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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.
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BackgroundCOVID-19 is infrequently complicated by secondary bacterial infection, but nevertheless antibiotic prescriptions are common. We used community-acquired pneumonia (CAP) as a benchmark to define the processes that occur in a bacterial pulmonary infection, and tested the hypothesis that baseline inflammatory markers and their response to antibiotic therapy could distinguish CAP from COVID-19. MethodsIn patients admitted to Royal Free Hospital (RFH) and Barnet Hospital (BH) we defined CAP by lobar consolidation on chest radiograph, and COVID-19 by SARS-CoV-2 detection by PCR. Data were derived from routine laboratory investigations. ResultsOn admission all CAP and >90% COVID-19 patients received antibiotics. We identified 106 CAP and 619 COVID-19 patients at RFH. CAP was characterised by elevated white cell count (WCC) and C-reactive protein (CRP) compared to COVID-19 (median WCC 12.48 (IQR 8.2-15.3) vs 6.78 (IQR 5.2-9.5) x106 cells/ml and median CRP CRP 133.5 (IQR 65-221) vs 86 (IQR 42-160) mg/L). Blood samples collected 48-72 hours into admission revealed decreasing CRP in CAP but not COVID-19 (CRP difference -33 (IQR -112 to +3.5) vs +15 (IQR -15 to +70) mg/L respectively). In the independent validation cohort (BH) consisting of 169 CAP and 181 COVID-19 patients, admission WCC >8.2x106 cells/ml or falling CRP during admission identified 95% of CAP cases, and predicted the absence of bacterial co-infection in 45% of COVID-19 patients. ConclusionsWe propose that in COVID-19 the absence of both elevated baseline WCC and antibiotic-related decrease in CRP can exclude bacterial co-infection and facilitate antibiotic stewardship efforts.