AIM:The number of pregnancies among women with cystic fibrosis (wwCF) has steadily increased over the past decade. However, the pharmacokinetics (PK) of elexacaftor-tezacaftor-ivacaftor (ETI) during gestation remains uncharacterized, despite its widespread use in this population. To date, no clinical trials have investigated the effectiveness, safety or PK profiles of ETI during pregnancy. Given the significant physiological changes that occur throughout gestation, which can alter drug PK, characterizing how pregnancy impacts ETI exposure represents a key step towards informing appropriate dosing strategies. Therefore, the aim of this analysis was to assess pregnancy effect on ETI PK. METHOD:As part of the French national observational cohort study, therapeutic drug monitoring was performed in 145 wwCF, including 14 pregnant participants. PK profiles for each compound were characterized using the previously published ETI adult population PK model from the same cohort, with model development and evaluation performed using Monolix® software. RESULTS:A total of 294 plasma samples, including 47 collected from pregnant participants, were drawn during routine clinical care. Pregnancy was found to significantly increase the apparent clearance of tezacaftor (0.97 to 1.44 L/h) and of ivacaftor (9.64 to 11.36 L/h), indicating a decrease in systemic exposure. CONCLUSION:These findings raise important questions regarding whether decreased total tezacaftor and ivacaftor exposure may compromise the sustained treatment efficacy. The necessity for dose adjustments during pregnancy remains to be evaluated from a PK (unbound ETI concentrations) and pharmacodynamic (clinical effectiveness) perspective, thus warranting further studies.

BACKGROUND:This study sought to describe the prevalence of lung hyperinflation in adults (≥18 years) with cystic fibrosis (awCF) and the effects of elexacaftor-tezacaftor-ivacaftor (ETI) on hyperinflation. METHODS:Consecutive awCF who initiated ETI at Cochin Hospital (Paris, France) and had performed body plethysmography within 12 months prior to ETI initiation were included. Abnormal lung volumes (including total lung capacity (TLC) and residual volume (RV)) were defined as > upper limit of normal (ULN) using the Global Lung Initiative reference values. Lung hyperinflation was defined as RV/TLC>ULN. Variables associated with hyperinflation prior to ETI initiation were identified using multivariate logistic regression analysis. Evolution of hyperinflation was examined by comparing data prior to and after 12 months on ETI. FINDINGS:Body plethysmography was available prior to ETI initiation in 297 awCF, of which 286 had also body plethysmography at 12 months after ETI initiation. Prior to ETI initiation, TLC, RV and RV/TLC ratio values greater than ULN were found in 14%, 69% and 76% of awCF, respectively. RV/TLC ratio inversely correlated with percent predicted forced expiratory volume in 1 s (ppFEV1; r=-0.86). Increasing age and the number of days on intravenous antibiotics in the previous year were independently associated with RV/TLC>ULN. RV/TLC decreased after 12 months of ETI (median (IQR) absolute decrease; -5.4 (-10.3 to -0.3) %, p<0.0001; n=286) but remained above ULN in 65% of awCF, including in some with normal ppFEV1. INTERPRETATION:Lung hyperinflation usually persists in awCF treated with ETI despite improvement in ppFEV1 and lung volumes.

BACKGROUND:Several countries reported a reduction in lung transplants for people with cystic fibrosis (pwCF) after elexacaftor-tezacaftor-ivacaftor (ETI) was introduced. We sought to evaluate how lung transplant indications evolved in relation to CFTR genotypes and the use of ETI. METHODS:All lung transplants performed on pwCF in France between 2015 and 2024 were identified using data from the French Agence de la Biomédecine. Individual-level patient data, including CFTR genotypes and use of ETI at the time of transplant, were obtained from the French CF reference network centers. RESULTS:Between 2015 and 2024, a total of 538 lung transplants were performed, including 461 first-time transplants and 77 re-transplants. The rate of first-time lung transplant was 13.4 per 1000 non-transplanted patients/year versus 1.8 per 1000 non-transplanted patients/year for 2015-2019 (prior to ETI availability) and 2020-2024 (following ETI availability), respectively (P < 0.0001); the rate of lung re-transplant was 10.2 per 1000 transplanted patients/year versus 7.7 per 1000 transplanted patients/year (P = 0.70). Treatment with ETI was prescribed prior to transplant in all F508del pwCF who received a first-time transplant since 2021 and in all those with non-F508del ETI-responsive variants since 2022. Eleven patients treated with ETI required lung transplant due to adverse effects leading to ETI discontinuation, concomitant severe liver disease or insufficient improvement of respiratory failure. CONCLUSION:ETI has reduced, but not eliminated, the need for a first-time lung transplant in pwCF. Indications for a first-time lung transplant persist in a small subset of pwCF who respond to ETI and in those with nonresponsive CFTR genotypes. Re-transplant remains an option for selected transplant recipients with chronic lung allograft dysfunction.

