Innate immune signaling in the olfactory epithelium reduces odorant receptor levels: modeling transient smell loss in COVID-19 patients
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Abstract
Post-infectious anosmias typically follow death of olfactory sensory neurons (OSNs) with a months-long recovery phase associated with parosmias. While profound anosmia is the leading symptom associated with COVID-19 infection, many patients regain olfactory function within days to weeks without distortions. Here, we demonstrate that sterile induction of anti-viral type I interferon signaling in the mouse olfactory epithelium is associated with diminished odor discrimination and reduced odor-evoked local field potentials. RNA levels of all class I, class II, and TAAR odorant receptors are markedly reduced in OSNs in a non-cell autonomous manner. We find that people infected with COVID-19 rate odors with lower intensities and have odor discrimination deficits relative to people that tested negative for COVID-19. Taken together, we propose that inflammatory-mediated loss of odorant receptor expression with preserved circuit integrity accounts for the profound anosmia and rapid recovery of olfactory function without parosmias caused by COVID-19.
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SciScore for 10.1101/2020.06.14.20131128: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Animals: All mouse work was in accordance with protocols approved by the Institutional Animal Care and Use Committee (IACUC) of Massachusetts General Hospital.
IRB: Humans: All human research was in accordance with the Institution Review Board (IRB) at Mass General Brigham.Randomization not detected. Blinding The video was analyzed for freezing, and the observer was blinded to the genotype. Power Analysis not detected. Sex as a biological variable Briefly, approximately 2 month old male ND1 (n = 4) and littermate control (n= 4) mice were habituated individually to a clean mouse cage separated by a parafilm curtain partition that divides the arena into two … SciScore for 10.1101/2020.06.14.20131128: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Animals: All mouse work was in accordance with protocols approved by the Institutional Animal Care and Use Committee (IACUC) of Massachusetts General Hospital.
IRB: Humans: All human research was in accordance with the Institution Review Board (IRB) at Mass General Brigham.Randomization not detected. Blinding The video was analyzed for freezing, and the observer was blinded to the genotype. Power Analysis not detected. Sex as a biological variable Briefly, approximately 2 month old male ND1 (n = 4) and littermate control (n= 4) mice were habituated individually to a clean mouse cage separated by a parafilm curtain partition that divides the arena into two compartments – one twice as large as the other – for 10 min. Table 2: Resources
Software and Algorithms Sentences Resources Q-PCR primers were designed using PrimerBank (8), TAARS as in used in (48), and were only used for analysis if they had an efficiency of at least 90%. PrimerBanksuggested: (PrimerBank, RRID:SCR_006898)Identifiable information was only accessed by research staff through the REDCap project and was utilized to access participant medical record number and their electronic health record to collect relevant medical variables and the timing and results from the COVID testing and the type of test used. REDCapsuggested: (REDCap, RRID:SCR_003445)Each statistical test was performed as described in the methods and figures legends using SAS, Microsoft Excel, or Apple Numbers. Microsoft Excelsuggested: (Microsoft Excel, RRID:SCR_016137)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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