Alveolar Membrane and Capillary Function in COVID-19 Convalescents: Insights from Chest MRI

Overview

Journal Eur Radiol

Specialty Radiology

Date 2024 Mar 9

PMID 38460013

Authors

Agilo Luitger Kern

Isabell Pink

Agnes Bonifacius

Till Kaireit

Milan Speth

Lea Behrendt

Filip Klimes

Andreas Voskrebenzev

Jens M Hohlfeld

Marius M Hoeper

Tobias Welte

Frank Wacker

Britta Eiz-Vesper

Jens Vogel-Claussen

Affiliations

Soon will be listed here.

Abstract

Objectives: To investigate potential presence and resolution of longer-term pulmonary diffusion limitation and microvascular perfusion impairment in COVID-19 convalescents.

Materials And Methods: This prospective, longitudinal study was carried out between May 2020 and April 2023. COVID-19 convalescents repeatedly and age/sex-matched healthy controls once underwent MRI including hyperpolarized Xe MRI. Blood samples were obtained in COVID-19 convalescents for immunophenotyping. Ratios of Xe in red blood cells (RBC), tissue/plasma (TP), and gas phase (GP) as well as lung surface-volume ratio were quantified and correlations with CD4/CD8 T cell frequencies were assessed using Pearson's correlation coefficient. Signed-rank tests were used for longitudinal and U tests for group comparisons.

Results: Thirty-five participants were recruited. Twenty-three COVID-19 convalescents (age 52.1 ± 19.4 years, 13 men) underwent baseline MRI 12.6 ± 4.2 weeks after symptom onset. Fourteen COVID-19 convalescents underwent follow-up MRI and 12 were included for longitudinal comparison (baseline MRI at 11.5 ± 2.7 weeks and follow-up 38.0 ± 5.5 weeks). Twelve matched controls were included for comparison. In COVID-19 convalescents, RBC-TP was increased at follow-up (p = 0.04). Baseline RBC-TP was lower in patients treated on intensive care unit (p = 0.03) and in patients with severe/critical disease (p = 0.006). RBC-TP correlated with CD4/CD8 T cell frequencies (R = 0.61/ - 0.60) at baseline. RBC-TP was not significantly different compared to matched controls at follow-up (p = 0.25).

Conclusion: Impaired microvascular pulmonary perfusion and alveolar membrane function persisted 12 weeks after symptom onset and resolved within 38 weeks after COVID-19 symptom onset.

Clinical Relevance Statement: Xe MRI shows improvement of microvascular pulmonary perfusion and alveolar membrane function between 11.5 ± 2.7 weeks and 38.0 ± 5.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease.

Key Points: • The study aims to investigate long-term effects of COVID-19 on lung function, in particular gas uptake efficiency, and on the cardiovascular system. • In COVID-19 convalescents, the ratio of Xe in red blood cells/tissue plasma increased longitudinally (p = 0.04), but was not different from matched controls at follow-up (p = 0.25). • Microvascular pulmonary perfusion and alveolar membrane function are impaired 11.5 weeks after symptom onset in patients after COVID-19, returning to normal in subjects without significant prior disease at 38.0 weeks.

References

Wang Y, Wang Y, Chen Y, Qin Q . Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol. 2020; 92(6):568-576. PMC: 7228347. DOI: 10.1002/jmv.25748. View

Jones T, Biele G, Muhlemann B, Veith T, Schneider J, Beheim-Schwarzbach J . Estimating infectiousness throughout SARS-CoV-2 infection course. Science. 2021; 373(6551). PMC: 9267347. DOI: 10.1126/science.abi5273. View

Wang Y, Dong C, Hu Y, Li C, Ren Q, Zhang X . Temporal Changes of CT Findings in 90 Patients with COVID-19 Pneumonia: A Longitudinal Study. Radiology. 2020; 296(2):E55-E64. PMC: 7233482. DOI: 10.1148/radiol.2020200843. View

Parekh M, Donuru A, Balasubramanya R, Kapur S . Review of the Chest CT Differential Diagnosis of Ground-Glass Opacities in the COVID Era. Radiology. 2020; 297(3):E289-E302. PMC: 7350036. DOI: 10.1148/radiol.2020202504. View

Han X, Fan Y, Alwalid O, Li N, Jia X, Yuan M . Six-month Follow-up Chest CT Findings after Severe COVID-19 Pneumonia. Radiology. 2021; 299(1):E177-E186. PMC: 7841877. DOI: 10.1148/radiol.2021203153. View

Yang S, Zhang Y, Shen J, Dai Y, Ling Y, Lu H . Clinical Potential of UTE-MRI for Assessing COVID-19: Patient- and Lesion-Based Comparative Analysis. J Magn Reson Imaging. 2020; 52(2):397-406. PMC: 7300684. DOI: 10.1002/jmri.27208. View

