Objective To clarify in patients with covid-19 the recovery rate of smell and taste, proportion with persistent dysfunction of smell and taste, and prognostic factors associated with recovery of smell and taste. Design Systematic review and meta-analysis. Data sources PubMed, Embase, Scopus, Cochrane Library, and medRxiv from inception to 3 October 2021. Review methods Two blinded reviewers selected observational studies of adults (≥18 years) with covid-19 related dysfunction of smell or taste. Descriptive prognosis studies with time-to-event curves and prognostic association studies of any prognostic factor were included. Data extraction and synthesis Two reviewers extracted data, evaluated study bias using QUIPS, and appraised evidence quality using GRADE, following PRISMA and MOOSE reporting guidelines. Using iterative numerical algorithms, time-to-event individual patient data (IPD) were reconstructed and pooled to retrieve distribution-free summary survival curves, with recovery rates reported at 30 day intervals for participants who remained alive. To estimate the proportion with persistent smell and taste dysfunction, cure fractions from Weibull non-mixture cure models of plateaued survival curves were logit transformed and pooled in a two stage meta-analysis. Conventional aggregate data meta-analysis was performed to explore unadjusted associations of prognostic factors with recovery. Main outcome measures The primary outcomes were the proportions of patients remaining with smell or taste dysfunction. Secondary outcomes were the odds ratios of prognostic variables associated with recovery of smell and taste. Results 18 studies (3699 patients) from 4180 records were included in reconstructed IPD meta-analyses. Risk of bias was low to moderate; conclusions remained unaltered after exclusion of four high risk studies. Evidence quality was moderate to high. Based on parametric cure modelling, persistent self-reported smell and taste dysfunction could develop in an estimated 5.6% (95% confidence interval 2.7% to 11.0%, I2=70%, τ2=0.756, 95% prediction interval 0.7% to 33.5%) and 4.4% (1.2% to 14.6%, I2=67%, τ2=0.684, 95% prediction interval 0.0% to 49.0%) of patients, respectively. Sensitivity analyses suggest these could be underestimates. At 30, 60, 90, and 180 days, respectively, 74.1% (95% confidence interval 64.0% to 81.3%), 85.8% (77.6% to 90.9%), 90.0% (83.3% to 94.0%), and 95.7% (89.5% to 98.3%) of patients recovered their sense of smell (I2=0.0-77.2%, τ2=0.006-0.050) and 78.8% (70.5% to 84.7%), 87.7% (82.0% to 91.6%), 90.3% (83.5% to 94.3%), and 98.0% (92.2% to 95.5%) recovered their sense of taste (range of I2=0.0-72.1%, τ2=0.000-0.015). Women were less likely to recover their sense of smell (odds ratio 0.52, 95% confidence interval 0.37 to 0.72, seven studies, I2=20%, τ2=0.0224) and taste (0.31, 0.13 to 0.72, seven studies, I2=78%, τ2=0.5121) than men, and patients with greater initial severity of dysfunction (0.48, 0.31 to 0.73, five studies, I2=10%, τ2<0.001) or nasal congestion (0.42, 0.18 to 0.97, three studies, I2=0%, τ2<0.001) were less likely to recover their sense of smell. Conclusions A substantial proportion of patients with covid-19 might develop long lasting change in their sense of smell or taste. This could contribute to the growing burden of long covid. Systematic review registration PROSPERO CRD42021283922. Additional data may be obtained from corresponding author STT (toh.song.tar{at}singhealth.com.sg) on reasonable request.

中文翻译：

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covid-19患者嗅觉和味觉功能障碍的预后和持续性：恢复曲线参数治愈模型的荟萃分析


目的 明确covid-19患者嗅觉和味觉的恢复率、持续性嗅觉和味觉功能障碍的比例以及与嗅觉和味觉恢复相关的预后因素。设计系统回顾和荟萃分析。数据来源 PubMed、Embase、Scopus、Cochrane Library 和 medRxiv，从开始到 2021 年 10 月 3 日。 审查方法 两名盲法审查员选择了对患有 covid-19 相关嗅觉或味觉功能障碍的成年人（≥18 岁）的观察性研究。包括时间-事件曲线的描述性预后研究以及任何预后因素的预后关联研究。数据提取和合成 两名评审员提取数据，使用 QUIPS 评估研究偏倚，并使用 GRADE 评估证据质量，遵循 PRISMA 和 MOOSE 报告指南。使用迭代数值算法，重建并汇总事件发生时间个体患者数据 (IPD)，以检索无分布的总结生存曲线，并以 30 天的间隔报告仍然存活的参与者的恢复率。为了估计持续性嗅觉和味觉功能障碍的比例，对来自稳定生存曲线的 Weibull 非混合治愈模型的治愈分数进行了 logit 转换并汇总在两阶段荟萃分析中。进行传统的汇总数据荟萃分析，以探索预后因素与恢复之间未经调整的关联。主要结果指标 主要结果是仍有嗅觉或味觉功能障碍的患者比例。次要结果是与嗅觉和味觉恢复相关的预后变量的优势比。结果 4180 份记录中的 18 项研究（3699 名患者）被纳入重建的 IPD 荟萃分析中。 偏倚风险为低至中等；排除四项高风险研究后，结论保持不变。证据质量为中等到高。根据参数治疗模型，估计有 5.6% 的人可能会出现持续性自我报告的嗅觉和味觉功能障碍（95% 置信区间为 2.7% 至 11.0%，I2=70%，τ2=0.756，95% 预测区间为 0.7% 至 33.5% ）和 4.4%（1.2% 至 14.6%，I2=67%，τ2=0.684，95% 预测区间 0.0% 至 49.0%）的患者分别。敏感性分析表明这些可能被低估。第 30、60、90 和 180 天分别为 74.1%（95% 置信区间 64.0% 至 81.3%）、85.8%（77.6% 至 90.9%）、90.0%（83.3% 至 94.0%）和 95.7% （89.5％至98.3％）的患者恢复了嗅觉（I2=0.0-77.2％，τ2=0.006-0.050）和78.8％（70.5％至84.7％），87.7％（82.0％至91.6％），90.3 %（83.5%至94.3%）和98.0%（92.2%至95.5%）恢复了味觉（范围I2=0.0-72.1%，τ2=0.000-0.015）。女性恢复嗅觉（比值比 0.52，95% 置信区间 0.37 至 0.72，七项研究，I2=20%，τ2=0.0224）和味觉（0.31、0.13 至 0.72，七项研究，I2=78）的可能性较小%，τ2=0.5121）高于男性，以及初始功能障碍严重程度更高的患者（0.48、0.31 至 0.73，五项研究，I2=10%，τ2<0.001）或鼻塞（0.42、0.18 至 0.97，三项研究） ，I2=0%，τ2<0.001) 恢复嗅觉的可能性较小。结论 相当一部分 covid-19 患者的嗅觉或味觉可能会发生长期持续的变化。这可能会加剧长期新冠疫情带来的日益沉重的负担。系统审评注册PROSPERO CRD42021283922。根据合理要求，可以从通讯作者 STT (toh.song.tar{at}singhealth.com.sg) 获取更多数据。