To What Extent do Social Determinants of Health Modulate Presentation, ITU Admission and Outcomes among Patients with SARS-COV-2 Infection? An Exploration of Household Overcrowding, Air Pollution, Housing Quality, Ethnicity, Comorbidities and Frailty.

Background: Internationally, researchers have called for evidence to support tackling health inequalities during the severe acute respiratory syndrome coronavirus 2 (COVID19) pandemic. Despite the 2020 Marmot review highlighting growing health gaps between wealthy and deprived areas, studies have not explored social determinants of health (ethnicity, frailty, comorbidities, household overcrowding, housing quality, air pollution) as modulators of presentation, intensive care unit (ITU) admissions and outcomes among COVID19 patients. There is an urgent need for studies examining social determinants of health including socioenvironmental risk factors in urban areas to inform the national and international landscape. Methods: An in-depth retrospective cohort study of 408 hospitalized COVID19 patients admitted to the Queen Elizabeth Hospital, Birmingham was conducted. Quantitative data analyses including a two-step cluster analysis were applied to explore the role of social determinants of health as modulators of presentation, ITU admission and outcomes. Results: Patients admitted from highest Living Environment deprivation indices were at increased risk of presenting with multi-lobar pneumonia and, in turn, ITU admission whilst patients admitted from highest Barriers to Housing and Services (BHS) deprivation Indies were at increased risk of ITU admission. Black, Asian and Minority Ethnic (BAME) patients were more likely, than Caucasians, to be admitted from regions of highest Living Environment and BHS deprivation, present with multi-lobar pneumonia and require ITU admission. Conclusion: Household overcrowding deprivation and presentation with multi-lobar pneumonia are potential modulators of ITU admission. Air pollution and housing quality deprivation are potential modulators of presentation with multi-lobar pneumonia. BAME patients are demographically at increased risk of exposure to household overcrowding, air pollution and housing quality deprivation, are more likely to present with multi-lobar pneumonia and require ITU admission. Irrespective of deprivation, consideration of the Charlson Comorbidity Score and the Clinical Frailty Score supports clinicians in stratifying high risk patients.

COVID-19 neutrophils show elevated migration and NETosis, which is reduced by PI3K inhibition

Rational: Evidence of neutrophil dysfunction in COVID-19 is based on transcriptomics. Cell functions are interwoven pathways, so understanding the effect of COVID-19 across neutrophil function may identify therapeutic targets. We examined neutrophil phenotype and function in 41 hospitalised, non-ICU COVID-19 patients versus 23 age-matched controls (AMC) and 26 community acquired pneumonia (CAP) patients. Method(s): Isolated neutrophils underwent ex vivo analyses for migration, phagocytosis and NETosis, and the effect of PI3K inhibition. Circulating DNAse 1 activity and levels of cfDNA were measured. Result(s): Compared to AMC and CAP, COVID-19 neutrophils demonstrated elevated transmigration (p=0.0397, A) and NETosis (p=0.0366, B), but impaired phagocytosis (p=0.0236, C) associated with impaired ROS generation (p<0.0001). COVID-19 and CAP patients showed increased systemic markers of NETosis including increased cfDNA (p=0.0153) and impaired DNAse activity (p<0.0.001, D). Ex vivo inhibition of PI3K gamma and delta reduced NET release by COVID-19 neutrophils (p=0.0156). Conclusion(s): COVID-19 is associated with neutrophil dysfunction across all main effector functions, with elevated migration, impaired antimicrobial responses and elevated NETosis. These changes represent a clear mechanism for tissue damage and highlight that targeting neutrophil function via PI3k may help modulate COVID-19 severity. (Figure Presented).

Functional Laryngeal Assessment in Patients with Tracheostomy Following COVID-19 a Prospective Cohort Study.

