BackgroundNeutrophil extracellular trap (NET) formation (NETosis) has been proposed as a contributor to the pathophysiology of Long COVID (LC). However, it remains unclear whether markers of systemic NETosis remain elevated in individuals with persistent symptoms years after the initial infection.MethodsTo assess NETosis, we quantified MPO-DNA, Histone DNA, and Citrullinated H3 levels in the plasma of 51 patients with prolonged LC (mean disease duration of three years), and compared them with 52 age- and sex-matched healthy controls.ResultsNo significant differences were observed between participants with LC and healthy controls for any of the three NETosis markers. Hierarchical clustering reveals no specific subgroups in the patient group. Furthermore, NETosis marker levels were not associated with overall symptom burden or individual symptom domains.ConclusionsIn this cohort of individuals with long-term LC, we found no evidence of persistent systemic NETosis. These findings suggest that elevated circulating NETosis markers are not a universal feature of long-term LC and may indicate that neutrophil activation observed during acute or early post-acute disease does not persist in long-term disease.

Background:Identifying and addressing long-term health and societal challenges after COVID-19 is a research priority. Objectives:To create an international, multidisciplinary COVID-19 database, and synthesise long-term outcomes, predictors and costs. Design:Systematic identification of COVID-19 data sets and meta-analysis of individual participant data on long-term outcomes after COVID-19. Setting:Contributed data were collected in clinical, community and research settings. Interventions:Interventions from original studies were included as covariates in models. Data sources:MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, PsycInfo® (American Psychological Association, Washington, DC, USA), Cumulative Index to Nursing and Allied Health Literature, World Health Organization Global Index Medicus, Epistemonikos, LitCOVID; World Health Organization International Clinical Trials Registry Platform; ClinicalTrials.gov and supplementary searches for studies (November 2019-November 2021) were searched for studies on > 10 people from cohort, case-control, survey or randomised controlled trial studies, across any setting, describing validated assessment instruments, symptoms, hospitalisation, discharge destination or mortality beyond 28-days after COVID-19 onset. Data were extracted by two independent reviewers. Methods:Principal investigators contributed fully anonymised individual participant data. Demography, equity and symptoms were described. Assessment instruments were mapped to the International Classification of Functioning, Disability and Health. Factors associated with outcomes at 3-6 months, 9-12 months and beyond 12 months of index infection, for n > 500 individual participant data and > 1 data set were described using ratio of difference, point estimates, odds ratio and 95% confidence interval, as appropriate. The Mixed Methods Appraisal Tool described study quality; models were appraised using a Grading of Recommendations Assessment, Development and Evaluation-informed approach; heterogeneity was described using I2. Outcome measures:Included overall perception of health, multidomain cognitive function, anxiety, depression, stress, post-traumatic stress disorder, fatigue, strength, walking ability, mobility, coping with daily life, breathlessness, mortality, later hospitalisation and health-related quality of life. Results:PRECIOUS collated 116 data sets from 40 countries (individual participant data = 62,849), comprising 20 randomised controlled trials, 13 case-control, 60 cohort 2 longitudinal, 1 survey and 20 other study types. Participants' median age was 58 years interquartile range (45-68); 34,185 (54.4%) were female; 158 unique symptoms and 137 unique assessment instruments were captured, predominantly describing International Classification of Function, Disability and Health-body functions. Women had poorer outcomes across 30/37 models, compared with men. In 15/37 models, pre-existing lung disease and increasing age were associated with poorer outcomes; hospitalisation, diabetes and chronic kidney disease were each associated with poorer outcomes in 8/37 models. Initial hospitalisation resulted in lower health-related quality of life that did not recover for up to 2 years after initial infection. Heterogeneity was low in 34/37 models; 22/37 models were of moderate and 11/37 were of low quality. Limitations:Use of secondary data limits available covariates, outcomes and time points to those included in primary data sets; evidence was primarily based on high-income countries. There was a lack of data on longer-term healthcare resource use to estimate the costs to the healthcare system. Conclusions:PRECIOUS contributes to the overall picture of long-term COVID-19 outcomes beyond the long-COVID condition and highlights poorer long-term outcomes in women and people with pre-existing comorbidities. Future work:Evidence gaps included healthcare resource use, isolation, loneliness, societal participation and return to work outcomes. Data are needed on the role of health inequity on long-term outcomes. Study registration:This study is registered as PROSPERO (CRD42020224323, IRAS ID: 293578). Funding:This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132895) and is published in full in Health and Social Care Delivery Research; Vol. 14, No. 29. See the NIHR Funding and Awards website for further award information.

