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Kotanidis, Christos P.; Xie, Cheng, Alexander, Donna, Rodrigues, Jonathan C. L.; Burnham, Katie, Mentzer, Alexander, O’Connor, Daniel, Knight, Julian, Siddique, Muhammad, Lockstone, Helen, Thomas, Sheena, Kotronias, Rafail, Oikonomou, Evangelos K.; Badi, Ileana, Lyasheva, Maria, Shirodaria, Cheerag, Lumley, Sheila F.; Constantinides, Bede, Sanderson, Nicholas, Rodger, Gillian, Chau, Kevin K.; Lodge, Archie, Tsakok, Maria, Gleeson, Fergus, Adlam, David, Rao, Praveen, Indrajeet, Das, Deshpande, Aparna, Bajaj, Amrita, Hudson, Benjamin J.; Srivastava, Vivek, Farid, Shakil, Krasopoulos, George, Sayeed, Rana, Ho, Ling-Pei, Neubauer, Stefan, Newby, David E.; Channon, Keith M.; Deanfield, John, Antoniades, Charalambos, Ahern, David J.; Ai, Zhichao, Ainsworth, Mark, Allan, Chris, Allcock, Alice, Angus, Brian, Ansari, M. Azim, Arancibia-Cárcamo, Carolina, Aschenbrenner, Dominik, Attar, Moustafa, Baillie, J. Kenneth, Barnes, Eleanor, Bashford-Rogers, Rachael, Bashyal, Archana, Beer, Sally, Berridge, Georgina, Beveridge, Amy, Bibi, Sagida, Bicanic, Tihana, Blackwell, Luke, Bowness, Paul, Brent, Andrew, Brown, Andrew, Broxholme, John, Buck, David, Burnham, Katie, Byrne, Helen, Camara, Susana, Ferreira, Ivan Candido, Charles, Philip, Chen, Wentao, Chen, Yi-Ling, Chong, Amanda, Clutterbuck, Elizabeth, Coles, Mark, Conlon, Christopher, Cornall, Richard, Cribbs, Adam, Curion, Fabiola, Davenport, Emma, Davidson, Neil, Davis, Simon, Dendrou, Calliope, Dequaire, Julie, Dib, Lea, Docker, James, Dold, Christina, Dong, Tao, Downes, Damien, Drakesmith, Hal, Dunachie, Susanna, Duncan, David, Eijsbouts, Chris, Esnouf, Robert, Espinosa, Alexis, Etherington, Rachel, Fairfax, Benjamin, Fairhead, Rory, Fang, Hai, Fassih, Shayan, Felle, Sally, Fernandez Mendoza, Maria, Ferreira, Ricardo, Fischer, Roman, Foord, Thomas, Forrow, Aden, Frater, John, Fries, Anastasia, Gallardo Sanchez, Veronica, Garner, Lucy, Geeves, Clementine, Georgiou, Dominique, Godfrey, Leila, Golubchik, Tanya, Gomez Vazquez, Maria, Green, Angie, Harper, Hong, Harrington, Heather, Heilig, Raphael, Hester, Svenja, Hill, Jennifer, Hinds, Charles, Hird, Clare, Ho, Ling-Pei, Hoekzema, Renee, Hollis, Benjamin, Hughes, Jim, Hutton, Paula, Jackson-Wood, Matthew, Jainarayanan, Ashwin, James-Bott, Anna, Jansen, Kathrin, Jeffery, Katie, Jones, Elizabeth, Jostins, Luke, Kerr, Georgina, Kim, David, Klenerman, Paul, Knight, Julian, Kumar, Vinod, Kumar Sharma, Piyush, Kurupati, Prathiba, Kwok, Andrew, Lee, Angela, Linder, Aline, Lockett, Teresa, Lonie, Lorne, Lopopolo, Maria, Lukoseviciute, Martyna, Luo, Jian, Marinou, Spyridoula, Marsden, Brian, Martinez, Jose, Matthews, Philippa, Mazurczyk, Michalina, McGowan, Simon, McKechnie, Stuart, Mead, Adam, Mentzer, Alexander, Mi, Yuxin, Monaco, Claudia, Montadon, Ruddy, Napolitani, Giorgio, Nassiri, Isar, Novak, Alex, O'Brien, Darragh, O'Connor, Daniel, O'Donnell, Denise, Ogg, Graham, Overend, Lauren, Park, Inhye, Pavord, Ian, Peng, Yanchun, Penkava, Frank, Pereira