Nosocomial Outbreak of SARS-CoV-2 in a “Non-COVID-19” Hospital Ward: Virus Genome Sequencing as a Key Tool to Understand Cryptic Transmission

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1. 

   NCRC

   Apr 22, 2021

   Our take

   This study, available as a preprint and thus not yet peer-reviewed, investigated a COVID-19 outbreak in two wards in a large hospital in Portugal. Large scale testing was initiated after a recently discharged patient presented to the emergency department and tested positive for COVID-19. This individual was also a close contact of a current inpatient in the hospital within a non-COVID-19 ward. In total, 27 out of 102 staff (26.4%) and 21 out of 92 (22.8%) inpatients in the single non-COVID-19 ward of interest tested positive. Whole-genome sequencing and bioinformatics analysis determined that cases were part of a single origin SARS-CoV-2 variant, belonging to the COG-UK lineage B.1.1 and Nextstrain clade 20B. Most individuals were asymptomatic during the time of testing, suggesting likely silent transmission. The …

   Our take

   This study, available as a preprint and thus not yet peer-reviewed, investigated a COVID-19 outbreak in two wards in a large hospital in Portugal. Large scale testing was initiated after a recently discharged patient presented to the emergency department and tested positive for COVID-19. This individual was also a close contact of a current inpatient in the hospital within a non-COVID-19 ward. In total, 27 out of 102 staff (26.4%) and 21 out of 92 (22.8%) inpatients in the single non-COVID-19 ward of interest tested positive. Whole-genome sequencing and bioinformatics analysis determined that cases were part of a single origin SARS-CoV-2 variant, belonging to the COG-UK lineage B.1.1 and Nextstrain clade 20B. Most individuals were asymptomatic during the time of testing, suggesting likely silent transmission. The findings highlight the importance of periodic testing of staff and patients in healthcare settings for earlier detection of cases, and prevention and control of outbreaks.

   Study design

   cross-sectional

   Study population and setting

   This study investigated a COVID-19 outbreak in a large hospital in Portugal, which provides care to about 250,000 people and has about 1,500 employees. An outbreak took place in a non-COVID-19 ward (Ward B) in Summer 2020. The investigation was triggered following presentation to the emergency department by an individual who had concluded a hospital stay three days prior in another ward (Ward A). This individual was a close contact of a current inpatient in the non-COVID-19 ward (Ward B). The inpatient and a clinician (from Ward B) presented with COVID-19 like symptoms and subsequently tested positive, triggering further testing of close contacts, or persons presenting with symptoms in both wards in the 15 days prior. In total, 245 staff and patients were tested for SARS-CoV-2. Nasal and oropharyngeal swabs were collected, and RT-PCR was performed. RNA samples that were positive for SARS-CoV-2 were sent for whole-genome sequencing and bioinformatics analysis.

   Summary of main findings

   No cases were detected among 51 persons tested in Ward A. However, in Ward B, 27 out of 102 staff (26.4%) and 21 out of 92 (22.8%) inpatients tested positive. Most staff were asymptomatic at testing and all recovered. While inpatients were mostly asymptomatic at testing, mortality rate was high, 12 out of 21 died (57.1%). Results of high-quality SARS-CoV-2 genome sequences from 39 positive samples (22 staff and 17 patients) showed that all cases were part of a single origin, belonging to the COG-UK lineage B.1.1 and Nextstrain clade 20B, with spike amino acid changes D614G and L176F. The investigators hypothesized that the virus was likely introduced to the ward a few weeks before the large screening, then spread through interactions among health care workers, and interactions between health care workers and patients. Patient-to-patient transmission was very limited. Following the investigation, the hospital put in place and reinforced stricter infection prevention and control measures.

   Study strengths

   Use of reverse-transcription PCR testing to confirm COVID-19 diagnosis. Genome sequences associated with the outbreak had >88% of the genome covered by at least 10-fold.

   Limitations

   While investigators hypothesized about which health care workers and patients could have been the index case given the epidemiologic and phylogenetic data, this could not be definitively determined.

   Value added

   This study highlights the usefulness of combining epidemiologic and genomic data in improving understanding about transmission of SARS-CoV-2.

   Read the original source
2. Version published to 10.3390/v13040604

   Apr 1, 2021
3. 

   ScreenIT

   Mar 1, 2021

   SciScore for 10.1101/2021.02.20.20248421: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Institutional Review Board Statement	not detected.
   Randomization	not detected.
   Blinding	not detected.
   Power Analysis	not detected.
   Sex as a biological variable	not detected.

   Table 2: Resources

   Software and Algorithms
   Sentences	Resources
   Briefly, naso and oropharyngeal swabs were collected from patients and HCW, and RNA was subsequently extracted using m2000sp Abbott and then subjected to real-time reverse transcription PCR (RT-PCR) assay targeting using m2000rt Abbott.	Abbott suggested: (Abbott, RRID:SCR_010477)
   Regions with depth of coverage below this threshold were automatically masked in INSaFLU pipeline by placing undefined bases “N” in the consensus sequence (whenever these regions enroll SNP phylogenetic …

   SciScore for 10.1101/2021.02.20.20248421: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Institutional Review Board Statement	not detected.
   Randomization	not detected.
   Blinding	not detected.
   Power Analysis	not detected.
   Sex as a biological variable	not detected.

   Table 2: Resources

   Software and Algorithms
   Sentences	Resources
   Briefly, naso and oropharyngeal swabs were collected from patients and HCW, and RNA was subsequently extracted using m2000sp Abbott and then subjected to real-time reverse transcription PCR (RT-PCR) assay targeting using m2000rt Abbott.	Abbott suggested: (Abbott, RRID:SCR_010477)
   Regions with depth of coverage below this threshold were automatically masked in INSaFLU pipeline by placing undefined bases “N” in the consensus sequence (whenever these regions enroll SNP phylogenetic markers, these were inspected to ensure the correct phylogenetic placement of all genomes).	INSaFLU suggested: None

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   Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

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   Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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   Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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   Results from JetFighter: We did not find any issues relating to colormaps.

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   Results from rtransparent:

   • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
   • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
   • No protocol registration statement was detected.

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   Read the original source
4. 

   Version published to 10.1101/2021.02.20.20248421v1 on medRxiv

   Feb 23, 2021