Discriminatory ability of gas chromatography-ion mobility spectrometry to identify patients hospitalised with COVID-19 and predict prognosis (preprint)

Background Tests that can diagnose COVID-19 rapidly and predict prognosis would be significantly beneficial. We studied the ability of breath analysis using gas chromatography-ion mobility spectrometry (GC-IMS) for diagnosis of COVID-19 and as a predictor for subsequent requirement for Continuous Positive Airway Pressure (CPAP). Methods We undertook a single centre prospective observational study in patients with COVID-19, other respiratory tract infections and healthy controls. Participants provided one breath sample for GC-IMS analysis. We used cross validation analysis to create models that were then tested against the original cohort data. Further multivariable analysis was undertaken to adjust for differences between the comparator groups. Results Between 01/02/2021 and 24/05/2021 we recruited 113 participants, of whom 72 (64%) had COVID-19, 20 (18%) had another respiratory tract infection and 21 (19%) were healthy controls. Differentiation between patients with COVID-19 and healthy controls, and patients with COVID-19 and those with other respiratory tract infections, was achieved with high accuracy. Identification of patients with subsequent requirement for CPAP was completed with moderate accuracy and was not independently associated on multivariable analysis. Conclusions We have shown that GC-IMS has a high capability to distinguish between acute COVID-19 infection and other disease states. Breath analysis shows promise as a predictor of subsequent requirement for CPAP in hospitalised patients with COVID-19. This platform has considerable benefits due to the test being rapid, non-invasive and not requiring specialist laboratory processing.

Evaluation of the Implementation of the 4C Mortality Score in United Kingdom hospitals during the second pandemic wave (preprint)

ABSTRACT The 4C Mortality Score (4C Score) was designed to risk stratify hospitalised patients with COVID-19. We assessed inclusion of 4C Score in COVID-19 management guidance and its documentation in patients' case notes in January 2021 in UK hospitals. 4C Score was included within guidance by 50% of sites, though score documentation in case notes was highly variable. Higher documentation of 4C Score was associated with score integration within admissions proformas, inclusion of 4C Score variables or link to online calculator, and management decisions. Integration of 4C Score within clinical pathways may encourage more widespread use.

Predictors of SARS-CoV-2 infection in a multi-ethnic cohort of United Kingdom healthcare workers: a prospective nationwide cohort study (UK-REACH) (preprint)

Introduction Healthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs. Methods We conducted a cross-sectional analysis using data from the United Kingdom Research study into Ethnicity And COVID-19 Outcomes in Healthcare workers (UK-REACH) cohort study. We used logistic regression to examine associations of demographic, household and occupational predictor variables with SARS-CoV-2 infection (defined by PCR, serology or suspected COVID-19) in a diverse group of HCWs. Results 2,496 of the 10,772 HCWs (23.2%) who worked during the first UK national lockdown in March 2020 reported previous SARS-CoV-2 infection. In an adjusted model, demographic and household factors associated with increased odds of infection included younger age, living with other key workers and higher religiosity. Important occupational risk factors associated with increased odds of infection included attending to a higher number of COVID-19 positive patients (aOR 2.49, 95%CI 2.03–3.05 for ≥21 patients per week vs none), working in a nursing or midwifery role (1.35, 1.15– 1.58, compared to doctors), reporting a lack of access to personal protective equipment (1.27, 1.15 – 1.41) and working in an ambulance (1.95, 1.52–2.50) or hospital inpatient setting (1.54, 1.37 – 1.74). Those who worked in Intensive Care Units were less likely to have been infected (0.76, 0.63–0.90) than those who did not. Black HCWs were more likely to have been infected than their White colleagues, an effect which attenuated after adjustment for other known predictors. Conclusions We identified key sociodemographic and occupational risk factors associated with SARS-CoV-2 infection amongst UK HCWs, and have determined factors that might contribute to a disproportionate odds of infection in HCWs from Black ethnic groups. These findings demonstrate the importance of social and occupational factors in driving ethnic disparities in COVID-19 outcomes, and should inform policies, including targeted vaccination strategies and risk assessments aimed at protecting HCWs in future waves of the COVID-19 pandemic. Trial registration ISRCTN 11811602