Pinho, Mariana, Perez, Elena, Pollard, Andrew, Powrie, Fiona, Psaila, Bethan, Quan, T. Phuong, Repapi, Emmanouela, Revale, Santiago, Silva-Reyes, Laura, Richard, Jean-Baptiste, Rich-Griffin, Charlotte, Ritter, Thomas, Rollier, Christine, Rowland, Matthew, Ruehle, Fabian, Salio, Mariolina, Sansom, Stephen Nicholas, Sanches Peres, Raphael, Santos Delgado, Alberto, Sauka-Spengler, Tatjana, Schwessinger, Ron, Scozzafava, Giuseppe, Screaton, Gavin, Seigal, Anna, Semple, Malcolm, Sergeant, Martin, Simoglou Karali, Christina, Sims, David, Skelly, Donal, Slawinski, Hubert, Sobrinodiaz, Alberto, Sousos, Nikolaos, Stafford, Lizzie, Stockdale, Lisa, Strickland, Marie, Sumray, Otto, Sun, Bo, Taylor, Chelsea, Taylor, Stephen, Taylor, Adan, Thongjuea, Supat, Thraves, Hannah, Todd, John, Tomic, Adriana, Tong, Orion, Trebes, Amy, Trzupek, Dominik, Tucci, Felicia Anna, Turtle, Lance, Udalova, Irina, Uhlig, Holm, van Grinsven, Erinke, Vendrell, Iolanda, Verheul, Marije, Voda, Alexandru, Wang, Guanlin, Wang, Lihui, Wang, Dapeng, Watkinson, Peter, Watson, Robert, Weinberger, Michael, Whalley, Justin, Witty, Lorna, Wray, Katherine, Xue, Luzheng, Yuen Yeung, Hing, Yin, Zixi, Young, Rebecca, Youngs, Jonathan, Zhang, Ping, Zurke, Yasemin-Xiomara, Banning, Adrian, Antonopoulos, Alexios, Bajaj, Amrita, Kelion, Andrew, Deshpande, Aparna, Kardos, Attila, Hudson, Benjamin, Koo, Bon-Kwon, Shirodaria, Cheerag, Xie, Cheng, Kotanidis, Christos, Mahon, Ciara, Berry, Colin, Adlam, David, Newby, David, Connolly, Derek, Scaletta, Diane, Alexander, Donna, Nicol, Ed, McAlindon, Elisa, Oikonomou, Evangelos, Pugliese, Francesca, Pontone, Gianluca, Benedetti, Giulia, He, Guo-Wei, West, Henry, Kondo, Hidekazu, Benedek, Imre, Das, Intrajeet, Deanfield, John, Graby, John, Greenwood, John, Rodrigues, Jonathan, Ge, Junbo, Channon, Keith, Fabritz, Larissa, Fan, Li-Juan, Kingham, Lucy, Guglielmo, Marco, Lyasheva, Maria, Schmitt, Matthias, Beer, Meinrad, Anderson, Michelle, Desai, Milind, Marwan, Mohamed, Takahashi, Naohiko, Mehta, Nehal, Dai, Neng, Screaton, Nicholas, Sabharwal, Nikant, Maurovich-Horvat, Pál, Rao, Praveen, Kotronias, Rafail, Kharbanda, Rajesh, Preston, Rebecca, Wood, Richard, Blankstein, Ron, Rajani, Ronak, Mirsadraee, Saeed, Munir, Shahzad, Thomas, Sheena, Neubauer, Stefan, Klömpken, Steffen, Petersen, Steffen, Achenbach, Stephan, Anthony, Susan, Mak, Sze, Mittal, Tarun, Benedek, Theodora, Sharma, Vinoda, Lin, Wen-Hua.
The Lancet Digital Health ; 2022.
Article in English | ScienceDirect | ID: covidwho-2004681

