ABSTRACT
COVID-19 pandemic had a great impact on mental health, both in the general population and psychiatric patients. Little is known about the difference between these two populations in perceiving the pandemic as a traumatic event. The aim of the study was to compare psychiatric patients and healthy controls (HC) in terms of change over time of post-traumatic (PTSD) symptoms. Demographic and clinical variables were collected. Impact of Event Scale Revised (IES-R) scores were registered at T1 as lockdown period (March-April 2020) and T2 as restarting (May-June 2020). Descriptive analyses and linear regression models were performed. A total of 166 outpatients and 57 HC were recruited. Time (F = 15.76; p < 0.001) and diagnosis (F = 4.94; p < 0.001) had a significant effect on the change of IES-R scores, which resulted T1 > T2 (p < 0.001), except for subjects affected by Obsessive-Compulsive Disorder (OCD). Overall, IES-R scores were < in patients than in HC (p = 0.02), particularly in the schizophrenia (SKZ) subgroup (p < 0.001). IES-R scores of subjects with personality disorders (PDs) resulted to be > HC, although not statistically significant. The lockdown period was perceived as more traumatic than the reopening phase by both groups, with the exception of OCD patients, probably because of the clinical worsening associated with the urge of control against risks of contamination. Overall, HC reported more PTSD symptoms than psychiatric patients did, particularly SKZ ones. PD patients, in contrast, may be more vulnerable to PTSD symptoms probably as a result of poor coping skills. Together with OCD patients, subjects with PDs may need closer monitoring during the different phases of the pandemic. Trial Registration: ClinicalTrials.gov Identifier: NCT04694482.
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Medium-sized cities are an important component of the settlement system and are often described as a joining link between urban and rural areas. However, in recent decades they have been impacted by growing competition from large cities which have tremendous appeal for the post-Fordist economy and for various segments of the population. This paper analyses the demographic trajectories of 99 medium-sized cities in Italy with provincial capital status, from the beginning of the twenty-first century to the outbreak of the COVID-19 pandemic. Over a twenty-year period marked by many difficulties for the Italian economy in an international context, what has the demographic performance of these cities been? The research addresses two areas. On the one hand, it analyses the demographic vitality of the provincial capitals compared to the metropolitan centres;on the other, it follows the redistribution of populations in the provincial capitals' urban areas, which coincide with the employment areas (Sistemi locali del lavoro). Significant behavioural discontinuities emerge between the decade of 2000-2010 and the following decade, which was characterised by a gradual recovery after the shock of the Great Recession. The picture was changed further by the COVID-19 pandemic. Furthermore, persistent differences between the medium-sized cities of Northern and Southern Italy stand out, but so do new internal divisions within the country, reframing this historical dualism.
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The SARS-CoV-2 is the betacoronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Severe COVID-19 affects approximately 10-15% of patients and results in prolonged morbidity and mortality. Little is known about the immunophenotypic changes of the lung parenchyma driven by the viral infection in patients who die of severe COVID-19. Ultrasound-guided lung biopsies (LB) were collected (IRB approval#1561/21) within few hours from death in 15 severe COVID-19 patients between November 2020 and January 2021, in two patients who underwent lung transplantation after COVID-19 and in one patient who had surgery for bacterial superinfection during COVID-19 disease. All samples underwent histologic and immunohistochemistry evaluation and molecular profiling using the nCounter Host Response and Coronavirus Panel plus. As controls, lungs from end-stage usual interstitial pneumonia (UIP;n=9) and from lobectomy for lung cancer (Norm;n=5) were used. Eleven lungs (61%) were positive for SARS-CoV-2 RNA. Signs of diffuse alveolar damage (DAD) were observed in 6 patients (30%). COVID-19 lungs showed a marked macrophage infiltration with M2 polarization compared with controls. Globally, COVID-19 lungs showed distinct molecular profiles from UIP or Norm lungs. Specifically, a marked upregulation of interferon-genes that was directly correlated with SARS-CoV-2 genes was seen in COVID-19 lungs. COVID-19-specific genes signatures (Log2FC >1.5;adj p<0.05) obtained using VENN diagram showed impairment of the STAT3-pathway accompanied by the upregulation of the NFkB signaling. Results herein provide new insights into lung alterations induced by severe COVID-19 and suggest novel potential targets for therapeutic intervention.
