Study explores rapid SARS-CoV-2 genome sequencing to help reduce hospital-acquired COVID-19 infections

In a recent study posted to the medRxiv* pre-print server, researchers examined whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole-genome sequencing (WGS) could be routinely used for infection prevention and control (IPC) in hospitals.

Study: Evaluating the effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control teams: the COG-UK hospital-onset COVID-19 infection study. Image Credit: peterschreiber.media/Shutterstock

Amid the ongoing coronavirus disease 2019 (COVID-19) pandemic, the mitigation of the nosocomial transmission of SARS-CoV-2, particularly hospital-acquired infections (HAIs), is a major area of concern for public health officials globally.

In the UK, HAIs accounted for over 5% of confirmed SARS-CoV-2 cases between August and March 2020 and represented 11% of COVID-19 cases within hospitals during this time period. The need to develop intervention measures to control or minimize the occurrence of nosocomial transmission is indeed urgent.

About the study

In the present study, researchers conducted a prospective non-randomized trial at 14 UK hospitals to evaluate the impact of the WGS-based interventions on IPC actions and the incidence of probable and definite HAIs.

The researchers recorded data for all those patients who did not have COVID-19 at the time of hospital admission but tested COVID-19-positive within or during 48 hours of hospital admission, i.e. exhibited hospital-onset COVID-19 infection (HOCI), using a customized sequence reporting tool (SRT). 

The study included the baseline data, collected throughout four weeks, followed by data collected over two intervention periods, defined as the time taken from diagnostic sampling to the return of WGS data to IPC teams. The intervention periods comprised of first eight weeks of ‘rapid’ sequencing and four weeks of ‘longer’ turnaround sequencing for each site. The targeted turnaround times of ‘rapid’ and ‘longer-turnaround’ sequencing phases were 48 hours and five to 10 days, respectively.

All the participating hospitals aimed to sequence all SARS-CoV-2 cases, including HOCI and non-HOCI cases during the intervention phase. The WGS and patient meta-data were integrated to produce a one-page report for IPC teams using SRT, which also helped researchers standardize data collection across sites. The researchers used a central study-specific database to study patient data in the light of information impacting the IPC implementation.      

There were two primary outcomes of the study- i) incidence of IPC-defined SARS-CoV-2 HAIs per week per 100 admitted non-COVID-19 inpatients and ii) for each HOCI, SRT identified linkage to individuals within an outbreak of SARS-CoV-2 nosocomial transmission using sequencing data. Notably, these linkages were not identified by pre-sequencing IPC evaluation during intervention phases. 

The study also reported any change to IPC actions following receipt of the SRT report for each HOCI during intervention phases and any recommended change to IPC actions as secondary outcomes. 

Findings

For the study period between 15 October 2020 and 26 April 2021, authors noted a total of 2,170 HOCIs of which 80% had at least one clinically significant comorbidity. All the 14 sites completed baseline and rapid sequencing intervention phases, with the average turnaround time in the rapid and the longer-turnaround phase being 5 and 13 days, respectively.

Although SRT reports for HOCIs returned in the intervention phases, only 9.3% of those returned within the target timeframes, of which 4.6% were in the rapid phase, and 21.2% were in the longer-turnaround intervention phase.

During the study period, while eight hospitals implemented ‘rapid’ followed by ‘longer-turnaround’ sequencing phases, the other five did the opposite; however, one hospital completely omitted the longer-turnaround sequencing because they considered it a reduction in their standard practice. Interestingly, while HOCIs diagnosed three to seven days after hospital admission were generally excluded from assessments of nosocomial SARS-CoV-2 infections, the SRT reports confirmed that 78.9% of these indeterminate HAIs were hospital-acquired. 

A secondary outcome of the study, IPC-defined SARS-CoV-2 hospital outbreaks are defined as a minimum of two HOCI cases in the same ward, with at least one having more than eight days from admission to symptom onset. The authors observed that the average number of HOCI incidence per IPC-defined SARS-CoV-2 hospital outbreaks was four per week per 100 non-COVID-19 inpatients, and the largest outbreak included 43 HOCIs.

Conclusions 

According to the authors of the study, to date, no other review has conducted WGS for acute IPC investigation of nosocomial transmission. This trial was run as part of routine practice with the UK National Health Service (NHS); therefore, the challenges faced in implementation reflected the real barriers present in the UK.

Outbreak investigations are inherently complex, hence interventions centered on IPC practices evaluated at the hospital level are required to generate high-quality evidence. IPC teams, particularly in the per-protocol analysis, had a positive perception about using WGS for outbreak investigation. 

The SRT rapidly combined sequence and patient meta-data to distinguish hospital and community-acquired infections within a clinically relevant time scale. Regarding cost, the difference in the cost of 'rapid' compared with 'longer-turnaround' hospital sample sequencing incurred low cost compared to the overall cost of such interventions used at present. Moreover, if continually used for public health purposes, the aggregated benefits would offset the added cost of rapid sequencing for IPC purposes.

Although this study did not directly show the impact of sequencing on the numbers of HAIs or outbreaks, the data evidence that these correlated with the high community SARS-CoV-2 rates suggested that even factors beyond the control of IPC had a major influence. 

To conclude, with faster turnaround times, WSG can inform ongoing IPC actions in managing nosocomial SARS-CoV-2 transmissions; subsequently, in close to 20% of COVID-19 cases, results returned within five days from sampling to inform IPC actions. For future research, the current study generated a wealth of data to overcome the challenges to realize the full potential of WGS for IPC practice at a larger scale.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Neha Mathur

Neha Mathur has a Master’s degree in Biotechnology and extensive experience in digital marketing. She is passionate about reading and music. When she is not working, Neha likes to cook and travel.