Postacute COVID-19 Syndrome: 129Xe MRI Ventilation Defects and Respiratory Outcomes 1 Year Later.

Background In individuals with postacute COVID-19 syndrome (PACS) and normal pulmonary function, xenon 129 (129Xe) MRI ventilation defects, abnormal quality-of-life scores, and exercise limitation were reported 3 months after infection; the longitudinal trajectory remains unclear. Purpose To measure and compare pulmonary function, exercise capacity, quality of life, and 129Xe MRI ventilation defect percent (VDP) in individuals with PACS evaluated 3 and 15 months after COVID-19 infection. Materials and Methods In this prospective study, participants with PACS aged 18-80 years were enrolled between July 2020 and August 2021 from two quaternary care centers. 129Xe MRI VDP, diffusing capacity of lung for carbon monoxide (Dlco), spirometry, oscillometry, 6-minute walk distance (6MWD), and St George Respiratory Questionnaire (SGRQ) scores were evaluated 3 months and 15 months after COVID-19 infection. Differences between time points were evaluated using the paired t test. Multivariable models were generated to explain exercise capacity and quality-of-life improvement. Odds ratios (ORs) were used to evaluate potential treatment influences. Results Overall, 53 participants (mean age, 55 years ± 18 [SD]; 27 women) attended both 3- and 15-month visits and were included in the analysis. The mean values for 129Xe MRI VDP (5.8% and 4.2%; P = .003), forced expiratory volume in the 1st second of expiration percent predicted (84% and 90%; P = .001), Dlco percent predicted (86% and 99%; P = .002), and SGRQ score (35 and 25; P < .001) improved between the 3- and 15-month visit. VDP measured 3 months after COVID-19 infection predicted the change in 6MWD (ß = -0.643, P = .006), while treatment with respiratory medication at 3 months predicted an improved quality-of-life score at 15 months (OR, 4.0; 95% CI: 1.2, 13.8; P = .03). Conclusion Pulmonary function, gas exchange, exercise capacity, quality of life, and 129Xe MRI ventilation defect percent (VDP) improved in participants with postacute COVID-19 syndrome at 15 months compared with 3 months after infection. VDP measured at 3 months after infection correlated with improved exercise capacity, while treatment with respiratory medication was associated with an improved quality-of-life score 15 months after infection. ClinicalTrials.gov registration no. NCT05014516 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Vogel-Claussen in this issue.

Longitudinal follow-up of postacute COVID-19 syndrome: DLCO, quality-of-life and MRI pulmonary gas-exchange abnormalities.

129Xe MRI red blood cell to alveolar tissue plasma ratio (RBC:TP) abnormalities have been observed in ever-hospitalised and never-hospitalised people with postacute COVID-19 syndrome (PACS). But, it is not known if such abnormalities resolve when symptoms and quality-of-life scores improve. We evaluated 21 participants with PACS, 7±4 months (baseline) and 14±4 months (follow-up) postinfection. Significantly improved diffusing capacity of the lung for carbon monoxide (DLCO, Δ=14%pred ;95%CI 7 to 21, p<0.001), postexertional dyspnoea (Δ=-0.7; 95%CI=-0.2 to -1.2, p=0.019), St George's Respiratory Questionnaire-score (SGRQ Δ=-6; 95% CI=-1 to -11, p=0.044) but not RBC:TP (Δ=0.03; 95% CI=0.01 to 0.05, p=0.051) were observed at 14 months. DLCO correlated with RBC:TP (r=0.60, 95% CI=0.22 to 0.82, p=0.004) at 7 months. While DLCO and SGRQ measurements improved, these values did not normalise 14 months post-infection. ClinicalTrials.gov NCT04584671.

Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-acute COVID-19 Syndrome.

