Combined epidemiological and genomic analysis of nosocomial SARS-CoV-2 infection early in the pandemic and the role of unidentified cases in transmission

Snell, Luke B; Fisher, Chloe L.; Taj, Usman; Stirrup, Oliver; Merrick, Blair; Alcolea-Medina, Adela; Charalampous, Themoula; Signell, Adrian W.; Wilson, Harry; Betancor, Gilberto; Ik, Mark Tan Kia; Cunningham, Emma; Cliff, Penelope R.; Pickering, Suzanne; Galão, Rui Pedro; Batra, Rahul; Neil, Stuart J. D.; Malim, Michael H.; Doores, Katie J.; Douthwaite, Sam; Nebbia, Gaia; Edgeworth, Jonathan D; Awan, Ali Raza

doi:10.1016/j.cmi.2021.07.040

Cited by 22 publications

(28 citation statements)

References 21 publications

(14 reference statements)

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“…To support the generalisability of our findings, we included studies with implicit and explicit definitions of nosocomial COVID-19. Accordingly, we catalogued a wide spectrum of case definitions, including combined epidemiological and genomic viral sequencing (38). We controlled for this variation in case definitions within our sensitivity analyses, for instance using outcomes meeting consensus international criteria for definite nosocomial infection wherever available.…”

Section: Discussionmentioning

confidence: 99%

“…As shown in Table 1, a range of case definitions were employed to distinguish community-acquired and nosocomial COVID-19. A fixed interval between admission and diagnosis was employed in 14/21 (62%) ranging from >2 days (37) >14 days (12), supplemented by additional patient-level clinical data (40) and viral whole genome sequencing (38). Seven studies primarily employed epidemiological nosocomial definitions, for instance a history of close contact with positive cases [n=3 (27,31,39)], or the absence of symptoms on admission with subsequent positive test [n=2 (10,30)].…”

Section: Case Definitionsmentioning

confidence: 99%

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A Systematic Review and Meta-Analysis of Inpatient Mortality Associated With Nosocomial and Community COVID-19 Exposes the Vulnerability of Immunosuppressed Adults

et al. 2021

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BackgroundLittle is known about the mortality of hospital-acquired (nosocomial) COVID-19 infection globally. We investigated the risk of mortality and critical care admission in hospitalised adults with nosocomial COVID-19, relative to adults requiring hospitalisation due to community-acquired infection.MethodsWe systematically reviewed the peer-reviewed and pre-print literature from 1/1/2020 to 9/2/2021 without language restriction for studies reporting outcomes of nosocomial and community-acquired COVID-19. We performed a random effects meta-analysis (MA) to estimate the 1) relative risk of death and 2) critical care admission, stratifying studies by patient cohort characteristics and nosocomial case definition.Results21 studies were included in the primary MA, describing 8,251 admissions across 8 countries during the first wave, comprising 1513 probable or definite nosocomial COVID-19, and 6738 community-acquired cases. Across all studies, the risk of mortality was 1.3 times greater in patients with nosocomial infection, compared to community-acquired (95% CI: 1.005 to 1.683). Rates of critical care admission were similar between groups (Relative Risk, RR=0.74, 95% CI: 0.50 to 1.08). Immunosuppressed patients diagnosed with nosocomial COVID-19 were twice as likely to die in hospital as those admitted with community-acquired infection (RR=2.14, 95% CI: 1.76 to 2.61).ConclusionsAdults who acquire SARS-CoV-2 whilst already hospitalised are at greater risk of mortality compared to patients admitted following community-acquired infection; this finding is largely driven by a substantially increased risk of death in individuals with malignancy or who had undergone transplantation. These findings inform public health and infection control policy and argue for individualised clinical interventions to combat the threat of nosocomial COVID-19, particularly for immunosuppressed groups.Systematic Review RegistrationPROSPERO CRD42021249023

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Section: Discussionmentioning

confidence: 99%

Section: Case Definitionsmentioning

confidence: 99%

A Systematic Review and Meta-Analysis of Inpatient Mortality Associated With Nosocomial and Community COVID-19 Exposes the Vulnerability of Immunosuppressed Adults

et al. 2021

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“…Consequently, only 5 patients were inappropriately placed on a COVID-19 negative ward over the 2-weeks. All were moved within 10 hours following laboratory PCR results and no onward transmission was identified by either hospital contact tracing combined with reviewing genome sequence results of isolates from available probable and definite hospital-acquired cases, important given potential for cryptic linkage between wards [ 13 ]. In addition, only three genuine false-positive results were identified from 906 tests during the high prevalence period.…”

Section: Discussionmentioning

confidence: 99%

“…95% confidence intervals were determined using the Wilson/Brown binomial test. All clinical SARS-CoV-2 genome sequence reports in the caseof LFD false-negative patients and for any sequenced first-isolate taken >8 days post-admission (defined as a hospital-acquired case) between January 7 th and February 28th were reviewed that used difference of <= 1 SNP difference to define linkage [ 13 ]. During the continuation phase data on admission bed space, symptom onset, and assessing clinician’s impression were not collected.…”

Section: Methodsmentioning

confidence: 99%

Real-world deployment of lateral flow SARS-CoV-2 antigen detection in the emergency department to provide rapid, accurate and safe diagnosis of COVID-19

Merrick¹,

Noronha²,

Batra³

et al. 2021

Infection Prevention in Practice

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“…Sequencing technologies can now be used for local outbreak investigation in near real-time, and this was implemented by some research centres for evaluation of nosocomial transmission from the early stages of the pandemic [2] . It has been demonstrated that sequencing can provide additional information on outbreak characteristics and transmission routes in comparison to traditional epidemiological investigation alone [2][3][4] . However, limited data are available on the feasibility of routine use of sequencing for infection prevention and control (IPC), or on its direct impact on IPC actions and nosocomial transmission rates.…”

Section: Introductionmentioning

confidence: 99%

Evaluating the effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control teams: the COG-UK hospital-onset COVID-19 infection study

Stirrup¹,

Blackstone

Mapp³

et al. 2022

Preprint

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Introduction Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings. Methods We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data-collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48h) and 4 weeks of 'longer-turnaround' (5-10 day) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital onset COVID-19 infections (HOCIs; detected ≥48h from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on incidence of probable/definite hospital-acquired infections (HAIs) was evaluated. Results A total of 2170 HOCI cases were recorded from October 2020-April 2021, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (IRR 1.60, 95%CI 0.85-3.01; P=0.14) or rapid (0.85, 0.48-1.50; P=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8% and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2% and 11.6% of cases where the report was returned. In a per-protocol sensitivity analysis there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Conclusion While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days.

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Combined epidemiological and genomic analysis of nosocomial SARS-CoV-2 infection early in the pandemic and the role of unidentified cases in transmission

Abstract: The COVID-19 Genomics UK (COG-UK) consortium, Combined epidemiological and genomic analysis of nosocomial SARS-CoV-2 infection early in the pandemic and the role of unidentified cases in transmission, Clinical Microbiology and Infection,

Cited by 22 publications

References 21 publications

A Systematic Review and Meta-Analysis of Inpatient Mortality Associated With Nosocomial and Community COVID-19 Exposes the Vulnerability of Immunosuppressed Adults

A Systematic Review and Meta-Analysis of Inpatient Mortality Associated With Nosocomial and Community COVID-19 Exposes the Vulnerability of Immunosuppressed Adults

Real-world deployment of lateral flow SARS-CoV-2 antigen detection in the emergency department to provide rapid, accurate and safe diagnosis of COVID-19

Evaluating the effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control teams: the COG-UK hospital-onset COVID-19 infection study

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