To explore laryngeal function of tracheostomised patients with COVID-19 in the acute phase, to identify ways teams may facilitate and expedite tracheostomy weaning and rehabilitation of upper airway function. Consecutive tracheostomised patients underwent laryngeal examination during mechanical ventilation weaning. Primary outcomes included prevalence of upper aerodigestive oedema and airway protection during swallow, tracheostomy duration, ICU frailty scores, and oral intake type. Analyses included bivariate associations and exploratory multivariable regressions. 48 consecutive patients who underwent tracheostomy insertion as part of their respiratory wean following invasive ventilation in a single UK tertiary hospital were included. 21 (43.8%) had impaired airway protection on swallow (PAS ≥ 3) with 32 (66.7%) having marked airway oedema in at least one laryngeal area. Impaired airway protection was associated with longer total artificial airway duration (p = 0.008), longer tracheostomy tube duration (p = 0.007), multiple intubations (p = 0.006) and was associated with persistent ICU acquired weakness at ICU discharge (p = 0.03). Impaired airway protection was also an independent predictor for longer tracheostomy tube duration (p = 0.02, Beta 0.38, 95% CI 2.36 to 27.16). The majority of our study patients presented with complex laryngeal findings which were associated with impaired airway protection. We suggest a proactive standardized scoring and review protocol to manage this complex group of patients in order to maximize health outcomes and ICU resources. Early laryngeal assessment may facilitate weaning from invasive mechanical ventilation and liberation from tracheostomy, as well as practical and objective risk stratification for patients regarding decannulation and feeding.

Dysfunctional neutrophil response in COVID-19 infection vary by subtype

S94 Figure 1Comparison of neutrophil effector functions between COVID-19 variants (alpha n=33, delta n=13, omicron n-14). A.% change in phagocytosis significantly increased between alpha and delta patients (p=0.0162). B. Fold change in cells migrated through a transwell pore to IL8 compared to vehicle control significantly reduced in omicron patients compared alpha and delta (vs alpha p=0.0018, vs delta p=0.0370). C. Neutrophil extracellular trap production after stimulation with PMA compared to vehicle control significantly reduced in omicron patients compared to alpha (p=0.0396)[Figure omitted. See PDF]DiscussionOur results showing changes in neutrophil „function and phenotype differ between variants of COVID-19 infection, potentially reflect viral evolution. This change in neutrophil function may contribute to the evolving clinical phenotype observed in patients. Our population of ward-based COVID-19 patients represents the majority of inpatient hospital burden where early intervention may prevent clinical deterioration. Targeting neutrophil function may be an effective way of improving infection outcome in the future.ReferenceBelchamber K, et al. Altered neutrophil phenotype and function in non-ICU hospitalised COVID-19 patients correlated with disease severity. medRxiv, 2021: p. 2021.06.08.21258535.

Association between vitamin D deficiency and extended duration of COVID-19 symptoms

Introduction and ObjectivesVitamin D (VD) is involved in immunity and inflammation through mechanisms such as renin inhibition and inflammatory cytokine reduction. There is already evidence to suggest that VDD may increase COVID-19 infection susceptibility, however research assessing the impact of VDD on COVID-19 symptom duration is limited. The aim of this research was to determine whether VDD is a significant independent risk factor for extended durations of COVID-19 symptoms.MethodsThe study included 392 healthcare workers who isolated due to COVID-19 symptoms during the first wave of the pandemic (12th to 22nd May 2020) as part of the convalescent immunity (COCO) study. Data on 8 symptom types and duration of symptoms were collected, including patients’ demographics and co-morbidities. Anti-SARS-Cov-2 antibodies were measured using a combined IgG, IgA and IgM ELISA (The Binding Site). Vitamin D status was determined by measurement of serum 25(OH)D3 using the AB SCIEX Triple Quad 4500 mass spectrometry system. VDD was defined as serum 25(OH)D3 <30 nmol/L.ResultsThrough univariate analysis of VDD and non-VDD staff, we initially showed VDD to be significantly associated with longer durations of body aches (median 7 days, IQR 5–14 vs. median 5 days, IQR 3–7.5;p=0.0075) and fatigue (median 12 days, IQR 7–14 vs. median 7 days, IQR 4–14;p=0.0127). VDD did not influence the duration of the other 6 symptoms analysed, such as cough and fever. Using binary logistic regression models, we confirm that VDD is a significant independent risk factor for extended durations of fatigue (OR 2.089, 95% CI 1.087–4.011;p=0.027) and body aches (OR 3.069, 95% CI 1.538–6.124;p=0.001). Additionally, VDD staff experienced a significantly greater quantity of symptoms compared to non-VDD staff (median 5, IQR 4–7 versus median 4, IQR 3–6;p=0.0030).ConclusionsThis is one of the first studies to investigate the influence of VDD on COVID-19 symptom duration. Our results indicate that VDD is a significant independent risk factor for a longer duration of body aches and fatigue. Larger studies are required to confirm these results and determine if VD supplementation could shorten symptoms.

