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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308351

ABSTRACT

Background: There is a current worldwide outbreak of a new type of coronavirus COVID-19. The number of confirmed infected cases is rapidly increasing. Method: This paper analyzes the characteristics of COVID-19 in comparison with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and influenza. Diagnostic data for foreign citizens evacuated from Wuhan were collected and compiled. Current prevention and control strategies have been analyzed. Results: COVID-19 is similar to SARS-CoV and MERS-CoV virologically and etiologically, but similar to influenza in epidemiology and virulence. The prevalence rate in Wuhan was inferred to be close to 1%. The comparison provides a new perspective for the future of the disease, and offers some advice in the prevention and control management strategy. Conclusion: The large number of patients and the strong occult nature are two big problems, making the virus difficult to eradicate. We need to contemplate the possibility of long-term co-existence with COVID-19.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315701

ABSTRACT

To address the expression pattern of the SARS-CoV-2 receptor ACE2 and the viral priming protease, TMPRSS2, in the respiratory tract, this study investigated RNA sequencing transcriptome profiling of samples of airway and oral mucosa. As shown, ACE2 has medium levels of expression in both small airway epithelium and masticatory mucosa, and high levels of expression in nasal epithelium. The expression of ACE2 is low in mucosal associated invariant T (MAIT) cells, and can’t be detected in alveolar macrophages. TMPRSS2 is highly expressed in small airway epithelium and nasal epithelium, and has lower expression in masticatory mucosa. Our results provide the molecular basis that the nasal mucosa is the most susceptible locus in the respiratory tract for SARS-CoV-2 infection and consequently for subsequent droplet transmission and should be the focus for protection against SARS-CoV-2 infection.

3.
Metabolism ; 129: 155156, 2022 04.
Article in English | MEDLINE | ID: covidwho-1654927

ABSTRACT

BACKGROUND: Both obesity and type 2 diabetes (T2D) are reported to be highly enriched in hospitalized COVID-19 patients. Due to the close correlation between obesity and T2D, it is important to examine whether obesity and T2D are independently related to COVID-19 hospitalization. OBJECTIVE: To examine the causal effect of obesity and T2D in hospitalized COVID-19 patients using Mendelian randomization (MR). RESEARCH DESIGN AND METHODS: This two-sample MR analysis applied genetic markers of obesity identified in the genome wide association study (GWAS) by the GIANT Consortium as instrumental variables (IVs) of obesity; and genetic markers of T2D identified by the DIAGRAM Consortium as IVs of T2D. The MR analysis was performed in hospitalized COVID-19 patient by the COVID-19 Host Genetics Initiative using the MR-Base platform. RESULTS: All 3 classes of obesity (Class 1/2/3) were shown as the causal risk factors of COVID-19 hospitalization; however, T2D doesn't increase the risk of hospitalization or critically ill COVID-19 as an independent factor. CONCLUSIONS: Obesity, but not T2D, is a primary risk factor of COVID-19 hospitalization.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Hospitalization/statistics & numerical data , Mendelian Randomization Analysis , Obesity/epidemiology , SARS-CoV-2 , Body Mass Index , COVID-19/genetics , COVID-19/therapy , Causality , Comorbidity , Diabetes Mellitus, Type 2/genetics , Genome-Wide Association Study , Humans , Obesity/classification , Obesity/genetics , Polymorphism, Single Nucleotide/genetics , Risk Factors , Severity of Illness Index
4.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295773

