Pilot study to evaluate hypercoagulation and inflammation using rotational thromboelastometry and calprotectin in COVID-19 patients.

INTRODUCTION: Abnormal coagulation and inflammation are hallmarks of SARs-COV-19. Stratifying affected patients on admission to hospital may help identify those who at are risk of developing severe disease early on. Rotational Thromboelastometry (ROTEM) is a point of care test that can be used to measure abnormal coagulation and calprotectin is a measure of inflammation. AIM: Assess if ROTEM can measure hypercoagulability on admission and identify those who will develop severe disease early on. Assess if calprotectin can measure inflammation and if there is a correlation with ROTEM and calprotectin. METHODS: COVID-19 patients were recruited on admission and ROTEM testing was undertaken daily for a period of 7 days. Additionally inflammatory marker calprotectin was also tested for the same period. RESULTS: 33 patients were recruited to the study out of which 13 were admitted to ITU and 20 were treated on the ward. ROTEM detected a hypercoagulable state on admission but did not stratify between those admitted to a ward or escalated to ITU. Calprotectin levels were raised but there was no statistical difference (p = 0.73) between patients admitted to a ward or escalated to ITU. Significant correlations were observed between FIBA5 (r = 0.62; p<0.00), FIBCFT (r = -0.57; p<0.00), FIBMCF (r = 0.64; p<0.00) and INMCF (r = 0.57; p<0.00) and calprotectin. CONCLUSION: COVID-19 patients were hypercoagulable on admission. The correlations between ROTEM and calprotectin underline the interactions between inflammation and coagulation.

Reverse-Transcription Loop-Mediated Isothermal Amplification Has High Accuracy for Detecting Severe Acute Respiratory Syndrome Coronavirus 2 in Saliva and Nasopharyngeal/Oropharyngeal Swabs from Asymptomatic and Symptomatic Individuals.

Previous studies have described reverse-transcription loop-mediated isothermal amplification (RT-LAMP) for the rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal/oropharyngeal swab and saliva samples. This multisite clinical evaluation describes the validation of an improved sample preparation method for extraction-free RT-LAMP and reports clinical performance of four RT-LAMP assay formats for SARS-CoV-2 detection. Direct RT-LAMP was performed on 559 swabs and 86,760 saliva samples and RNA RT-LAMP on extracted RNA from 12,619 swabs and 12,521 saliva samples from asymptomatic and symptomatic individuals across health care and community settings. For direct RT-LAMP, overall diagnostic sensitivity (DSe) was 70.35% (95% CI, 63.48%-76.60%) on swabs and 84.62% (95% CI, 79.50%-88.88%) on saliva, with diagnostic specificity of 100% (95% CI, 98.98%-100.00%) on swabs and 100% (95% CI, 99.72%-100.00%) on saliva, compared with quantitative RT-PCR (RT-qPCR); analyzing samples with RT-qPCR ORF1ab CT values of ≤25 and ≤33, DSe values were 100% (95% CI, 96.34%-100%) and 77.78% (95% CI, 70.99%-83.62%) for swabs, and 99.01% (95% CI, 94.61%-99.97%) and 87.61% (95% CI, 82.69%-91.54%) for saliva, respectively. For RNA RT-LAMP, overall DSe and diagnostic specificity were 96.06% (95% CI, 92.88%-98.12%) and 99.99% (95% CI, 99.95%-100%) for swabs, and 80.65% (95% CI, 73.54%-86.54%) and 99.99% (95% CI, 99.95%-100%) for saliva, respectively. These findings demonstrate that RT-LAMP is applicable to a variety of use cases, including frequent, interval-based direct RT-LAMP of saliva from asymptomatic individuals who may otherwise be missed using symptomatic testing alone.

COVID-19 Oximetry @home: evaluation of patient outcomes.

BACKGROUND: COVID-19 has placed unprecedented demands on hospitals. A clinical service, COVID-19 Oximetry @home (CO@h) was launched in November 2020 to support remote monitoring of COVID-19 patients in the community. Remote monitoring through CO@h aims to identify early patient deterioration and provide timely escalation for cases of silent hypoxia, while reducing the burden on secondary care. METHODS: We conducted a retrospective service evaluation of COVID-19 patients onboarded to CO@h from November 2020 to March 2021 in the North Hampshire (UK) community led service (a collaboration of 15 General Practitioner (GP) practices covering 230 000 people). We have compared outcomes for patients admitted to Basingstoke and North Hampshire Hospital who were CO@h patients (COVID-19 patients with home monitoring of oxygen saturation (SpO2; n=115), with non-CO@h patients (those directly admitted without being monitored by CO@h (n=633)). Crude and adjusted OR analysis was performed to evaluate the effects of CO@h on patient outcomes of 30-day mortality, Intensive care unit (ICU) admission and hospital length of stay greater than 3, 7, 14 and 28 days. RESULTS: Adjusted ORs for CO@h show an association with a reduction for several adverse patient outcome: 30-day hospital mortality (p<0.001, OR 0.21, 95% CI 0.08 to 0.47), hospital length of stay larger than 3 days (p<0.05, OR 0.62, 95% CI 0.39 to 1.00), 7 days (p<0.001, OR 0.35, 95% CI 0.22 to 0.54), 14 days (p<0.001, OR 0.22 95% CI, 0.11 to 0.41), and 28 days (p<0.05, OR 0.21, 95% CI 0.05 to 0.59). No significant reduction ICU admission was observed (p>0.05, OR 0.43, 95% CI 0.15 to 1.04). Within 30 days of hospital admission, there were no hospital readmissions for those on the CO@h service as opposed to 8.7% readmissions for those not on the service. CONCLUSIONS: We have demonstrated a significant association between CO@h and better patient outcomes; most notably a reduction in the odds of hospital lengths of stays longer than 7, 14 and 28 days and 30-day hospital mortality.