Introduction Les grossesses chez les femmes transplantées pulmonaires sont considérées à haut risque du fait de la fréquence élevée d’hypertension artérielle, de diabète et d’infections. Il existe par ailleurs un risque certain d’allo-immunisation HLA lié à la grossesse, pouvant potentiellement aboutir chez les patientes greffées à un rejet humoral. Quelques cas ont été décrits chez des femmes transplantées rénales, hépatiques et cardiaques, mais ce risque n’avait jamais été étudié en transplantation pulmonaire. L’objectif de notre étude est d’étudier le risque d’apparition d’un rejet humoral dans l’année suivant la grossesse, celui-ci associant l’apparition d’anticorps anti-HLA dirigés contre le donneur (Donnor Specific Antibodies, DSA) et une dégradation de la fonction respiratoire. Méthodes Il s’agit d’une étude rétrospective multicentrique menée dans les 11 centres de transplantation pulmonaire français. Elle concernait les femmes transplantées pulmonaires ayant présenté une grossesse, aboutie ou non, entre le 1er janvier 2012 et le 31 décembre 2021. Résultats Soixante-seize grossesses ont été incluses chez 52 patientes. Il s’agissait principalement de femmes transplantées bi-pulmonaires (n=43 ; 82,7 %), sur mucoviscidose (n=40 ; 76,9 %) ou hypertension pulmonaire (n=11 ; 21 %), dont l’âge moyen à la transplantation était de 24±5 ans, et au début de la grossesse de 31±5 ans. Sur l’ensemble des grossesses, 43 (56,6 %) ont abouti à la naissance d’enfants, dont une grossesse gémellaire, tandis que les autres ont mené à une interruption de grossesse (n=8 ; 10,5 %) ou une fausse couche (n=25 ; 32,9 %). Cinq rejets humoraux (6,6 %) ont été identifiés dans l’année suivant la grossesse, avec un délai moyen de survenue de 6,24±6,02 mois. Deux des 5 grossesses ont abouti à la naissance d’un nouveau-né et 3 à une interruption de grossesse. Ces 5 rejets humoraux ont abouti à la perte du greffon avec 2 décès et 3 retransplantations. Concernant les critères de jugements secondaires, 17 grossesses (22,4 %) ont entraîné une allo-immunisation de novo et 2 autres (2,6 %) une majoration d’une allo-immunisation préexistante. Quand les anticorps anti-HLA étaient des DSA de novo (n=5), un rejet humoral apparaissait dans tous les cas. Trois grossesses ont été suivies d’un rejet aigu cellulaire sans rejet humoral et une grossesse suivie d’un rejet réversible neutrophilique. Aucun facteur de risque de développer un rejet humoral n’a été identifié. Une analyse de survie exploratoire n’a pas montré de différence significative dans une situation d’allo-immunisation. Conclusion La grossesse chez les femmes transplantées pulmonaires semble être à risque d’allo-immunisation HLA et d’apparition de rejet humoral dans l’année qui la suit. Le rejet humoral post grossesse a été responsable d’une perte du greffon pulmonaire dans 100 % des cas de notre étude. Le suivi des anticorps anti-HLA doit donc être rapproché et prolongé durant l’année suivant la grossesse. Une évaluation du risque de rejet humoral par un typage HLA du père en préconceptionnel comparé à celui du greffon peut se discuter. Un typage HLA de l’enfant sur sang ombilical peut également être proposé afin de renforcer l’immunosuppression en cas d’antigènes HLA communs entre le greffon et l’enfant.