ABSTRACT
Medium-sized cities are an important component of the settlement system and are often described as a joining link between urban and rural areas. However, in recent decades they have been impacted by growing competition from large cities which have tremendous appeal for the post-Fordist economy and for various segments of the population. This paper analyses the demographic trajectories of 99 medium-sized cities in Italy with provincial capital status, from the beginning of the twenty-first century to the outbreak of the COVID-19 pandemic. Over a twenty-year period marked by many difficulties for the Italian economy in an international context, what has the demographic performance of these cities been? The research addresses two areas. On the one hand, it analyses the demographic vitality of the provincial capitals compared to the metropolitan centres;on the other, it follows the redistribution of populations in the provincial capitals' urban areas, which coincide with the employment areas (Sistemi locali del lavoro). Significant behavioural discontinuities emerge between the decade of 2000-2010 and the following decade, which was characterised by a gradual recovery after the shock of the Great Recession. The picture was changed further by the COVID-19 pandemic. Furthermore, persistent differences between the medium-sized cities of Northern and Southern Italy stand out, but so do new internal divisions within the country, reframing this historical dualism. © Institute of Geography and Spatial Organization Polish Academy of Sciences • Warsaw • 2022.
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Virtual reality appears an interesting technology to offer healthcare workers innovative programs for managing stress and anxiety during the COVID-19 pandemic and when the crisis will be over. However, the unfamiliarity and the cost of virtual reality could represent significant technical and socioeconomic obstacles in its adoption in the mental health panorama. Therefore, this study aimed to explore in a sample of doctors and nurses the use of virtual reality, their interest in this technology, and the availability to spend for purchasing a virtual reality system. Forty-four doctors and nurses completed an online survey (72.2% female;mean age 41.5 ± 10.7). Results showed that: (a) most healthcare practitioners have never tried virtual reality and have a low level of knowledge of this technology, regardless of profession, gender, and age group;(b) healthcare workers showed medium interest in using virtual reality-based programs for stress and anxiety management, both at home and in the hospital, with differences between men and women (p <.01);(c) the cost of virtual reality systems represents for many doctors and nurses a critical barrier to the use of this technology for psychological support. © 2022, Springer Nature Switzerland AG.
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Background: Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2), has resulted in an ongoing world-wide pandemic. Vaccination is the key countermeasure of the COVID-19 pandemic. Data on the efficacy, safety and immunogenicity of COVID-19 vaccination in patients with hemophilia -and in particular in those with HIV -are still scarce. Aim(s): The aim of our study was to characterize the immunogenicity and biomarkers of coagulation and endothelial perturbation after mRNA-COVID- 19 vaccination in HIV-positive hemophilic patients. Method(s): We collected blood from 24 adult HIV-positive hemophilic patients followed at our centre (19 with hemophilia A, 5 with hemophilia B) before and two weeks after the administration of the complete vaccination schedule with mRNA-1273 (Moderna Biotech). Most patients had severe hemophilia (n = 21). We measured antibodies to SARS-CoV- 2 spike protein by Elecsys (Roche) to assess immunogenicity and we evaluated protein C, VWF, D-dimer plasma levels as biomarkers of coagulation and endothelial perturbation. Anti-Platelet Factor 4 (PF4) antibodies were also measured. Result(s): Before vaccination, three patients out of 24 showed anti-Spike IgG levels >0.8 U/ml (cut-off value). Two weeks after completing the vaccination schedule, all patients had high values of anti-Spike IgG (min-max 2,387-12,500 U/ml). Mean (standard deviation) basal values of protein C, VWF and D-dimer (106 +/- 21%, 171 +/- 45%, 593 +/- 692 ng/ml respectively) were not significantly different from values measured two weeks after the second dose of vaccine (103 +/- 20%, 162 +/- 43%, 583 +/- 531 ng/ml). Anti-PF4 antibodies were detected in three patients with no associated clinical manifestations. None of the patients reported bleeding in the site of inoculation nor serious adverse events after the vaccination. Conclusion(s): Since immune abnormalities can occur in HIV-positive patients, it is important to collect data on COVID-19 vaccination immunogenicity. We demonstrated that hemophilic HIV-positive patients have a normal antibody response against SARS-CoV- 2 spike protein. In addition, mRNA-1273 had no effect on coagulation and endothelial perturbation.