Background:Literature on pregnancy after heart and/or lung transplantation (heart transplantation (HTx), lung transplantation (LTx), heart lung transplantation (HLTx)) remains sparse. This study assessed short- and long-term outcomes of pregnancies post-thoracic organ transplantation across Europe and analyzed center management of these patients. Methods:European centers provided retrospective data on post-HTx/LTx pregnancies and center strategies for handling transplant recipients with a pregnancy wish. Descriptive statistics and linear regression analysis were used. Results:Forty-two females had 50 pregnancies across 12 European centers. Pregnancy-induced hypertension occurred in 50% (HTx), 28% (LTx), and 20% (HLTx), and preeclampsia in 19%, 16%, and 20%, respectively. Preterm birth (<37 weeks) occurred in 23% (HTx) and 68% (LTx), and birth weight <2,500 g in 8% and 58%, respectively. Live birth rate was 98%. In multivariable analysis, a trend for higher birth weight with higher pre-pregnancy estimated glomerular filtration rate was observed (B 13.3, 95% CI -1.7-28.4, p = 0.08). Graft function remained stable in most patients during and after pregnancy. During follow-up (mean 15 years, range 5-31 post-transplantation), 6/40 mothers (15%) died (1 HTx, 2 LTx, 3 HLTx), with their children aged 0-11 years. No specific physical health problems were mentioned in 29/30 children (age 0-22 years). Physician opinions towards pregnancy differed from reluctant (31%) to positive (69%), with numerous management variations. Conclusions:We show reassuring pregnancy outcomes for post-HTx, LTx, and HLTx patients in an exclusive European cohort, despite high pregnancy complication rates. Graft function and overall maternal survival appear unaffected. We highlight differences in pregnancy management between centers and suggest development of a uniform approach.

The number of organ donation after euthanasia (ODE) procedures in the Netherlands has grown substantially, yet their contribution to the lung donor pool remains unclear. There is no clinical consensus on how these potential ODE lung donors should be assessed. We aimed to describe the total contribution of ODE to the lung donor pool in the Netherlands and describe the assessment of potential ODE lung donors. We collected data from all ODE procedures performed between 2012 and 2024 in the Netherlands. We assessed the number of ODE lungs offered, rejected, accepted, and transplanted, comparing characteristics of discarded and transplanted lungs. Of 1166 lung donors, 664 (60%) were donation after circulatory death donors, of which 154 (23%) were ODE lung donors. The total proportion of donor lungs from ODE lung donors acceptable to offer for lung transplantation was 117, of which 104 (89%) were transplanted. Evaluation prior to donation was highly variable, with medical history and chest computed tomography most affecting acceptance decisions. Short-term outcomes were excellent, with 1-year survival of 84%. Our findings indicate that ODE lung donors are increasingly important in the Netherlands, with high acceptance rates, despite highly variable evaluation methods. Standardizing the assessment of potential ODE lung donors could further improve acceptance rates and enhance the contribution of ODE to the lung donor pool.