Quantification and prognostic significance of interferon-γ secreting SARS-CoV-2 responsive T cells in hospitalised patients with acute COVID-19 (preprint)

Little is known about T-cell responses during acute coronavirus disease-2019 (COVID-19). We measured T-cell interferon gamma (IFN-{gamma}) responses to spike 1 (S1), spike 2 (S2), nucleocapsid (N) and membrane (M) SARS-CoV-2 antigens using the T-SPOT(R) Discovery SARS-CoV-2 assay, a proven EliSPOT technology, in 114 hospitalised adult COVID-19 patients and assessed their association with clinical disease phenotype. T-SPOT(R) Discovery SARS-CoV-2 responses were detectable within 2 days of a positive PCR and did not correlate with vaccination status or symptom duration. Higher responses to S1 protein associated with a higher symptom burden, and serum IL-6 levels. Despite treatment with dexamethasone this subgroup was also at greater risk of requiring continuous positive airway pressure (CPAP) in the days following sampling. Higher T-cell responses measured using T-SPOT(R) Discovery SARS-CoV-2 associate with progressive disease in acute COVID-19 disease and may have utility as a prognostic biomarker that should be evaluated in larger cohorts.

Access to personal protective equipment in healthcare workers during the COVID-19 pandemic in the United Kingdom: results from a nationwide cohort study (UK-REACH) (preprint)

ObjectivesTo determine the prevalence and predictors of self-reported access to appropriate personal protective equipment (aPPE) for healthcare workers (HCWs) in the United Kingdom (UK) during the first UK national COVID-19 lockdown (March 2020) and at the time of questionnaire response (December 2020 - February 2021). DesignTwo cross sectional analyses using data from a questionnaire-based cohort study. SettingNationwide questionnaire from 4th December 2020 to 28th February 2021. ParticipantsA representative sample of HCWs or ancillary workers in a UK healthcare setting aged 16 or over, registered with one of seven main UK healthcare regulatory bodies. Main outcome measureBinary measure of self-reported aPPE (access all of the time vs access most of the time or less frequently) at two timepoints: the first national lockdown in the UK (primary analysis) and at the time of questionnaire response (secondary analysis). Results10,508 HCWs were included in the primary analysis, and 12,252 in the secondary analysis. 3702 (35.2%) of HCWs reported aPPE at all times in the primary analysis; 6806 (83.9%) reported aPPE at all times in the secondary analysis. After adjustment (for age, sex, ethnicity, migration status, occupation, aerosol generating procedure exposure, work sector, work region, working hours, night shift frequency and trust in employing organisation), older HCWs (per decade increase in age: aOR 1.2, 95% CI 1.16-1.26, p<0.001) and those working in Intensive Care Units (1.61, 1.38 - 1.89, p<0.001) were more likely to report aPPE at all times. Those from Asian ethnic groups compared to White (0.77, 0.67-0.89, p<0.001), those in allied health professional (AHPs) and dental roles (vs those in medical roles; AHPs: 0.77, 0.68 - 0.87, p<0.001; dental: 0.63, 0.49-0.81, p<0.001), and those who saw a higher number of COVID-19 patients compared to those who saw none ([≥]21 patients 0.74, 0.61-0.90, p=0.003) were less likely to report aPPE at all times in the primary analysis. aPPE at all times was also not uniform across UK regions (reported access being better in South West and North East England than London). Those who trusted their employing organisation to deal with concerns about unsafe clinical practice, compared to those who did not, were twice as likely to report aPPE at all times (2.18, 1.97-2.40, p<0.001). With the exception of occupation, these factors were also significantly associated with aPPE at all times in the secondary analysis. ConclusionsWe found that only a third of HCWs in the UK reported aPPE at all times during the period of the first lockdown and that aPPE had improved later in the pandemic. We also identified key sociodemographic and occupational determinants of aPPE during the first UK lockdown, the majority of which have persisted since lockdown was eased. These findings have important public health implications for HCWs, particularly as cases of infection and long-COVID continue to rise in the UK. Trial registrationISRCTN 11811602 What is already known on this topicAccess to personal protective equipment (PPE) is crucial to protect healthcare workers (HCWs) from infection. Limited data exist concerning the prevalence of, and factors relating to, PPE access for HCWs in the United Kingdom (UK) during the COVID-19 pandemic. What this study addsOnly a third of HCWs reported having access to appropriate PPE all of the time during the first UK national lockdown. Older HCWs, those working in Intensive Care Units and those who trusted their employing organisation to deal with concerns about unsafe clinical practice, were more likely to report access to adequate PPE. Those from Asian ethnic groups (compared to White ethnic groups) and those who saw a high number of COVID-19 were less likely to report access to adequate PPE. Our findings have important implications for the mental and physical health of HCWs working during the pandemic in the UK.

