels were reduced at day 28, suggesting that the initial rise may have been due to the contribution of CIP. The groups were well-balanced, without statistically significant differences in demographics or co-morbidities or use of remdesivir or dexamethasone. In participants transfused with CIP, the rate of ICU transfer was 13.8% compared to 27.1% for controls with a hazard ratio 0.506 (95% CI 0.165-1.554), and 28-day mortality was 6.9% compared to 10.4% for controls, hazard ratio 0.640 (95% CI 0.124-3.298). IMPORTANCE Transfusion of high-titer CIP to non-critically ill patients early after admission with COVID-19 respiratory disease was associated with significantly increased anti-SARS-CoV-2 specific antibodies (compared to baseline) and a non-significant reduction in ICU transfer and death (compared to controls). This prospective phase II trial provides a suggestion that the antiviral effects of CIP from early in the COVID-19 pandemic may delay progression to critical illness and death in specific patient populations. This study informs the optimal timing and potential population of use for CIP in COVID-19, particularly in settings without access to other interventions, or in planning for future coronavirus pandemics.


Subject(s)
Antibodies, Viral/administration & dosage , COVID-19/immunology , COVID-19/therapy , Critical Illness/therapy , Plasma/immunology , SARS-CoV-2/immunology , Aged , COVID-19/mortality , Female , Humans , Immunization, Passive , Male , Middle Aged , Prospective Studies , SARS-CoV-2/genetics
4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325537

ABSTRACT

Background: Coronavirus Disease 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts. SARS-CoV-2 was isolated from faecal samples and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as the virome) that play a role in regulating host immunity and disease pathophysiology. Understanding gut virome perturbation that underlies SARS-CoV-2 infection and severity is an unmet need. Methods: : We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender and co-morbidities. All subjects had faecal specimens sampled at inclusion. Blood specimens were collected for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serial faecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the faecal RNA and DNA virome. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood parameters. Results: : Patients with COVID-19 showed underrepresentation of Pepper mild mottle virus (RNA virus) and multiple bacteriophage lineages (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in faecal samples, compared to non-COVID-19 subjects. Such gut virome alterations persisted up to 30 days after disease resolution. Faecal virome in SARS-CoV-2 infection harboured more stress-, inflammation- and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Baseline fecal abundance of 10 virus species (1 RNA virus, Pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease COVID-19 severity. These viruses inversely correlated with blood levels of pro-inflammatory proteins, white cells and neutrophils. Among the 10 COVID-19 severity-associated DNA virus species, 4 showed inverse correlation with age;5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects. Conclusions: Both enteric RNA and DNA virome in COVID-19 patients were different from non-COVID-19 subjects, which persisted after disease resolution of COVID-19. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age may partly explain that older subjects are prone to severe and worse COVID-19 outcomes. Altogether our data highlight the importance of human gut virome in severity and potentially therapeutics of COVID-19.

5.
Social Sciences ; 11(2):75, 2022.
Article in English | MDPI | ID: covidwho-1686954

ABSTRACT

The COVID-19 pandemic disrupted many young adults’lives educationally, economically, and personally. This study investigated associations between COVID-19-related disruption and perception of increases in internalising symptoms among young adults and whether these associations were moderated by earlier measures of adolescent positivity and future orientation and parental psychological control. Participants included 1329 adolescents at Time 1, and 810 of those participants as young adults (M age = 20, 50.4% female) at Time 2 from 9 countries (China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States). Drawing from a larger longitudinal study of adolescent risk taking and young adult competence, this study controlled for earlier levels of internalising symptoms during adolescence in examining these associations. Higher levels of adolescent positivity and future orientation as well as parent psychological control during late adolescence helped protect young adults from sharper perceived increases in anxiety and depression during the first nine months of widespread pandemic lockdowns in all nine countries. Findings are discussed in terms of how families in the 21st century can foster greater resilience during and after adolescence when faced with community-wide stressors, and the results provide new information about how psychological control may play a protective role during times of significant community-wide threats to personal health and welfare.