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Background: COVID-19 is associated with an increased risk of venous thrombosis, even when patients are on standard-dose antithrombotic prophylaxis. Hence, the identification of biomarkers of thrombosis helps tailoring dosage of antithrombotic prophylaxis. D-dimer has been extensively employed as a biomarker and cut-off values at hospital admission have been proposed to stratify the risk of thrombosis and make decision on prophylaxis. However, D-dimer measurement is not standardized, and it is unknown if the cut-off values used for decision making can be used interchangeably between methods. Aim(s): To assess for concordance of results obtained with different commercially available laboratory methods measuring D-dimer. Method(s): Plasma samples collected from COVID-19 patients at the Hospital of Cremona were evaluated for D-dimer with three widely used immunoturbidimetric methods (Liatest D-di, Stago, Asnieres, France;D-dimer HS 500, Werfen, Orangeburg, NY;Innovance D-dimer, Siemens, Marburg, Germany). Result(s): A total of 87 COVID-19 patients [54 male and 33 female, median age of 73 years (range 28-98)] were enrolled in the study. No significant differences were found between mean D-dimer concentrations obtained with the three methods even when stratifying D-dimer levels in 4 groups (<1000, 1000-2000, 2000-5000, >5000 ng/mL) (Figure 1). The three methods showed substantial result agreement [Stago-vs- Werfen and Siemens-vs- Stago (Cohen's kappa coefficient of 0.760 and 0.699, respectively)] to an almost perfect agreement [Siemens-vs- Werfen (Cohen's kappa coefficient of 0.811)], with a p-value < 0.001. Results from the three methods showed a good linear correlation (Rho = 0.94) (Figure 2). Conclusion(s): The relatively good concordance of D-dimer results among the three investigated methods indicates that D-dimer cut-off values could be used interchangeably regardless of the method used for testing. The results pave the way to clinical trials aimed to assess the value of D-dimer as a biomarker to make decision on the intensity of antithrombotic prophylaxis in COVID-19 patients. (Figure Presented).
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Virtual reality can help individuals to manage stress and anxiety. In addition to its efficacy in reducing stress and anxiety through relaxation, virtual reality can be helpful for psychoeducation. However, to date, few studies have explored this topic. Therefore, this mixed-methods sequential explanatory study, aimed to investigate the usability, sense of presence, emotional response, and effect on learning of MIND-VR, a psychoeducational virtual experience created to offer information on stress and anxiety. Twenty healthcare workers (60% female;mean age 43 ± 10) tried MIND-VR. Psychometric outcomes served as quantitative variables, while participant interviews provided qualitative data. Results showed that the virtual reality psychoeducational experience: (a) was highly usable and satisfying;(b) increased positive emotions (i.e., happiness and surprise) and decreased negative emotions (i.e., fear, sadness) and state anxiety;(c) elicited a strong sense of presence, especially spatial presence;and (d) was practical, simple, motivating, and engaging for learning information about stress and anxiety. These findings offer promising insights into that virtual reality may be an effective tool to provide psychoeducation. © 2022 by the authors.