ABSTRACT

Summary Background Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19. Methods For this prospective outcomes validation study, we developed a radiotranscriptomic platform that uses RNA sequencing data from human internal mammary artery biopsies to develop novel radiomic signatures of vascular inflammation from CT angiography images. We then used this platform to train a radiotranscriptomic signature (C19-RS), derived from the perivascular space around the aorta and the internal mammary artery, to best describe cytokine-driven vascular inflammation. The prognostic value of C19-RS was validated externally in 435 patients (331 from study arm 3 and 104 from study arm 4) admitted to hospital with or without COVID-19, undergoing clinically indicated pulmonary CT angiography, in three UK National Health Service (NHS) trusts (Oxford, Leicester, and Bath). We evaluated the diagnostic and prognostic value of C19-RS for death in hospital due to COVID-19, did sensitivity analyses based on dexamethasone treatment, and investigated the correlation of C19-RS with systemic transcriptomic changes. Findings Patients with COVID-19 had higher C19-RS than those without (adjusted odds ratio [OR] 2·97 [95% CI 1·43–6·27], p=0·0038), and those infected with the B.1.1.7 (alpha) SARS-CoV-2 variant had higher C19-RS values than those infected with the wild-type SARS-CoV-2 variant (adjusted OR 1·89 [95% CI 1·17–3·20] per SD, p=0·012). C19-RS had prognostic value for in-hospital mortality in COVID-19 in two testing cohorts (high [≥6·99] vs low [<6·99] C19-RS;hazard ratio [HR] 3·31 [95% CI 1·49–7·33], p=0·0033;and 2·58 [1·10–6·05], p=0·028), adjusted for clinical factors, biochemical biomarkers of inflammation and myocardial injury, and technical parameters. The adjusted HR for in-hospital mortality was 8·24 (95% CI 2·16–31·36, p=0·0019) in patients who received no dexamethasone treatment, but 2·27 (0·69–7·55, p=0·18) in those who received dexamethasone after the scan, suggesting that vascular inflammation might have been a therapeutic target of dexamethasone in COVID-19. Finally, C19-RS was strongly associated (r=0·61, p=0·00031) with a whole blood transcriptional module representing dysregulation of coagulation and platelet aggregation pathways. Interpretation Radiotranscriptomic analysis of CT angiography scans introduces a potentially powerful new platform for the development of non-invasive imaging biomarkers. Application of this platform in routine CT pulmonary angiography scans done in patients with COVID-19 produced the radiotranscriptomic signature C19-RS, a marker of cytokine-driven inflammation driving systemic activation of coagulation and responsible for adverse clinical outcomes, which predicts in-hospital mortality and might allow targeted therapy. Funding Engineering and Physical Sciences Research Council, British Heart Foundation, Oxford BHF Centre of Research Excellence, Innovate UK, NIHR Oxford Biomedical Research Centre, Wellcome Trust, Onassis Foundation.

2.
Radiology ; : 220252, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-2001926
3.
Eur Heart J ; 43(11): 1157-1172, 2022 03 14.
Article in English | MEDLINE | ID: covidwho-1853028

ABSTRACT

Emerging as a new epidemic, long COVID or post-acute sequelae of coronavirus disease 2019 (COVID-19), a condition characterized by the persistence of COVID-19 symptoms beyond 3 months, is anticipated to substantially alter the lives of millions of people globally. Cardiopulmonary symptoms including chest pain, shortness of breath, fatigue, and autonomic manifestations such as postural orthostatic tachycardia are common and associated with significant disability, heightened anxiety, and public awareness. A range of cardiovascular (CV) abnormalities has been reported among patients beyond the acute phase and include myocardial inflammation, myocardial infarction, right ventricular dysfunction, and arrhythmias. Pathophysiological mechanisms for delayed complications are still poorly understood, with a dissociation seen between ongoing symptoms and objective measures of cardiopulmonary health. COVID-19 is anticipated to alter the long-term trajectory of many chronic cardiac diseases which are abundant in those at risk of severe disease. In this review, we discuss the definition of long COVID and its epidemiology, with an emphasis on cardiopulmonary symptoms. We further review the pathophysiological mechanisms underlying acute and chronic CV injury, the range of post-acute CV sequelae, and impact of COVID-19 on multiorgan health. We propose a possible model for referral of post-COVID-19 patients to cardiac services and discuss future directions including research priorities and clinical trials that are currently underway to evaluate the efficacy of treatment strategies for long COVID and associated CV sequelae.