BACKGROUND: In patients with post-acute COVID-19 syndrome (PACS), abnormal gas-transfer and pulmonary vascular density have been reported, but such findings have not been related to each other or to symptoms and exercise limitation. The pathophysiologic drivers of PACS in patients previously infected with COVID-19 who were admitted to in-patient treatment in hospital (or ever-hospitalized patients) and never-hospitalized patients are not well understood. PURPOSE: To determine the relationship of persistent symptoms and exercise limitation with xenon 129 (129Xe) MRI and CT pulmonary vascular measurements in individuals with PACS. MATERIALS AND METHODS: In this prospective study, patients with PACS aged 18-80 years with a positive polymerase chain reaction COVID-19 test were recruited from a quaternary-care COVID-19 clinic between April and October 2021. Participants with PACS underwent spirometry, diffusing capacity of the lung for carbon monoxide (DLco), 129Xe MRI, and chest CT. Healthy controls had no prior history of COVID-19 and underwent spirometry, DLco, and 129Xe MRI. The 129Xe MRI red blood cell (RBC) to alveolar-barrier signal ratio, RBC area under the receiver operating characteristic curve (AUC), CT volume of pulmonary vessels with cross-sectional area 5 mm2 or smaller (BV5), and total blood volume were quantified. St George's Respiratory Questionnaire, International Physical Activity Questionnaire, and modified Borg Dyspnea Scale measured quality of life, exercise limitation, and dyspnea. Differences between groups were compared with use of Welch t-tests or Welch analysis of variance. Relationships were evaluated with use of Pearson (r) and Spearman (ρ) correlations. RESULTS: Forty participants were evaluated, including six controls (mean age ± SD, 35 years ± 15, three women) and 34 participants with PACS (mean age, 53 years ± 13, 18 women), of whom 22 were never hospitalized. The 129Xe MRI RBC:barrier ratio was lower in ever-hospitalized participants (P = .04) compared to controls. BV5 correlated with RBC AUC (ρ = .44, P = .03). The 129Xe MRI RBC:barrier ratio was related to DLco (r = .57, P = .002) and forced expiratory volume in 1 second (ρ = .35, P = .03); RBC AUC was related to dyspnea (ρ = -.35, P = .04) and International Physical Activity Questionnaire score (ρ = .45, P = .02). CONCLUSION: Xenon 129 (129Xe) MRI measurements were lower in participants previously infected with COVID-19 who were admitted to in-patient treatment in hospital with post-acute COVID-19 syndrome, 34 weeks ± 25 after infection compared to controls. The 129Xe MRI measures were associated with CT pulmonary vascular density, diffusing capacity of the lung for carbon monoxide, exercise capacity, and dyspnea. Clinical trial registration no.: NCT04584671 © RSNA, 2022 Online supplemental material is available for this article See also the editorial by Wild and Collier in this issue.

129Xe MRI ventilation defects in ever-hospitalised and never-hospitalised people with post-acute COVID-19 syndrome.

BACKGROUND: Patients often report persistent symptoms beyond the acute infectious phase of COVID-19. Hyperpolarised 129Xe MRI provides a way to directly measure airway functional abnormalities; the clinical relevance of 129Xe MRI ventilation defects in ever-hospitalised and never-hospitalised patients who had COVID-19 has not been ascertained. It remains unclear if persistent symptoms beyond the infectious phase are related to small airways disease and ventilation heterogeneity. Hence, we measured 129Xe MRI ventilation defects, pulmonary function and symptoms in ever-hospitalised and never-hospitalised patients who had COVID-19 with persistent symptoms consistent with post-acute COVID-19 syndrome (PACS). METHODS: Consenting participants with a confirmed diagnosis of PACS completed 129Xe MRI, CT, spirometry, multi-breath inert-gas washout, 6-minute walk test, St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnoea scale, modified Borg scale and International Physical Activity Questionnaire. Consenting ever-COVID volunteers completed 129Xe MRI and pulmonary function tests only. RESULTS: Seventy-six post-COVID and nine never-COVID participants were evaluated. Ventilation defect per cent (VDP) was abnormal and significantly greater in ever-COVID as compared with never-COVID participants (p<0.001) and significantly greater in ever-hospitalised compared with never-hospitalised participants who had COVID-19 (p=0.048), in whom diffusing capacity of the lung for carbon-monoxide (p=0.009) and 6-minute walk distance (6MWD) (p=0.005) were also significantly different. 129Xe MRI VDP was also related to the 6MWD (p=0.02) and post-exertional SpO2 (p=0.002). Participants with abnormal VDP (≥4.3%) had significantly worse 6MWD (p=0.003) and post-exertional SpO2 (p=0.03). CONCLUSION: 129Xe MRI VDP was significantly worse in ever-hospitalised as compared with never-hospitalised participants and was related to 6MWD and exertional SpO2 but not SGRQ or mMRC scores. TRIAL REGISTRATION NUMBER: NCT05014516.