Multi-organ structural and functional deficits in association with long COVID: a population-based case-control study

Alba Fernandez Sanles; Lucy J Goudswaard; Dylan M Williams; Betty Raman; Ellen J. Thompson; Michele Orini; Siana Jones; Alexandra Jamieson; Lee Hamill Howes; Andrew Wong; Vedika Handa; Carole Hélène Sudre; Laura Saunders; Nathan  Cheetham; Alex Whitmarsh; Mary Ni Lochlainn; Jim  Wild; Stephen M Smith; Stefan  Piechnik; Stefan Neubauer; Claire J Steves; Nicholas John  Timpson; Nishi Chaturvedi; Alun D Hughes

Multi-organ structural and functional deficits in association with long COVID: a population-based case-control study

Alba Fernandez Sanles, Lucy J Goudswaard, Dylan M Williams, Betty Raman, Ellen J. Thompson, Michele Orini, Siana Jones, Alexandra Jamieson, Lee Hamill Howes, Andrew Wong, Vedika Handa, Carole Hélène Sudre, Laura Saunders, Nathan Cheetham, Alex Whitmarsh, Mary Ni Lochlainn, Jim Wild, Stephen M Smith, Stefan Piechnik, Stefan NeubauerClaire J Steves, Nicholas John Timpson, Nishi Chaturvedi, Alun D Hughes

Research output: Contribution to journal › Article (Academic Journal) › peer-review

Abstract

Background:
Multi-system impacts of long COVID remain unknown. We compared multi-system deficits between people with long COVID and controls.

Methods:
A case-control study recruited from the Avon Longitudinal Study of Parents and Children and TwinsUK population cohorts. Cases (141) had long COVID (evidence of COVID-19 infection and persistent symptoms ≥4 weeks post infection); controls (280) included people making a full recovery in <4 weeks, people self-reporting long COVID like symptoms but without wild- type SARS-CoV-2 virus antibodies, and people without symptoms or history of COVID-19 infection. Participants underwent multi-system MRI, (cardiac, brain, lung, kidney), measurement of blood pressure and autonomic function, tests of exercise performance, spirometry, renal function, strength and physical capability. System-specific deficits were summed to a total potential score of 27.

Findings:
Participants attended clinic between 2021-23. Overall deficit score in cases was 0.22 (95% CI -0.44,0.88) units greater than controls, adjusted for age, sex, ethnicity, cohort
membership and relatedness. This estimate was little changed (0.32 (-0.34, 0.98)) when
additionally adjusted for educational status, index of multiple deprivation, physical activity, smoking and co-morbidity. Restricting cases to those reporting at least fatigue (46) increased the excess deficit score to 0.81 (-0.19,1.81) units in the minimally adjusted model. A difference was only observed in the vascular domain, largely attributable to elevated blood pressure, showing a 1.76 (1.04,2.97) multivariable adjusted odds ratio excess in cases, and 3.04 (1.36,6.80) when restricted to cases with fatigue.

Interpretation:
People with community-based long COVID should be reassured that there is not marked residual deficit across multiple systems. However, blood pressure measurement and control should be included in clinical follow-up.

Original language	English
Journal	Lancet Respiratory Medicine
Publication status	Submitted - 12 Feb 2026

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Fernandez Sanles, A., Goudswaard, L. J., Williams, D. M., Raman, B., Thompson, E. J., Orini, M., Jones, S., Jamieson, A., Hamill Howes, L., Wong, A., Handa, V., Sudre, C. H., Saunders, L., Cheetham, N., Whitmarsh, A., Ni Lochlainn, M., Wild, J., Smith, S. M., Piechnik, S., ... Hughes, A. D. (2026). Multi-organ structural and functional deficits in association with long COVID: a population-based case-control study. Manuscript submitted for publication.