Introduction La dyskinésie ciliaire primitive (DCP) est une maladie génétique rare responsable de dilatations des bronches diffuses, associées chez certains patients à une anomalie de la latéralité des organes. La maladie se complique rarement d’une insuffisance respiratoire chronique qui peut justifier d’une transplantation pulmonaire. L’objectif de cette étude est de décrire l’activité et les résultats de la transplantation pulmonaire pour DCP en France, et de mieux caractériser les patients transplantés. Méthodes Il s’agit d’une étude rétrospective multicentrique. La population cible était l’ensemble des patients transplantés en France avec une indication de DCP, depuis le début de l’activité de greffe jusqu’au 1er mai 2024. Résultats Les données de 33 patients greffés entre 2006 et 2024 ont été recueillies dans huit centres français. Ces greffes représentent 0,58 % des transplantations pulmonaires réalisées sur cette période en France. La proportion d’hommes (n=18, 54,5 %) et de femmes (n=15, 45,5 %) était équilibrée. La moitié des patients présentait une anomalie de la latéralité des organes (n=16 soit 48,5 %, dont 15 situs inversus). L’âge médian à la greffe était de 52,3ans. Leur fonction respiratoire était déjà très altérée cinq ans avant la greffe avec un VEMS médian à 35,0 % de la valeur théorique. Ils étaient tous insuffisants respiratoires chroniques sous oxygénothérapie de longue durée. Une large proportion était colonisée à Pseudomonas aeruginosa (n=31, 93,9 %), avec en médiane trois cures d’antibiothérapie intra-veineuse dans l’année avant la greffe. En post-greffe, la médiane de survie globale est de 7,9ans, et la médiane de survie sans dysfonction chronique du greffon de 6,7ans. La survie globale a augmenté de manière non significative entre la première période (février 2006–janvier 2015) et la deuxième période de greffe (février 2015–janvier 2024) (HR : 0,606, IC95 % [0,195; 1,890], p=0,3680); elle est en revanche comparable entre les patients avec et sans anomalie de la latéralité des organes. Il existe une augmentation non significative des complications anastomotiques nécessitant un geste thérapeutique, chez les patients avec anomalie de latéralité des organes (n=9, 56,3 %) en comparaison aux patients sans anomalie de la latéralité des organes (n=4, 23,5 %, p=0,080). Conclusion La dyskinésie ciliaire primitive est une indication très rare de transplantation pulmonaire en France, avec des résultats satisfaisants en termes de survie.

Background:Elexacaftor-tezacaftor-ivacaftor (ETI) became available for adults with cystic fibrosis (CF) in 2019, but its impact on CF-related diabetes (CFRD) remains unclear. Methods:A single-center retrospective cohort study was conducted among adults with CFRD to examine the change in insulin dose-adjusted Hemoglobin A1c (IDAA1c). Linear mixed effects model (LMEM) analysis was used to investigate the change in IDAA1c between baseline and 24 months of follow up, comparing an ETI-treated group to an unexposed group. Baseline values were those documented at treatment initiation for the ETI-treated group and in March 2020 (±3 months) for the unexposed group. Results:A total of 49 adults were included, 39 were treated with ETI and 10 were not. Median [Interquartile range] time since CFRD diagnosis at baseline was 13 [7-18] and 14 [10-18] years, respectively (p = 0.610). In the ETI-treated group, mean weight increased by a 4.44 kg (95 % Confidence Interval, 95 %CI: 3.08 to 5.79, p < 0.001), insulin total daily dose decreased by 5 units (95 %CI: -9 to 0, p = 0.033), and hemoglobin A1c (%) decreased by 0.65 points (95 %CI: -0.96 to -0.34, p < 0.001). No change was observed in the unexposed group. LMEM analysis found a numerically significant association between ETI and decreased IDAA1c, estimated at -1.14 points (95 %CI: -2.35 to 0.06, p = 0.067) after adjusting for age, sex, time since CFRD diagnosis and the introduction of Metformin. Conclusion:A numerically significant association between ETI and IDAA1c decrease was observed in adults with established CFRD after 24 months of treatment, suggesting ETI contributed to improved glycemic control.

