Robust smoothing of left-censored time series data with a dynamic linear model to infer SARS-CoV-2 RNA concentrations in wastewater

Wastewater sampling for the detection and monitoring of SARS-CoV-2 has been developed and applied at an unprecedented pace, however uncertainty remains when interpreting the measured viral RNA signals and their spatiotemporal variation. The proliferation of measurements that are below a quantifiable threshold, usually during non-endemic periods, poses a further challenge to interpretation and time-series analysis of the data. Inspired by research in the use of a custom Kalman smoother model to estimate the true level of SARS-CoV-2 RNA concentrations in wastewater, we propose an alternative left-censored dynamic linear model. Cross-validation of both models alongside a simple moving average, using data from 286 sewage treatment works across England, allows for a comprehensive validation of the proposed approach. The presented dynamic linear model is more parsimonious, has a faster computational time and is represented by a more flexible modelling framework than the equivalent Kalman smoother. Furthermore we show how the use of wastewater data, transformed by such models, correlates more closely with regional case rate positivity as published by the Office for National Statistics (ONS) Coronavirus (COVID-19) Infection Survey. The modelled output is more robust and is therefore capable of better complementing traditional surveillance than untransformed data or a simple moving average, providing additional confidence and utility for public health decision making. © 2023, American Institute of Mathematical Sciences. All rights reserved.

MEDIA REPORTING OF LABOUR SHORTAGES IN UK HORTICULTURE DURING THE COVID-19 PANDEMIC: THE USE OF WARTIME METAPHORS IN THE SELECTIVE UNVEILING OF PRECARIOUS WORK/WORKERS

Over the 21st century almost all of the UK's harvest labour has been foreign-bom. The COVID-19 crisis (from March 2020) threatened UK food security by limiting this supply of low-wage foreign labour into the UK. In response a national campaign was launched to get a domestic 'Land Army' to 'Feed the Nation' and 'Pick for Britain' (the three main epithets used). The article profiles this campaign. We show that the COVID-19 crisis put low-wage harvest labour into the spotlight when this labour is usually hidden from public view. Potentially, such unveiling could have challenged the economics of the food production system. However, we argue that the rupture was stage-managed by invoking a wartime rhetoric and three key concomitant roles of the victim-hero farmer, the good migrant, and the reluctant British-based understudy. These emphasised the valiant nature of harvest work and framed migrant workers as (temporary) heroes helping to save the nation. In contrast, British-based workers' reluctance to embrace precarious work was framed as personal deficiency rather than a structural failure to create decent jobs. In all, the spotlight cast on the low-wage rural economy by the COVID-19 crisis was carefully targeted and stage-managed and did not challenge the persistence of precarious horticultural work. Copyright © 2022 CSIC.

Impact of COVID-19 on critical care nosocomial infection rates

Introduction: Critical care nosocomial infection (CCNI) increases risk of patient mortality and morbidity [1,2]. The impact of the Coronavirus 19 (2019-nCoV) pandemic on CCNI in terms of increased strain and infection control measures, is uncertain. Departmental strain has the potential to confound impact of infection control measures aimed to reduce CCNI incidence. This study will describe the impact of 2019-nCoV on non-COVID CCNI incidence and mortality. Methods: A retrospective cohort study of adult patients admitted to critical care in one Central London teaching hospital. CCNI incidence, (diagnosed ≥ 48 h post critical care admission), was compared between pre (Jan 2019-Feb 2020) and peak COVID (Mar 2020-Jun 2020). Results: Of 2,266 patients, 1788 were admitted pre and 478 peak COVID. Mean age was 57.2 years and 56.1 years pre and peak COVID respectively, with 35.5% and 37.4% of patients, female. There was a significant increase in rate of total CCNI incidence (1.6% to 3.6%) in the pre and peak period respectively. There was a significant increase in rate of incidence of gram negative bacterium and C. diff, but not in gram positive bacterium, MRSA, VRE and fungus. The increase in rate of peak (23.5%) compared to pre COVID (13.5%) CCNI non-COVID mortality, was not significant (Table 1). Conclusions: Increased infection control measures did not protect against non-COVID CCNI and mortality across all infection types. Increased strain is likely to confound additional infection control measures and resulted in excess patient non-COVID CCNI and mortality, secondary to the pandemic. Greater emphasis is needed to protect other patients from expected CCNIs. (Table Presented).

