Safety and Immunogenicity of the AntiCOVID19 Vaccines in a Cohort of Lung Transplant Recipients

Lung transplant recipients (LuTxR) are at greater risk of COVID-19 and have attenuated response to vaccinations. In Italy, immunocompromised patients received the indication to be administered mRNA vaccines only. We aimed to evaluate the safety and immunogenicity of these vaccines in our cohort of LuTxR;we are now presenting the preliminary data of their serologic responses. We conducted a single-center observational prospective study including all consecutive LuTxR who were administered two doses of mRNA antiCOVID19 vaccine at our institution in March 2021;NCT05116748. We investigated the incidence of systemic and local adverse events and, in order evaluate immunogenicity, we used ImmunoAssay in ECLIA for the quantitative detection of anti-protein S1 (spike) antibodies (including IgG) on venous blood samples at 60 and 80 (+/- 10) days from the vaccine administration. 116 patients were enrolled, 52 females. Table 1 summarizes the basic characteristics of our population. Figure 1 focalizes on different serologic responses based on immunosuppressive regimens. No serious adverse events were reported. The most common solicited adverse events were fever (52% of our patients), headache, fatigue, myalgia, chills, and injection-site pain. Our initial findings are reassuring. Humoral SARS-CoV-2 specific immunity in our cohort of patients tended to be stronger than expected. mRNA vaccines appeared to be safe in the transplant population, and have not raised serious concern about the possible onset of graft dysfunction or other serious adverse events in the first period after their administration. [ABSTRACT FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Telemonitoring: An Opportunity to Improve Multidisciplinary Care in Lung Transplanted Patients

Purpose: Telemedicine has been successfully employed in a wide range of specialties. We hereby present the results of a pivotal study we ran in our centre just before the COVID19 pandemic. Methods: This was a prospective study including all adult cystic fibrosis patients who underwent lung transplant (LuTx) from September 2017 to August 2019. Patients were randomized into two groups;patients assigned to the first arm (intervention) received a home medical assistant (HMA) system device, to which a pulse oximeter and a spirometer with reusable turbine were integrated;they were asked to perform a spirometry and register their SpO2 at rest and on effort on a twice-weekly basis. All the data were digitally transmitted to our centre, where physiotherapists and physicians were able to analyse them real-time. Both the groups received traditional hospital-based follow-up. Results: 32 patients were enrolled, 16 in each group. No statistically significant difference was found between the two groups (see Table 1).With reference to the telemonitoring group:- Adherence to telemonitoring significantly decreased during the 12months period of follow up (see figure 1).- Hospital reported data were consistent with the last being registered with the HMA device.- Of note, two patients were requested to anticipate their hospital routine visit because of a FEV1 decrease being reported on their HMA device, in order to rule out possible acute lung allograft dysfunction.- 13 out of 16 patients reported a high degree of satisfaction with the telemonitoring experience. Conclusion: The COVID19 pandemic highlighted the necessity to investigate alternative practices to treat chronically ill individuals. In our study, telemonitoring proved to be a valuable tool to improve quality health care to LuTx recipients, especially for those who live far from the transplant centre. We are now implementing this approach scheduling online video consultations. Further research should be focused on standardizing quality of telemedicine services.

COVID19 in Lung Transplanted Patients: Chronicles from an Italian Epicenter

Purpose Lombardy was one of the hardest hit regions in Italy during the COVID19 pandemic. We hereby report our experience with SARS-CoV2 infection in lung transplant recipients. Methods We retrospectively collected clinical data on all the consecutive cases of COVID19 in our centre, based in Milan, from March 2020 to August 2021. Diagnosis was always confirmed by a positive nucleic acid amplification test (RT-PCR) for SARS-CoV-2 on nasopharyngeal swab and/or tracheal aspirate. Results 21 patients were diagnosed with COVID19. Figure 1 summarizes the clinical course of these individuals. We reduced immunosuppressive regimen in all these patients, typically holding the antiproliferative agent and augmenting steroids;when hospitalized, everybody received initial empiric antibiotic treatment with piperacillin/tazobactam and high-dose LMWH. Hydroxychloroquine was used only in the "first wave" (4 patients). One patient was compassionately administered anakinra and remdesivir as a “rescue therapy”. Lymphocitopenia was a common presenting sign (14 patients, 66%). Aspergillus co-infection occurred in 5 patients (24%). Mortality rate was 29%;4 out of these 6 patients were affected by CLAD and 3 had chronic kidney disease. Of note, in March 2021, we tested all our patients for anti-SARS-CoV-2 nucleocapsid antibodies before starting vaccinations: we found three additional seropositive patients, who were not included in the present analysis, but had been presumably affected by an asymptomatic/mild form of the disease. Conclusion Apart from immunosuppression, the majority of our patients presented at least one risk factor for mortality in COVID-19 (diabetes, chronic kidney disease, arterial hypertension) and, for this reason, we felt that they should be hospitalized to enable close monitoring and prompt management of possible complications and deterioration. Clinical course seemed favorable in only two thirds of our patients but, for the time being, none of these individuals showed sign of new-onset CLAD after COVID19.

Lung Allograft Dysfunction in a COVID-19 Transplanted Patient is Associated with a Peculiar Immunopathological Phenotype

Purpose Lung transplantation (LT) after severe SARS-CoV-2 infection is emerging as a life-saving medical procedure for selected patients who experience acute respiratory distress syndrome (ARDS). We present the first immunopathological evaluation of a lung allograft rejection in a patient who underwent LT because of irreversible ARDS related to COVID-19. Methods Two male patients with irreversible ARDS caused by COVID-19 underwent bilateral LT at our Institution. A surveillance transbronchial biopsy (TBB) was performed 2 months after LT in the first patient (Pt#1), while the second patient (Pt#2) died because of allograft rejection at day 62 post LT and explanted lungs were retrieved. CT imaging of the lungs was performed three days before death. Morphological examination was performed by H&E, whereas the immunophenotyping was performed by immunohistochemistry. Results Imaging and morphological examination of Pt#2 lungs indicated the presence of a graft dysfunction with features of a restrictive, widespread usual interstitial pneumonia-like syndrome (Fig. 1A, B). The immunophenotyping showed that B-lymphocytes (CD20-positive) were nearly absent, CD8-T-cells were not particularly expanded (mean positive cells within the lung stroma=13.8%;Fig. 1C), and the CD4/CD8 ratio was not decreased (Fig. 1D). The T-regs (Foxp3-positive) were 6% of the overall population (Fig. 1E). Analysis of the immune checkpoint molecules PD1, Tigit, CTLA4 and PDL1 showed that the expression of PD-L1 alone was highly increased in vases and in alveolar cells of rejected lungs, whereas it was nearly undetectable in the TBB from Pt#1 (Fig. 1F, G). Conclusion PDL1 expression in vases was previously documented as a sign of indirect ARDS. Together with our preliminary data, we can hypothesize that PDL1 may play a role in tissue effacement and graft failure, possibly indicating poor allograft prognosis.