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Background: Interaction between HIV and SARS-CoV-2 infection has not yet been fully characterized. To this purpose, an in-vitro HIV/SARS-CoV-2 coinfection assay was set up. Furthermore, the results obtained in the in-vitro model were verified in a cohort of HIV/SARS-CoV-2 coinfected young individuals. Methods: We designed an in-vitro SARS-CoV-2/HIV coinfection. We challenged PBMCs derived from 10 healthy volunteers with 1 ng/1×106 cells of HIV-1BaL and subsequently co-cultured them with a human lung epithelial cell line (CaLu3) infected with SARS-CoV-2 at 0.015 MOI. At 96 hours post HIV-1 infection, both PBMCs and CaLu3 cells were harvested for mRNA expression and proteomic analysis. Furthermore, we enrolled 85 ART-treated HIV-vertically transmitted patients (mean age 22.4 years) followed at the Unit of Pediatric Infectious Diseases, Sacco Hospital in Milan, Italy. Real-time PCR was performed to detect SARS-CoV-2 and plasma samples were tested for anti-SARS-CoV-2-specific IgG (Euroimmun Kit). The subjects who contracted SARS-CoV-2 infection (H+/S+) were compared to the HIV-positive, SARS-CoV-2 negative ones (H+/S-) and to a cohort of SARS-CoV-2 positive, HIV-negative age-matched patients (H-/S+, mean age 22.8 years). We evaluated mRNA expression of factors involved in the anti-viral immune response on PBMCs upon stimulation with SARS-CoV-2 antigens (Quantigene Plex assay) and secreted cytokines/chemokines on plasma (Multiplex Cytokine Array). Results: We observed a significant reduction of SARS-CoV-2 replication on CaLu3 cells when exposed to HIV-pre-infected PBMCs in-vitro. IL-10 expression and production were significantly higher in the coinfected condition, in both CaLu3 cells and PBMCs. The upregulation of IL-10 was associated to higher expression levels of STAT3. In the HIV-vertically transmitted cohort, 4 out of 85 subjects contracted SARS-CoV-2 infection (H+/S+). All H+/S+ patients were asymptomatic. Similarly to the data obtained in-vitro, a significant increase in both expression and production of IL-10 emerged in comparison to H+/S-and H-/S+. Conclusion: In-vitro, a dampening in SARS-CoV-2 replication, along with a higher IL-10 mRNA expression and production, have been observed in the HIV/SARS-CoV-2 coinfected condition. Presumably, IL-10 exerted its activity through the STAT3 pathway. These results were confirmed in HIV/SARS-CoV-2 coinfected subjects in which an upregulation of IL-10 was observed. Our data might be useful defining HIV/SARS-CoV-2 coinfected young individuals pathogenesis.
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Background: Recent studies highlight the dynamic nature of virus-host interaction during SARS-CoV-2 infection, raising intriguing questions about the role and timing of interferon (IFN) responses. In fact, SARS-CoV-2 delays/antagonizes Type-I, and to a definitely lesser extent, Type II-IFNs. While paving the way for potential antiviral therapies based on immune activation, the molecular mechanisms linking different IFN pathways to SARS-CoV-2 susceptibility remain to be elucidated. The present study investigates the role of Type-I &-II IFNs in SARS-CoV-2 replication in human lung cells, with a focus on molecular pathways related with innate and adaptive immunity. Methods: Human lung carcinoma cells (CaLu3) were pretreated with IFN-α,-β or-γ (from 1 to 1000 U/mL), O.N. Cells were infected with SARS-CoV-2 (MOI 0.05) for 3h, and IFNs were added during infection. In another set of experiments, IFNs were added only p.i. Supernatants were harvested at 24 and 48h p.i. to assess viral replication by RT-qPCR, and to quantify the levels of cytokines/chemokines through Multiplex assay. At 48h post-infection, cells were collected and RNA was retrotranscribed to investigate a variety of transcriptional targets. Cell viability was assessed by MTT. Results are presented as the average of the relative expression units to the GAPDH gene, calculated by the 2-ΔΔCt equation. Statistical analyses were performed through the Student t-test. Results: Pretreatment with both Type-I &-II IFNs dramatically reduces SARS-CoV-2 replication in the absence of cell toxicity. Such an effect is maintained, though at a lower magnitude, when IFNs are added only p.i. The antireplicative effects of Type-I &-II IFNs are associated with both convergent and divergent mechanisms. Both Types decrease the expression and/or protein levels of most pro-inflammatory mediators while augmenting anti-inflammatory and anti-apoptotic factors. Surprisingly, IFN-γ shows the strongest effect in potentiating antiviral effectors besides boosting adaptive immunity pathways. Remarkably, a convergent effect of both IFN Types is observed upon the expression of genes associated with DA activity, including DA receptors (D1-D5) and the DA transporter (DAT), which are dramatically altered by SARS-CoV-2. Conclusion: Both Type-I &-II IFNs halt SARS-CoV-2 replication by acting through complementary mechanisms. Their effects also disclose a potential role for DA activity, and neuromodulators in general, in host immunity during SARS-CoV-2 infection in pulmonary cells.
