Department of Laboratory Medicine and Pathology, Azienda USL of Modena, Modena, Italy.
Health and Social Regional Agency of Emilia-Romagna Region, Bologna, Italy.
Eur J Clin Invest. 2022 Feb;52(2):e13706. doi: 10.1111/eci.13706. Epub 2021 Dec 5.
Molecular-based tests used to identify symptomatic or asymptomatic patients infected by SARS-CoV-2 are characterized by high specificity but scarce sensitivity, generating false-negative results. We aimed to estimate, through a systematic review of the literature, the rate of RT-PCR false negatives at initial testing for COVID-19.
We systematically searched Pubmed, Embase and CENTRAL as well as a list of reference literature. We included observational studies that collected samples from respiratory tract to detect SARS-CoV-2 RNA using RT-PCR, reporting the number of false-negative subjects and the number of final patients with a COVID-19 diagnosis. Reported rates of false negatives were pooled in a meta-analysis as appropriate. We assessed the risk of bias of included studies and graded the quality of evidence according to the GRADE method. All information in this article is current up to February 2021.
We included 32 studies, enrolling more than 18,000 patients infected by SARS-CoV-2. The overall false-negative rate was 0.12 (95%CI from 0.10 to 0.14) with very low certainty of evidence. The impact of misdiagnoses was estimated according to disease prevalence; a range between 2 and 58/1,000 subjects could be misdiagnosed with a disease prevalence of 10%, increasing to 290/1,000 misdiagnosed subjects with a disease prevalence of 50%.
This systematic review showed that up to 58% of COVID-19 patients may have initial false-negative RT-PCR results, suggesting the need to implement a correct diagnostic strategy to correctly identify suspected cases, thereby reducing false-negative results and decreasing the disease burden among the population.
用于识别感染 SARS-CoV-2 的有症状或无症状患者的基于分子的检测具有高特异性但敏感性低，会产生假阴性结果。我们旨在通过对文献进行系统评价来估计 COVID-19 初始检测时 RT-PCR 的假阴性率。
我们系统地检索了 Pubmed、Embase 和 CENTRAL 以及一系列参考文献。我们纳入了收集呼吸道样本以使用 RT-PCR 检测 SARS-CoV-2 RNA 的观察性研究，报告了假阴性患者数量和最终 COVID-19 诊断患者数量。适当时，将报告的假阴性率汇总进行荟萃分析。我们评估了纳入研究的偏倚风险，并根据 GRADE 方法对证据质量进行分级。本文中的所有信息均截至 2021 年 2 月。
我们纳入了 32 项研究，共纳入了 18000 多名感染 SARS-CoV-2 的患者。总体假阴性率为 0.12（95%CI 为 0.10 至 0.14），证据确定性极低。根据疾病流行率估计了误诊的影响；在疾病流行率为 10%的情况下，每 1000 名受试者中可能有 2 至 58 人误诊，在疾病流行率为 50%的情况下，每 1000 名受试者中可能有 290 人误诊。
这项系统评价表明，多达 58%的 COVID-19 患者可能最初的 RT-PCR 结果为假阴性，这表明需要实施正确的诊断策略来正确识别疑似病例，从而减少假阴性结果并降低人群中的疾病负担。