Kern A, Gutberlet M, Qing K, Voskrebenzev A, Klimes F, Kaireit T . Regional investigation of lung function and microstructure parameters by localized Xe chemical shift saturation recovery and dissolved-phase imaging: A reproducibility study. Magn Reson Med. 2018; 81(1):13-24. DOI: 10.1002/mrm.27407. View

Kern A, Gutberlet M, Voskrebenzev A, Klimes F, Rotarmel A, Wacker F . Mapping of regional lung microstructural parameters using hyperpolarized Xe dissolved-phase MRI in healthy volunteers and patients with chronic obstructive pulmonary disease. Magn Reson Med. 2018; 81(4):2360-2373. DOI: 10.1002/mrm.27559. View

Kern A, Biller H, Klimes F, Voskrebenzev A, Gutberlet M, Renne J . Noninvasive Monitoring of the Response of Human Lungs to Low-Dose Lipopolysaccharide Inhalation Challenge Using MRI: A Feasibility Study. J Magn Reson Imaging. 2019; 51(6):1669-1676. DOI: 10.1002/jmri.27000. View

10.

Kern A, Gutberlet M, Alsady T, Welte T, Wacker F, Hohlfeld J . Investigating short-time diffusion of hyperpolarized Xe in lung air spaces and tissue: A feasibility study in chronic obstructive pulmonary disease patients. Magn Reson Med. 2020; 84(4):2133-2146. DOI: 10.1002/mrm.28264. View

11.

Li H, Zhao X, Wang Y, Lou X, Chen S, Deng H . Damaged lung gas exchange function of discharged COVID-19 patients detected by hyperpolarized Xe MRI. Sci Adv. 2020; 7(1). PMC: 7775756. DOI: 10.1126/sciadv.abc8180. View

12.

Grist J, Chen M, Collier G, Raman B, Abueid G, McIntyre A . Hyperpolarized Xe MRI Abnormalities in Dyspneic Patients 3 Months after COVID-19 Pneumonia: Preliminary Results. Radiology. 2021; 301(1):E353-E360. PMC: 8168952. DOI: 10.1148/radiol.2021210033. View

13.

Grist J, Collier G, Walters H, Kim M, Chen M, Abu Eid G . Lung Abnormalities Detected with Hyperpolarized Xe MRI in Patients with Long COVID. Radiology. 2022; 305(3):709-717. PMC: 9134268. DOI: 10.1148/radiol.220069. View

14.

Matheson A, McIntosh M, Kooner H, Lee J, Desaigoudar V, Bier E . Persistent Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-acute COVID-19 Syndrome. Radiology. 2022; 305(2):466-476. PMC: 9272782. DOI: 10.1148/radiol.220492. View

15.

Plummer J, Willmering M, Cleveland Z, Towe C, Woods J, Walkup L . Childhood to adulthood: Accounting for age dependence in healthy-reference distributions in Xe gas-exchange MRI. Magn Reson Med. 2022; 89(3):1117-1133. PMC: 9792434. DOI: 10.1002/mrm.29501. View

16.

Saunders L, Collier G, Chan H, Hughes P, Smith L, Watson J . Longitudinal Lung Function Assessment of Patients Hospitalized With COVID-19 Using H and Xe Lung MRI. Chest. 2023; 164(3):700-716. PMC: 10036146. DOI: 10.1016/j.chest.2023.03.024. View

17.

Matheson A, McIntosh M, Kooner H, Abdelrazek M, Albert M, Dhaliwal I . Longitudinal follow-up of postacute COVID-19 syndrome: DL, quality-of-life and MRI pulmonary gas-exchange abnormalities. Thorax. 2023; 78(4):418-421. PMC: 10086459. DOI: 10.1136/thorax-2022-219378. View

18.

Puntmann V, Carerj M, Wieters I, Fahim M, Arendt C, Hoffmann J . Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020; 5(11):1265-1273. PMC: 7385689. DOI: 10.1001/jamacardio.2020.3557. View

19.

Tavakolpour S, Rakhshandehroo T, Wei E, Rashidian M . Lymphopenia during the COVID-19 infection: What it shows and what can be learned. Immunol Lett. 2020; 225:31-32. PMC: 7305732. DOI: 10.1016/j.imlet.2020.06.013. View

20.

Breton G, Mendoza P, Hagglof T, Oliveira T, Schaefer-Babajew D, Gaebler C . Persistent cellular immunity to SARS-CoV-2 infection. J Exp Med. 2021; 218(4). PMC: 7845919. DOI: 10.1084/jem.20202515. View