7.
Signal Transduct Target Ther ; 7(1): 7, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1606287

ABSTRACT

Activation-induced cytidine deaminase (AID) initiates class-switch recombination and somatic hypermutation (SHM) in antibody genes. Protein expression and activity are tightly controlled by various mechanisms. However, it remains unknown whether a signal from the extracellular environment directly affects the AID activity in the nucleus where it works. Here, we demonstrated that a deubiquitinase USP10, which specifically stabilizes nuclear AID protein, can translocate into the nucleus after AKT-mediated phosphorylation at its T674 within the NLS domain. Interestingly, the signals from BCR and TLR1/2 synergistically promoted this phosphorylation. The deficiency of USP10 in B cells significantly decreased AID protein levels, subsequently reducing neutralizing antibody production after immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or human immunodeficiency virus type 1 (HIV-1) nanoparticle vaccines. Collectively, we demonstrated that USP10 functions as an integrator for both BCR and TLR signals and directly regulates nuclear AID activity. Its manipulation could be used for the development of vaccines and adjuvants.


Subject(s)
AIDS Vaccines/immunology , B-Cell Activating Factor/immunology , COVID-19 Vaccines/immunology , Cytidine Deaminase/immunology , HIV-1/immunology , Nanoparticles , SARS-CoV-2/immunology , Signal Transduction/immunology , Ubiquitin Thiolesterase/immunology , Ubiquitination/immunology , AIDS Vaccines/genetics , Animals , B-Cell Activating Factor/genetics , COVID-19 Vaccines/genetics , Cytidine Deaminase/genetics , HEK293 Cells , HIV-1/genetics , Humans , Mice , Mice, Knockout , SARS-CoV-2/genetics , Signal Transduction/genetics , Ubiquitin Thiolesterase/genetics
8.
Dev Psychopathol ; : 1-16, 2021 Dec 13.
Article in English | MEDLINE | ID: covidwho-1569192

ABSTRACT

Prior to the COVID-19 pandemic, adolescents (N = 1,330; Mages = 15 and 16; 50% female), mothers, and fathers from nine countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, United States) reported on adolescents' internalizing and externalizing problems, adolescents completed a lab-based task to assess tendency for risk-taking, and adolescents reported on their well-being. During the pandemic, participants (Mage = 20) reported on changes in their internalizing, externalizing, and substance use compared to before the pandemic. Across countries, adolescents' internalizing problems pre-pandemic predicted increased internalizing during the pandemic, and poorer well-being pre-pandemic predicted increased externalizing and substance use during the pandemic. Other relations varied across countries, and some were moderated by confidence in the government's handling of the pandemic, gender, and parents' education.

11.
Gastroenterology ; 162(2): 548-561.e4, 2022 02.
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.


Subject(s)
COVID-19/microbiology , Fatty Acids, Volatile/biosynthesis , Gastrointestinal Microbiome/genetics , Immunity/physiology , Isoleucine/biosynthesis , Adult , Biomarkers/blood , Case-Control Studies , Feces/microbiology , Female , Humans , Male , Metagenomics , Middle Aged , Phylogeny , SARS-CoV-2 , Severity of Illness Index
12.
BMJ Open ; 11(7): e047076, 2021 07 23.
Article in English | MEDLINE | ID: covidwho-1322821

