ABSTRACT
Introduction: Over 200,000 patients survive an intensive care admission each year in the United Kingdom (UK). For patients, survival is frequently beset by a range of chronic disabilities. Approximately 50% must navigate an often complex convalescence, while suffering serious and persistent symptoms of post-traumatic stress disorder (PTSD), anxiety and/or depression.1 Eye-movement desensitisation and reprocessing (EMDR) is a trauma-focussed psychological therapy, recommended for treating PTSD by the International Society for Traumatic Stress Studies2 and NICE.3 However, EMDR has never been systematically investigated for patient benefit following intensive care admission. Objective(s): CovEMERALD4 evaluated the feasibility of delivering a randomised controlled trial (RCT), testing the effect of EMDR on the psychological health of intensive care survivors, following COVID-19 related critical illness. We also provide preliminary evidence of the effect on clinically relevant outcomes. Findings will inform the design of a subsequent fully-powered RCT. Method(s): This feasibility RCT was conducted at a single-centre, teaching hospital in the UK (University Hospital Southampton). Patients were eligible if they were admitted to intensive care for over 24-hours with confirmed COVID-19, were above 18 years of age, were recruited within 3-months of hospital discharge, and had no cognitive impairment or pre-existing psychotic diagnosis. Participants were randomised (1:1) to receive either up to 8 sessions of remotely-delivered EMDR (Recent traumatic events protocol) or standard care alone as the control group (CG). Psychometric evaluation was undertaken at Baseline and 6-months after hospital discharge. Result(s): Seventy-five consecutive patients were screened at hospital discharge, from October 2020 to April 2021. 51 eligible patients approached. 26 (51%) provided consent. Reasons for declining participation were;no psychological distress (n=16), no internet access (n=7) and being physically unready (n=2). Demographic variables were balanced between groups. Of the 13 patients randomised to EMDR, one withdrew prior to intervention: the remaining attended all sessions recommended by the psychological therapists (mean of 3-4 sessions per patient), giving an overall adherence of 93%. One patient from each group declined the 6-month follow-up evaluation, so trial completion was possible in 23 of 26 (88%) participants. No reasons for trial withdrawal were given. There were no attributable adverse events. Mean change in PTSD score (PTSD Checklist-Civilian) from Baseline to 6-months, was -8 (SD=10.49) in the EMDR group vs. +0.75 (SD=15.17) in CG (p=0.126). Mean change in anxiety (Hospital Anxiety and Depression Scale-Anxiety) was -0.45 (SD=2.3) following EMDR vs. -0.83 (SD=4.0) in the CG (p=0.787), and median change in depression (HADS-D) was -2(IQR:-3.0,1.0) following EMDR vs. +1(IQR-1.5,2.0) in the CG (p=0.263). Figure 1. Box-plot of change in PTSD symptoms (PCL-C) from baseline to 6-months post-hospital discharge for control group and EMDR intervention group. Conclusion(s): EMDR can improve psychological recovery following an intensive care admission for COVID-19, and appeared feasible and safe. Although not powered to determine clinical effectiveness, this single-centre feasibility study returned a positive signal, in reducing PTSD and depressive symptoms. A full results manuscript will be submitted prior to congress. CovEMERALD has supported a successful NIHR doctoral fellowship application, during which protocol refinements will be tested, within existing, and recommended rehabilitation pathways. Trial activity and progression will be consistent with the Medical Research Council framework for developing and evaluating complex healthcare interventions.5.
ABSTRACT
Background: SARS-CoV-2 virus infects host cells through ACE2 and TMPRSS2 receptors. Protein levels of ACE2 and TMPRSS2 have not been assessed in allergic airways. Method(s): We collected biopsies of endobronchial tissue from steroid-naive mild allergic asthmatics (AA n=23) and non-asthmatic controls (NA n=11), and inferior nasal turbinate tissue from AA with allergic rhinitis (AR n=8) and nonAA/AR controls (NR n=5). Tissue was immune-stained for SARS-CoV-2 receptor ACE2 and surface protein TMPRSS2. The number of immuno-positive cells in epithelium and laminae propria was expressed per mm2 of tissue. Result(s): The number of cells expressing ACE2 was higher in AA endobronchial tissue compared to NA control and AR nasal tissue. TMPRSS2 was higher in AR nasal tissue compared to NR control, and higher in control NA endobronchial tissue versus control NR nasal tissue. Co-expression of ACE2+TMPRSS2 was higher in AA endobronchial tissue versus NA control and trending higher in AR nasal tissue versus NR control (p=0.08). Conclusion(s): Overall, ACE2 is more highly expressed in endobronchial tissue versus nasal tissue, suggesting SARS-CoV-2 may more readily infect lower versus upper airways. It is unknown whether the higher expression of ACE2 and ACE2+TMPRSS2 observed in the airways of mild allergic asthmatic donors versus control donors translates to higher susceptibility to infection.