Ethnicity and clinical outcomes in COVID-19A Systematic Review and Meta-analysis (preprint)

ImportanceThe association of ethnicity with outcomes in patients with COVID-19 is unclear. ObjectiveTo determine whether the risk of SARS-CoV-2 infection, COVID-19 intensive care unit (ICU) admission and mortality are associated with ethnicity. Data SourcesWe searched all English language articles published 1st December 2019 - 30th June 2020 within MEDLINE, EMBASE, PROSPERO and the Cochrane library using indexing terms for COVID-19 and ethnicity, as well as manuscripts awaiting peer review on MedRxiv during the same period. Study SelectionIncluded studies reported original clinical data, disaggregated by ethnicity, on patients with confirmed or suspected COVID-19. We excluded correspondence, area level, modelling and basic science articles. Two independent reviewers screened articles for inclusion. Of 926 identified articles, 35 were included in the meta-analyses. Data Extraction and SynthesisThe review was conducted according to PRISMA guidelines. Reviewers independently extracted data using a piloted form on: (1) rates of infection, ICU admission and mortality by ethnicity; and (2) unadjusted and adjusted data comparing ethnic minority and White groups. Data were pooled using random effects models. Main Outcomes and MeasuresOutcomes were: (1) infection with SARS-CoV-2 confirmed on molecular testing; (2) ICU admission; and (3) mortality in COVID-19 confirmed and suspected cases. Results13,535,562 patients from 35 studies were included in the meta-analyses. Black, Asian and Hispanic individuals had a greater risk of infection compared to White individuals (Black: pooled adjusted RR: 2.06, 95% CI: 1.59-2.67; Asian: 1.35, 95%CI: 1.15-1.59; Hispanic: 1.77, 95% CI: 1.39-2.25). Black individuals were significantly more likely to be admitted to ICU than White individuals (pooled adjusted RR: 1.61, 95% CI: 1.02-2.55). Risk of mortality was similar across ethnicities among hospitalised patients, but increased among Asian and Mixed ethnic groups in the general population. ConclusionsBlack, Asian and Hispanic ethnic groups are at increased risk of SARS-CoV-2 infection. Black individuals may be more likely to require ICU admission for COVID-19. There may also be disparities in risk of death from COVID-19 at a population level. Our findings are of critical public health importance and should inform policy on minimising SARS-CoV-2 exposure in ethnic minority groups. KEY POINTSO_ST_ABSQuestionC_ST_ABSIs ethnicity associated with vulnerability to, and outcomes from, coronavirus disease 2019 (COVID-19)? FindingsIn this systematic review and meta-analysis, rates of infection and outcomes from COVID-19 were compared between ethnic groups. Individuals from Black, Asian and Hispanic ethnicity were significantly more vulnerable to SARS-CoV-2 infection than those of White ethnicity. Black individuals were more likely to need intensive care unit (ICU) admission for COVID-19 than White individuals. Risk of mortality was similar across ethnicities among hospitalised patients, but increased among Asian and Mixed ethnic groups in the general population. MeaningThere is strong evidence for an increased risk of SARS-CoV-2 infection amongst ethnic minorities, and targeted public health policies are required to reduce this risk.