Infections In Lung Transplant Recipients Research Articles

Clinical characteristics and prognosis of SARS-CoV-2 infection in lung transplant recipients

ObjectiveThis study aimed to investigate the clinical manifestations and prognosis of lung transplant (LTx) recipients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease (COVID-19) pandemic.MethodsThe research participants were LTx recipients who underwent surgery and were regularly followed up at our center. From 1 December 2022 to 28 February 2023, during the COVID-19 pandemic in China, research participants were interviewed either online or in person. SARS-CoV-2 nucleic acid or self-tested antigens were detected according to accessibility. Diagnosis and treatment were performed according to the Diagnosis and Treatment Plan for COVID-19 (10th edition) issued by the National Health Commission of the People's Republic of China. Hospitalized patients underwent chest imaging examinations, routine blood tests, biomarkers for infection and inflammation, and biochemical tests, all of which were taken and recorded. Data were analyzed to describe the features of COVID-19 in LTx recipients.ResultsIn total, 52 patients were enrolled in this study, comprising 48 men and 4 women, with a mean age of 51.71 ± 11.67 years. By 1 December 2022, the mean survival period was 33.87 ± 25.97 months, of which 84.61% of the patients (44/52) had a survival period longer than 12 months. The SARS-CoV-2 infection rate in these LTx recipients was 82.69% (43/52), with 3.85% (2/52) of the infected recipients being asymptomatic, 50.00% (26/52) of the infected recipients experiencing mild COVID-19, 11.54% (6/52) having moderate COVID-19, and 17.31% (9/52) having severe or critical COVID-19. The mortality rate among severe and critical patients was 66.67% (6/9).ConclusionLTx recipients in this cohort exhibited a notable susceptibility to SARS-CoV-2, with 82.69% of individuals diagnosed with COVID-19. Moreover, the mortality rate among critically ill patients was high.

Low Mortality Associated with COVID-19 Infection in Lung Transplant Recipients at a Single Center

Lung Transplant Recipients (LTR) are particularly vulnerable to severe infection, hospitalization, and death due to community acquired respiratory viruses. As a result, the global SARS-Cov-2 pandemic poses a higher risk to this population. We aim to study the lung function, severity of infection and mortality among LTR at a single center. A retrospective chart review was performed on all LTR at the University of San Diego, California Medical Center between June 2020 and September 2022. Spirometry was performed at 1-2 months and then again 3 months after infection. Patients were closely monitored for the development of acute cellular rejection (ACR). 72 LTR were infected with COVID-19. 37.5% required hospital admission, of which 25.9% required management in the intensive care unit (ICU). 73.6% LTR had received at least one vaccination dose prior to infection. Post-infection, the median drop in FEV1 was 140 mL and FVC was 25 mL within 1-2 months. At 3 months post-infection the median reduction in FVC was slightly larger at 75 ml, while median decline in FEV1 decreased to 55 ml. Overall, the rates of ACR and mortality in this population were both 4.2%. Additionally, monoclonal antibody (mAb) therapy reduced hospitalization (20.9% vs 62%) and mortality (0% vs 10.3%), Our study found low rates of ACR and mortality in LTR with confirmed COVID-19, despite the statistically significant decline in FEV1, and trends with FVC. The use of vaccinations and mAb therapy decreased rates of hospitalizations, with mAb therapy reducing mortality as well.

(1427) - Association of Donor Derived Cell-Free DNA Fractions with Acute Rejection and Pulmonary Infections in Lung Transplant Recipients

(1427) - Association of Donor Derived Cell-Free DNA Fractions with Acute Rejection and Pulmonary Infections in Lung Transplant Recipients

(134) - The Ability of an Electronic Nose to Distinguish Between Infections in Lung Transplant Recipients

(134) - The Ability of an Electronic Nose to Distinguish Between Infections in Lung Transplant Recipients

A case report of drug interaction between co-packaged nirmatrelvir-ritonavir and tacrolimus causing hyponatremia in a lung transplant recipient

BackgroundCoronavirus disease 2019 (COVID-19) infection in lung transplant recipients can be lethal owing to the use of immunosuppressants. Antiviral agents may be administered to these patients. Co-packaged nirmatrelvir-ritonavir is a new agent currently being used in combination.Case presentationIn this report, we present a case of a 64-year-old woman, a lung transplant recipient, who experienced hyponatremia and showed a high serum tacrolimus concentration following the administration of the co-packaged nirmatrelvir-ritonavir combination.ConclusionAlthough the nirmatrelvir-ritonavir and tacrolimus combination is not contraindicated, other treatment strategies should be considered first, if available, and the dose of tacrolimus should be reduced when using the nirmatrelvir-ritonavir combination. In cases where combination therapy is necessary, serum tacrolimus levels should be closely monitored in lung transplant recipients. Documentation of more such reports is important to identify drug interactions between nirmatrelvir-ritonavir and other agents, with the aim of preventing severe adverse effects.