Elexacaftor–tezacaftor–ivacaftor (ETI), a combination of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, has become the therapeutic standard of care for most people with cystic fibrosis (pwCF). People with cystic fibrosis exhibit differences in CFTR genotypes and have important differences in phenotypic characteristics including age, body weight, pancreatic status, disease severity, and comorbidities. While these differences predict large interindividual variability (IIV) in ETI exposure, there is a unique dose regimen recommended for adults. This raises questions around the “one-dose fits all” strategy. The aims of this study were to describe real-world population pharmacokinetics (Pop-PK) of ETI in adults with CF and identify factors associated with IIV. As part of the ongoing French national observational cohort study the Pop-PK analysis included 552 plasma concentrations drawn routinely from 325 adults with CF. A one-compartment model with first order absorption and elimination best represented all three compounds, and an additional lag-time for elexacaftor PK data. Large IIV was observed in ETI, with an area under the curve (AUC0–24h for elexacaftor and tezacaftor, and AUC0–12h for ivacaftor) ranging respectively, from 58.7–422.9 mg⋅h/L; 38.0–207.7 mg⋅h/L and 4.9–64.9 mg⋅h/L. The main sources of IIV identified in the final ETI Pop-PK models were body weight, age, exocrine pancreatic insufficiency and CFTR genotype. This study established the first ETI Pop-PK analysis in adults with CF and identified several covariates that explain IIV. Therapeutic drug monitoring may be beneficial for patients with a small body weight, older ages, carrying one ETI-responsive CFTR variant or those with no exocrine pancreatic insufficiency and especially for patients who combine these characteristics. Therapeutic drug monitoring may also prove to be useful in individuals experiencing adverse events, in those with reduced effectiveness, or to help manage non-adherence issues.

PURPOSE:The purpose of this study was to evaluate the relationship between structural abnormalities on CT and lung function prior to and after initiation of elexacaftor-tezacaftor-ivacaftor (ETI) in adults with cystic fibrosis (CF) using a deep learning model. MATERIALS AND METHODS:A deep learning quantification model was developed using 100 chest computed tomography (CT) examinations of patients with CF and 150 chest CT examinations of patients with various other bronchial diseases to quantify seven types of abnormalities. This model was then applied to an independent dataset of CT examinations of 218 adults with CF who were treated with ETI. The relationship between structural abnormalities and percent predicted forced expiratory volume in one second (ppFEV1) was examined using general linear regression models. RESULTS:The deep learning model performed as well as radiologists for the quantification of the seven types of abnormalities. Chest CT examinations obtained before to and one year after the initiation of ETI were analyzed. The independent structural predictors of ppFEV1 prior to ETI were bronchial wall thickening (P = 0.011), mucus plugging (P < 0.001), consolidation/atelectasis (P < 0.001), and mosaic perfusion (P < 0.001). An increase in ppFEV1 after initiation of ETI independently correlated with a decrease in bronchial wall thicknening (-49 %; P = 0.004), mucus plugging (-92 %; P < 0.001), centrilobular nodules (-78 %; P = 0.009) and mosaic perfusion (-14 %; P < 0.001). Younger age (P < 0.001), greater mucus plugging extent (P = 0.016), and centrilobular nodules (P < 0.001) prior to ETI initiation were independent predictors of ppFEV1 improvement. CONCLUSION:A deep learning model can quantify CT lung abnormalities in adults with CF. Lung function impairment in adults with CF is associated with muco-inflammatory lesions on CT, which are largely reversible with ETI, and with mosaic perfusion, which appear less reversible and is presumably related to irreversible damage. Predictors of lung function improvement are a younger age and a greater extent of muco-inflammatory lesions obstructing the airways.

