Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Harvard Medical School, Boston, Massachusetts, USA.
Clin Infect Dis. 2023 Mar 4;76(5):850-860. doi: 10.1093/cid/ciac830.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments.
All individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥45 days after an initial positive test, with both tests between 14 March and 30 December 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value <35 at repeat testing. For each included subject, likelihood of reinfection was assessed by viral genomic analysis of all available specimens with a Ct value <35, structured Ct trajectory criteria, and case-by-case review by infectious diseases physicians.
Among 1569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present and was successful for 14/65 (22%) subjects. Six subjects had genomically supported reinfection, and 8 subjects had genomically supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically supported reinfections.
Despite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections.
严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)再感染的情况了解甚少,部分原因是很少有研究系统地应用基因组分析来区分再感染和与初始感染相关的持续 RNA 检测。我们旨在通过独立的基因组、临床和实验室评估来评估 SARS-CoV-2 再感染和持续 RNA 检测的特征。
所有在大型学术医疗中心接受 SARS-CoV-2 核酸扩增试验(NAAT)≥45 天的个体,初始阳性试验后进行了两次检测,两次检测均在 2020 年 3 月 14 日至 12 月 30 日之间,均进行了潜在再感染的分析。纳入标准要求≥2 次阳性 NAAT 采集时间相隔≥45 天,且重复检测的 Ct 值<35。对于每个纳入的受试者,通过对所有 Ct 值<35 的可用标本进行病毒基因组分析、结构 Ct 轨迹标准以及传染病医生的逐个病例审查,评估再感染的可能性。
在 1569 名初始阳性 NAAT 后≥45 天重复 SARS-CoV-2 检测的个体中,有 65 名(4%)符合队列纳入标准。病毒基因组分析确定了存在的突变,并成功分析了 14/65(22%)受试者的标本。6 名受试者有基因组支持的再感染,8 名受试者有基因组支持的持续 RNA 检测。与病毒基因组分析相比,临床和实验室评估正确区分了 12/14(86%)受试者的再感染和持续 RNA 检测,但漏诊了 2/6(33%)有基因组支持的再感染。
尽管与病毒基因组分析总体一致性良好,但临床和基于 Ct 值的评估未能识别出 33%的有基因组支持的再感染。扩大基因组分析的临床应用将提高 SARS-CoV-2 再感染的检测。