Alterations of lung microbiota in lung transplant recipients with pneumocystis jirovecii pneumonia

BackgroundIncreasing evidence revealed that lung microbiota dysbiosis was associated with pulmonary infection in lung transplant recipients (LTRs). Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungal pathogen that frequently causes lethal pneumonia in LTRs. However, the lung microbiota in LTRs with P. jirovecii pneumonia (PJP) remains unknow.MethodsIn this prospective observational study, we performed metagenomic next-generation sequencing (mNGS) on 72 bronchoalveolar lavage fluid (BALF) samples from 61 LTRs (20 with PJP, 22 with PJC, 19 time-matched stable LTRs, and 11 from LTRs after PJP recovery). We compared the lung microbiota composition of LTRs with and without P. jirovecii, and analyzed the related clinical variables.ResultsBALFs collected at the episode of PJP showed a more discrete distribution with a lower species diversity, and microbiota composition differed significantly compared to P. jirovecii colonization (PJC) and control group. Human gammaherpesvirus 4, Phreatobacter oligotrophus, and Pseudomonas balearica were the differential microbiota species between the PJP and the other two groups. The network analysis revealed that most species had a positive correlation, while P. jirovecii was correlated negatively with 10 species including Acinetobacter venetianus, Pseudomonas guariconensis, Paracandidimonas soli, Acinetobacter colistiniresistens, and Castellaniella defragrans, which were enriched in the control group. The microbiota composition and diversity of BALF after PJP recovery were also different from the PJP and control groups, while the main components of the PJP recovery similar to control group. Clinical variables including age, creatinine, total protein, albumin, IgG, neutrophil, lymphocyte, CD3+CD45+, CD3+CD4+ and CD3+CD8+ T cells were deeply implicated in the alterations of lung microbiota in LTRs.ConclusionsThis study suggests that LTRs with PJP had altered lung microbiota compared to PJC, control, and after recovery groups. Furthermore, lung microbiota is related to age, renal function, nutritional and immune status in LTRs.

The changing landscape of infections in the lung transplant recipient.

Infections in lung transplant recipients remain a major challenge and can affect lung allograft function and cause significant morbidity and mortality. New strategies for the prevention and treatment of infection in lung transplantation have emerged and are reviewed. For important vaccine preventable infections (VPIs), guidance has been updated for at risk solid organ transplant (SOT) recipients. However, data on the efficacy of newer vaccines in lung transplant, including the respiratory syncytial virus (RSV) vaccine, are limited. Studies demonstrate improved vaccination rate with Infectious Diseases consultation during pretransplant evaluation. Two new antiviral agents for the treatment and prevention of cytomegalovirus (CMV) in SOT, letermovir and maribavir, are bein incorporated into clinical care. CMV-specific cell-mediated immune function assays are more widely available. Antibiotics for the management of multidrug resistant pathogens and Burkholderia cepacia complex have been described in case series and case reports in lung transplant. Although new vaccines and novel therapies for preventing and treating infections are available, larger studies evaluating efficacy in lung transplant recipients are needed.

Risk Factors for Invasive Fungal Infection in Lung Transplant Recipients on Universal Antifungal Prophylaxis.

Many centers use universal antifungal prophylaxis after lung transplant, but risk factors for invasive fungal infection (IFI) in this setting are poorly described. This retrospective, single-center cohort study including 603 lung transplant recipients assessed risk factors for early (within 90 days of transplant) invasive candidiasis (IC) and invasive mold infection (IMI) and late (90-365 days after transplant) IMI using Cox proportional hazard regression. In this cohort, 159 (26.4%) patients had 182 IFIs. Growth of yeast on donor culture (hazard ratio [HR], 3.30; 95% CI, 1.89-5.75) and prolonged length of stay (HR, 1.02; 95% CI, 1.01-1.03) were associated with early IC risk, whereas transplantation in 2016 or 2017 (HR, 0.21; 95% CI, 0.06-0.70; HR, 0.25; 95% CI, 0.08-0.80, respectively) and female recipient sex (HR, 0.53; 95% CI, 0.30-0.93) were associated with reduced risk. Antimold therapy (HR, 0.21; 95% CI, 0.06-0.78) was associated with lower early IMI risk, and female donor sex (HR, 0.40; 95% CI, 0.22-0.72) was associated with lower late IMI risk. Recent rejection was a risk factor for late IMI (HR, 1.73; 95% CI, 1.02-2.95), and renal replacement therapy predisposed to early IC, early IMI, and late IMI (HR, 5.67; 95% CI, 3.01-10.67; HR, 7.54; 95% CI, 1.93-29.45; HR, 5.33; 95% CI, 1.46-19.49, respectively). In lung transplant recipients receiving universal antifungal prophylaxis, risk factors for early IC, early IMI, and late IMI differ.