COVID-19 Is Associated with Endothelial Dysfunction and Enhanced Plasma Thrombin Generation Despite Pharmacological Thromboprophylaxis

Background Hospitalised patients with severe COVID-19 (requiring critical care level support) appear to be at increased risk of thrombosis despite standard pharmacological thromboprophylaxis. The magnitude of thrombotic risk in patients with COVID-19 of moderate severity (not requiring critical care) is less clear. The optimal approach to thromboprophylaxis (and the role of intensified thromboprophylaxis) remains to be determined. Evidence of endothelial dysfunction has been widely reported in COVID-19 (particularly in severe COVID) and this may contribute to hypercoagulability. Aim To assess differences in patterns of hypercoagulability and endothelial dysfunction between a group of patients with moderate COVID-19 and a group of age-matched hospitalized patients (SARS-CoV-2 PCR negative) receiving low molecular weight heparin (LMWH) thromboprophylaxis. Methods Blood was collected from individuals admitted to hospital with COVID-19 of moderate severity (not requiring critical care level support) and a group of age-matched patients admitted with infective/inflammatory illness (SARS-CoV-2 PCR negative). All subjects received standard-dose LMWH thromboprophylaxis, with blood drawn at 12 hours post-dose (and with measurement of anti-FXa activity levels). Circulating levels of endothelial & fibrinolytic markers including ICAM, PAI-1, VCAM, soluble thrombomodulin (sTM), and tissue plasminogen activator (tPA) were determined by ELISA. Thrombin generation (TG) in platelet-poor plasma was assessed by calibrated automated thrombography in the presence of tissue factor (Final concentration, 1pM & 5pM), thrombomodulin (TM) (Final concentration, 6.25nM), and an inhibitory anti-tissue factor pathway inhibitor antibody (anti-TFPI;Final concentration 100μg/mL). Results 14 COVID-19 positive subjects and 11 hospitalized controls were recruited. There were no differences in mean age (69.7±4.5 vs 61.6±4.7 years;p= 0.2) or mean Body mass index (25.7±1.1 vs 22.7±1.2 Kg/m2;p=0.1) between groups. No COVID-19 patient or control required critical care support. In the COVID group, radiological evidence of pneumonitis [diffuse (n=3) or peripheral infiltrates (n=7)] was present in the majority of cases. None of the COVID-19 cases were requiring supplemental oxygen at the time of recruitment. All controls were admitted with either respiratory or urinary infection [radiological evidence of pneumonia in 4/11;supplemental oxygen requirement in 2/11, (28-36% FiO2 via nasal cannula)]. Plasma levels of sTM, ICAM, PAI-1 & VCAM were similar in both groups. Levels of t-PA were significantly higher in the COVID group (8.31±4.35 vs 4.91±2.37 ng/mL;p= 0.005). Despite similar plasma anti-Xa activity in both groups (0.06 vs 0.04 IU/mL;p=0.2), mean endogenous thrombin potential (ETP) was significantly higher in the COVID group (1929±119.7 vs 1528±138.9 nM*min;p=0.02), although peak thrombin was similar (173.6±26 vs 161.5±31nM). ETP-TM ratio was similar between groups (0.3±0.1 vs 0.2±0.1;p=0.3). Despite increased ETP, the lag time to thrombin generation was significantly prolonged in the COVID group (8.3±0.6 vs 5.8±0.5 mins, p= 0.006). This pattern has previously been observed in vascular diseases associated with altered plasma tissue factor pathway inhibitor (TFPI) activity. In the presence of an anti-TFPI antibody, the difference in lagtime between groups was attenuated (4.7±0.2 vs 3.5±0.1 mins;p= 0.002) and the difference in overall thrombin generation (delta TG) between both groups became significantly increased (Fig.1). Conclusion Plasma thrombin generation is enhanced in patients with non-severe COVID-19 despite pharmacological thromboprophylaxis. Endothelial dysfunction is also observed in this group and appears to modulate parameters of plasma thrombin generation. The clinical implications of these observations are not known although clinical studies of intensified thromboprophylaxis in attenuating thrombotic risk and other complications are ongoing. Fig 1. Inhibition of TFPI activity enhances thrombin generation in COVID-19. n the presence of an inhibitory anti-TFPI antibody, peak plasma thrombin generation was enhanced in COVID-19 in contrast to that observed among SARS-CoV-2 PCR negative hospitalised patients (339.6+25.2 vs 247.4+10.1, p=0.01). [Formula presented] Disclosures: Maguire: Actelion: Research Funding;Bayer Pharma: Research Funding. Ni Ainle: Daiichi-Sankyo: Research Funding;Actelion: Research Funding;Leo Pharma: Research Funding;Bayer Pharma: Research Funding. Kevane: Leo Pharma: Research Funding.