Cardiovascular subphenotypes in patients with COVID-19 pneumonitis whose lungs are mechanically ventilated: a single-centre retrospective observational study.

Unsupervised clustering methods of transthoracic echocardiography variables have not been used to characterise circulatory failure mechanisms in patients with COVID-19 pneumonitis. We conducted a retrospective, single-centre cohort study in ICU patients with COVID-19 pneumonitis whose lungs were mechanically ventilated and who underwent transthoracic echocardiography between March 2020 and May 2021. We performed latent class analysis of echocardiographic and haemodynamic variables. We characterised the identified subphenotypes by comparing their clinical parameters, treatment responses and 90-day mortality rates. We included 305 patients with a median (IQR [range]) age 59 (49-66 [16-83]) y. Of these, 219 (72%) were male, 199 (65%) had moderate acute respiratory distress syndrome and 113 (37%) did not survive more than 90 days. Latent class analysis identified three cardiovascular subphenotypes: class 1 (52%; normal right ventricular function); class 2 (31%; right ventricular dilation with mostly preserved systolic function); and class 3 (17%; right ventricular dilation with systolic impairment). The three subphenotypes differed in their clinical characteristics and response to prone ventilation and outcomes, with 90-day mortality rates of 22%, 42% and 73%, respectively (p < 0.001). We conclude that the identified subphenotypes aligned with right ventricular pathophysiology rather than the accepted definitions of right ventricular dysfunction, and these identified classifications were associated with clinical outcomes.

Applying a COVID Virtual Ward model, assessing patient outcomes and staff workload.

A COVID virtual ward (CVW) is recommended by NHS England, but 'usual care' outcomes have not been reported. A retrospective study of all adults with COVID-19 attending Queen Elizabeth Hospital Birmingham between 01/06/2020-31/01/2021, assessed against CVW criteria and followed for 28 days. Of 2301 COVID-19 patients, 571(25%) would have met CVW criteria. Of these, 325(57%) were discharged after review and 246(43%) admitted. Of admitted patients who met CVW criteria, 81% required hospital-supported therapies; 11% died. Of the 325 discharged, 13% re-presented, 9% with COVID-related symptoms, 2% required intensive care admission, and one died (0.3%). In this comparison, discharging patients without a CVW did not lead to more re-presentations, re-admissions, ITU escalations or deaths compared to published outcomes for hospitals with a CVW.

Elevated NETosis and migration but impaired anti-microbial responses in neutrophils from non-ICU, hospitalized COVID-19 patients

RationalInfection with the SARS-CoV2 virus is associated with elevated neutrophil counts. Evidence of neutrophil dysfunction in COVID-19 is based predominantly on transcriptomics or single functional assays. Cell functions are interwoven pathways, and so understanding the effect of COVID-19 across the spectrum of neutrophil function may identify therapeutic targets to treat disease.ObjectivesExamine neutrophil phenotype and functional capacity in COVID-19 patients versus age-matched controls (AMC).MethodsIsolated neutrophils from 41 non-ICU COVID-19 patients and 23 AMC underwent ex vivo analyses for migration, phagocytosis of Streptococcus pneumoniae, reactive oxygen species (ROS) generation, neutrophil extracellular trap formation (NETosis) and cell surface receptor expression. Serum DNAse 1 activity was measured, alongside circulating levels of cell-free (cf)DNA, myeloperoxidase (MPO), VEGF, IL-6 and sTNFRI. All measurements were correlated to clinical outcome. Serial sampling on day 3–5 post hospitalisation were also measured.ResultsCompared to AMC, COVID-19 neutrophils demonstrated elevated transmigration (p=0.0397) and NETosis (p=0.0366), but impaired phagocytosis (p=0.0236) associated with impaired ROS generation (p<0.0001). Surface expression of CD54 (p<0.0001) and CD11c (p=0.0008) was significantly increased and CD11b significantly decreased (p=0.0229) on COVID-19 patient neutrophils. On day 3–5 follow-up, levels of senescent neutrophils increased compared to day 1 (indicated by decreased CXCR2 and elevated CXCR4 expression (p=0.0332)). COVID-19 patients showed increased systemic markers of NETosis including increased cfDNA (p=0.0153) and impaired DNAse activity (p<0.0.001). MPO, VEGF, sTNFRI, and IL-6 (p<0001) were elevated in COVID-19, which positively correlated with disease severity by 4C score.ConclusionCOVID-19 is associated with neutrophil dysfunction across all main effector functions, with altered phenotype, elevated migration, impaired antimicrobial responses and elevated NETosis. These changes represent a clear mechanism for tissue damage and highlight that targeting neutrophil function may help modulate COVID-19 severity.Please refer to page A189 for declarations of interest related to this abstract.

