esell17
commented
4 years ago These results have implications for developing a diagnostic test for SARS-CoV-2 infection based on olfactory performance.
- What did they analyze? They analyzed publicly available mouse, nonhuman primate and human RNA sequencing (RNASeq) and single cell sequencing (scSeq) datasets that include definitive olfactory epithelium populations to look at CoV-2-related gene expression. They also mapped scSeq data across different datasets to compare observed gene expression levels from nasal samples to samples obtained from other airway tissues.
- What methods did they use? Human scSeq previously published data sets were downloaded from publicly available source GEO. The group then filtered the data and ultimately ended up with a human scSeq dataset that contained 33358 cells. Data from a European Genome archive was also downloaded. A subset of these two datasets were combined for mapping between cell types. The two datasets were normalized using different strategies and from what I can tell appropriately combined by log-transforming the set that had not already been log normalized prior to publication.
- Does this paper study COVID-19, SARS-CoV-2, or a related disease and/or virus? This paper studies gene expression of genes implicated in SARS-CoV-2 infection in normal, healthy cell populations.
- What is the main finding (or a few main takeaways)? Results from this study indicate that olfactory epithelial support cells, stem cells and cells in the nasal respiratory epithelium express two key genes implicated in CoV2 entry, ACE2 and TMPRSS2. These results support the idea that that non-neural cells in the olfactory epithelium express CoV entry-associated molecules, suggesting that infection of these cells could directly or indirectly lead to olfactory dysfunction. This hypothesis, if validated, could link gene expression patterns in subpopulations of olfactory cells to the clinical observation of anosmia in COVID-19 patients.
- What does this paper tell us about the background and/or diagnostics/therapeutics for COVID-19 / SARS-CoV-2? These results provide are early but important step for developing a diagnostic test for SARS-CoV-2 infection for individuals with smell loss that could supplement or substitute more expensive and invasive forms of diagnostic testing for SARS-CoV-2 infection.
- Do you have any concerns about methodology or the interpretation of these results beyond this analysis? The results of this paper are very preliminary for understanding the pathophysiology of anosmia in patients with COVID-19. This group shows that two of the genes thought to be important in SARS-CoV-2 infection, ACE2 and TMPRSS2, are present in certain subpopulations of the olfactory epithelium. Much more research is still needed to understand viral entry and olfactory damage in patients with COVID-19.
Title: Non-neural expression of SARS-CoV-2 entry genes in the olfactory epithelium suggests mechanisms underlying anosmia in COVID-19 patients
Please paste a link to the paper or a citation here:
Link: https://www.biorxiv.org/content/10.1101/2020.03.25.009084v2
What is the paper's Manubot-style citation?
Citation: @doi:10.1101/2020.03.25.009084
Please list some keywords (3-10) that help identify the relevance of this paper to COVID-19
Which areas of expertise are particularly relevant to the paper?
Questions to answer about each paper:
Please provide 1-2 sentences introducing the study and its main findings
This study analyzes bulk and single-cell RNA-seq data to identify cells of the olfactory epithelium that express proteins mediating viral entry, a potential explanation for anosmia, one of the earliest signs of SARS-CoV-2 infection.
Study question(s) being investigated:
What type of testing scenario is being considered?
Is it a screening test (used for individuals with no symptoms), diagnostic test (used for individuals with symptoms), or definitive test (used for individuals who have had previous positive test results on diagnostic or screening tests)?
Study population:
What is the model system (e.g., human study, animal model, cell line study)?
What is the sample size?
What is the "pre-test" probability of disease in the study population (i.e., what is the anticipated prevalence of the disease?)
For human studies, the following are related to the pre-test probability:
What countries/regions are considered?
What is the age range, gender, other relevant characteristics?
What is the setting of the study (e.g., random sample of school children, retirement communities, etc.)?
What other specific inclusion-exclusion criteria are considered?
Reference test:
What reference test is considered as a "gold standard" comparator for the test under investigation?
Test assignment:
How are the new and reference tests assigned?
Examples of assignment could include: Recruited individuals have initially undergone neither the new nor the reference test; individuals tested as positive or negative by the reference test undergo the new test; individuals who have undertaken the new test are assessed by the standard test.
Are there any other relevant details about the study design?
Depending on how individuals are chosen, the test may be biasing towards more sick or less sick individuals or very clear-cut positive/negative cases. Any factors that would influence this bias should be included here.
Test conduct:
How were tests performed?
Describe technical details of assays used, when measurements were taken and by whom, etc. for both the new and standard tests.
Test Assessment
Describe how individuals are classified as positive or negative, e.g. if a threshold is used.
Is there evidence that the test is precise/reproducible when repeated more than once?
Are measurements complete?
For example: Do some participants undergo just one test (the new or the reference test)? Are there individuals with inconclusive results?
Results summary:
What are the estimated sensitivity, specificity, positive predictive value (PPV), and negative predicted value (NPV)?
Note that the PPV and NPV represent "post-test" probabilities of disease and are generally more meaningful than sensitivity and specificity. Sometimes the post-test odds will be given instead.
What are the confidence bounds around these intervals?
Interpretation of results for study population:
How good is the test at ruling in or ruling out a disease based on the post-test probabilities?
Are there identified side affects of the test?
Is patient adherence to the test likely to be an issue?
Extrapolation of conclusions to other groups of individuals
How well is the test likely to work in populations with different pretest odds?
For example, if the prevalence is lower, then the PPV will also be lower, but the NPV will be higher.
How costly is the test?
How difficult is it to perform the test in different settings?
Could the test be combined with other existing tests?
Summary of reliability
1-2 sentences on concluding remarks, including summary of strengths, weaknesses, limitations.
Progress
Check off the components as they are completed. If the component is not applicable, check the box as well.