ABSTRACT

Objective The cytokines, LIGHT (TNFSF14) and Interleukin-18 (IL-18), are two important therapeutic targets due to their central roles in the function of activated T cells and inflammatory injury. LIGHT was recently shown to play a major role in COVID19 induced acute respiratory distress syndrome (ARDS), reducing mortality and hospital stay. This study aims to investigate the associations of LIGHT and IL-18 with non-COVID19 related ARDS, acute hypoxic respiratory failure (AHRF) or acute kidney injury (AKI), secondary to viral or bacterial sepsis. Research Design and Methods A cohort of 280 subjects diagnosed with sepsis, including 91 cases with sepsis triggered by viral infections, were investigated in this study and compared to healthy controls. Serum LIGHT, IL-18, and 59 other biomarkers (cytokines, chemokines and acute-phase reactants) were measured and associated with symptom severity. Results ARDS was observed in 36% of the patients, with 29% of the total patient cohort developing multi-organ failure (failure of two or more organs). We observed significantly increased LIGHT level (>2SD above mean of healthy subjects) in both bacterial sepsis patients (P=1.80E-05) and patients with sepsis from viral infections (P=1.78E-03). In bacterial sepsis, increased LIGHT level associated with ARDS, AKI and higher Apache III scores, findings also supported by correlations of LIGHT with other biomarkers of organ failures, suggesting LIGHT may be an inflammatory driver. IL-18 levels were highly variable across individuals, and consistently correlated with Apache III scores, mortality, and AKI, in both bacterial and viral sepsis. Conclusions For the first time, we demonstrate independent effects of LIGHT and IL-18 in septic organ failures. LIGHT levels are significantly elevated in non-COVID19 sepsis patients with ARDS and/or multi-organ failures suggesting that anti-LIGHT therapy may be effective therapy in a subset of patients with sepsis. Given the large variance of plasma IL-18 among septic subjects, targeting this pathway raises opportunities that require a precision application.

5.
Viruses ; 12(10)2020 10 16.
Article in English | MEDLINE | ID: covidwho-1389518

ABSTRACT

To address the expression pattern of the SARS-CoV-2 receptor ACE2 and the viral priming protease TMPRSS2 in the respiratory tract, this study investigated RNA sequencing transcriptome profiling of samples of airway and oral mucosa. As shown, ACE2 has medium levels of expression in both small airway epithelium and masticatory mucosa, and high levels of expression in nasal epithelium. The expression of ACE2 is low in mucosal-associated invariant T (MAIT) cells and cannot be detected in alveolar macrophages. TMPRSS2 is highly expressed in small airway epithelium and nasal epithelium and has lower expression in masticatory mucosa. Our results provide the molecular basis that the nasal mucosa is the most susceptible locus in the respiratory tract for SARS-CoV-2 infection and consequently for subsequent droplet transmission and should be the focus for protection against SARS-CoV-2 infection.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/genetics , Peptidyl-Dipeptidase A/biosynthesis , Pneumonia, Viral/genetics , Serine Endopeptidases/biosynthesis , Virus Internalization , Angiotensin-Converting Enzyme 2 , COVID-19 , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Epithelium/metabolism , Epithelium/virology , Gene Expression , Gene Expression Profiling , Humans , Nasal Mucosa/metabolism , Nasal Mucosa/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , Respiratory System/metabolism , Respiratory System/virology , SARS-CoV-2 , Serine Endopeptidases/genetics
6.
FEBS Lett ; 595(13): 1819-1824, 2021 07.
Article in English | MEDLINE | ID: covidwho-1220171

ABSTRACT

We previously observed enhanced immunoglobulin A (IgA) responses in severe COVID-19, which might confer damaging effects. Given the important role of IgA in immune and inflammatory responses, the aim of this study was to investigate the dynamic response of the IgA isotype switch factor TGF-ß1 in COVID-19 patients. We observed, in a total of 153 COVID-19 patients, that the serum levels of TGF-ß1 were increased significantly at the early and middle stages of COVID-19, and correlated with the levels of SARS-CoV-2-specific IgA, as well as with the APACHE II score in patients with severe disease. In view of the genetic association of the TGF-ß1 activator THBS3 with severe COVID-19 identified by the COVID-19 Host Genetics Initiative, this study suggests TGF-ß1 may play a key role in COVID-19.


