Nosocomial Influenza Outbreak Investigation Informed by Genomic Analyses

Precision surveillance combining genomic sequencing and conventional surveillance was able to delineate a large nosocomial influenza A virus (IAV) outbreak and map the source to a single patient. The findings from this investigation, published in Clinical Infectious Diseases, revealed the source of the outbreak was not health care workers (HCWs) as was initially believed.

Over 12 days in early 2019, 89 HCWs and 18 inpatients within a single hospital were identified as cases of influenza-like illness, triggering the investigation. During this investigation, 91 inpatients and 290 HCWs were screened via temperature checks, symptom surveys, and molecular testing for IAV, influenza B, and respiratory syncytial virus. Of these, 18 patients (19.8%) and 89 HCWs (29.7%) tested positive for IAV.

The HCWs testing positive were distributed across 29 different work assignments and 87 of the 89 (>90%) were vaccinated with the quadrivalent seasonal influenza virus vaccine 2 to 5 months before diagnosis (average: 108 days). Investigators highlight that most of these HCWs had minor symptoms not normally classified as influenza-like illness due to the absence of fever. This prompted the removal of fever as a requirement from the investigation’s case definitions.

Complete genomic sequences were obtained for 214 IAV isolates, 126 from the original hospital where investigation and surveillance were performed and 88 from a second hospital undergoing surveillance only. Comparison revealed a cluster of 66 isolates differing by 3 or fewer single-nucleotide variants (SNVs), suggesting a single viral clone was behind the outbreak.

The outbreak cluster was identified as influenza A H1N1pdm09 and was found in 43 HCWs and 17 inpatients. All HCWs included in this cluster had been vaccinated. Outbreak virus strains with representative variants, 5 in total, were cultured for functional characterization and did not show antigenic drift. A further analysis of genomes from cases identified by the conventional investigation during days 0 to 3 of the outbreak and the mining of electronic records provided a timeline of the earliest 9 cases. An interaction network based on available contact records found that almost all cases trace back to these 9 cases and identified the origin as a single patient and a few interactions in the emergency department.  

Biospecimens from 22 HCWs whose tests were performed at labs outside of the health system in question were unavailable, limiting the investigation results. Also, only partial genomes were recovered from 2 specimens linked to the epidemiological outbreak investigation.

According to investigators, enhanced screening and isolation of emergency department patients with respiratory symptoms, even when not their primary complaint, are important steps to mitigating outbreaks. Also, better recognition by leadership that HCW transmission can occur with mild symptoms along with improved education of staff to avoid working while ill and extended sick leave were recommended by investigators. Finally, the investigators believe these findings are applicable to a range of respiratory pathogens, including SARS-CoV-2, and that implementation of precision surveillance will be critical for identification and mitigation of nosocomial outbreaks.

Disclosure: One study author declared an affiliation with Sema4.


Javaid W, Ehni J, Gonzalez-Reiche AS, et al. Real-time investigation of a large nosocomial influenza A outbreak informed by genomic epidemiology. Clin Infect Dis. Published online November 30, 2020. doi:10.1093/cid/ciaa1781