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Introduction: From the very beginning, COVID-19 pandemic had a great impact not only on physical, but also on mental health, both in general population and psychiatric patients. Self-isolation, fear of virus exposure and of death, unemployment and poor social network have increased psychological distress and Post-Traumatic Stress Disorder (PTSD) symptoms [1]. Nevertheless, little is known about the difference between subjects affected by mental disorders and healthy individuals in perceiving the pandemic as a traumatic event [2]. Aim: Comparing psychiatric patients and healthy controls (HC) in terms of change over time of post-traumatic symptoms. Methods: Data about demographic and clinical variables were retrospectively collected. Impact of Event Scale Revised (IES-R) scores were registered referring at two time points: T1, during the so-called ‘Phase I’ in March-April 2020 (lockdown period) and T2, during the so-called ‘Phase II’ in May-June 2020 (restarting). Descriptive analyses and linear regression models were performed. Summary of results: A total of 166 outpatients were recruited: 66 patients (39.8%) were affected by Schizophrenia (SKZ), 29 patients (17.5%) by Bipolar Disorder (BD), 36 patients (21.7%) by Major Depressive Disorder (MDD), 17 patients (10.2%) by Anxiety or Obsessive-Compulsive Disorder (OCD), and 18 (10.8%) by Personality Disorders (PDs). HC sample included 57 individuals from general population. The tests of fixed effects showed that time (F=65.44;p<0.001) and diagnosis (F=2.84;p=0.02) each had a significant effect on the change of IES-R scores. In particular, IES-R scores at T1 were overall higher than T2 scores (p<0.001), except for OCD patients. Moreover, patients presented lower IES-R scores than HC (p=0.02), independently from diagnosis. When HC have been compared with the different diagnostic groups, SKZ patients resulted to have significantly lower IES-R scores than HC (p=0.004). Differently, only PD patients showed higher IES-R scores than HC, but the result did not reach the statistical significance (p=0.44). Conclusions: In general, both patients and HC presented a significant decrease of IES-R scores between T1 and T2, when the pandemic showed a decline and preventive restrictions have been removed;only OCD patients have shown a different trend, which can be explained by a global worsening of obsession and compulsion, associated with the urge of control against risks of contamination [3]. Comparing patients and HC, higher scores on IES-R scale have been observed in HC: this trend is particularly meaningful in SKZ subgroup, and it may be explained considering the limited awareness about the risk of infection, associated with less fear or striking emotion related to pandemic [4]. PD patients, in contrast, were found to be more affected by social restrictions than HC, probably because of a greater vulnerability to PTSD symptomatology and poorer coping skills [5], pointing out the need to implement telematic interventions, such as psychotherapy and group therapy. This is, to our knowledge, one of the few studies evaluating and comparing the psychological distress perceived by psychiatric patients (including all major diagnoses) and HC during the first wave of COVID-19 pandemic. Conflict of interest Disclosure statement: The study has been registered on ClinicalTrials.gov with the following ID number: NCT04694482
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Introduction: SARS-CoV-2 infection causes a pulmonary disease (COVID-19) which spread worldwide in 2020, leading the World Health Organization (WHO) to declare a pandemic [1] and the Italian government firstly to declare a state of emergency, then to impose restrictive measures lasting about two months. COVID-19 pandemic generated fear, anxiety, depression and post-traumatic symptoms in the general population [2,3] as well as among subjects affected by mental disorders [4]. Little is known about which different psychopathological changes the pandemic caused among individuals affected by different psychiatric disorders. Aims: To investigate potential psychopathological changes over time during the first wave of COVID-19 pandemic comparing different psychiatric disorders. Methods: Data about demographic/clinical variables and psychopathological status were retrospectively collected. Specific psychometric scales were administered at three time points: T0 as outbreak