Objective:The logistics and planning involved in lung transplantation (LuTx) are complex. Recent advancements in LuTx surgery have introduced the possibility of deferring surgery to daytime hours and might reduce the burden on operating personnel and improve patient outcomes; however, this might interfere with the daytime program and could be labor-intensive and costly. Therefore, this study sought to investigate the effect of time of surgery on LuTx outcomes. Methods:Adult patients undergoing LuTx between 2010 and 2022 were included in this single-center retrospective cohort study. Patients were categorized as the night group if at least 1 hour of their operation occurred between 2 am and 6am. Otherwise, they were assigned to the day group. The primary outcome for this study was intensive care unit length of stay. Secondary outcomes included 30-day and 1-year survival, bronchiolitis-obliterans syndrome-free survival, time to extubation, rethoracotomy, need for extracorporeal circulatory support, blood loss and transfusion parameters, and ischemic, implant, and operating times. Both unadjusted comparisons and multivariable regression analyses were performed. Results:In total, 227 patients (day: n = 142, night: n = 85) were included in this study. After multivariable regression, no differences were found in survival, ICU and hospital length of stay, time to extubation, or operation duration. Additionally, no significant differences were found for bronchiolitis-obliterans free-survival, ischemic and implant times, use of extracorporeal circulation, wound complications, rethoracotomies, and the majority of blood loss and transfusion data in the unadjusted analysis. Conclusions:No differences were found between the day and night group regarding survival, length of stay, time to extubation and other (post-)operative outcomes. These findings indicate that performing LuTx surgery at night is safe, provided that this complex care is well-organized and delivered by a dedicated team.

Background Elexacaftor/Tezacaftor/Ivacaftor (ETI) for people with CF (PwCF) after lung transplantation (LTx) has been restrained due to uncertainties regarding efficacy and drug interactions. Given the persistence of extrapulmonary symptoms post-LTx, this prospective study aims to investigate the benefits and safety of ETI for PwCF post-LTx. Methods Between Nov 2022-Nov 2023 ETI was offered to PwCF post-LTx with at least one F508del mutation in 3 Dutch LTx centers. PwCF were considered eligible if they had either a BMI ≤ 19 kg/m², chronic rhinosinusitis (CRS), uncontrolled diabetes or gastrointestinal (GI) symptoms. BMI, HbA1c, SNOT-22 score, GI Symptom Tracker, CF Questionnaire-Revised (CFQ-R), FEV1, creatinine, changes in calcineurin inhibitor (CNI) doses and levels were compared between baseline and 3 months follow-up. Results Fifty-five PwCF post-LTx were included, of whom 5 were excluded because of ETI discontinuation due to side effects, within 3 month follow-up. Three months results showed a decrease in SNOT-22 score (p< 0.001) and GI symptoms (all 4, p< 0.05), an increase in BMI (p= 0.012) and CFQ-R (6 domains, p< 0.05). Median CNI daily dose had to be reduced from 6 to 4 mg (p< 0.001), to maintain stable CNI trough levels. Creatinine increased from 110 (87−141) to 115 (92−125) umol/L (p= 0.002). Conclusion ETI for PwCF post-LTx shows favorable effects on CRS, GI symptoms, and quality of life, but not on BMI and HbA1c. Due to its high cost, careful consideration and further studies are required. Monitoring renal function and CNI trough levels is recommended.

Complications like acute cellular rejection (ACR) and infection are known risk factors for the development of chronic lung allograft dysfunction, impacting long-term patient and graft survival after lung transplantation (LTx). Differentiating between complications remains challenging and time-sensitive, highlighting the need for accurate and rapid diagnostic modalities. We assessed the ability of exhaled breath analysis using an electronic nose (eNose) to distinguish between ACR, infection, and mechanical complications in LTx recipients (LTR) presenting with suspected complications. LTR with suspected complications and subsequently proven diagnosis underwent exhaled breath analysis using an eNose. Supervised machine learning was used to assess the eNose's ability to discriminate between complications. Next, we determined the added value of the eNose measurement on top of standard clinical parameters. In 90 LTR, 161 measurements were performed during suspected complications, with 84 proven diagnoses. The eNose could distinguish between ACR, infection, and mechanical complications with 74% accuracy, and ACR and infection with 82% accuracy. Combining eNose measurements with standard clinical parameters improved diagnostic accuracy to 88% (P 1/4.0139), with 94% sensitivity and 80% specificity. Exhaled breath analysis using eNose technology is a promising, noninvasive, diagnostic modality for distinguishing LTx complications, enabling timely diagnosis and interventions.