Subject(s)
COVID-19 , Heart Diseases , Myocarditis , COVID-19/complications , Humans , Myocarditis/etiology , SARS-CoV-2
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296652

ABSTRACT

Background: There are currently no effective pharmacological or non-pharmacological interventions for Long-COVID. To identify potential therapeutic targets, we focussed on previously described four recovery clusters five months after hospital discharge, their underlying inflammatory profiles and relationship with clinical outcomes at one year. Methods PHOSP-COVID is a prospective longitudinal cohort study, recruiting adults hospitalised with COVID-19 across the UK. Recovery was assessed using patient reported outcomes measures (PROMs), physical performance, and organ function at five-months and one-year after hospital discharge. Hierarchical logistic regression modelling was performed for patient-perceived recovery at one-year. Cluster analysis was performed using clustering large applications (CLARA) k-medoids approach using clinical outcomes at five-months. Inflammatory protein profiling from plasma at the five-month visit was performed. Findings 2320 participants have been assessed at five months after discharge and 807 participants have completed both five-month and one-year visits. Of these, 35.6% were female, mean age 58.7 (SD 12.5) years, and 27.8% received invasive mechanical ventilation (IMV). The proportion of patients reporting full recovery was unchanged between five months 501/165 (25.6%) and one year 232/804 (28.9%). Factors associated with being less likely to report full recovery at one year were: female sex OR 0.68 (95% CI 0.46-0.99), obesity OR 0.50 (95%CI 0.34-0.74) and IMV OR 0.42 (95%CI 0.23-0.76). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate/cognitive, mild relating to the severity of physical, mental health and cognitive impairments at five months in a larger sample. There was elevation of inflammatory mediators of tissue damage and repair in both the very severe and the moderate/cognitive clusters compared to the mild cluster including interleukin-6 which was elevated in both comparisons. Overall, there was a substantial deficit in median (IQR) EQ5D-5L utility index from pre-COVID (retrospective assessment) 0.88 (0.74-1.00), five months 0.74 (0.60-0.88) to one year: 0.74 (0.59-0.88), with minimal improvements across all outcome measures at one-year after discharge in the whole cohort and within each of the four clusters. Interpretation The sequelae of a hospital admission with COVID-19 remain substantial one year after discharge across a range of health domains with the minority in our cohort feeling fully recovered. Patient perceived health-related quality of life remains reduced at one year compared to pre-hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.

5.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294849

ABSTRACT

Background The impact of COVID-19 on physical and mental health, and employment following hospitalisation is poorly understood. Methods PHOSP-COVID is a multi-centre, UK, observational study of adults discharged from hospital with a clinical diagnosis of COVID-19 involving an assessment between two- and seven-months later including detailed symptom, physiological and biochemical testing. Multivariable logistic regression was performed for patient-perceived recovery with age, sex, ethnicity, body mass index (BMI), co-morbidities, and severity of acute illness as co-variates. Cluster analysis was performed using outcomes for breathlessness, fatigue, mental health, cognition and physical function. Findings We report findings of 1077 patients discharged in 2020, from the assessment undertaken a median 5 [IQR4 to 6] months later: 36% female, mean age 58 [SD 13] years, 69% white ethnicity, 27% mechanical ventilation, and 50% had at least two co-morbidities. At follow-up only 29% felt fully recovered, 20% had a new disability, and 19% experienced a health-related change in occupation. Factors associated with failure to recover were female, middle-age, white ethnicity, two or more co-morbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial and weakly related to acute severity. Four clusters were identified with different severities of mental and physical health impairment: 1) Very severe (17%), 2) Severe (21%), 3) Moderate with cognitive impairment (17%), 4) Mild (46%), with 3%, 7%, 36% and 43% feeling fully recovered, respectively. Persistent systemic inflammation determined by C-reactive protein was related to cluster severity, but not acute illness severity. Interpretation We identified factors related to recovery from a hospital admission with COVID-19 and four different phenotypes relating to the severity of physical, mental, and cognitive health five months later. The implications for clinical care include the potential to stratify care and the need for a pro-active approach with wide-access to COVID-19 holistic clinical services. Funding: UKRI and NIHR

6.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294398

ABSTRACT

Background The longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19. Methods Fifty-eight patients and thirty matched controls underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months. Findings At 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T 1 (marker of inflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pVO 2 ) on CPET. By 6 months, 53% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (−4·3 mls/m 2 , P =0·005) decreased and RV ejection fraction (+3·2%, P =0·0003) increased. Native T 1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak VO 2 , although better, were abnormal in patients versus controls. 31% had reduced pVO 2 secondary to fatigue and submaximal tests. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures. Interpretation In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health. Funding NIHR Oxford and Oxford Health BRC, Oxford BHF CRE, UKRI and Wellcome Trust.