The changing characteristics of COVID-19 presentations. A regional comparison of SARS-CoV-2 hospitalised patients during the first and second wave

BACKGROUND: This study assesses COVID-19 hospitalised patient demography and outcomes during wave 1 and wave 2, prior to new variants of the virus. METHODS: All patients with a positive SARS-CoV-2 swab between 10th March 2020 and 5th July 2020 (wave 1) and 1st September 2020 and 16th November 2020 (wave 2) admitted to University Hospitals Birmingham NHS Foundation Trust were included (n=4856), followed for 28 days. RESULTS: Wave 2 patients were younger, more ethnically diverse, had less co-morbidities and disease presentation was milder on presentation. After matching for these factors, mortality was reduced, but without differences in intensive care admissions. CONCLUSION: Prior to new SARS-CoV-2 variants, outcomes for hospitalised patients with COVID-19 were improving but with similar intensive care needs.

Epidemiological and clinical profile of healthcare providers affected with COVID-19 at civil hospital, medicity campus, Ahmedabad, Gujarat

Background: SARS-CoV-2 has spread globally at a rapid pace, causing significant morbidity and mortality. Healthcare providers are especially vulnerable to infection with important implications. There might be adverse effects on their health, they could transmit the infection to vulnerable patients, family contacts and other staff if not quickly isolated and high rates of infection could cause problems due to health system manpower shortage. Methodology: A cross-sectional study was conducted where a preformed semi-structured questionnaire was sent using Google forms. A total of 311 healthcare providers were sent the form out of which 161 responded. Analysis was done using Microsoft Excel 2019 and Google Forms. Result: 75.16% healthcare providers always wore PPE, 11.18% wore it as per duty requirements and 13.66% used mask and sanitizer in non Covid duty areas. They were infected even with use of protective measures. 14.91% reported having co morbidities. Hypertension 8.7% followed by Diabetes 4.96% was the commonest. A significant association was present between sex and work profile of respondents with hospital admission.

Mechanical ventilation utilization in covid-19: A systematic review and meta-analysis

Introduction and Objectives In December 2019, SARS-CoV-2 caused a global pandemic with a viral infection called COVID-19. The disease usually causes respiratory symptoms but in a small proportion of patients can lead to pneumonitis, Adult Respiratory Distress Syndrome and death. Invasive Mechanical Ventilation (IMV) is considered a life-saving treatment for COVID-19 patients and a huge demand for IMV devices was reported globally. This review aimed to provide insight on the initial IMV practices for COVID-19 patients in the initial phase of the pandemic. Methods Electronic databases (Embase and MEDLINE) were searched for applicable articles using relevant keywords. The references of included articles were hand searched. Articles that reported the use of IMV in adult COVID-19 patients between December 2019 and 23rd of April were included in the review. The NIH quality assessment tool for cohort and cross-sectional studies was used to appraise studies. Results 106 abstracts were identified from the databases search, of which 16 were included. 4 studies were included in the meta-analysis. In total, 9988 patients were included across all studies. The overall cases of COVID-19 requiring IMV ranged from 2-75%. Increased age and pre-existing comorbidities increased the likelihood of IMV requirement. The reported mortality rate in patients receiving IMV ranged between 50-100%. On average, IMV was required and initiated between 10-10.5 days from symptoms onset. When invasively ventilated, COVID-19 patients required IMV for a median of 10-17 days across studies. Little information was provided on ventilatory protocols or management strategies and was inconclusive. Conclusions In these initial reporting studies for the first month of the pandemic, patients receiving IMV were older and had more pre-existing co-morbidities than those who did not require IMV. The mortality rate was high in COVID-19 patients who received IMV. Studies are needed to evaluate protocols and modalities of IMV to improve outcomes and identify the populations most likely to benefit from IMV.

