Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge

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.

Keywords: COVID-19; Coronavirus; Follow up; Magnetic Resonance Imaging; Medium term; Mental health; Multiorgan effects; Post-hospital discharge; SARS-CoV-2 infection; Survivors.

Conflict of interest statement

Dr. Raman reports grants from NIHR Oxford Biomedical Research Centre, grants from United Kingdom Research Innovation Award, during the conduct of the study. Dr. Cassar reports grants from NIHR Oxford Biomedical Research Centre, during the conduct of the study. Dr. Tunnicliffe reports grants from NIHR Oxford Biomedical Research Centre, during the conduct of the study; shareholding in Perspectum, outside the submitted work; In addition, Dr. Tunnicliffe has a patent Systems and methods for gated mapping of T1 values in abdominal visceral organs GB2497668B licensed to Perspectum, a patent Multi-parametric magnetic resonance diagnosis and staging of liver disease GB2498254B licensed to Perspectum, and a patent Processing MR relaxometry data of visceral tissue to obtain a corrected value of relaxometry data based on a normal iron content for the visceral tissue GB2513474B licensed to Perspectum. Dr. Okell reports grants from Wellcome Trust/Royal Society, during the conduct of the study; personal fees from SBGNeuro, personal fees from Oxford University Press, personal fees from Siemens Healthineers, outside the submitted work; In addition, Dr. Okell has a patent Combined angiography and perfusion using radial imaging and arterial spin labeling pending, a patent Off-resonance Correction for Pseudo-continuous Arterial Spin Labeling pending, a patent Estimation of blood flow rates issued, a patent Fast analysis method for non-invasive imaging of blood flow using vessel-encoded arterial spin labelling with royalties paid to Siemens Healthineers, and a patent Quantification of blood volume flow rates from dynamic angiography data with royalties paid to Siemens Healthineers. Dr. Lewandowski reports non-financial support from Perspectum as a minority share-holder. Dr. Jenkinson reports personal fees from Oxford University Innovations, outside the submitted work. Dr. Channon reports grants funding from the British Heart Foundation and the National Institute for Health Research. Dr. Ferreira reports grants from British Heart Foundation, grants from National Institute Health Research Oxford Biomedical Research Centre, during the conduct of the study. Dr. Piechnik has a patent US patent 61/387,591 licensed to Siemens, a patent US patent 61/630,508 licensed to Perspectum, and a patent US patent 61-630,510 licensed to Perspectum. Dr. Pavlides reports other from Perspectum, outside the submitted work. Dr. Neubauer reports grants from Oxford NIHR Biomedical Research Centre, grants from UKRI, during the conduct of the study; personal fees and other from Perspectum Diagnostics, outside the submitted work; In addition, Dr. Neubauer has a patent Multi-parametric magnetic resonance diagnosis & staging of liver disease licensed to Perspectum.

Crown Copyright © 2020 Published by Elsevier Ltd.

Figures

Fig. 1

Systemic effects of COVID-19 and relationship with inflammatory response. A, B: Comparison of cardiopulmonary exercise test (CPET) parameters (VO2 max and VE/VCO2) between comorbidity-matched control and COVID-19 survivors. C: Relationship between VE/VCO2 and white cell count in COVID-19. D, E: Comparison of susceptibility weighted T2* signal (left and right thalamus) and MoCA scores between control and COVID-19 survivors. F: Relationship between periventricular white matter hyperintensity volume (pWMH) volume and white cell count in COVID-19. G, H: Comparison of myocardial native T1 (base and mid ventricle) between control and COVID-19 survivors. I: Relationship between basal native T1 and C-reactive protein (CRP). J, K: Comparison of liver T1 and iron-corrected liver T1 between control and COVID-19 survivors (these values cannot be compared to the LiverMultiScan cT1). L: Relationship between iron-corrected liver T1 and CRP in COVID-19. M, N: Comparison of average cortical kidney T1 and corticomedullary differentiation in control and COVID-19 survivors. O: Relationship between average cortical kidney T1 and CRP in COVID-19 (p-values for comparisons are from Student's t-tests for all variables; Spearman's correlation coefficient and p-values are reported for correlations, # signifies p-values were derived from comparison of variables that were Gaussianised and deconfounded).

Fig. 2

A: Quality of life (Short Form-36) radar plot for patients and controls. B,C: Burden of depression and anxiety among patients. A: The radar plot demonstrates that patients with COVID-19 (blue line) were more likely to experience impairment in energy, general health, physical health, social and emotional well-being and increased pain when compared to controls (orange line). Both physical and emotional factors caused significant role limitations among patients. B, C: 19% of hospitalised COVID-19 patients had moderate to severe self-reported symptoms of depression and 14% of hospitalised COVID-19 patients had moderate to severe self-reported symptoms of anxiety.