BACKGROUND:The forced expiratory volume in one second (FEV1) is the standard measure used to monitor the lung function after lung transplantation. However, little is known about the FEV1 trajectories post transplantation, and their associations with clinical outcomes. METHODS:Adult patients who received a bilateral lung transplant between January 1, 2010 and January 1, 2021 were included from 15 centers in France, Belgium, Austria and the US. Three French centers formed the development cohort and the remaining centers formed the external validation cohorts. All centers performed routine spirometry measurements commencing shortly after lung transplantation and continuing at regular intervals of maximum three months afterwards. Recipient, donor and transplant characteristics were collected. Latent class mixed models were used to identify FEV1 trajectories. The number of FEV1 trajectories was defined according to the Akaike Information Criterion, Bayesian Information Criterion, the discrimination, the entropy and the interpretability of the model. FINDINGS:A total of 2305 patients were included with 59 034 FEV1 measurements collected. The median follow-up post-transplantation was 4.3 years (IQR 2.3-6.2). In the development cohort (n=605), the best latent class mixed model identified seven clinically meaningful FEV1 trajectories. Trajectory #1 (25.6%) was characterized by patients with moderate and stable lung function (3-year patient survival = 79.9%); trajectory #2 (24.0%) and #3 (27.3%) were characterized by patients with moderate/high and stable lung function (3-year patient survival = 96.6% and 95.7% respectively); trajectory #4 (3.8%) was characterized by patients with increasing lung function (3-year patient survival = 69.6%); trajectory #5 (11.7%) was characterized by patients with a slow decline (3-year patient survival = 90.1%); and trajectory #6 (3.0%) and #7 (4.6%) were characterized by patients with accelerated decline (3-year patient survival = 33.3% and 59.5% respectively). Patients belonging to trajectories were associated with gender (p=0.020) and underlying disease (p=0.004). Similar FEV1 trajectories and patient outcomes were identified in the external validation cohorts on the basis of independent analyses. The trajectories were also confirmed in a series of subpopulations. Last, FEV1 value and slope at 1 year post transplant were strongly associated with FEV1 trajectories, in both the development cohort and the external validation cohorts. INTERPRETATION:We identified and validated FEV1 trajectories that capture different clinical scenarios associated with post-transplant recipient outcomes. Our results may provide the basis for a trajectory-based risk assessment of lung transplant recipients. FUNDING:"Vaincre la mucoviscidose" grant, the association Grégory Lemarchal, ANR grant, PHRC grant, the FP7 collaborative project, IRSRPL grant, the Fondation du Souffle and PLUTO DITCAP grant from Vaincre la Mucoviscidose and Association Grégory Lemarchal.

BACKGROUND:Pregnancies in women with lung transplants are considered high-risk due to comorbidities. There is a risk of pregnancy-related antihuman leukocyte antigen alloimmunization, which can potentially lead to antibody-mediated rejection in transplant patients. A few such cases have been reported in women receiving kidney, liver, or heart transplants, but this risk has never been studied in lung transplantation. The aim of our study was to investigate the risk of developing antibody-mediated rejection in the year following pregnancy. METHODS:This is a multicenter retrospective study carried out in 11 French lung transplant centers. We included lung transplant recipients who had a pregnancy between January 1, 2012 and December 31, 2021. RESULTS:Seventy-six pregnancies were included in 52 patients. These were mainly women with double lung transplantation (n = 43; 82.7%). Cystic fibrosis (n = 40; 76.9%) and pulmonary hypertension (n = 11; 21%) were the main underlying diseases for transplantation. Of the 76 pregnancies, 43 (56.6%) resulted in the birth of live children, while the others resulted in abortion (n = 8; 10.5%) or miscarriage (n = 25; 32.9%). Five antibody-mediated rejections (6.6%) were identified in the year following pregnancy, with a mean time of 6.24 ± 6.02 months between the end of pregnancy and rejection. All 5 rejections resulted in graft loss, of which 2 deaths and 3 retransplantations. Nineteen pregnancies (25%) resulted in alloimmunization. When antihuman leukocyte antigen antibodies were de novo donor-specific antibodies (n = 5), antibody-mediated rejection occurred in all cases. CONCLUSIONS:Pregnancy in female lung transplant recipients appears to be at risk of humoral rejection in the year following pregnancy.

Background This study sought to evaluate the impact of elexacaftor/tezacaftor/ivacaftor (ETI) on lung structural abnormalities in adults with cystic fibrosis (awCF) with a specific focus on the reversal of bronchial dilatations. Methods Chest computed tomography (CT) scans performed prior to and 12 months after initiation of ETI were visually reviewed for possible reversal of bronchial dilatations. AwCF with and without reversal of bronchial dilatations (the latter served as controls, with three controls per case) were selected. Visual Brody score, bronchial and arterial diameters, and lung volume were measured on CT. Results Reversal of bronchial dilatations was found in 12/235 (5%) awCF treated with ETI. 12 awCF with and 36 without reversal of bronchial dilatations were further analysed (male 56%, mean± sd age 31.6±8.5 years, F508del/F508del CFTR 54% and mean forced expiratory volume in 1 s 58.8±22.3% predicted). The Brody score improved overall from 79.4±29.8 to 54.8±32.3 (p<0.001). Reversal of bronchial dilatations was confirmed by a decrease in bronchial lumen diameter in cases from 3.9±0.9 to 3.2±1.1 mm (p<0.001), whereas it increased in awCF without reversal of bronchial dilatations (from 3.5±1.1 to 3.6±1.2 mm; p=0.002). Reversal of bronchial dilatations occurred in cylindrical (not varicose or saccular) bronchial dilatations. Lung volumes decreased by −6.6±10.7% in awCF with reversal of bronchial dilatations but increased by +2.3±9.6% in controls (p=0.007). Conclusions Although bronchial dilatations are generally considered irreversible, ETI was associated with reversal, which was limited to the cylindrical bronchial dilatation subtype, and occurred in a small subset of awCF. Initiating ETI earlier in life may reverse early bronchial dilatations.

