Initiation of extracorporeal photopheresis in lung transplant patients with mild to moderate refractory BOS: A single-center real-life experience.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the main limitation to long-term survival following lung transplantation. Several studies generated promising results regarding the efficacy of extracorporeal photopheresis (ECP) in BOS management. We aimed to compare FEV1 evolution in ECP-treated versus non-ECP treated patients among BOS recipients. METHODS: Overall, 25 BOS patients were included after receiving optimized treatment. Data were collected retrospectively. Twelve patients with moderate and refractory BOS received ECP treatment. RESULTS: Among non-ECP treated control patients (n = 13), six experienced persistent decline without undergoing ECP for various reasons. ECP stabilized pre-ECP lung function during the subsequent 6 to 24 months (repeated measures one-way Anova, p = 0.002), without any significant impact observed by either FEV1 decline speed prior to ECP or time between BOS diagnosis and ECP onset. ECP-treated patients displayed a similar risk of an additional permanent 20% or higher drop in FEV1 after BOS onset compared to controls, but a lower risk compared to control decliners (p = 0.05). ECP quickly stabilized FEV1 decline in refractory BOS patients compared to non-treated decliners. CONCLUSIONS: We confirmed that this therapeutic option against refractory BOS can be managed in a medium-size LTx center, with a satisfactory efficacy and an acceptable tolerance.

Torque teno virus DNA load as a predictive marker of antibody response to a three-dose regimen of COVID-19 mRNA-based vaccine in lung transplant recipients.

BACKGROUND: Previous studies have reported that lung transplant recipients (LTR) develop a poor response to two doses of COVID-19 vaccine, but data regarding the third dose are lacking. We investigated the antibody response after three doses of mRNA vaccine in LTR and its predictive factors. METHODS: A total of 136 LTR, including 10 LTR previously infected and 126 COVID-19-naive LTR, were followed during and after three doses of mRNA vaccine. We retrospectively measured anti-receptor-binding domain (RBD) IgG response and neutralizing antibodies. In a posthoc analysis, we used a multivariate logistic regression model to assess the association between vaccine response and patient characteristics, including viral DNA load (VL) of the ubiquitous Torque teno virus (TTV) (optimal cut-off set by ROC curve analysis), which reflects the overall immunosuppression. RESULTS: After 3 doses, 47/126 (37.3%) COVID-19-naive LTR had positive anti-RBD IgG (responders) and 14/126 (11.1%) had antibody titers above 264 Binding Antibody Units/mL. None neutralized the omicron variant versus 7 of the 10 previously infected LTR. Nonresponse was associated with TTV VL ≥6.2 log10 copies/mL before vaccination (Odds Ratio (OR) = 17.87, 95% confidence interval (CI95) = 3.02-105.72), mycophenolate treatment (OR = 4.73, CI95 = 1.46-15.34) and BNT162b2 (n = 34; vs mRNA-1273, n = 101) vaccine (OR = 6.72, CI95 = 1.75-25.92). In second dose non-responders, TTV VL ≥6.2 or <3.2 log10 copies/mL before the third dose was associated with low (0/19) and high (9/10) rates of seroconversion. CONCLUSION: COVID-19-naive LTR respond poorly to three doses of mRNA vaccine, especially those with high TTV VL. Future studies could further evaluate this biomarker as a guide for vaccine strategies.

Atypical Unilateral SARS-CoV-2 Pneumonia in a Single Lung Re-Transplanted Patient: A Case Report.

BACKGROUND: Since December 2019, the SARS-CoV-2 pandemic significantly has impacted the medical community. When infected with SARS-CoV-2, most of the patients developed bilateral pneumonia. We have herein presented the atypical case of a patient who developed unilateral SARS-CoV-2 pneumonia, affecting only the second lung allograft re-transplanted (re-LTX). CASE PRESENTATION: A SARS-CoV-2 infection occurred in a 2-dose vaccinated patient with LTx with a history of second unilateral lung transplantation performed after an end-stage bronchiolitis obliterans syndrome. The first symptoms started with a flu-like syndrome, and the patient's clinical condition worsened with nonsevere acute respiratory failure requiring conventional oxygen therapy. Treatment consisted in administrating specific anti-SARS-CoV-2 monoclonal antibodies along with probabilistic antibiotherapy, anticoagulation, and steroids. On day 7, the patient was discharged from hospital. We aimed to assess this atypical unilateral pneumonia based on different explorations. A ventilation scintigraphy showed a severe ventilation decrease owing to end-stage bronchiolitis obliterans syndrome within the left first allograft, which may be associated with asymmetrical virus diffusion between the 2 lungs. We did not identify any other relevant differences with respect to the 2 donors' clinical characteristics. Using specific immunohistochemistry staining against angiotensin converting enzyme-2 receptor, the main known receptor for SARS-CoV-2 binding on airway epithelial cells, no staining difference was observed between the 2 lung biopsies that were collected at re-LTx from each lung. CONCLUSIONS: With the present case report, we aimed to highlight how this kind of unusual presentation may be caused by the difference of ventilation between the 2 lungs.