@article{41eb3bf00dd24ee691332e91243f1bf2,

title = "Multi-organ structural and functional deficits in association with long COVID: a population-based case-control study",

abstract = "Background: Multi-system impacts of long COVID remain unknown. We compared multi-system deficits between people with long COVID and controls. Methods: A case-control study recruited from the Avon Longitudinal Study of Parents and Children and TwinsUK population cohorts. Cases (141) had long COVID (evidence of COVID-19 infection and persistent symptoms ≥4 weeks post infection); controls (280) included people making a full recovery in <4 weeks, people self-reporting long COVID like symptoms but without wild- type SARS-CoV-2 virus antibodies, and people without symptoms or history of COVID-19 infection. Participants underwent multi-system MRI, (cardiac, brain, lung, kidney), measurement of blood pressure and autonomic function, tests of exercise performance, spirometry, renal function, strength and physical capability. System-specific deficits were summed to a total potential score of 27. Findings: Participants attended clinic between 2021-23. Overall deficit score in cases was 0.22 (95\% CI -0.44,0.88) units greater than controls, adjusted for age, sex, ethnicity, cohort membership and relatedness. This estimate was little changed (0.32 (-0.34, 0.98)) when additionally adjusted for educational status, index of multiple deprivation, physical activity, smoking and co-morbidity. Restricting cases to those reporting at least fatigue (46) increased the excess deficit score to 0.81 (-0.19,1.81) units in the minimally adjusted model. A difference was only observed in the vascular domain, largely attributable to elevated blood pressure, showing a 1.76 (1.04,2.97) multivariable adjusted odds ratio excess in cases, and 3.04 (1.36,6.80) when restricted to cases with fatigue. Interpretation: People with community-based long COVID should be reassured that there is not marked residual deficit across multiple systems. However, blood pressure measurement and control should be included in clinical follow-up.",

author = "\{Fernandez Sanles\}, Alba and Goudswaard, \{Lucy J\} and Williams, \{Dylan M\} and Betty Raman and Thompson, \{Ellen J.\} and Michele Orini and Siana Jones and Alexandra Jamieson and \{Hamill Howes\}, Lee and Andrew Wong and Vedika Handa and Sudre, \{Carole H{\'e}l{\`e}ne\} and Laura Saunders and Nathan Cheetham and Alex Whitmarsh and \{Ni Lochlainn\}, Mary and Jim Wild and Smith, \{Stephen M\} and Stefan Piechnik and Stefan Neubauer and Steves, \{Claire J\} and Timpson, \{Nicholas John\} and Nishi Chaturvedi and Hughes, \{Alun D\}",

year = "2026",

month = feb,

day = "12",

language = "English",

journal = "Lancet Respiratory Medicine",

issn = "2213-2600",

publisher = "Elsevier Limited",

}

Fernandez Sanles, A, Goudswaard, LJ, Williams, DM, Raman, B, Thompson, EJ, Orini, M, Jones, S, Jamieson, A, Hamill Howes, L, Wong, A, Handa, V, Sudre, CH, Saunders, L, Cheetham, N, Whitmarsh, A, Ni Lochlainn, M, Wild, J, Smith, SM, Piechnik, S, Neubauer, S, Steves, CJ, Timpson, NJ, Chaturvedi, N & Hughes, AD 2026, 'Multi-organ structural and functional deficits in association with long COVID: a population-based case-control study', Lancet Respiratory Medicine.

TY - JOUR

T1 - Multi-organ structural and functional deficits in association with long COVID

T2 - a population-based case-control study

AU - Fernandez Sanles, Alba

AU - Goudswaard, Lucy J

AU - Williams, Dylan M

AU - Raman, Betty

AU - Thompson, Ellen J.

