Chemosensation and COVID-19

我们编写了我们的临床方案，以便很快提交给IRB。然而，通过与其他研究人员的合作，我们已经发表了一些关于这个主题的手稿。 COVID-19的多模式影响和缺乏可感知的鼻塞表明，严重急性呼吸综合征冠状病毒株2（SARS-CoV-2）感染可能会破坏感觉神经机制。鉴于我们对SARS-CoV-2发病机制的了解有限，我们与全球化学传感研究联盟（GCCR）的其他成员在Neuron上共同撰写了一篇综述，其中提出了未来的实验来阐明疾病机制，并强调了这项正在进行的工作与理解病毒如何更广泛地改变大脑功能的相关性。随着这些症状不断被报道，我们在《过敏与鼻科学》杂志上撰写了一篇由罗萨里奥博士（博士后）领导的评论文章，描述了嗅觉在人类健康中的作用，重点关注冠状病毒。迄今为止，多达80%或更多的SARS-CoV-2感染患者报告嗅觉丧失、嗅觉减退、味觉丧失、味觉障碍或化学感觉改变。自我报告的化学感觉感知变化可以预测患者是否会对SARS-CoV-2检测呈阳性。许多早期的化学感觉和COVID-19研究缺乏客观的化学感觉评估，这增加了化学感觉障碍比目前认识到的更普遍的可能性。我们与Danielle Reed博士（Monell Chemical Senses Center）一起发表了一项系统综述和荟萃分析。在这项分析中，我们报告说，客观的措施是一个更敏感的方法来识别嗅觉损失，因为感染SARS-CoV-2。值得注意的是，在大流行的早期阶段，使用主观指标虽然是权宜之计，但低估了嗅觉丧失的真实流行率。在第二项预先注册的横断面研究中，使用23种语言的众包问卷来评估自我报告最近呼吸道疾病的个人的症状，我们发现嗅觉丧失是症状性COVID-19感染的最佳预测因素。我们发现，在单一和累积特征模型中，疾病期间的嗅觉丧失是症状性COVID-19感染的最佳预测因子（ROC AUC=0.72），其他特征没有提供显著的模型改进。我们无法预测任何其他结果（例如，严重程度、住院、ICU住院），因为我们在第一次调查中没有询问住院情况。有了这些数据，我们开发了ODoR-19工具，这是一个0-10的量表，用于筛查最近的嗅觉丧失，目前正在临床人群中验证。考虑到实验室对化学感觉和肥胖的兴趣，以及肥胖个体表现出嗅觉和味觉能力改变的知识，我们使用GCCR的数据进行了二次分析。我们比较了患有呼吸道疾病的参与者自我报告的化学感受能力，这些参与者报告了阳性（C19+; n = 5156）或阴性（C19-; n = 659）COVID-19实验室检测结果，他们自我报告为肥胖（C19+; n = 433，C19-; n = 86）或非肥胖。我们发现，与C19-组相比，C19+在疾病期间表现出更大的嗅觉，味觉和化学感觉下降，尽管这些症状在肥胖和非肥胖的参与者之间没有差异。在68%报告从呼吸系统疾病症状中恢复的参与者（n=3431 C19+和n= 539 C19-）中，恢复后的化学感觉感知在C19+和C19-诊断中没有差异，并且自我报告肥胖。我们的结论是，尽管假定对化学感觉刺激的敏感性较低，但患有肥胖症的COVID-19受访者与没有肥胖症的受访者经历了类似的自我报告的化学感觉丧失，并且在两组中，自我报告的化学感觉症状对COVID-19的预测相似。 如前所述，我们在COVID-19疫情期间建立了内部合作。AUD患者患COVID-19的风险更高。我们开始评估由Ramchandani博士和Diazgranados博士领导的自然历史COVID-19影响酒精研究中收集的数据。

We wrote our clinical protocol for submission to IRB soon. However, through collaborations with other investigators both intramural and extramural we have published a number of manuscripts regarding this topic. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms. Given our limited understanding of SARS-CoV-2 pathogenesis early in the pandemic, we co-authored a review in Neuron with other members of the Global Consortium for Chemosensory Research (GCCR), where future experiments were proposed to elucidate disease mechanisms, and highlighted the relevance of this ongoing work to understanding how the virus may alter brain function more broadly. As these symptoms continued to be reported, we wrote a commentary led by Dr. Rosario Jaime-Lara (postdoctoral fellow) in Allergy and Rhinology describing the role of olfaction in human health with a focus on coronaviruses. To date as many as 80% or more of patients infected with SARS-CoV-2 report anosmia, hyposmia, ageusia, dysgeusia, or changes in chemesthesis. Self-reported changes in chemosensory perception can predict whether a patient will test positive for SARS-CoV-2. Many of the early chemosensory and COVID-19 studies lacked objective chemosensory assessment, raising the possibility that chemosensory disturbances are even more prevalent than currently appreciated. Together with Dr. Danielle Reed (Monell Chemical Senses Center), we published a systematic review and meta-analysis. In this analysis, we reported that objective measures were a more sensitive method to identify smell loss because of infection with SARS-CoV-2. Of note, the use of subjective measures, while expedient during the early stages of the pandemic, underestimated the true prevalence of smell loss. In a second preregistered, cross-sectional study that used a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness, we showed that smell loss is the best predictor of symptomatic COVID-19 infection. We found that smell loss during illness was the best predictor of symptomatic COVID-19 infection in both single and cumulative feature models (ROC AUC=0.72), with additional features providing no significant model improvement. We were not able to predict any other outcome (e.g., severity, hospitalization, ICU hospitalization) since we did not ask about hospitalization in that first survey. With this data in hand, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss currently being validated in clinical populations by others. Given the lab's interest in chemosensation and obesity as well as the knowledge that individuals with obesity show alterations in smell and taste abilities, we conducted a secondary analysis using data from the GCCR. We compared self-reported chemosensory ability in participants with a respiratory illness reporting a positive (C19+; n = 5156) or a negative (C19-; n = 659) COVID-19 laboratory test outcome, who self-reported to be obese (C19+; n = 433, C19-; n = 86) or non-obese. We found that compared to the C19- group, C19+ exhibited a greater decline in smell, taste, and chemesthesis during illness, though these symptoms did not differ between participants with obesity and without obesity. In 68% of participants who reported recovery from respiratory illness symptoms (n=3431 C19+ and n= 539 C19-), post-recovery chemosensory perception did not differ in C19+ and C19- diagnosis, and by self-reported obesity. We conclude that despite a presumed lower sensitivity to chemosensory stimuli, COVID-19 respondents with obesity experience a similar self-reported chemosensory loss as those without obesity, and in both groups self-reported chemosensory symptoms are similarly predictive of COVID-19. Intramurally, as discussed, We established collaborations during the COVID-19 pandemic. Patients with AUD are at higher risk of COVID-19. We began to evaluate the data collected in the natural history COVID-19 impact alcohol study led by Drs. Ramchandani and Diazgranados.