Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a prospective, community-based study

Andrea Dennis, Malgorzata Wamil, Johann Alberts, Jude Oben, Daniel J Cuthbertson, Dan Wootton, Michael Crooks, Mark Gabbay, Michael Brady, Lyth Hishmeh, Emily Attree, Melissa Heightman, Rajarshi Banerjee, Amitava Banerjee, COVERSCAN study investigators, Andrea Dennis, Malgorzata Wamil, Johann Alberts, Jude Oben, Daniel J Cuthbertson, Dan Wootton, Michael Crooks, Mark Gabbay, Michael Brady, Lyth Hishmeh, Emily Attree, Melissa Heightman, Rajarshi Banerjee, Amitava Banerjee, COVERSCAN study investigators

Abstract

Objective: To assess medium-term organ impairment in symptomatic individuals following recovery from acute SARS-CoV-2 infection.

Design: Baseline findings from a prospective, observational cohort study.

Setting: Community-based individuals from two UK centres between 1 April and 14 September 2020.

Participants: Individuals ≥18 years with persistent symptoms following recovery from acute SARS-CoV-2 infection and age-matched healthy controls.

Intervention: Assessment of symptoms by standardised questionnaires (EQ-5D-5L, Dyspnoea-12) and organ-specific metrics by biochemical assessment and quantitative MRI.

Main outcome measures: Severe post-COVID-19 syndrome defined as ongoing respiratory symptoms and/or moderate functional impairment in activities of daily living; single-organ and multiorgan impairment (heart, lungs, kidneys, liver, pancreas, spleen) by consensus definitions at baseline investigation.

Results: 201 individuals (mean age 45, range 21-71 years, 71% female, 88% white, 32% healthcare workers) completed the baseline assessment (median of 141 days following SARS-CoV-2 infection, IQR 110-162). The study population was at low risk of COVID-19 mortality (obesity 20%, hypertension 7%, type 2 diabetes 2%, heart disease 5%), with only 19% hospitalised with COVID-19. 42% of individuals had 10 or more symptoms and 60% had severe post-COVID-19 syndrome. Fatigue (98%), muscle aches (87%), breathlessness (88%) and headaches (83%) were most frequently reported. Mild organ impairment was present in the heart (26%), lungs (11%), kidneys (4%), liver (28%), pancreas (40%) and spleen (4%), with single-organ and multiorgan impairment in 70% and 29%, respectively. Hospitalisation was associated with older age (p=0.001), non-white ethnicity (p=0.016), increased liver volume (p<0.0001), pancreatic inflammation (p<0.01), and fat accumulation in the liver (p<0.05) and pancreas (p<0.01). Severe post-COVID-19 syndrome was associated with radiological evidence of cardiac damage (myocarditis) (p<0.05).

Conclusions: In individuals at low risk of COVID-19 mortality with ongoing symptoms, 70% have impairment in one or more organs 4 months after initial COVID-19 symptoms, with implications for healthcare and public health, which have assumed low risk in young people with no comorbidities.

Trial registration number: NCT04369807; Pre-results.

Keywords: COVID-19; epidemiology; health policy; public health.

Conflict of interest statement

Competing interests: AD, RB and MB are employees of Perspectum.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
Flow from recruitment to enrolment of 201 patients with post-COVID-19 syndrome.
Figure 2
Figure 2
Percentage of patients (black) and controls (grey) with individual organ measures outside of the predefined normal range. Lines represent significant difference in the proportions between the two groups, with *p

Figure 3

Multiorgan impairment in low-risk individuals…

Figure 3

Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome by gender and hospitalisation.

Figure 3
Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome by gender and hospitalisation.

Figure 4

Percentage of reported symptoms during…

Figure 4

Percentage of reported symptoms during the acute phases of the illness within those…

Figure 4
Percentage of reported symptoms during the acute phases of the illness within those with evidence of organ impairment for each organ separately. Darker red indicates higher percentage of reported symptoms per impaired organ. There are no distinct patterns of symptoms relating to each impaired organ, but a high burden of symptoms in individuals is highlighted.