Subject(s)
COVID-19/immunology , Immunoglobulin A/blood , SARS-CoV-2/immunology , Thrombospondins/genetics , Transforming Growth Factor beta1/blood , APACHE , Adult , Aged , Antibodies, Viral/blood , COVID-19/blood , COVID-19/genetics , Female , Humans , Immunoglobulin A/metabolism , Male , Middle Aged , Polymorphism, Single Nucleotide
8.
ERJ Open Res ; 7(1)2021 Jan.
Article in English | MEDLINE | ID: covidwho-1076123

ABSTRACT

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients may suffer persistent systemic inflammation and multiple organ failure, leading to a poor prognosis. RESEARCH QUESTION: To examine the relevance of the novel inflammatory factor heparin-binding protein (HBP) in critically ill COVID-19 patients, and evaluate the correlation of the biomarker with disease progression. STUDY DESIGN AND METHODS: 18 critically ill COVID-19 patients who suffered from respiratory failure and sepsis, including 12 cases who experienced a rapidly deteriorating clinical condition and six cases without deterioration, were investigated. They were compared with 15 age- and sex- matched COVID-19-negative patients with respiratory failure. Clinical data were collected and HBP levels were investigated. RESULTS: HBP was significantly increased in critically ill COVID-19 patients following disease aggravation and tracked with disease progression. HBP elevation preceded the clinical manifestations for up to 5 days and was closely correlated with patients' pulmonary ventilation and perfusion status. INTERPRETATION: HBP levels are associated with COVID-19 disease progression in critically ill patients. As a potential mediator of disease aggravation and multiple organ injuries that are triggered by continuing inflammation and oxygen deficits, HBP warrants further study as a disease biomarker and potential therapeutic target.

9.
Viruses ; 12(11)2020 10 29.
Article in English | MEDLINE | ID: covidwho-902676

ABSTRACT

There is a current pandemic of a new type of coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of confirmed infected cases has been rapidly increasing. This paper analyzes the characteristics of SARS-CoV-2 in comparison with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and influenza. COVID-19 is similar to the diseases caused by SARS-CoV and MERS-CoV virologically and etiologically, but closer to influenza in epidemiology and virulence. The comparison provides a new perspective for the future of the disease control, and offers some ideas in the prevention and control management strategy. The large number of infectious people from the origin, and the highly infectious and occult nature have been two major problems, making the virus difficult to eradicate. We thus need to contemplate the possibility of long-term co-existence with COVID-19.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Influenza, Human/epidemiology , Influenza, Human/transmission , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/transmission , Betacoronavirus/isolation & purification , COVID-19 , Humans , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Pandemics , SARS-CoV-2
10.
J Med Internet Res ; 22(8): e20914, 2020 08 14.
Article in English | MEDLINE | ID: covidwho-736597

ABSTRACT

BACKGROUND: The coronavirus disease (COVID-19) pandemic began in Wuhan, China, in December 2019. Wuhan had a much higher mortality rate than the rest of China. However, a large number of asymptomatic infections in Wuhan may have never been diagnosed, contributing to an overestimated mortality rate. OBJECTIVE: This study aims to obtain an accurate estimate of infections in Wuhan using internet data. METHODS: In this study, we performed a combined analysis of the infection rate among evacuated foreign citizens to estimate the infection rate in Wuhan in late January and early February. RESULTS: Based on our analysis, the combined infection rate of the foreign evacuees was 0.013 (95% CI 0.008-0.022). Therefore, we estimate the number of infected people in Wuhan to be 143,000 (range 88,000-242,000), which is significantly higher than previous estimates. Our study indicates that a large number of infections in Wuhan were not diagnosed, which has resulted in an overestimated case fatality rate. CONCLUSIONS: Increased awareness of the original infection rate of Wuhan is critical for proper public health measures at all levels, as well as to eliminate panic caused by overestimated mortality rates that may bias health policy actions by the authorities.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , COVID-19 , China/epidemiology , Humans , Pandemics , Public Health , SARS-CoV-2
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