COVID-19 is associated with heterogeneous outcome. Early identification of a severe progression of the disease is essential to properly manage the patients and improve their outcome. Biomarkers reflecting an increased inflammatory response, as well as individual features including advanced age, male gender, and pre-existing comorbidities, are risk factors of severe COVID-19. Yet, these features show limited accuracy for outcome prediction. The aim was to evaluate the prognostic value of whole blood transcriptome at an early stage of the disease. Blood transcriptome of patients with mild pneumonia was profiled. Patients with subsequent severe COVID-19 were compared to those with favourable outcome, and a molecular predictor based on gene expression was built. Unsupervised classification discriminated patients who would later develop a COVID-19-related severe pneumonia. The corresponding gene expression signature reflected the immune response to the viral infection dominated by a prominent type I interferon, with IFI27 among the most over-expressed genes. A 48-genes transcriptome signature predicting the risk of severe COVID-19 was built on a training cohort, then validated on an external independent cohort, showing an accuracy of 81% for predicting severe outcome. These results identify an early transcriptome signature of severe COVID-19 pneumonia, with a possible relevance to improve COVID-19 patient management.

In people with cystic fibrosis and advanced lung disease, circulating neutrophils were often elevated under clinically stable conditions. Treatment with elexacaftor-tezacaftor-ivacaftor for 12 months is associated with normalisation of neutrophil counts. http://bit.ly/3gtgDFx

Question addressed by the studyDo three coronavirus disease 2019 (COVID-19) vaccine doses induce a serological response in lung transplant recipients?MethodsWe retrospectively included 1071 adults (551 (52%) males) at nine transplant centres in France. Each had received three COVID-19 vaccine doses in 2021, after lung transplantation. An anti-spike protein IgG response, defined as a titre >264 BAU·mL−1after the third dose (median (interquartile range (IQR)) 3.0 (1.7–4.1) months), was the primary outcome and adverse events were the secondary outcomes. Median (IQR) age at the first vaccine dose was 54 (40–63) years and median (IQR) time from transplantation to the first dose was 64 (30–110) months.ResultsMedian (IQR) follow-up after the first dose was 8.3 (6.7–9.3) months. A vaccine response developed in 173 (16%) patients. Factors independently associated with a response were younger age at vaccination, longer time from transplantation to vaccination and absence of corticosteroid or mycophenolate therapy. After vaccination, 51 (5%) patients (47 non-responders (47/898 (5%)) and four (4/173 (2%)) responders) experienced COVID-19, at a median (IQR) of 6.6 (5.1–7.3) months after the third dose. No responders had severe COVID-19 compared with 15 non-responders, including six who died of the disease.ConclusionsFew lung transplant recipients achieved a serological response to three COVID-19 vaccine doses, indicating a need for other protective measures. Older age and use of mycophenolate or corticosteroids were associated with absence of a response. The low incidence of COVID-19 might reflect vaccine protectionviacellular immunity and/or good adherence to shielding measures.

To describe clinical and early shoulder-girdle MR imaging findings in severe COVID-19–related intensive care unit-acquired weakness (ICU-AW) after ICU discharge. A single-center prospective cohort study of all consecutive patients with COVID-19–related ICU-AW from November 2020 to June 2021. All patients underwent similar clinical evaluations and shoulder-girdle MRI within the first month and then 3 months (± 1 month) after ICU discharge. We included 25 patients (14 males; mean [SD] age 62.4 [12.5]). Within the first month after ICU discharge, all patients showed severe proximal predominant bilateral muscular weakness (mean Medical Research Council total score = 46.5/60 [10.1]) associated with bilateral, peripheral muscular edema-like MRI signals of the shoulder girdle in 23/25 (92 • We describe the clinical and shoulder-girdle MRI findings of COVID-19–related severe intensive care unit-acquired weakness. • This information can be used by clinicians to achieve a nearly specific diagnosis, distinguish alternative diagnoses, assess functional prognosis, and select the more appropriate health care rehabilitation and shoulder impairment treatment.