Tissue factor-stimulated plasma thrombin generation is enhanced in hospitalised patients with COVID-19 despite pharmacological thromboprophylaxis

Background : COVID-19 confers an increased risk of thrombosis however the mechanisms underlying this coagulopathy and the optimal approach to thromboprophylaxis are unknown. Thrombotic risk is likely greatest among patients with severe COVID-19 requiring critical organ support however patients with moderate disease may be at risk and might also benefit from intensified thromboprophylaxis. Aims : To characterise plasma thrombin generation (TG) in patients with COVID-19 of moderate severity, treated with pharmacological thromboprophylaxis. Methods : Blood was collected from individuals admitted to hospital with COVID-19 of moderate severity (not requiring critical care support) and a group of age-matched patients admitted with infective/ inflammatory illness (negative for COVID-19). All subjects received standard dose low molecular weight heparin (LMWH) thromboprophylaxis with samples taken at time of predicted trough levels (confirmed by measuring anti-FXa activity). TG in platelet-poor plasma was determined by calibrated automated thrombography in the presence/absence of tissue factor (TF) (ppp-LOW reagent, 1 pM TF & 4 μM phospholipid;MP-reagent, 4 μM phospholipid;Thrombinoscope BV™). Results : Fourteen COVID-19 positive subjects and 11 hospitalised COVID-19 negative controls were recruited. Mean trough plasma anti-Xa activity was similar in both groups (0.06 vs 0.04 IU/mL;P = 0.2). In the presence of TF, mean endogenous thrombin potential was significantly higher in the COVID group in comparison to controls (1929 ± 119.7 vs 1528 ± 138.9 nM∗min;P = 0.02). Peak thrombin was also higher in COVID-19 (267.3 ± 22.2 vs 208.6 ± 17.8 nM;P = 0.06). Despite increased TG overall, lagtime to TG was significantly prolonged in COVID-19 (8.1 ± 0.5 vs 6.2 ± 0.5 mins;P = 0.02). No difference in any parameter of TG was observed between groups in the absence of TF. Conclusions : Despite pharmacological thromboprophylaxis plasma TG is enhanced in COVID-19. The underlying mechanisms remain to be elucidated. Specific clinical implications of increased TG despite pharmacological thromboprophylaxis have yet to be determined although clinical trials evaluating intensified anticoagulant regimens in a similar population are ongoing.

Impact of COVID-19 on platelet activity and the platelet releasate

Background : Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected over 100 million globally to date. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Several studies to date suggest a role for platelets in COVID-19-associated thrombosis. Aims : To assess the impact of COVID-19 on platelet activity and to characterise the proteome of the platelet releasate from COVID-19 patients, compared with healthy controls. Methods : Ethical approval was granted by the Institutional Review Board of the Mater Misericordiae University Hospital. Haematologic parameters of patients with severe COVID-19 disease (requiring intensive care;n = 34), with non-severe disease (not requiring intensive care;n = 20) and in general medical in-patients without COVID-19 ( n = 20) were assessed. Platelet function and activity were evaluated by secretion and platelet marker analysis ( n = 6 each cohort). The proteome of the platelet releasate was assessed using label-free mass spectrometry. Results : We demonstrated agonist-induced ADP release was 30-to-90 fold higher in COVID-19 patients compared with hospitalized controls (Fig. 1) and circulating levels of platelet-factor 4 (PF4), soluble P-selectin (sP-selectin) and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that COVID-19 patients possess hyperactive circulating platelets combined with a decreased activation threshold. Mass spectrometry analysis identified over 400 proteins from the releasate of COVID-19 patients and controls, including a multitude of inflammatory, vasoactive and vesicular proteins. The release of a subset of highly-relevant platelet proteins was modified based on the severity of COVID-19 infection. controls (Fig. 1) and circulating levels of platelet-factor 4 (PF4), soluble P-selectin (sP-selectin) and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that COVID-19 patients possess hyperactive circulating platelets combined with a decreased activation threshold. Mass spectrometry analysis identified over 400 proteins from the releasate of COVID-19 patients and controls, including a multitude of inflammatory, vasoactive and vesicular proteins. The release of a subset of highly-relevant platelet proteins was modified based on the severity of COVID-19 infection.