ABSTRACT
Rationale: The incidence of SARS-CoV-2 infection and the impact of corticosteroid treatment in patients with symptomatic airway disease has been a concern. We examined airway expression of SARS-CoV-2 receptors following allergen challenge and steroid intervention in asthmatic patients. Method(s): From steroid-naive mild allergic asthmatic (AA n=23) we collected endobronchial biopsies pre and 24hr post allergen inhalation challenge (AIC). In a subset of AA with allergic rhinitis (AR n=8) we collected inferior nasal turbinate biopsies pre and 24hr post-nasal allergen challenges (NAC) after placebo treatment or after 21 days of 22 mg BID triamcinolone nasal spray. FEV1 and PNIF expressed as % fall from baseline quantified the early (ER, 0-2h) and late (LR, 3-7h) airway responses post challenge. Epithelium and laminae propria were immunostained for ACE2 and TMPRSS2 and expressed as # cells/mm2. Result(s): AIC reduced FEV1 (31% ER, 19% LR) and the number of bronchial cells immunopositive for ACE2, TMPRSS2 and double positive for ACE2/TMPRSS2 (P=0.0002, P=0.04, P=0.02, respectively). The PNIF reduction by NAC (69% ER, 49% LR) was attenuated by triamcinolone (31% ER, 18% LR), but without changes in ACE2 or TMPRSS2 in nasal tissue after NAC or steroid treatment (all P>0.05). In the nasal tissue, significantly fewer cells expressed ACE2 compared to bronchi (P=0.007). Conclusion(s): ACE2 and TMPRSS2 expression in bronchial tissue is reduced in the T2 microenvironment post allergen challenge, however it is unknown if this protects lower airways from SARS-CoV-2 infection. Low expression of ACE2 and TMPRSS2 in nasal tissue made it difficult to determine the effects of NAC or steroid.
ABSTRACT
BACKGROUND: Acute kidney injury (AKI) is a common manifestation among patients critically ill with SARS-CoV-2 infection (Coronavirus 2019) and is associated with significant morbidity and mortality. The pathophysiology of renal failure in this context is not fully understood, but likely to be multifactorial. The intensive care unit outcomes of patients following COVID-19 acute critical illness with associated AKI have not been fully explored. We conducted a cohort study to investigate the risk factors for acute kidney injury in patients admitted to and intensive care unit with COVID-19, its incidence and associated outcomes. METHODS: We reviewed the medical records of all patients admitted to our adult intensive care unit suffering from SARS-CoV-2 infection from 14th March 2020 until 12th May 2020. Acute kidney injury was defined using the Kidney Disease Improving Global Outcome (KDIGO) criteria. The outcome analysis was assessed up to date as 3rd of September 2020. RESULTS: A total of 81 patients admitted during this period. All patients had acute hypoxic respiratory failure and needed either noninvasive or invasive mechanical ventilatory support. Thirty-six patients (44%) had evidence of AKI (Stage I-33%, Stage II-22%, Renal Replacement Therapy (RRT)-44%). All patients with AKI stage III had RRT. Age, diabetes mellitus, immunosuppression, lymphopenia, high D-Dimer levels, increased APACHE II and SOFA scores, invasive mechanical ventilation and use of inotropic or vasopressor support were significantly associated with AKI. The peak AKI was at day 4 and mean duration of RRT was 12.5 days. The mortality was 25% for the AKI group compared to 6.7% in those without AKI. Among those received RRT and survived their illness, the renal function recovery is complete and back to baseline in all patients. CONCLUSION: Acute kidney injury and renal replacement therapy is common in critically ill patients presenting with COVID-19. It is associated with increased severity of illness on admission to ICU, increased mortality and prolonged ICU and hospital length of stay. Recovery of renal function was complete in all survived patients.