Long COVID (LC) is a long-term debilitating disease of which the exact pathophysiology is unknown. A dysregulated immune response resulting in hyperresponsive immune cells is hypothesized as a key mechanism in the development of LC. Several studies suggest that acute infections can leave lasting epigenetic changes, which result in heightened immune reactivity. Upon stimulation, these primed immune cells may exhibit exaggerated responses. This form of epigenetic memory can contribute to altered immune dynamics, particularly in response to induction of type I Interferons (IFN-I) pathway activation using a viral mimic. Therefore, we investigated if LC patients exhibit a hyperresponsive response towards viral mimics in comparison with healthy controls (HC). PBMCs of two distinct LC cohorts, characterized by a different disease course and duration, were collected and transfected using Lyovec with the cGAS and RIG-I agonists G3-YSD and 3p-RNA followed by measurement of IFN-I bioactivity with a reporter cell line. Transfection of PBMCs of LC patients with the cGAS and RIG-I agonists resulted in increased IFN-I bioactivity in comparison with HC. Unsupervised hierarchical clustering revealed two distinct clusters, each predominantly composed of either patients or HC. In addition, a moderate correlation between RIG-I stimulation with 3p-RNA and fatigue severity scores was found. These data show a hyperresponsive phenotype of immune cells of LC patients upon stimulation with viral mimics. The current availability of biologicals and small molecule inhibitors that interfere with aberrant IFN-I pathway activation underscores the importance of pursuing future investigations into this phenomenon.

Post-transplant diabetes mellitus (PTDM) affects up to 34

Background:Many patients experience long-lasting health problems after COVID-19. The study aimed to assess 3-year trajectories of a comprehensive set of patient-reported outcome measures (PROMs) in patients hospitalized for COVID-19, particularly focusing on the 2- to 3-year trajectory. Additionally, we evaluated prevalence of post-exertional malaise (PEM) at 3 years, its risk factors, co-occurring health problems, and the 3-year trajectories of patients with and without PEM. Methods:The CO-FLOW multicentre prospective cohort study followed up adults hospitalized for COVID-19 in 7 hospitals, located in the Netherlands. Study assessments were performed at 3, 6, 12, 24, and 36 months post-discharge, conducted between July 1, 2020, and May 22, 2024. PROMs on recovery, symptoms, fatigue, mental health, cognition, participation, sleep quality, work status, health-related quality of life (HRQoL), and PEM were collected. Generalized estimating equations were used to assess health trajectories and multivariable logistic regression to identify risk factors for PEM. Findings:In total, 299/344 (87%) patients completed the 3-year follow-up and were included in the analysis. Complete recovery rates increased (p < 0.001), from 12% at 3 months to 24% at 3 years. Symptoms of impaired fitness, fatigue, and muscle weakness (all p < 0.0019) and PROMs for fatigue score, participation, return to work, and HRQoL (all p < 0.005) improved significantly over time, while PROMs for cognitive failures worsened (p < 0.001). Between the 2- and 3-year visits, memory problems (OR 1.4 [1.1-1.7], p < 0.001), and scores of fatigue (MD +1.0 [0.4-1.6], p = 0.002), cognitive failures (MD +2.2 [0.9-3.4], p < 0.001), and SF-36 mental component summary (-2.2 [-3.1 to -1.3], p < 0.001) significantly worsened. At 3 years, 66% of patients experienced fatigue, 63% impaired fitness, 59% memory problems, and 53% concentration problems. PROMs showed that 62% reported poor sleep quality, 55% fatigue, and 28% cognitive failures. PEM was reported by 105/292 (36%) patients at 3 years; risk factors were female sex (OR 3.4 [95% CI 1.9-6.0], p < 0.001), pre-existing pulmonary disease (3.0 [1.7-5.6], p < 0.001), physical inactivity pre-COVID-19 (2.3 [1.2-4.1], p = 0.008), and ICU treatment for COVID-19 (1.8 [1.02-3.0], p = 0.04). Concurrent fatigue, cognitive failures, and dyspnea were more common in patients with (42%) than without (6%) PEM. Patients with PEM showed poor health outcomes throughout the entire follow-up period, including worsening fatigue and HRQoL during the third year. Interpretation:Many health problems persisted up to 3 years post-discharge, with self-reported fatigue and cognitive problems worsening in the third year. PEM was common, and linked to a more severe phenotype of long COVID. These findings highlight the urgent need to optimize treatment options and investigate underlying pathological mechanisms of COVID-19. Funding:The Netherlands Organisation for Health Research and Development (ZonMw); Rijndam Rehabilitation; Laurens.