ABSTRACT

OBJECTIVES: In response to the COVID-19 pandemic there have been significant developments in research, its conduct and the supporting ethical framework. While many protocols have been delayed, halted or modified, other research efforts have been accelerated, generating controversy. The goal of this paper is to determine the rates of references surrounding the ethical oversight of research as reported in current COVID-19-related research publications. DESIGN: Scoping review. SETTING: Population-based observational or interventional studies from December 2019 to May 2020 with sample size of two or more. Studies were searched through electronic databases including Medline, EMBASE, and Cochrane CENTRAL Register of Controlled Trials. PARTICIPANTS: Eligibility criteria included participants within published studies who tested positive for COVID-19. MAIN OUTCOMES AND MEASURES: Data were extracted and charting methods included taking note of references to ethical frameworks, institutional review board (IRB), ethics committee (EC) or research ethics board (REB) involvement, consent processes, and other variables. RESULTS: 11 556 articles were screened, with 656 included in the final analysis. References to ethics were present in 530 (80.8%) studies, with 491 (74.8%) involving IRB/ECs/REBs and 126 (19.2%) not referencing ethics. Consent processes were outlined in 201 (30.6%) studies, with 198 (30.2%) reporting that they obtained consent waivers, however, 257 (39.2%) did not mention consent at all. Differences (p<0.001) in ethics-related references were apparent when analysed by continent, publication type, sample size and IF. CONCLUSIONS: The majority of published articles pertaining to COVID-19 research made mention of ethical considerations, however, national and regional variations in research ethics review requirements introduce heterogeneity between studies and raise important questions about the conduct of scientific research during global public emergencies. TRIAL REGISTRATION NUMBER: Open Science Framework: https://osfio/z67wb.


Subject(s)
COVID-19 , Ethics Committees, Research , Ethics, Research , Humans , Pandemics , SARS-CoV-2
13.
Front Med (Lausanne) ; 8: 689568, 2021.
Article in English | MEDLINE | ID: covidwho-1295660

ABSTRACT

Objective: Early identification of coronavirus disease 2019 (COVID-19) patients with worse outcomes may benefit clinical management of patients. We aimed to quantify pneumonia findings on CT at admission to predict progression to critical illness in COVID-19 patients. Methods: This retrospective study included laboratory-confirmed adult patients with COVID-19. All patients underwent a thin-section chest computed tomography (CT) scans showing evidence of pneumonia. CT images with severe moving artifacts were excluded from analysis. Patients' clinical and laboratory data were collected from medical records. Three quantitative CT features of pneumonia lesions were automatically calculated using a care.ai Intelligent Multi-disciplinary Imaging Diagnosis Platform Intelligent Evaluation System of Chest CT for COVID-19, denoting the percentage of pneumonia volume (PPV), ground-glass opacity volume (PGV), and consolidation volume (PCV). According to Chinese COVID-19 guidelines (trial version 7), patients were divided into noncritical and critical groups. Critical illness was defined as a composite of admission to the intensive care unit, respiratory failure requiring mechanical ventilation, shock, or death. The performance of PPV, PGV, and PCV in discrimination of critical illness was assessed. The correlations between PPV and laboratory variables were assessed by Pearson correlation analysis. Results: A total of 140 patients were included, with mean age of 58.6 years, and 85 (60.7%) were male. Thirty-two (22.9%) patients were critical. Using a cutoff value of 22.6%, the PPV had the highest performance in predicting critical illness, with an area under the curve of 0.868, sensitivity of 81.3%, and specificity of 80.6%. The PPV had moderately positive correlation with neutrophil (%) (r = 0.535, p < 0.001), erythrocyte sedimentation rate (r = 0.567, p < 0.001), d-Dimer (r = 0.444, p < 0.001), high-sensitivity C-reactive protein (r = 0.495, p < 0.001), aspartate aminotransferase (r = 0.410, p < 0.001), lactate dehydrogenase (r = 0.644, p < 0.001), and urea nitrogen (r = 0.439, p < 0.001), whereas the PPV had moderately negative correlation with lymphocyte (%) (r = -0.535, p < 0.001). Conclusions: Pneumonia volume quantified on initial CT can non-invasively predict the progression to critical illness in advance, which serve as a prognostic marker of COVID-19.