7.
Front Neurol ; 12: 753284, 2021.
Article in English | MEDLINE | ID: covidwho-1518509

ABSTRACT

SARS-CoV-2 infection has been shown to damage multiple organs, including the brain. Multiorgan MRI can provide further insight on the repercussions of COVID-19 on organ health but requires a balance between richness and quality of data acquisition and total scan duration. We adapted the UK Biobank brain MRI protocol to produce high-quality images while being suitable as part of a post-COVID-19 multiorgan MRI exam. The analysis pipeline, also adapted from UK Biobank, includes new imaging-derived phenotypes (IDPs) designed to assess the possible effects of COVID-19. A first application of the protocol and pipeline was performed in 51 COVID-19 patients post-hospital discharge and 25 controls participating in the Oxford C-MORE study. The protocol acquires high resolution T1, T2-FLAIR, diffusion weighted images, susceptibility weighted images, and arterial spin labelling data in 17 min. The automated imaging pipeline derives 1,575 IDPs, assessing brain anatomy (including olfactory bulb volume and intensity) and tissue perfusion, hyperintensities, diffusivity, and susceptibility. In the C-MORE data, IDPs related to atrophy, small vessel disease and olfactory bulbs were consistent with clinical radiology reports. Our exploratory analysis tentatively revealed some group differences between recovered COVID-19 patients and controls, across severity groups, but not across anosmia groups. Follow-up imaging in the C-MORE study is currently ongoing, and this protocol is now being used in other large-scale studies. The protocol, pipeline code and data are openly available and will further contribute to the understanding of the medium to long-term effects of COVID-19.

8.
Lancet Respir Med ; 9(11): 1275-1287, 2021 11.
Article in English | MEDLINE | ID: covidwho-1514340

ABSTRACT

BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. INTERPRETATION: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. FUNDING: UK Research and Innovation and National Institute for Health Research.


Subject(s)
COVID-19 , Health Status , Mental Health , Acute Disease , Adult , Aged , COVID-19/complications , Cognition , Comorbidity , Female , Follow-Up Studies , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , United Kingdom/epidemiology
9.
EClinicalMedicine ; 41: 101159, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1471951

ABSTRACT

BACKGROUND: The longitudinal trajectories of cardiopulmonary abnormalities and symptoms following infection with coronavirus disease (COVID-19) are unclear. We sought to describe their natural history in previously hospitalised patients, compare this with controls, and assess the relationship between symptoms and cardiopulmonary impairment at 6 months post-COVID-19. METHODS: Fifty-eight patients and thirty matched controls (single visit), recruited between 14th March - 25th May 2020, underwent symptom-questionnaires, cardiac and lung magnetic resonance imaging (CMR), cardiopulmonary exercise test (CPET), and spirometry at 3 months following COVID-19. Of them, forty-six patients returned for follow-up assessments at 6 months. FINDINGS: At 2-3 months, 83% of patients had at least one cardiopulmonary symptom versus 33% of controls. Patients and controls had comparable biventricular volumes and function. Native cardiac T1 (marker of fibroinflammation) and late gadolinium enhancement (LGE, marker of focal fibrosis) were increased in patients at 2-3 months. Sixty percent of patients had lung parenchymal abnormalities on CMR and 55% had reduced peak oxygen consumption (pV̇O2) on CPET. By 6 months, 52% of patients remained symptomatic. On CMR, indexed right ventricular (RV) end-diastolic volume (-4·3 mls/m2, P=0·005) decreased and RV ejection fraction (+3·2%, P=0·0003) increased. Native T1 and LGE improved and was comparable to controls. Lung parenchymal abnormalities and peak V̇O2, although better, were abnormal in patients versus controls. 31% had reduced pV̇O2 secondary to symptomatic limitation and muscular impairment. Cardiopulmonary symptoms in patients did not associate with CMR, lung function, or CPET measures. INTERPRETATION: In patients, cardiopulmonary abnormalities improve over time, though some measures remain abnormal relative to controls. Persistent symptoms at 6 months post-COVID-19 did not associate with objective measures of cardiopulmonary health. FUNDING: The authors' work was supported by the NIHR Oxford Biomedical Research Centre, Oxford British Heart Foundation (BHF) Centre of Research Excellence (RE/18/3/34214), United Kingdom Research Innovation and Wellcome Trust. This project is part of a tier 3 study (C-MORE) within the collaborative research programme entitled PHOSP-COVID Post-hospitalization COVID-19 study: a national consortium to understand and improve long-term health outcomes, funded by the Medical Research Council and Department of Health and Social Care/National Institute for Health Research Grant (MR/V027859/1) ISRCTN number 10980107.

10.
EClinicalMedicine ; 31: 100683, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1291524

ABSTRACT

BACKGROUND: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. METHODS: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. FINDINGS: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p<0.0001 to 0.044). INTERPRETATION: A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness. FUNDING: NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.

