比較唾液檢體和鼻咽拭子檢體用於SARS-CoV-2的診斷: 系統性文獻回顧、統合分析與臨床試驗計劃書

Abstract

背景 一種名為 SARS-CoV-2 的新型冠狀病毒於 2019 年 12 月在全球迅速傳播，並 於 2020 年 3 月被世界衛生組織 (WHO) 認定為大型流行病。鼻咽拭子 (NPS) 是實時逆轉錄聚合酶鏈反應 (RT-PCR) 用於檢測 SARS-CoV-2 的推薦樣本，但 它在樣本採集和醫護人員安全方面存在一些局限性。由於唾液樣本在採樣過程 中的有效性，在最近的研究中受到了很多關注。唾液採集更容易、侵入性更 小，對衛生專業人員受到感染的風險也最少。它可以成功的自我管理，並且在 需要重複採檢時受到民眾的歡迎。這項統合分析的目的是對於這些有被感染風 險並且之前和陽性確診者有重疊足跡需要自我管理的人，檢查唾液作為檢測 SARS-CoV-2 感染替代診斷樣本的可行性。 目的 檢查檢測結果與 SARS-CoV-2 之間的潛在相關性，並比較唾液和NPS基於 RT-PCR 分子檢測結果的靈敏度、特異性和 sROC 曲線。我們還在篩選中比較 有症狀和無症狀組，以評估唾液的可行性。 方法 在準備系統性回顧和統合分析時遵守了 PRISMA for Diagnostic Test Accuracy (PRISMA-DTA, 2018) 的標準規範。我們設計使用我們的 PICO 來評估唾液 RT-PCR 診斷 SARS-CoV-2 與 NPS RT-PCR 的靈敏度、特異性和 sROC 曲 線。我們搜索關鍵字“(COVID-19 OR COVID19 OR n-CoV19 OR SARS-CoV-2 OR SARS-CoV2) AND (Diagnosis OR Diagnostic OR PCR OR RT-PCR) AND (Saliva OR Salivary OR "Oral fluid" OR Sputum) ” 在 PubMed、Web of science和 Embase 中找到評估唾液樣本作為 SARS-CoV-2 檢測樣本方法的研究，時 間為 2020 年 1 月1日至 2022 年 9 月 2 日。在納入的研究當中，唾液和鼻 咽樣本必須同時採集並且由同樣的檢測方法執行。測試結果必需要能呈現 2 X 2的靈敏度和特異性表格。我們還使用 QUADAS-2 來評估系統性回顧納入研究 的偏差和適用性。 結果 總共有 25,624 對樣本構成了我們的統合分析。根據定義假設這些患者的 NPS RT-PCR 在該時間點的靈敏度為 100%，特異性為 100%，我們評估唾液 RT- PCR 的總體敏感性為 83%(95% CI 78%–86%)，總體特異性為 98%(95% CI 97%–98%)， sROC 曲線的曲線下面積(AUC) 為 0.97 (95% CI 0.95–0.98)。統 合分析的漏斗圖 p 值 = 0.846 不顯著，表明我們的分析結果沒有明顯的發表偏 差。通過唾液檢測的應用進行 SARS-CoV-2 感染的監測不僅可以證實了唾液檢 體用於檢測 SARS-CoV-2 的卓越可靠性，而且還顯示了它在應用上的可行性。

Background A novel coronavirus called SARS-CoV-2 quickly spread over the world in December 2019 and was recognized as a pandemic by the World Health Organization (WHO) in March 2020. Nasopharyngeal swabs (NPS) are the recommend specimen for Real- time reverse transcription polymerase chain reaction (RT-PCR) for the detection of SARS-CoV-2, but it has some limits in specimen collection and safety concerns for healthcare personnel. Due to its usefulness in the sampling process, saliva has received a lot of attention in recent study. Saliva collection is easier, less invasive and minimal risk to health professionals, it can be self-administered successfully and is popular with the public when needs repeated sampling. The purpose of this meta- analysis was to examine the viability of saliva as a surrogate diagnostic specimen for detection of SARS-CoV-2 infection in individuals who are at risk of infection and who have previously had overlapping footprints that required self-management. Objective To examine potential correlations between test findings and SARS-CoV-2 and compare the sensitivity, specificity and summary receiver operating characteristic (sROC) curves of RT-PCR based molecular test results from saliva to NPS. We also compare the symptomatic and asymptomatic group in screening to evaluate the feasibility of the saliva. Methods The PRISMA for Diagnostic Test Accuracy (McInnes et al., 2018) standard requirements were adhered to in the preparation of this systematic review and meta- analysis. We can evaluate the sensitivity, specificity and sROC curves of saliva RT- PCR for the diagnosis of SARS-CoV-2 to the NPS RT-PCR using our PICO design. We search keywords “(COVID-19 OR COVID19 OR n-CoV19 OR SARS-CoV-2 OR SARS-CoV2) AND (Diagnosis OR Diagnostic OR PCR OR RT-PCR) AND (Saliva OR Salivary OR "Oral fluid" OR Sputum)” in PubMed、Web of science and Embase and find articles evaluating saliva samples as a screening method for SARS-CoV-2 from 01 Jan 2020 to 02 Sep 2022. In this article, saliva and nasopharyngeal samples must be collected at the same time and tested by the same method. The test results can present a table of confusion with sensitivity and specificity. We also use QUADAS-2 for assessing the bias and applicability of included studies in systematic reviews. Results With all, 25,624 pairs of samples made up our meta-analysis. We assessed the overall sensitivity of saliva RT-PCR to be 83% (95% CI 78% - 86%) and the overall specificity to be 98% (95% CI 97% - 98%), presuming by definition that these patients had 100% sensitivity and 100% specificity for the NPS test at that time point. The area under curve (AUC) of sROC curve which was 0.97 (95% CI 0.95 - 0.98). The funnel plot's p value=0.846 of the meta-analysis is not significant, indicating that our analysis's findings are free from significant publication bias. The application of detection by monitoring SARS-CoV-2 infection in saliva not only it can be realized the excellent reliability of detecting SARS-CoV-2 infection proven but also shown the viability how it will provide.