14.
Front Immunol ; 12: 686240, 2021.
Article in English | MEDLINE | ID: covidwho-1285294

ABSTRACT

A disruption of the crosstalk between the gut and the lung has been implicated as a driver of severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback. We aimed to test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 negative controls. We investigated the potential links between plasma markers of gut barrier integrity, microbial translocation, systemic inflammation, metabolome, lipidome, and glycome, and COVID-19 severity. We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and translocation of bacterial and fungal products into the blood. These markers of disrupted intestinal barrier integrity and microbial translocation correlate strongly with higher levels of markers of systemic inflammation and immune activation, lower levels of markers of intestinal function, disrupted plasma metabolome and glycome, and higher mortality rate. Our study highlights an underappreciated factor with significant clinical implications, disruption in gut functions, as a potential force that may contribute to COVID-19 severity.


Subject(s)
COVID-19/immunology , Gastrointestinal Microbiome/immunology , Inflammation/immunology , Intestines/physiology , SARS-CoV-2/physiology , Female , Glycomics , Haptoglobins/metabolism , Humans , Lipidomics , Male , Metabolomics , Middle Aged , Permeability , Protein Precursors/metabolism , Tight Junctions/metabolism
15.
Environmental Research Letters ; 16(5), 2021.
Article in English | ProQuest Central | ID: covidwho-1223300

ABSTRACT

The massive lockdown of global cities during the COVID-19 pandemic is substantially improving the atmospheric environment, which for the first time, urban mobility is virtually reduced to zero, and it is then possible to establish a baseline for air quality. By comparing these values with pre-COVID-19 data, it is possible to infer the likely effect of urban mobility and spatial configuration on the air quality. In the present study, a time-series prediction model is enhanced to estimate the nationwide NO2 concentrations before and during the lockdown measures in the United States, and 54 cities are included in the study. The prediction generates a notable NO2 difference between the observations if the lockdown is not considered, and the changes in urban mobility can explain the difference. It is found that the changes in urban mobility associated with various road textures have a significant impact on NO2 dispersion in different types of climates.

16.
mBio ; 12(2)2021 04 20.
Article in English | MEDLINE | ID: covidwho-1195825

ABSTRACT

Beyond neutralization, antibodies binding to their Fc receptors elicit several innate immune functions including antibody-dependent complement deposition (ADCD), antibody-dependent cell-mediated phagocytosis (ADCP), and antibody-dependent cell-mediated cytotoxicity (ADCC). These functions are beneficial, as they contribute to pathogen clearance; however, they also can induce inflammation. We tested the possibility that qualitative differences in SARS-CoV-2-specific antibody-mediated innate immune functions contribute to coronavirus disease 2019 (COVID-19) severity. We found that anti-S1 and anti-RBD antibodies from hospitalized COVID-19 patients elicited higher ADCD but lower ADCP compared to antibodies from nonhospitalized COVID-19 patients. Consistently, higher ADCD was associated with higher systemic inflammation, whereas higher ADCP was associated with lower systemic inflammation during COVID-19. Our study points to qualitative, differential features of anti-SARS-CoV-2 specific antibodies as potential contributors to COVID-19 severity. Understanding these qualitative features of natural and vaccine-induced antibodies will be important in achieving optimal efficacy and safety of SARS-CoV-2 vaccines and/or COVID-19 therapeutics.IMPORTANCE A state of hyperinflammation and increased complement activation has been associated with coronavirus disease 2019 (COVID-19) severity. However, the pathophysiological mechanisms that contribute to this phenomenon remain mostly unknown. Our data point to a qualitative, rather than quantitative, difference in SARS-CoV-2-specific antibodies' ability to elicit Fc-mediated innate immune functions as a potential contributor to COVID-19 severity and associated inflammation. These data highlight the need for further studies to understand these qualitative features and their potential contribution to COVID-19 severity. This understanding could be essential to develop antibody-based COVID-19 therapeutics and SARS-CoV-2 vaccines with an optimal balance between efficacy and safety.