Figure 5

Natural history of post-COVID-19 syndrome,…

Figure 5

Natural history of post-COVID-19 syndrome, the COVERSCAN study in low-risk individuals (N=201) and…

Figure 5
Natural history of post-COVID-19 syndrome, the COVERSCAN study in low-risk individuals (N=201) and policy recommendations.
Figure 3
Figure 3
Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome by gender and hospitalisation.
Figure 4
Figure 4
Percentage of reported symptoms during the acute phases of the illness within those with evidence of organ impairment for each organ separately. Darker red indicates higher percentage of reported symptoms per impaired organ. There are no distinct patterns of symptoms relating to each impaired organ, but a high burden of symptoms in individuals is highlighted.
Figure 5
Figure 5
Natural history of post-COVID-19 syndrome, the COVERSCAN study in low-risk individuals (N=201) and policy recommendations.

References

    1. World Health Organization . Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected. interim guidance 13 March 2020, 2020. Available:
    1. Pavon AG, Meier D, Samim D, et al. . First documentation of persistent SARS-Cov-2 infection presenting with late acute severe myocarditis. Can J Cardiol 2020;36:1326.e5–1326.e7. 10.1016/j.cjca.2020.06.005
    1. Puntmann VO, Carerj ML, Wieters I. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol 2019;2020:1265–73.
    1. Tabary M, Khanmohammadi S, Araghi F, et al. . Pathologic features of COVID-19: a Concise review. Pathol Res Pract 2020;216:153097. 10.1016/j.prp.2020.153097
    1. Alqahtani SA, Schattenberg JM. Liver injury in COVID-19: the current evidence. United European Gastroenterol J 2020;8:509–19. 10.1177/2050640620924157
    1. Somasundaram NP, Ranathunga I, Ratnasamy V, et al. . The impact of SARS-Cov-2 virus infection on the endocrine system. J Endocr Soc 2020;4:1–22. 10.1210/jendso/bvaa082
    1. Farouk SS, Fiaccadori E, Cravedi P, et al. . COVID-19 and the kidney: what we think we know so far and what we don't. J Nephrol 2020;33:1213–8. 10.1007/s40620-020-00789-y
    1. Lai A, Pasea L, Banerjee A. Estimating excess mortality in people with cancer and multimorbidity in the COVID-19 emergency. BMJ Open 2020;10:e043828.
    1. Banerjee A, Pasea L, Harris S, et al. . Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study. The Lancet 2020;395:1715–25. 10.1016/S0140-6736(20)30854-0
    1. Banerjee A, Chen S, Pasea L. Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic. Eur J Prev Cardiol 2020. 10.1093/eurjpc/zwaa155
    1. Raman B, Cassar MP, Tunnicliffe EM, et al. . Medium-Term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge. EClinicalMedicine 2021;31:100683. 10.1016/j.eclinm.2020.100683
    1. Horton R. Offline: COVID-19 is not a pandemic. The Lancet 2020;396:874. 10.1016/S0140-6736(20)32000-6
    1. Shovlin CL, Vizcaychipi MP. Implications for COVID-19 triage from the ICNARC report of 2204 COVID-19 cases managed in UK adult intensive care units. Emerg Med J 2020;37:332–3. 10.1136/emermed-2020-209791
    1. Docherty AB, Harrison EM, Green CA, et al. . Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ 2020;369:m1985–12. 10.1136/bmj.m1985
    1. Williamson EJ, Walker AJ, Bhaskaran K, et al. . Factors associated with COVID-19-related death using OpenSAFELY. Nature 2020;584:430–6. 10.1038/s41586-020-2521-4
    1. Office for National Statistics . The prevalence of long COVID symptoms and COVID-19 complications, 2020. Available:
    1. del Rio C, Collins LF, Malani P. Long-Term health consequences of COVID-19. JAMA 2020;324:1723. 10.1001/jama.2020.19719
    1. Carfì A, Bernabei R, Landi F, et al. . Persistent symptoms in patients after acute COVID-19. JAMA 2020;324:603–5. 10.1001/jama.2020.12603
    1. Nabavi N. Long covid: how to define it and how to manage it. BMJ 2020;370:m3489. 10.1136/bmj.m3489