11.
J Cardiovasc Magn Reson ; 23(1): 77, 2021 06 10.
Article in English | MEDLINE | ID: covidwho-1266491

ABSTRACT

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, myocardial injury is increasingly reported and associated with adverse outcomes. However, the pathophysiology, extent of myocardial injury and clinical significance remains unclear. METHODS: COVID-HEART is a UK, multicentre, prospective, observational, longitudinal cohort study of patients with confirmed COVID-19 and elevated troponin (sex-specific > 99th centile). Baseline assessment will be whilst recovering in-hospital or recently discharged, and include cardiovascular magnetic resonance (CMR) imaging, quality of life (QoL) assessments, electrocardiogram (ECG), serum biomarkers and genetics. Assessment at 6-months includes repeat CMR, QoL assessments and 6-min walk test (6MWT). The CMR protocol includes cine imaging, T1/T2 mapping, aortic distensibility, late gadolinium enhancement (LGE), and adenosine stress myocardial perfusion imaging in selected patients. The main objectives of the study are to: (1) characterise the extent and nature of myocardial involvement in COVID-19 patients with an elevated troponin, (2) assess how cardiac involvement and clinical outcome associate with recognised risk factors for mortality (age, sex, ethnicity and comorbidities) and genetic factors, (3) evaluate if differences in myocardial recovery at 6 months are dependent on demographics, genetics and comorbidities, (4) understand the impact of recovery status at 6 months on patient-reported QoL and functional capacity. DISCUSSION: COVID-HEART will provide detailed characterisation of cardiac involvement, and its repair and recovery in relation to comorbidity, genetics, patient-reported QoL measures and functional capacity. CLINICAL TRIAL REGISTRATION: ISRCTN 58667920. Registered 04 August 2020.


Subject(s)
COVID-19/complications , Heart Diseases/virology , Research Design , Biomarkers/blood , Comorbidity , Contrast Media , Electrocardiography , Female , Heart Diseases/physiopathology , Humans , Longitudinal Studies , Magnetic Resonance Imaging, Cine , Male , Multicenter Studies as Topic , Myocardial Perfusion Imaging , Observation , Pneumonia, Viral/virology , Prospective Studies , Quality of Life , Risk Factors , SARS-CoV-2 , Troponin/blood , United Kingdom , Walk Test
12.
Aging Clin Exp Res ; 33(4): 1133-1144, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1120008

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) disproportionately affects older people. Observational studies suggest indolent cardiovascular involvement after recovery from acute COVID-19. However, these findings may reflect pre-existing cardiac phenotypes. AIMS: We tested the association of baseline cardiovascular magnetic resonance (CMR) phenotypes with incident COVID-19. METHODS: We studied UK Biobank participants with CMR imaging and COVID-19 testing. We considered left and right ventricular (LV, RV) volumes, ejection fractions, and stroke volumes, LV mass, LV strain, native T1, aortic distensibility, and arterial stiffness index. COVID-19 test results were obtained from Public Health England. Co-morbidities were ascertained from self-report and hospital episode statistics (HES). Critical care admission and death were from HES and death register records. We investigated the association of each cardiovascular measure with COVID-19 test result in multivariable logistic regression models adjusting for age, sex, ethnicity, deprivation, body mass index, smoking, diabetes, hypertension, high cholesterol, and prior myocardial infarction. RESULTS: We studied 310 participants (n = 70 positive). Median age was 63.8 [57.5, 72.1] years; 51.0% (n = 158) were male. 78.7% (n = 244) were tested in hospital, 3.5% (n = 11) required critical care admission, and 6.1% (n = 19) died. In fully adjusted models, smaller LV/RV end-diastolic volumes, smaller LV stroke volume, and poorer global longitudinal strain were associated with significantly higher odds of COVID-19 positivity. DISCUSSION: We demonstrate association of pre-existing adverse CMR phenotypes with greater odds of COVID-19 positivity independent of classical cardiovascular risk factors. CONCLUSIONS: Observational reports of cardiovascular involvement after COVID-19 may, at least partly, reflect pre-existing cardiac status rather than COVID-19 induced alterations.


Subject(s)
COVID-19 , Aged , Aged, 80 and over , Biological Specimen Banks , COVID-19 Testing , Female , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , Phenotype , Predictive Value of Tests , SARS-CoV-2 , Stroke Volume , United Kingdom/epidemiology , Ventricular Function, Left
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