Subject(s)
Antibodies, Viral , COVID-19/immunology , Immunity, Innate , SARS-CoV-2/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antibody Specificity , Antibody-Dependent Cell Cytotoxicity , Biomarkers/blood , COVID-19/etiology , COVID-19/virology , Case-Control Studies , Cohort Studies , Complement Activation , Female , Humans , Immunoglobulin Fc Fragments/immunology , Inflammation/blood , Inflammation/etiology , Inflammation/immunology , Male , Middle Aged , Pandemics , Phagocytosis , Receptors, Fc/immunology , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology
17.
Eur Radiol ; 31(10): 7925-7935, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1184663

ABSTRACT

OBJECTIVES: To develop and validate a machine learning model for the prediction of adverse outcomes in hospitalized patients with COVID-19. METHODS: We included 424 patients with non-severe COVID-19 on admission from January 17, 2020, to February 17, 2020, in the primary cohort of this retrospective multicenter study. The extent of lung involvement was quantified on chest CT images by a deep learning-based framework. The composite endpoint was the occurrence of severe or critical COVID-19 or death during hospitalization. The optimal machine learning classifier and feature subset were selected for model construction. The performance was further tested in an external validation cohort consisting of 98 patients. RESULTS: There was no significant difference in the prevalence of adverse outcomes (8.7% vs. 8.2%, p = 0.858) between the primary and validation cohorts. The machine learning method extreme gradient boosting (XGBoost) and optimal feature subset including lactic dehydrogenase (LDH), presence of comorbidity, CT lesion ratio (lesion%), and hypersensitive cardiac troponin I (hs-cTnI) were selected for model construction. The XGBoost classifier based on the optimal feature subset performed well for the prediction of developing adverse outcomes in the primary and validation cohorts, with AUCs of 0.959 (95% confidence interval [CI]: 0.936-0.976) and 0.953 (95% CI: 0.891-0.986), respectively. Furthermore, the XGBoost classifier also showed clinical usefulness. CONCLUSIONS: We presented a machine learning model that could be effectively used as a predictor of adverse outcomes in hospitalized patients with COVID-19, opening up the possibility for patient stratification and treatment allocation. KEY POINTS: • Developing an individually prognostic model for COVID-19 has the potential to allow efficient allocation of medical resources. • We proposed a deep learning-based framework for accurate lung involvement quantification on chest CT images. • Machine learning based on clinical and CT variables can facilitate the prediction of adverse outcomes of COVID-19.


Subject(s)
COVID-19 , Humans , Machine Learning , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
18.
Microbiome ; 9(1): 91, 2021 04 14.
Article in English | MEDLINE | ID: covidwho-1183579

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts. SARS-CoV-2 was isolated from fecal samples, and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as the virome) that play a role in regulating host immunity and disease pathophysiology. Understanding gut virome perturbation that underlies SARS-CoV-2 infection and severity is an unmet need. METHODS: We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender and co-morbidities. All subjects had fecal specimens sampled at inclusion. Blood specimens were collected for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serial fecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the fecal RNA and DNA virome. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood parameters. RESULTS: Patients with COVID-19 showed underrepresentation of Pepper mild mottle virus (RNA virus) and multiple bacteriophage lineages (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in fecal samples, compared to non-COVID-19 subjects. Such gut virome alterations persisted up to 30 days after disease resolution. Fecal virome in SARS-CoV-2 infection harbored more stress-, inflammation-, and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Baseline fecal abundance of 10 virus species (1 RNA virus, pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease COVID-19 severity. These viruses inversely correlated with blood levels of pro-inflammatory proteins, white cells, and neutrophils. Among the 10 COVID-19 severity-associated DNA virus species, 4 showed inverse correlation with age; 5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects. CONCLUSIONS: Both enteric RNA and DNA virome in COVID-19 patients were different from non-COVID-19 subjects, which persisted after disease resolution of COVID-19. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age may partly explain that older subjects are prone to severe and worse COVID-19 outcomes. Altogether, our data highlight the importance of human gut virome in severity and potentially therapeutics of COVID-19. Video Abstract.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Child, Preschool , DNA , Gastrointestinal Microbiome/genetics , Humans , RNA , SARS-CoV-2 , Virome
19.
Med Sci Monit ; 27: e929280, 2021 Apr 07.
Article in English | MEDLINE | ID: covidwho-1171226

