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SARS-CoV-2 proteins

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    Exploring causal relationships between COVID-19 MESHD and cardiometabolic disorders MESHD: A bi-directional Mendelian randomization study

    Authors: Yong XIANG; Carlos Kwan-Long CHAU; Jinghong QIU; Shitao RAO; Hon-Cheong So

    doi:10.1101/2021.03.20.21254008 Date: 2021-03-20 Source: medRxiv

    Background: More than 100 million cases of COVID-19 MESHD have been reported worldwide. A number of risk factors for infection or severe infection have been identified, however observational studies were subject to confounding bias. In addition, there is still limited knowledge about the complications or medical consequences of the disease. Methods: Here we performed bi-directional Mendelian randomization (MR) analysis to evaluate causal relationships between liability to COVID-19 MESHD (and severe/ critical infection MESHD) and a wide range of around 30 cardiometabolic disorders MESHD ( CMD MESHD) or traits. Genetic correlation (rg) was assessed by LD score regression(LDSC). The latest GWAS summary statistics from the COVID-19 MESHD Host Genetics Initiative was used, which comprised comparisons of general population controls with critically ill, hospitalized and any infected cases. Results: Overall we observed evidence that liability to COVID-19 MESHD or severe infection may be causally associated with higher risks of type 2 diabetes mellitus MESHD(T2DM), chronic kidney disease MESHD(CKD), ischemic stroke MESHD (especially large artery stroke MESHD[LAS]) and heart failure MESHD(HF) when compared to the general population. On the other hand, our findings suggested that liability to atrial fibrillation MESHD ( AF MESHD), stroke MESHD (especially LAS), obesity MESHD, diabetes MESHD (T1DM and T2DM), low insulin sensitivity MESHD insulin HGNC sensitivity and impaired renal function MESHD (low eGFR HGNC and diabetic kidney disease MESHD) may be causal risk factors for COVID-19 MESHD or severe disease. In genetic correlation analysis, T2DM, CAD, obesity MESHD, fasting insulin HGNC, CKD, gout MESHD, stroke MESHD and urate showed positive rg with critical or hospitalized infection. All above findings passed multiple testing correction at a false discovery rate (FDR)<0.05. Conclusions: In summary, this study provides evidence for tentative bi-directional causal associations between liability to COVID-19 MESHD and severe disease and a number of CM disorders MESHD. Further replications and prospective studies are required to verify the findings.

    Expression of ACE2 and TMPRSS2 proteins in the upper and lower aerodigestive tracts of rats

    Authors: Rumi Ueha; Taku Sato; Takao Goto; Akihito Yamauchi; Kenji Kondo; Tatsuya Yamasoba

    doi:10.1101/2020.05.14.097204 Date: 2020-05-15 Source: bioRxiv

    Objective Patients with coronavirus disease 2019 MESHD ( COVID-19 MESHD), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit not only respiratory symptoms but also symptoms of chemo-sensitive disorders MESHD and kidney failure MESHD. Cellular entry of SARS-CoV-2 depends on the binding of its spike protein PROTEIN to a cellular receptor named angiotensin-converting enzyme 2 (ACE2), and the subsequent spike protein PROTEIN-priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). Thus, high expression of ACE2 and TMPRSS2 are considered to enhance the invading capacity of SARS-CoV-2.Methods To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS-CoV-2, we investigated the expression of ACE2 and TMPRSS2 proteins in the aerodigestive tracts of the tongue, hard palate MESHD with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, lung, and kidney of rats through immunohistochemistry.Results Strong co-expression of ACE2 and TMPRSS2 proteins was observed in the nasal respiratory epithelium, trachea, bronchioles, alveoli, kidney, and taste buds of the tongue. Remarkably, TMPRSS2 expression was much stronger in the peripheral alveoli than in the central alveoli. These results coincide with the reported clinical symptoms of COVID-19 MESHD, such as the loss of taste, loss of olfaction MESHD, respiratory dysfunction MESHD, and acute nephropathy MESHD.Conclusions A wide range of organs have been speculated to be affected by SARS-CoV-2 depending on the expression levels of ACE2 and TMPRSS2. Differential distribution of TMPRSS2 in the lung indicated the COVID-19 MESHD symptoms to possibly be exacerbated by TMPRSS2 expression. This study might provide potential clues for further investigation of the pathogenesis of COVID-19 MESHD.Level of Evidence NACompeting Interest StatementThe authors have declared no competing interest.View Full Text

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MeSH Disease
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SARS-CoV-2 Proteins


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