Diagnostic accuracy of loop-mediated isothermal amplification coupled to nanopore sequencing (LamPORE) for the detection of SARS-CoV-2 infection at scale in symptomatic and asymptomatic populations.

OBJECTIVES: Rapid, high throughput diagnostics are a valuable tool, allowing the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in populations so as to identify and isolate people with asymptomatic and symptomatic infections. Reagent shortages and restricted access to high throughput testing solutions have limited the effectiveness of conventional assays such as quantitative RT-PCR (RT-qPCR), particularly throughout the first months of the coronavirus disease 2019 pandemic. We investigated the use of LamPORE, where loop-mediated isothermal amplification (LAMP) is coupled to nanopore sequencing technology, for the detection of SARS-CoV-2 in symptomatic and asymptomatic populations. METHODS: In an asymptomatic prospective cohort, for 3 weeks in September 2020, health-care workers across four sites (Birmingham, Southampton, Basingstoke and Manchester) self-swabbed with nasopharyngeal swabs weekly and supplied a saliva specimen daily. These samples were tested for SARS-CoV-2 RNA using the Oxford Nanopore LamPORE system and a reference RT-qPCR assay on extracted sample RNA. A second retrospective cohort of 848 patients with influenza-like illness from March 2020 to June 2020 were similarly tested from nasopharyngeal swabs. RESULTS: In the asymptomatic cohort a total of 1200 participants supplied 23 427 samples (3966 swab, 19 461 saliva) over a 3-week period. The incidence of SARS-CoV-2 detection using LamPORE was 0.95%. Diagnostic sensitivity and specificity of LamPORE was >99.5% (decreasing to approximately 98% when clustered estimation was used) in both swab and saliva asymptomatic samples when compared with the reference RT-qPCR test. In the retrospective symptomatic cohort, the incidence was 13.4% and the sensitivity and specificity were 100%. CONCLUSIONS: LamPORE is a highly accurate methodology for the detection of SARS-CoV-2 in both symptomatic and asymptomatic population settings and can be used as an alternative to RT-qPCR.

Comparison of outcomes of neurosurgical operations performed before and during the COVID-19 pandemic: a matched cohort study.

OBJECTIVE: To determine how the first wave of the COVID-19 pandemic affected outcomes for all operatively managed neurosurgical patients, not only those positive for SARS-CoV-2. DESIGN: Matched cohort (pairwise method). SETTING: A single tertiary neurosurgical referral centre at a large UK Major Trauma Centre. PARTICIPANTS: During the first COVID-19 wave, 231 neurosurgical cases were performed. These cases were matched to cases from 2019. Cases were matched for age (±10 years), primary pathology and surgical procedure. Cases were excluded from analysis if either the age could not be matched to within 10 years, or the primary pathology or procedure was too unique. After exclusions, 191 cases were included in final analysis. OUTCOME MEASURES: Primary outcomes were 30-day mortality and postoperative pulmonary complications. Secondary outcomes included Glasgow Outcome Score (GOS) on discharge, length of stay (LoS), operative and anaesthetic times and grade of primary surgeon. An exploratory outcome was the SARS-CoV-2 status of patients. RESULTS: There was no significant difference between the pandemic and matched cohorts in 30-day mortality, pulmonary complications, discharge GOS, LoS, operative or anaesthetic times. There was a significant difference in the variation of grade of primary surgeon. Only 2.2% (n=5) of patients had a SARS-CoV-2 positive swab. CONCLUSION: During the first UK wave of the COVID-19 pandemic, the mortality, morbidity and functional outcomes of operatively managed neurosurgical patients at University Hospitals Birmingham were not significantly affected compared with normal practice. The grade of primary surgeon was significantly more senior and adds to the growing body of evidence that demonstrates how the pandemic has negatively impacted UK surgical training. Mixing COVID-19 positive, unknown and negative cases did not significantly impact on outcomes and indicates that further research is required to support the implementation of evidence-based surgical pathways, such as COVID-light sites, throughout the next stage of the pandemic.