ABSTRACT

BACKGROUND In addition to sociodemographic and COVID-19- related factors, the needs of school support, including material, psychological and information support, have seldom been discussed as factors influencing anxiety and depression among college students during the COVID-19 pandemic. MATERIAL AND METHODS In this cross-sectional study, 3351 college students from China were surveyed through questionnaires about their sociodemographic and COVID-19 characteristics, the needs of school support, and their experiences with anxiety and depression. RESULTS Anxiety and depression were reported by 6.88% and 10.50% of students, respectively. Married, higher education, non-medical, and urban students had significantly higher risks of anxiety or depression. Additionally, symptoms such as cough and fever, especially when following a possible contact with suspected individuals, quarantine history of a personal contact, going out 1-3 times a week, not wearing a mask, and spending 2-3 hours browsing COVID-19-related information were significantly associated with the occurrence of anxiety or depression. Those who used methods to regulate their emotional state, used a psychological hotline, and who had visited a psychiatrist showed higher anxiety or depression. Those who used online curricula and books, used preventive methods for COVID-19, and who had real-time information about the epidemic situation of the school showed lower anxiety and depression. CONCLUSIONS In addition to sociodemographic and COVID-19-related aspects, students' needs for psychological assistance and information from schools were also associated with anxiety and depression among college students.


Subject(s)
Anxiety/epidemiology , COVID-19/psychology , Depression/epidemiology , Schools/organization & administration , Students/psychology , Adolescent , Adult , Anxiety/prevention & control , Anxiety/psychology , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Communicable Disease Control/standards , Cross-Sectional Studies , Depression/prevention & control , Depression/psychology , Female , Financial Support , Health Education/organization & administration , Health Education/statistics & numerical data , Hotlines/organization & administration , Hotlines/statistics & numerical data , Humans , Information Dissemination , Male , Mental Health , Pandemics/prevention & control , Prevalence , Psychosocial Support Systems , Schools/economics , Schools/standards , Socioeconomic Factors , Students/statistics & numerical data , Surveys and Questionnaires/statistics & numerical data , Young Adult
20.
Clin Infect Dis ; 71(16): 2109-2113, 2020 11 19.
Article in English | MEDLINE | ID: covidwho-1153167

ABSTRACT

BACKGROUND: Healthcare workers (HCWs) at the frontline are facing a substantial risk of infection during the coronavirus disease 2019 (COVID-19) outbreak. METHODS: We acquired information and data on general information on and infection and death status of HCWs in Wuhan during the COVID-19 outbreak and completed statistical analyses. RESULTS: We obtained the data on 2457 infected cases among HCWs in Wuhan, China. More than half of the infected individuals were nurses (52.06%), whereas 33.62% of infected cases were doctors and 14.33% of cases were medical staff. In particular, the case infection rate of nurses (2.22%) was remarkably higher than that of doctors (1.92%). Most infected cases among HCWs were female (72.28%). A majority of the infected HCWs (89.26%) came from general hospitals, followed by specialized hospitals (5.70%) and community hospitals (5.05%). The case infection rate of HCWs (2.10%) was dramatically higher than that of non-HCWs (0.43%). The case fatality rate of HCWs (0.69%) was significantly lower than that of non-HCWs (5.30%). CONCLUSIONS: The infection risk of HCWs is clearly higher than that of non-HCWs. HCWs play an essential role in fighting the pandemic. The analysis of the infection status of HCWs is essential to attract enough attention from the public, provide effective suggestions for government agencies, and improve protective measures for HCWs.


Subject(s)
COVID-19/epidemiology , China/epidemiology , Cross-Sectional Studies , Disease Outbreaks/statistics & numerical data , Female , Health Personnel/statistics & numerical data , Humans , Male , Pandemics
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