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 IndexABSTRACT
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/geneticsABSTRACT
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.