BACKGROUND:Organ donation after medical assistance in dying (DCD-V) is becoming increasingly common in the few countries where medical-assistance in dying is legalized. While donor warm ischemia time may be shorter compared with controlled donation after circulatory death, the use of high doses of euthanasic drugs could impact posttransplant outcomes. To assess whether DCD-V is a safe and effective method to expand the organ donor pool, it is important to examine the posttransplant results. This systematic review aims to evaluate the outcomes of DCD-V heart, lung, liver, kidney, and pancreatic islets transplantation. METHODS:A systematic literature search was conducted in the EMBASE, MEDLINE, Web of Science, and Google Scholar databases for studies reporting clinical outcomes following transplantation with DCD-V grafts. The primary outcome was graft survival. RESULTS:The search identified 550 studies, of which 19 were included for qualitative and 7 for quantitative analysis. Graft survival rates for DCD-V grafts were comparable to those for controlled donation after circulatory death grafts. CONCLUSIONS:The limited data from this review suggests that DCD-V provides acceptable outcomes and appears safe in lung and kidney transplantation, but caution is warranted in liver transplantation.

Background There are limited data on optimal management of chronic lung allograft dysfunction (CLAD). We aimed to describe the variability of diagnostic and therapeutic practices in Europe. Methods A structured questionnaire was sent to 71 centres in 24 countries. Questions were related to contemporary clinical practices for workup, monitoring and treatment of CLAD. The number of lung transplant procedures and patients in follow-up were collected. Results 44 centres (62%) responded from 20 countries, representing 74% of European activity. The prevalence of CLAD was estimated at 9.1 cases per million population (25th and 75th percentiles of 4.4, 15.7). Preferred initial workup for probable CLAD consisted of chest computed tomography (CT) (inspiratory 91% and expiratory 74%), donor-specific antibody (DSA) measurement (86%), bronchoalveolar lavage (BAL) (85%) and transbronchial biopsy (81%). For monitoring of definite CLAD, inspiratory CT (67%), DSA (61%) and BAL (43%) were preferred. Body plethysmography was unavailable for 16% of cases. Prophylaxis was based on preventing infections (cytomegalovirus 99%, inhaled antibiotics 70% and antifungals 65%), tacrolimus-based immunosuppression (96%), azithromycin (72%) and universal proton pump inhibitor treatment (84%). First-line treatment of CLAD was based on azithromycin (82%) and steroid augmentation (74%). Photopheresis was used in 26% of cases. Conclusion Current European practice CLAD detection is based on spirometry, inspiratory CT and DSA, with limited access to plethysmography and expiratory CT. Prophylactic treatment is based on azithromycin, tacrolimus-based immunosuppression and treatment of risk factors. No single treatment strategy is universally used, highlighting the need for an effective treatment of CLAD. The preferred first-line strategy is azithromycin and steroid augmentation.

Background:COVID-19 patients frequently experience pulmonary embolism (PE), but its long-term consequences remain uncertain. Objectives:To assess the impact of PE in COVID-19 patients on health outcomes at 3 months after hospitalization. Methods:In this multicenter cross-sectional study, we aggregated data from existing databases to evaluate the impact of PE on health outcomes at 3 months after hospitalization. We assessed 1) questionnaires on health-related quality of life (5-level EuroQol 5-dimensional questionnaire [EQ-5D-5L] questionnaire), anxiety, depression, cognitive failure, and posttraumatic stress disorder; 2) pulmonary function tests (diffusing capacity of the lungs for carbon monoxide [DLCO] and spirometry); and 3) radiological abnormalities. We developed 3 models to assess the association between PE and the EQ-5D-5L index and the percentage of predicted DLCO (DLCO%): a crude model (model 1), adjusted for age, sex, and presence of comorbidities (model 2), and model 2 additionally adjusted for intensive care unit admission (model 3). Results:We included 465 patients who had been hospitalized for COVID-19, of whom 102 (21.9%) had developed a PE during admission. Patients with PE had poorer EQ-5D-5L index values, more impairment in pulmonary functions, and more frequent radiological abnormalities than patients without PE. Symptoms of anxiety, depression, cognitive failure, and posttraumatic stress disorder did not differ between the 2 groups. In model 2, PE was associated with lower EQ-5D-5L index and lower DLCO%. After additionally adjusting for intensive care unit admission, the association between PE and lower EQ-5D-5L index (mean difference = -0.069, [95% CI, -0.12 to -0.017]) remained but not between PE and DLCO%. Conclusion:Our findings suggest that PE in COVID-19 patients is associated with reduced health-related quality of life at 3 months after hospitalization. While PE may be a marker of COVID-19 severity, its presence during hospitalization could indicate potential long-term health issues, which may be considered during follow-up care.