L12 To what extent are social determinants of health, including household overcrowding, air pollution and housing quality deprivation, modulators of presentation, ITU admission and outcomes among patients with SARS-COV-2 infection in an urban catchment area in Birmingham, United Kingdom?

BackgroundInternationally, researchers have called for evidence to support tackling health inequalities during the COVID19 pandemic. UK Office for National Statistics data suggests that patients in regions of most deprived overall Index of Multiple Deprivation Score (IMDS) are twice as likely to die of COVID19 than other causes. The Intensive Care National Audit and Research Centre (ICNARC) report that Black, Asian and Minority Ethnic (BAME) patients account for 34% of critically ill COVID19 patients nationally despite constituting 14% of the population. This paper is the first to explore the roles of social determinants of health, including specific IMDS sub-indices with indicators for household overcrowding deprivation (Barriers to Housing and Services subindex (BHS)), indoor housing quality deprivation and outdoor air pollution deprivation (Living Environment subindex (LE)) as modulators of presentation, Intensive Care Unit(ITU) admission and outcomes among COVID19 patients of all ethnicities.MethodsAn in-depth retrospective cohort study of 408 hospitalised COVID19 patients admitted to Queen Elizabeth Hospital, Birmingham was conducted. Quantitative data analyses including two-step cluster analyses were applied.ResultsPatients admitted from highest LE deprivation sub-indices were at increased risk of presenting with multi-lobar pneumonia and, in turn, ITU admission. Patients admitted from highest BHS deprivation sub-indices were at increased risk of ITU admission. BAME patients were more likely, than white patients, to present with multi-lobar pneumonia, be admitted to ITU and be admitted from highest BHS and LE deprivation indices. Comorbidities and frailty significantly increased the risk of death among COVID19 patients irrespective of deprivation.ConclusionsAir pollution and housing quality deprivation are potential modulators of presentation with multi-lobar pneumonia. Household overcrowding deprivation and presentation with multi-lobar pneumonia are potential modulators of ITU admission. Patents of BAME ethnicity are more likely to be admitted from regions of highest air pollution, housing quality and household overcrowding deprivation;this is likely to contribute an explanation towards the higher ITU admissions reported among COVID19 BAME patients. Consideration of Charlson Comorbidity and Clinical Frailty Scores on admission supports clinicians in stratifying high risk patients. These findings have urgent implications for supporting front line clinical decisions, disseminating practical advice around applying social distancing messages at the household level and informing wider pandemic strategy.This study has been cited by several national and international public bodies including Public Health England and UK Parliament as evidence to support the COVID19 strategic response.

Renal impairment and its impact on clinical outcomes in patients who are critically ill with COVID-19: a multicentre observational study.

Renal impairment is common in patients who are critically ill with coronavirus disease-19 (COVID-19). We examined the association between acute and chronic kidney disease with clinical outcomes in 372 patients with coronavirus disease-19 admitted to four regional intensive care units between 10 March 2020 and 31 July 2020. A total of 216 (58%) patients presented with COVID-19 and renal impairment. Acute kidney injury and/or chronic kidney disease was associated with greater in-hospital mortality compared with patients with preserved renal function (107/216 patients (50%) (95%CI 44-57) vs. 32/156 (21%) (95%CI 15-28), respectively; p < 0.001, relative risk 2.4 (95%CI 1.7-3.4)). Mortality was greatest in patients with renal transplants (6/7 patients (86%) (95%CI 47-100)). Mortality rates increased in patients with worsening renal injury according to the Kidney Disease: Improving Global Outcomes classification: stage 0 mortality 33/157 patients (21%) (95%CI 15-28) vs. stages 1-3 mortality 91/186 patients (49%) (95%CI 42-56); p < 0.001, relative risk 2.3 (95%CI 1.7-3.3). Survivors were less likely to require renal replacement therapy compared with non-survivors (57/233 patients (24%) vs. 64/139 patients (46%), respectively; p < 0.001, relative risk 1.9 (95%CI 1.4-2.5)). One-fifth of survivors who required renal replacement therapy acutely in intensive care continued to require renal support following discharge. Our data demonstrate that renal impairment in patients admitted to intensive care with COVID-19 is common and is associated with a high mortality and requirement for on-going renal support after discharge from critical care. Our findings have important implications for future pandemic planning in this patient cohort.