    1. Greenhalgh T, Knight M, A’Court C, et al. . Management of post-acute covid-19 in primary care. BMJ 2020;13:m3026. 10.1136/bmj.m3026
    1. National Institute for Health Research . New risk prediction model could help improve guidance for people shielding from COVID-19, 2020. Available:
    1. Hill AD, Fowler RA, Pinto R, et al. . Long-term outcomes and healthcare utilization following critical illness – a population-based study. Crit Care 2016;20:1–10. 10.1186/s13054-016-1248-y
    1. Perrin R, Riste L, Hann M, et al. . Into the looking glass: post-viral syndrome post COVID-19. Med Hypotheses 2020;144:110055. 10.1016/j.mehy.2020.110055
    1. George PM, Barratt SL, Condliffe R, et al. . Respiratory follow-up of patients with COVID-19 pneumonia. Thorax 2020;75:1009–16. 10.1136/thoraxjnl-2020-215314
    1. Jiang DH, McCoy RG. Planning for the Post-COVID syndrome: how payers can mitigate long-term complications of the pandemic. J Gen Intern Med 2020;35:3036–9. 10.1007/s11606-020-06042-3
    1. Janssen MF, Pickard AS, Golicki D, et al. . Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L across eight patient groups: a multi-country study. Qual Life Res 2013;22:1717–27. 10.1007/s11136-012-0322-4
    1. Yorke J, Moosavi SH, Shuldham C, et al. . Quantification of dyspnoea using descriptors: development and initial testing of the Dyspnoea-12. Thorax 2010;65:21–6. 10.1136/thx.2009.118521
    1. Hobbins A, Barry L, Kelleher D, et al. . The health of the residents of ireland: population norms for Ireland based on the EQ-5D-5L descriptive system – a cross sectional study. HRB Open Res 2018;1:22. 10.12688/hrbopenres.12848.1
    1. Gupta A, Madhavan MV, Sehgal K, et al. . Extrapulmonary manifestations of COVID-19. Nat Med 2020;26:1017–32. 10.1038/s41591-020-0968-3
    1. Palmer K, Monaco A, Kivipelto M, et al. . The potential long-term impact of the COVID-19 outbreak on patients with non-communicable diseases in Europe: consequences for healthy ageing. Aging Clin Exp Res 2020;32:1189–94. 10.1007/s40520-020-01601-4
    1. Menni C, Valdes AM, Freidin MB, et al. . Real-Time tracking of self-reported symptoms to predict potential COVID-19. Nat Med 2020;26:1037–40. 10.1038/s41591-020-0916-2
    1. Mandal S, Barnett J, Brill S, et al. . “Long-COVID”: a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19. Thorax 2020:thoraxjnl-2020-215818.
    1. Chau VQ, Giustino G, Mahmood K, et al. . Cardiogenic shock and hyperinflammatory syndrome in young males with COVID-19. Circ Hear Fail 2020:556–9.
    1. Rajpal S, Tong MS, Borchers J, et al. . Cardiovascular magnetic resonance findings in competitive athletes recovering from COVID-19 infection. JAMA Cardiol 2020:5–7.
    1. Mathew D, Giles JR, Baxter AE, et al. . Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020;369:eabc8511. 10.1126/science.abc8511
    1. Wynants L, Van Calster B, Collins GS, et al. . Prediction models for diagnosis and prognosis of covid-19: systematic review and critical appraisal. BMJ 2020;369:m1328.
    1. PHOSP-COVID . Post-HOSPitalisation COVID-19 study, 2020. Available:
    1. NHS . NHS to offer ‘long covid’ sufferers help at specialist centres, 2020. Available:
    1. National Institute for Healh and Care Excellence . COVID-19 rapid guideline: managing the long-term effects of COVID-19, 2020. Available:
    1. Ferreira VM, Piechnik SK, Dall’Armellina E, et al. . Native T1-mapping detects the location, extent and patterns of acute myocarditis without the need for gadolinium contrast agents. J Cardiovasc Magn Reson 2014;16:1–11. 10.1186/1532-429X-16-36
    1. Gibson LM, Paul L, Chappell FM, et al. . Potentially serious incidental findings on brain and body magnetic resonance imaging of apparently asymptomatic adults: systematic review and meta-analysis. BMJ 2018;14:k4577. 10.1136/bmj.k4577

Source: PubMed

3
S'abonner