Perspectives of Interstitial Lung Disease Patients and Carers During COVID-19

Aim To gain an understanding of the impact of COVID-19 on the daily life, healthcare needs, mental wellbeing and outlook of patients with Interstitial Lung Disease (ILD) and their caregivers. Methods ILD patients and caregivers were invited to participate in a quantitative survey. Respondents could self-select to then participate in in-depth structured telephone interviews. Survey data was compared to Department of Health COVID-19 public opinion tracker findings for the comparable time period. Results There were 170 survey respones (111 patients and 59 caregivers) and 14 in-depth interview participants. 32% (n=36) of patients and 42% (n=25) of caregivers expressed extreme worry regarding COVID-19 on a 1-10 scale. 83% (n=92) of patients expressed concern about safe hospital access, 33% (n=37) had received a telephone consultation with their clinician, 43% (n=48) reported test delays, 47% (n=52) were exercising less, 23% (n=26) reported worse sleep and 15% (n=17) reported being financially worse off. Carers reported that sleep was worse for 58% (n=34), 42% (n=25) reported being worse off financially, and 40% (n=24) reported a worse diet. Worry (66%, n=39), stress (51%, n=30), anxiety (49%, n=29) were commonly reported by carers. Discussion ILD patients and caregivers reported higher levels of worry regarding COVID-19 compared to the general public. Alternative pathways for quality ILD patient care and interventions to reduce the burden of care on ILD caregivers are required.

Perspectives of interstitial lung disease healthcare professionals during covid-19

We examined the impact of COVID-19 on the daily lives, mental wellbeing, training and support needs of healthcare professionals (HCPs) working in interstitial lung disease (ILD), and implications for ILD patient care. We invited ILD HCPs to participate in a quantitative survey, following which respondents (n=49) self-selected to participate in structured telephone interviews (n=9). Worry (43%, n=21) and frustration (43%, n=21) were the most commonly reported emotions by survey respondents. Interviewees reported significant impacts on their daily lives and mental wellbeing. Few of the interviewees had received self-care (n=1, 11%) or mental healthcare training (n=2, 22%). Wellbeing supports were available, but interviewees reported deprioritising self-care. Interviewees reported concern about the impact of appointment cancellations on ILD patients. Virtual clinics were considered useful, but interviewees reported some limitations. COVID-19 profoundly impacted the daily lives and mental wellbeing of ILD HCPs and affected ILD care delivery, with implications for occupational health, HCP training and ILD patient services.

Patient-reported symptom severity and pulse oximetry in the COVID-19 remote monitoring programme in ireland

Rationale: A total of 60,287 (1,267/100,000) cases of Covid-19 (SARS-CoV-2) were recorded in Ireland by 30 October 2020. An important strategy to free up in-hospital capacity was development of a remote monitoring platform to support at-home care or early discharge of lower-risk patients with mild/moderate Covid-19 symptoms. Methods: The monitoring platform consisted of a patient-facing app + pulse oximeter (Bluetoothconnected Nonin 3230) enabling patients to record symptoms (e.g. breathlessness, diarrhea;severity rated on a 10-point scale), temperature & oxygen saturation (SpO2). Patients were prompted to record measurement 4 times/day. Patient-recorded data was viewed in real time by their healthcare centre via a dedicated web-based monitoring portal. Criteria for remote monitoring included: Covid-19 symptoms, positive for SARS-CoV-2, young age, absence of serious concomitant conditions, need for continued observation post-discharge. Treatment centres emailed app installation instructions and supplied a pulse oximeter to their patients. Treatment centres & patients received alerts if pulse oximetry values crossed pre-defined thresholds. Results: Between 13 March and 31 October 2020, 1,045 patients at 8 primary & 15 secondary care centres had used the remote monitoring platform [median duration: 13 days (interquartile range 10-23 days)]. 11 patients were admitted to hospital and 12 previously hospitalized patients were readmitted. 933 patients (89%) gave consent to use of their pseudonymised data for research. Symptoms and physiological markers of severity of infection varied considerably. 871 patients recorded breathlessness data with 53 rating severity as 6/10 and 23 as 8/10. 300 patients recorded diarrhea data with 24 rating severity as 6/10 and 6 as 8/10 (see Figure). SpO2 data were available for 907 patients. 733 patients reported SpO2 94-96%, 334 reported SpO2 92-93%and 265 patients reported SpO2 ≤91% at least once during the monitoring period. Conclusions: Remote monitoring of Covid-19 in appropriate patients can free up in-hospital capacity. The majority of these patients were willing to provide pseudonymised data to support research on Covid-19. .