Objectives

To analyse nosocomial transmission in the early stages of the coronavirus 2019 (COVID-19) pandemic at a large multisite healthcare institution. Nosocomial incidence is linked with infection control interventions.

Methods

Viral genome sequence and epidemiological data were analysed for 574 consecutive patients, including 86 nosocomial cases, with a positive PCR test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first 19 days of the pandemic.

Results

Forty-four putative transmission clusters were found through epidemiological analysis; these included 234 cases and all 86 nosocomial cases. SARS-CoV-2 genome sequences were obtained from 168/234 (72%) of these cases in epidemiological clusters, including 77/86 nosocomial cases (90%). Only 75/168 (45%) of epidemiologically linked, sequenced cases were not refuted by applying genomic data, creating 14 final clusters accounting for 59/77 sequenced nosocomial cases (77%). Viral haplotypes from these clusters were enriched 1–14x (median 4x) compared to the community. Three factors implicated unidentified cases in transmission: (a) community-onset or indeterminate cases were absent in 7/14 clusters (50%), (b) four clusters (29%) had additional evidence of cryptic transmission, and (c) in three clusters (21%) diagnosis of the earliest case was delayed, which may have facilitated transmission. Nosocomial cases decreased to low levels (0–2 per day) despite continuing high numbers of admissions of community-onset SARS-CoV-2 cases (40–50 per day) and before the impact of introducing universal face masks and banning hospital visitors.

Conclusion

Genomics was necessary to accurately resolve transmission clusters. Our data support unidentified cases—such as healthcare workers or asymptomatic patients—as important vectors of transmission. Evidence is needed to ascertain whether routine screening increases case ascertainment and limits nosocomial transmission.

中文翻译：

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大流行早期院内 SARS-CoV-2 感染的流行病学和基因组分析以及不明病例在传播中的作用

目标

分析 2019 年冠状病毒 (COVID-19) 大流行早期阶段大型多地点医疗机构的医院传播情况。院内发病率与感染控制干预措施有关。

方法

对 574 名连续患者（包括 86 名院内病例）的病毒基因组序列和流行病学数据进行了分析，这些患者在大流行的前 19 天内对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 进行了 PCR 检测呈阳性。

结果

通过流行病学分析发现了 44 个假定的传播聚集性；其中包括 234 例和所有 86 例院内病例。从流行病学聚集性病例中的 168/234 (72%) 例中获得了 SARS-CoV-2 基因组序列，其中包括 77/86 例院内病例 (90%)。只有 75/168 (45%) 的流行病学相关的测序病例没有被基因组数据驳斥，从而创建了 14 个最终簇，占 59/77 已测序的院内病例 (77%)。与群落相比，这些簇中的病毒单倍型富集了 1-14 倍（中位数 4 倍）。三个因素涉及不明病例的传播：(a) 7/14 集群 (50%) 中不存在社区发病或不确定的病例，(b) 4 个集群 (29%) 有隐秘传播的额外证据，(c)三个集群（21%）最早病例的诊断被延迟，这可能促进了传播。尽管社区发病的 SARS-CoV-2 病例入院人数持续增加（每天 40-50 例），并且在引入通用口罩和禁止医院访客的影响之前，院内病例已降至较低水平（每天 0-2 例）。

结论

基因组学对于准确解析传播簇是必要的。我们的数据支持不明病例（例如医护人员或无症状患者）作为重要的传播媒介。需要证据来确定常规筛查是否可以增加病例查明并限制院内传播。