Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge
Raman B., Cassar MP., Tunnicliffe EM., Filippini N., Griffanti L., Alfaro-Almagro F., Okell T., Sheerin F., Xie C., Mahmod M., Mózes FE., Lewandowski AJ., Ohuma EO., Holdsworth D., Lamlum H., Woodman MJ., Krasopoulos C., Mills R., Kennedy McConnell FA., Wang C., Arthofer C., Lange FJ., Andersson J., Jenkinson M., Antoniades C., Channon KM., Shanmuganathan M., Ferreira VM., Piechnik SK., Klenerman P., Brightling C., Talbot NP., Petousi N., Rahman NM., Ho L-P., Saunders K., Geddes JR., Harrison PJ., Pattinson K., Rowland MJ., Angus BJ., Gleeson F., Pavlides M., Koychev I., Miller KL., Mackay C., Jezzard P., Smith SM., Neubauer S.
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The medium-term effects of Coronavirus disease (COVID-19) on multiple organ health, exercise capacity, cognition, quality of life and mental health are poorly understood.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Fifty-eight COVID-19 patients post-hospital discharge and 30 comorbidity-matched controls were prospectively 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.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>At 2-3 months from disease-onset, 64% of patients experienced persistent breathlessness and 55% complained of significant fatigue. On MRI, tissue signal abnormalities were seen in the lungs (60%), heart (26%), liver (10%) and kidneys (29%) of patients. COVID-19 patients also exhibited tissue changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domain relative to controls. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance (405±118m vs 517±106m in controls, p<0.0001) were significantly reduced in patients. The extent of extra-pulmonary MRI abnormalities and exercise tolerance correlated with serum markers of ongoing inflammation and severity of acute illness. Patients were more likely to report symptoms of moderate to severe anxiety (35% versus 10%, p=0.012) and depression (39% versus 17%, p=0.036) and a significant impairment in all domains of quality of life compared to controls.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>A significant proportion of COVID-19 patients discharged from hospital experience ongoing symptoms of breathlessness, fatigue, anxiety, depression and exercise limitation at 2-3 months from disease-onset. Persistent lung and extra-pulmonary organ MRI findings are common. In COVID-19 survivors, chronic inflammation may underlie multiorgan abnormalities and contribute to impaired quality of life.</jats:p></jats:sec><jats:sec><jats:title>Funding</jats:title><jats:p>NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.</jats:p></jats:sec>