Purpose: Historically, the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator Kaftrio has been withheld from lung transplant (LTx) recipients with Cystic Fibrosis (CF) due to uncertainty regarding its efficacy, concerns about potential drug interactions and costs. The focus of Kaftrio therapy has been on pulmonary improvement instead of extrapulmonary benefits. However, considering the multi-systemic nature of CF, and the persistence of extrapulmonary symptoms after LTx, Kaftrio may also have potential relevant benefits for CF patients post-transplant.

Abstract Background Patient experiences with COVID-19 aftercare remain largely unknown. We evaluated COVID-19 aftercare from a patient perspective one year after hospitalization, assessing satisfaction and its associated factors, and unmet needs. Methods The Satisfaction with COVID-19 Aftercare Questionnaire (SCAQ) was developed as part of a multicenter prospective cohort study and administered one year after hospital discharge. The SCAQ assesses (1) patient satisfaction, comprising information provision, rehabilitation, follow-up by hospitals and general practitioners (GPs), the most important aftercare topics, and overall satisfaction, and (2) unmet needs. Results 487/561 (87%) COVID-19 patients completed the SCAQ, all had been discharged from the hospital between March 2020 and May 2021. Among responders, the median age of patients was 60 (IQR 54–67) years, 338 (69%) were male, and the median length of stay in the hospital was 13 (6–27) days. Patients were least satisfied with information on who could be contacted with questions when health problems arise (59% satisfied or very satisfied). Many patients (75%) received rehabilitation, most frequently community-based (70%). Across the different community-based therapies, ≥ 60% of patients were satisfied with shared-decision making and ≥ 70% with the received therapy; a majority (≥ 79%) indicated a preference for receiving the same therapy again if needed. Regarding follow-up by hospitals, 86% of patients received this follow-up, most frequently visiting a pulmonologist (96%), being generally satisfied with the received aftercare. Aftercare from GPs was received by 39% of patients, with 88% being satisfied with the GP’s availability and 79% with referral to appropriate aftercare providers. Patients (> 50%) considered information-related items most important in aftercare. Overall, patients rated their satisfaction with aftercare 8/10 (7–9) points. Those who received medical rehabilitation (versus no rehabilitation, adjusted beta 0.61 [95%CI 0.11 to 1.11], p = 0.02) or aftercare by a hospital medical specialist (1.1 [0.46 to 1.64], p < 0.001) or GP (0.39 [0.053 to 0.72], p = 0.023) reported significantly higher satisfaction than those without such aftercare. Unmet needs were reported by 35% of patients, with lack of information (20%) and lack of additional aftercare and/or involvement of their GP (19%) being the most frequently reported. Conclusion Despite the forced quick development of COVID-19 aftercare, patients were generally satisfied. Follow-up by healthcare professionals and information provision is important to meet patients’ aftercare needs.

