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Preprint in English | medRxiv | ID: ppmedrxiv-22270799


IntroductionViral 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. MethodsWe 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. ResultsA 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. ConclusionWhile 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.

Preprint in English | medRxiv | ID: ppmedrxiv-21259107


BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.1.7 has been associated with an increased rate of transmission and disease severity among subjects testing positive in the community. Its impact on hospitalised patients is less well documented. MethodsWe collected viral sequences and clinical data of patients admitted with SARS-CoV-2 and hospital-onset COVID-19 infections (HOCIs), sampled 16/11/2020 - 10/01/2021, from eight hospitals participating in the COG-UK-HOCI study. Associations between the variant and the outcomes of all-cause mortality and intensive therapy unit (ITU) admission were evaluated using mixed effects Cox models adjusted by age, sex, comorbidities, care home residence, pregnancy and ethnicity. ResultsSequences were obtained from 2341 inpatients (HOCI cases = 786) and analysis of clinical outcomes was carried out in 2147 inpatients with all data available. The hazard ratio (HR) for mortality of B.1.1.7 compared to other lineages was 1.01 (95% CI 0.79-1.28, P=0.94) and for ITU admission was 1.01 (95% CI 0.75-1.37, P=0.96). Analysis of sex-specific effects of B.1.1.7 identified increased risk of mortality (HR 1.30, 95% CI 0.95-1.78) and ITU admission (HR 1.82, 95% CI 1.15-2.90) in females infected with the variant but not males (mortality HR 0.82, 95% CI 0.61-1.10; ITU HR 0.74, 95% CI 0.52-1.04). ConclusionsIn common with smaller studies of patients hospitalised with SARS-CoV-2 we did not find an overall increase in mortality or ITU admission associated with B.1.1.7 compared to other lineages. However, women with B.1.1.7 may be at an increased risk of admission to intensive care and at modestly increased risk of mortality.

Preprint in English | medRxiv | ID: ppmedrxiv-21252978


AimsThere is a lack of biomarkers validated for assessing clinical deterioration in COVID-19 patients upon presentation to secondary or tertiary care. This evaluation looked at the potential clinical application of C-Reactive Protein, Procalcitonin, Mid-Regional pro-adrenomedullin (MR-proADM) and White Cell Count to support prediction of clinical outcomes. Methods135 patients presenting to Hampshire Hospitals NHS Foundation Trust between April and June 2020 confirmed to have COVID-19 via RT-qPCR were included. Biomarkers from within 24 hours of admission were used to predict disease progression by Cox regression and area under the receiver operating characteristic (AUROC) curves. The endpoints assessed were 30-day all-cause mortality, intubation and ventilation, critical care admission and non-invasive ventilation (NIV) use. ResultsElevated MR-proADM was shown to have the greatest ability to predict 30-day mortality adjusting for age, cardiovascular, renal and neurological disease. A significant association was also noted between raised MR-proADM and CRP concentrations and the requirement for critical care admission and non-invasive ventilation. ConclusionsThe measurement of MR-proADM and CRP in patients with confirmed COVID-19 infection upon admission shows significant potential to support clinicians in identifying those at increased risk of disease progression and need for higher level care, subsequently enabling prompt escalation in clinical interventions.

Preprint in English | medRxiv | ID: ppmedrxiv-21251350


Low procalcitonin (PCT) concentrations (<0.5ng/mL) can facilitate exclusion of bacterial co-infection in viral infections, including COVID-19. However, costs associated with PCT measurement preclude universal adoption, indicating a need to identify settings where PCT provides clinical information beyond that offered by other inflammatory markers, such as C-reactive protein (CRP) and white cell count (WCC). In an unselected cohort of 299 COVID-19 patients, we tested the hypothesis that PCT<0.5ng/mL was associated with lower levels of CRP and WCC. We demonstrated that CRP values below the geometric mean of the entire patient population had a negative predictive value for PCT<0.5ng/mL of 97.6% and 100% at baseline and 48 hours into admission respectively, and that this relationship was not confounded by intensive care admission or microbiological findings. CRP-guided PCT testing algorithms can reduce costs and support antimicrobial stewardship strategies in COVID-19.