The social and clinical impact of the COVID-19 epidemic on the Strasbourg lung transplant cohort: A single-center retrospective cohort study.

The clinical and social impacts of the COVID-19 epidemic on lung transplant (LTx) recipients remain poorly known. We aimed to evaluate its social, clinical, and behavioral consequences on the LTx patients followed in Strasbourg university hospital. A questionnaire was used to collect details concerning patients' lifestyles, their protection methods used to avoid COVID-19 contamination, and clinical infection-related information for March 2020. A specific score was created to quantify patients' contacts and the associated risk of infectious contagion. Data were collected from 322 patients (91.2%). A majority reported a higher application than usual of social distancing and barrier measures. 43.8% described infectious-related symptoms and 15.8% needed an anti-infective treatment. There was no difference in symptom onset according to age, native lung disease, diabetes, or obesity. Nineteen patients were tested for COVID-19, and four were diagnosed positive, all with a favorable outcome. The infection risk contact score was higher for symptomatic patients (p: 0.007), those needing extra-medical appointments (p < .001), and those receiving anti-infective treatments (p = .02). LTx patients reported a careful lifestyle and did not seem at higher risk for COVID-19. Our score showed encouraging preliminary results and could become a useful tool for the usual infection-related follow-up of the LTx patients.

Bilateral Acute Cardioembolic Limb Ischemia After Coronavirus Disease 2019 Pneumonia in a Lung Transplant Recipient: A Case Report.

Very few cases of lung transplant patients affected by coronavirus disease 2019 (COVID-19) have been reported to date. A 31-year-old patient who underwent bilateral lung transplantation for cystic fibrosis in 2012 was admitted for severe acute lower limb pain. He had a confirmed exposure to COVID-19 and a 3-week history of upper respiratory tract infection. Whole-body computed tomography (CT) angiography revealed an occlusion of the 2 common femoral arteries. CT angiography detected an intracardiac thrombus in the left ventricle. Chest CT angiography showed ground-glass opacities consistent with COVID-19. A bilateral femoral surgical embolectomy using Fogarty catheter was successfully performed. Specific reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 performed on an extracted thrombus was negative, but IgM antibodies specific for COVID-19 were detected. Cardiac magnetic resonance imaging demonstrated a subendocardial and almost transmural late gadolinium enhancement in the mid and distal inferolateral and inferior wall segments, consistent with a nonrecent myocardial infarction and an apical centimetric thrombus adjacent to the lesion. Thrombophilia laboratory tests found the presence of a positive lupus anticoagulant. Treatment with low-molecular-weight heparin and aspirin was prescribed. On day 13, the patient was discharged from the hospital. This case underlines the need to be vigilant with respect to the thrombotic complications of COVID-19 and raises the issue of thrombosis prevention in COVID-19 patients.

SARS-CoV-2 Pneumonia in Hospitalized Asthmatic Patients Did Not Induce Severe Exacerbation.

BACKGROUND: Viral infections are known to exacerbate asthma in adults. Previous studies have found few patients with asthma among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia cases. However, the relationship between SARS-CoV-2 infection and severe asthma exacerbation is not known. OBJECTIVE: To assess the frequency of asthma exacerbation in patients with asthma hospitalized for SARS-CoV-2 pneumonia and compare symptoms and laboratory and radiological findings in patients with and without asthma with SARS-CoV-2 pneumonia. METHODS: We included 106 patients between March 4 and April 6, 2020, who were hospitalized in the Chest Diseases Department of Strasbourg University Hospital; 23 had asthma. To assess the patients' asthma status, 3 periods were defined: the last month before the onset of COVID-19 symptoms (p1), prehospitalization (p2), and during hospitalization (p3). Severe asthma exacerbations were defined according to Global INitiative for Asthma guidelines during p1 and p2. During p3, we defined severe asthma deterioration as the onset of breathlessness and wheezing requiring systemic corticosteroids and inhaled ß2 agonist. RESULTS: We found no significant difference between patients with and without asthma in terms of severity (length of stay, maximal oxygen flow needed, noninvasive ventilation requirement, and intensive care unit transfer); 52.2% of the patients with asthma had Global INitiative for Asthma step 1 asthma. One patient had a severe exacerbation during p1, 2 patients during p2, and 5 patients were treated with systemic corticosteroids and inhaled ß2 agonist during p3. CONCLUSIONS: Our results demonstrate that patients with asthma appeared not to be at risk for severe SARS-CoV-2 pneumonia. Moreover, SARS-CoV-2 pneumonia did not induce severe asthma exacerbation.