Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Research data supporting "How butterflies keep their cool: physical and ecological traits influence thermoregulatory ability and population trends"

Abstract. 1. Understanding which factors influence the ability of individuals to respond to changing temperatures is fundamental to species conservation under climate change. 2. We investigated how a community of butterflies responded to fine-scale changes in air temperature, and whether species-specific responses were predicted by ecological or morphological traits. 3. Using data collected across a UK reserve network, we investigated the ability of 29 butterfly species to buffer thoracic temperature against changes in air temperature. First, we tested whether differences were attributable to taxonomic family, morphology or habitat association. We then investigated the relative importance of two buffering mechanisms: behavioural thermoregulation versus fine-scale microclimate selection. Finally, we tested whether species’ responses to changing temperatures predicted their population trends from a UK-wide dataset. 4. We found significant interspecific variation in buffering ability, which varied between families and increased with wing length. We also found interspecific differences in the relative importance of the two buffering mechanisms, with species relying on microclimate selection suffering larger population declines over the last 40 years than those that could alter their temperature behaviourally. 5. Our results highlight the importance of understanding how different species respond to fine-scale temperature variation, and the value of taking microclimate into account in conservation management to ensure favourable conditions are maintained for temperature-sensitive species. $$\$$ Methods. Data were collected in the UK, on four calcareous grassland reserves in Bedfordshire owned and managed by The Wildlife Trust for Bedfordshire, Cambridgeshire & Northamptonshire (Totternhoe Quarry [-0.56836, 51.89199], Totternhoe Knolls [-0.58039, 51.88989], Pegsdon Hills [-0.37020, 51.95354] and Blows Downs [-0.49580, 51.88321]); at two sites in Cumbria (Irton Fell [-3.34000, 54.40672] and Haweswater [-2.84598, 54.50756]); at one site in Scotland owned and managed by the National Trust for Scotland (Ben Lawers [-4.27326, 56.53287]); and at a calcareous grassland reserve in Wiltshire owned and managed by the Royal Society for the Protection of Birds (Winterbourne Downs [-1.68500, 51.14963]). Between April and September 2009 in Bedfordshire, and between May and September 2018 at all sites, adult butterflies were surveyed at each site. After recording the behaviour of each butterfly when first encountered, we caught as many individuals as possible using a butterfly net. We did not chase individuals, to ensure that the temperature recorded reflected the activity of the butterfly prior to capture. Immediately after capture, we used a fine (0.25 mm) mineral-insulated type K thermocouple and hand-held indicator (Tecpel Thermometer 305B) to record external thoracic temperatures (Tbody). Only three individual devices were used for data collection, and were calibrated to the same readings prior to use. The thermocouple was pressed gently onto an exposed area of each butterfly’s thorax, while the butterfly was held securely in the net, away from the hands of the recorder to avoid artificially elevating the recording or causing any damage to the butterfly. Butterflies were then released. A second temperature recording was then taken at the same location in free air, in the shade, at waist height (Tair). In 2018, for butterflies perching on vegetation at the time of capture, a third temperature reading was taken by holding the thermocouple a centimetre above the perch location (Tperch). Information on habitat specialisation was added from Asher et al. (2001), mean wingspan was taken from Eeles (2020), and colour category was determined by assigning each species a score from 1 (white) to 6 (black) on the basis of how pale/dark wing colours appeared by eye (see Bladon et al. 2020 for details). $$\$$ References. Asher J, Warren MS, Fox R, Harding P, Jeffcoate G & Jeffcoate S (2001) The Millennium Atlas of Butterflies in Britain and Ireland. Oxford: Oxford University Press. Bladon AJ, Lewis M, Bladon EK, Buckton S, Corbett S, Ewing SR, Hayes MP, Hitchcock GE, Knock RI, Lucas CBH, McVeigh A, Menéndez R, Walker J, Fayle T & Turner EC (2020) How butterflies keep their cool: physical and ecological traits influence thermoregulatory ability and population trends. Journal of Animal Ecology. Eeles P (2020) UK Butterflies. Retrieved from UK Butterflies website: https://ukbutterflies.co.uk/index.phpIsaac Newton Trust/Wellcome Trust ISSF/University of Cambridge Joint Research Grants Scheme, The Wildlife Trust for Bedfordshire, Cambridgeshire and Northamptonshire, J Arthur Ramsay Trust Fund , European Research Council advanced grant , Award: 66960

How butterflies keep their cool: Physical and ecological traits influence thermoregulatory ability and population trends.

Understanding which factors influence the ability of individuals to respond to changing temperatures is fundamental to species conservation under climate change. We investigated how a community of butterflies responded to fine-scale changes in air temperature, and whether species-specific responses were predicted by ecological or morphological traits. Using data collected across a UK reserve network, we investigated the ability of 29 butterfly species to buffer thoracic temperature against changes in air temperature. First, we tested whether differences were attributable to taxonomic family, morphology or habitat association. We then investigated the relative importance of two buffering mechanisms: behavioural thermoregulation versus fine-scale microclimate selection. Finally, we tested whether species' responses to changing temperatures predicted their population trends from a UK-wide dataset. We found significant interspecific variation in buffering ability, which varied between families and increased with wing length. We also found interspecific differences in the relative importance of the two buffering mechanisms, with species relying on microclimate selection suffering larger population declines over the last 40 years than those that could alter their temperature behaviourally. Our results highlight the importance of understanding how different species respond to fine-scale temperature variation, and the value of taking microclimate into account in conservation management to ensure favourable conditions are maintained for temperature-sensitive species.Isaac Newton Trust/Wellcome Trust ISSF/University of Cambridge Joint Research Grants Scheme RG89529 The Wildlife Trust for Bedfordshire, Cambridgeshire and Northamptonshire The J Arthur Ramsay Trust Fund European Research Council advanced grant 66960