BackgroundAfter the outbreak of COVID-19, new post-hospital aftercare for patients with COVID-19 had to be established which healthcare professionals (HCPs) had to implement in their healthcare settings.PurposeThis study aimed to evaluate HCPs' perspective on the organization of COVID-19 post-hospital aftercare and identify barriers and facilitators regarding this aftercare in the Netherlands.MethodsIn this mixed-methods study we sent out a survey 1 and 2 years after the COVID-19 outbreak in the Netherlands to healthcare institutions (HCIs) and asked HCPs across multiple disciplines involved in the COVID-19 post-hospital aftercare to participate. The survey comprised three parts: (1) demographics; (2) the Care Process Self-Evaluation Tool as quantitative measure (CPSET; five domains; scoring range 0-100) to assess HCPs' perspective on COVID-19 post-hospital aftercare; and (3) barriers and facilitators regarding this aftercare as a qualitative measure. Descriptive statistics and thematic analysis were performed.ResultsAt 1 year, 82 HCPs from 48 HCIs, and at 2 years, 29 HCPs from 24 HCIs participated in the survey. Overall, HCPs had a favorable perspective on COVID-19 aftercare in both assessments. The CPSET domain 'patient-focused organization' scored highest (median 81.7 [interquartile range 75.0-90.0] and 85.0 [78.3-96.7]) and 'monitoring of follow-up care' lowest (67.1 [55.7-75.7] and 70.0 [52.0-86.7]) at 1 and 2 years, respectively. According to HCPs the COVID-19 post-hospital aftercare solutions to overcome the identified barriers include a clear follow-up and referral procedures with emphasis on multidisciplinary treatment, employment of more HCPs, and extension of treatment duration.ConclusionWe concluded that HCPs generally held a positive perspective on COVID-19 aftercare, despite its rapid development and reliance on expert opinion. Key steps in improving COVID-19 aftercare include using quality indicators for monitoring of follow-up care, establishing a well-defined aftercare pathway, addressing resource constraints, and enhancing multidisciplinary collaboration and communication. These insights obtained from HCPs are crucial for policymakers and national healthcare authorities to further improve COVID-19 post-hospital aftercare and for pandemic preparedness.

A potential beneficial effect of hyperbaric oxygen therapy (HBOT) on complaints of long COVID was found, leading to increased demand for this treatment despite many remaining clinical questions and lack of formal guideline recommendations and reimbursement. A registry was set up in order to gain more insight into patient characteristics and (long-term) outcomes of long COVID patients undergoing HBOT. Patient-reported outcome measures were collected at baseline, after treatment and at 3-month follow up. The primary outcome measures were the mental and physical component score (MCS/PCS) of the SF-36 questionnaire 3 months after HBOT. A clinically relevant positive or negative response was defined as an increase or decrease of ≥10% in MCS and/or PCS after 3 months. Secondary outcomes included the EQ-5D, severity of complaints and ability to work. In this prospective registry of 232 long COVID patients, 65% of long term-ill patients had a clinically relevant increase in quality of life. However, 15% of the patients experienced deterioration in quality of life. Symptoms that showed most improvement were predominantly in the cognitive domain. This indicates that HBOT may have a positive effect on complaints of long COVID, but alertness for worsening of the condition should be exercised. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT06159309 ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Medical Ethical Review Board (METC) of Erasmus University of Rotterdam gave ethical approval for this I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

BackgroundData on cellular response and the decay of antibodies and T cells in time are scarce in lung transplant recipients (LTRs). Additionally, the development and durability of humoral and cellular immune responses have not been investigated in patients on the waitlist for lung transplantation (WLs). Here, we report our 6-month follow-up of humoral and cellular immune responses of LTRs and WLs, compared with controls.MethodsHumoral responses to two doses of the mRNA-1273 vaccination were assessed by determining spike (S)-specific IgG antibodies and neutralizing antibodies. Cellular responses were investigated by interferon gamma (IFN-γ) release assay (IGRA) and IFN-γ ELISpot assay at 28 days and 6 months after the second vaccination.ResultsIn LTRs, the level of antibodies and T-cell responses was significantly lower at 28 days after the second vaccination. Also, WLs had lower antibody titers and lower T-cell responses compared with controls. Six months after the second vaccination, all groups showed a decrease in antibody titers and T-cell responses. In WLs, the rate of decline of neutralizing antibodies and T-cell responses was significantly higher than in controls.ConclusionOur results show that humoral and cellular responses in LTRs, if they develop, decrease at rates comparable with controls. In contrast, the inferior cellular responses and the rapid decay of both humoral and cellular responses in the WL groups imply that WLs may not be protected adequately by two vaccinations and repeat boostering may be necessary to induce protection that lasts beyond the months immediately post-transplantation.