of pandemic, T1 as lockdown period, T2 as reopening. Primary outcomes: Brief Psychiatry Rating Scale (BPRS), Clinical Global Impression (CGI), Hamilton Anxiety Rating Scale (HAM-A). Secondary outcomes: Disability Scale (DISS), Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAM-D), Montgomery and Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Descriptive analyses and linear regression models were performed. Summary of results: A total of 166 outpatients were included. Overall, psychometric scores showed a significant worsening at T1 with a mild improvement at T2 (p<0.05). Only psychotic and OC symptoms did not significantly improve at T2. Primary outcomes: time had a significant effect on the change of BPRS (F=26.56;p<0.001), CGI-severity (F=8.29;p<0.001), CGI-improvement (F=41.88;p<0.001) and HAM-A (F=33.63;p<0.001) scores. BPRS and CGI-S scores were higher among subjects affected by personality disorders (PDs) than in the depressed (MDD) and anxiety/obsessive-compulsive (OC) groups (p<0.05). PD patients also showed higher HAM-A scores than schizophrenia (SKZ) ones (p=0.02). Secondary outcomes: Time had a significant effect on the change of DISS-stress (F=40.80;p<0.001), DISS-support (F=9.26;p<0.001), HAM-D (F=9.50;p<0.001) and MADRS (F=9.40;p<0.001) scores. The time effect was not significant for DISS-disability (F=1.23;p=0.29), PANSS (F=1.37;p=0.26), YMRS (F=2.84;p=0.06) and Y-BOCS (F=0.55;p=0.59) scores. DISS-disability scores were higher in the PD group with respect to bipolar disorder (BD) (p=0.009), MDD (p<0.001) and anxiety/OCD (p=0.03) groups;SKZ and BD patients had lower DISS-stress scores than PD ones (both p values = 0.02). Conclusions: Patients affected by PDs showed to be particularly affected by the negative effects of outbreaks on mental health and perhaps they require specific clinical attention in case of traumatic events such as pandemics. Moreover, although SKZ patients reported lower anxiety levels than PD ones, the worsening of psychotic and OC symptoms should be strictly monitored by clinicians, as these aspects did not improve with the end of lockdown measures. Further studies on larger samples would allow an in-depth comparison of the psychopathological impact of pandemics between the different psychiatric diagnoses. The study has been registered on ClinicalTrials.gov with the following ID number: NCT04694482 No conflict of interest
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Purpose Persons with intellectual disability and/or low-functioning autism spectrum didorder are with high support need (ID/ASD-HSN) are among the people who are most vulnerable to the COVID-19 pandemic. The specific vulnerability and the protective factors for persons with ID/LF-ASD attending residential and rehabilitative facilities have however received little attention. This paper aims to describe how two facilities located in the Italian COVID-19 red zone faced the risks associated with the spread of the pandemic and the results they have achieved so far. Design/methodology/approach Interventions to contrast the spread of the pandemic and preserve clients' health conditions have been systematically monitored and recorded since the very beginning of the pandemic. Findings 26/138 clients had to undergo clinical screening and laboratory tests for COVID-like symptomatology, but only one resulted affected by COVID-19 and survived. Considering that Lombardy had 89,595 cases and 16,262 deaths (January-May 2020), one COVID-19 case/138 clients is a good result. Temporarily limiting physical contacts with friends/family in favor of reducing the burden of risk and adopting a system of prevention/safety strategies directed for persons with ID/LF-ASD attending and their caregivers have been useful measures. Research limitations/implications Structured or semi-structured interviews (using professional caregivers as informant) to confirm behavioral and emotional changes in the clients could not be carried out because of lack of time and resources (which were captured by the management of the pandemic) and could be the next goal for our residential facilities to implement the management of epidemic acute phases in a research-oriented view. Originality/value This study is a service evaluation report about facing COVID-19 pandemic. Only few such studies are present in medical literature about ID/ASD.
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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.