AU - Orini, Michele

AU - Jones, Siana

AU - Jamieson, Alexandra

AU - Hamill Howes, Lee

AU - Wong, Andrew

AU - Handa, Vedika

AU - Sudre, Carole Hélène

AU - Saunders, Laura

AU - Cheetham, Nathan

AU - Whitmarsh, Alex

AU - Ni Lochlainn, Mary

AU - Wild, Jim

AU - Smith, Stephen M

AU - Piechnik, Stefan

AU - Neubauer, Stefan

AU - Steves, Claire J

AU - Timpson, Nicholas John

AU - Chaturvedi, Nishi

AU - Hughes, Alun D

PY - 2026/2/12

Y1 - 2026/2/12

N2 - Background: Multi-system impacts of long COVID remain unknown. We compared multi-system deficits between people with long COVID and controls. Methods: A case-control study recruited from the Avon Longitudinal Study of Parents and Children and TwinsUK population cohorts. Cases (141) had long COVID (evidence of COVID-19 infection and persistent symptoms ≥4 weeks post infection); controls (280) included people making a full recovery in <4 weeks, people self-reporting long COVID like symptoms but without wild- type SARS-CoV-2 virus antibodies, and people without symptoms or history of COVID-19 infection. Participants underwent multi-system MRI, (cardiac, brain, lung, kidney), measurement of blood pressure and autonomic function, tests of exercise performance, spirometry, renal function, strength and physical capability. System-specific deficits were summed to a total potential score of 27. Findings: Participants attended clinic between 2021-23. Overall deficit score in cases was 0.22 (95% CI -0.44,0.88) units greater than controls, adjusted for age, sex, ethnicity, cohort membership and relatedness. This estimate was little changed (0.32 (-0.34, 0.98)) when additionally adjusted for educational status, index of multiple deprivation, physical activity, smoking and co-morbidity. Restricting cases to those reporting at least fatigue (46) increased the excess deficit score to 0.81 (-0.19,1.81) units in the minimally adjusted model. A difference was only observed in the vascular domain, largely attributable to elevated blood pressure, showing a 1.76 (1.04,2.97) multivariable adjusted odds ratio excess in cases, and 3.04 (1.36,6.80) when restricted to cases with fatigue. Interpretation: People with community-based long COVID should be reassured that there is not marked residual deficit across multiple systems. However, blood pressure measurement and control should be included in clinical follow-up.

AB - Background: Multi-system impacts of long COVID remain unknown. We compared multi-system deficits between people with long COVID and controls. Methods: A case-control study recruited from the Avon Longitudinal Study of Parents and Children and TwinsUK population cohorts. Cases (141) had long COVID (evidence of COVID-19 infection and persistent symptoms ≥4 weeks post infection); controls (280) included people making a full recovery in <4 weeks, people self-reporting long COVID like symptoms but without wild- type SARS-CoV-2 virus antibodies, and people without symptoms or history of COVID-19 infection. Participants underwent multi-system MRI, (cardiac, brain, lung, kidney), measurement of blood pressure and autonomic function, tests of exercise performance, spirometry, renal function, strength and physical capability. System-specific deficits were summed to a total potential score of 27. Findings: Participants attended clinic between 2021-23. Overall deficit score in cases was 0.22 (95% CI -0.44,0.88) units greater than controls, adjusted for age, sex, ethnicity, cohort membership and relatedness. This estimate was little changed (0.32 (-0.34, 0.98)) when additionally adjusted for educational status, index of multiple deprivation, physical activity, smoking and co-morbidity. Restricting cases to those reporting at least fatigue (46) increased the excess deficit score to 0.81 (-0.19,1.81) units in the minimally adjusted model. A difference was only observed in the vascular domain, largely attributable to elevated blood pressure, showing a 1.76 (1.04,2.97) multivariable adjusted odds ratio excess in cases, and 3.04 (1.36,6.80) when restricted to cases with fatigue. Interpretation: People with community-based long COVID should be reassured that there is not marked residual deficit across multiple systems. However, blood pressure measurement and control should be included in clinical follow-up.

M3 - Article (Academic Journal)

SN - 2213-2600

JO - Lancet Respiratory Medicine

JF - Lancet Respiratory Medicine

ER -

Multi-organ structural and functional deficits in association with long COVID: a population-based case-control study

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