Prevention and Management of Infections in Lung Transplant Recipients.

Anti-rejection medications are essential in preventing organ rejection amongst solid organ transplant recipients; however, these agents also cause profound immunosuppression, predisposing lung transplant recipients (LTRs) to infectious complications. The timely management including prevention, diagnosis, and treatment of such infectious complications is vital to prevent significant morbidity and mortality in solid organ transplant recipients and allograft dysfunction. LTRs are inundated with microbes that may be recognized as commensals in hosts with intact immune systems. Bacterial infections are the most common ones, followed by viral pathogens. Indications of a brewing infectious process may be subtle. Hence, the importance of adapting vigilance around isolated hints through symptomatology and signs is pivotal. Signals to suggest an infectious process, such as fever and leukocytosis, may be dampened by immunosuppressive agents. One must also be vigilant about drug interactions of antibiotics and immunosuppressive agents. Treatment of infections can become challenging, as antimicrobials can interact with immunosuppressive agents, and antimicrobial resistance can surge under antimicrobial pressure. Transplant infectious disease physicians work in concert with transplant teams to obtain specimens for diagnostic testing and follow through with source control when possible. This heavily impacts medical decisions and fosters a multidisciplinary approach in management. Furthermore, the reduction of immunosuppression, although it augments the risk of allograft rejection, is as crucial as the initiation of appropriate antimicrobials when it comes to the management of infections.

Immediate Postoperative COVID-19 Infection after Lung Transplantation: A Systematic Review and Case Series.

With new variants challenging the effectiveness of preventive measures, we are beginning to recognize the reality that COVID-19 will continue to pose an endemic threat. The manifestations of COVID-19 in lung transplant recipients during index admission are poorly understood with very few cases reported in recent lung transplant recipients. Optimal management of immunosuppression and antiviral therapy in recent transplant recipients is challenging. We performed a retrospective analysis identifying lung transplant recipients at our institution who contracted COVID-19 in the immediate postoperative period (within index admission). In addition, we performed a systematic review from January 2020 to August 2023 identifying all publications on the PUBMED database regarding COVID-19 infection in lung transplant recipients during index admission. We report four cases of COVID-19 pneumonia in lung transplant recipients in the immediate postoperative period and we describe the clinical course, treatment options, and immunosuppression changes to manage this unique clinical problem. All patients made a full recovery and were eventually discharged home. Within our review of the literature, the most prevalent presenting symptoms were cough, dyspnea, and fatigue. Six (75%) patients decreased or held their antimetabolite. The two most common treatments were monoclonal antibodies (38%) and remdesivir (63%). Although previous literature demonstrates that COVID-19 can be deadly in recent lung transplant recipients, rapid treatment with anti-viral therapy/immunotherapy, deescalating immunosuppression, and treatment of respiratory decompensation with Decadron was effective in our patients.

Differentiation between lung allograft rejection and infection using donor-derived cell-free DNA and pathogen detection by metagenomic next-generation sequencing

BackgroundIn lung transplant recipients (LTRs), the primary causes of mortality are rejection and infection, which often present similar symptoms, making differentiation challenging. This study aimed to explore the diagnostic efficacy of plasma donor-derived cell-free DNA (dd-cfDNA) in conjunction with metagenomic next-generation sequencing (mNGS) for pathogen detection in differentiation between lung allograft rejection and infection in LTRs experiencing new-onset pulmonary complications. MethodsWe conducted a retrospective study on 188 LTRs who underwent lung or heart-lung transplantation at our institution from 2015 to 2021. The LTRs were categorized into three groups: stable, rejection, and infection. We measured plasma dd-cfDNA levels and utilized both mNGS and culture methods to identify pathogens in the bronchoalveolar lavage fluid (BALF). ResultsThe rejection group exhibited the highest levels of plasma dd-cfDNA (median 1.34 %, interquartile range [IQR] 1.06–2.19 %) compared to the infection group (median 0.72 %, IQR 0.62–1.07 %) and the stable group (median 0.69 %, IQR 0.58–0.78 %) (both p < 0.001). Within the infection group, a significantly higher level of dd-cfDNA was observed in the cytomegalovirus infection subgroup (p < 0.001), but not in the fungal (p > 0.05) or bacterial infection subgroups (p > 0.05), when compared to the stable group. Elevated dd-cfDNA levels, in combination with negative mNGS results, strongly indicated lung allograft rejection, with a positive predictive value and negative predictive value of 88.7 % and 99.2 %, respectively. ConclusionsPlasma dd-cfDNA in combination with BALF pathogen detection by mNGS shows satisfactory accuracy in differentiating lung allograft rejection from infectious complications.

Incidence and severity of SARS-CoV-2 infection in lung transplant recipients in the Omicron era

Incidence and severity of SARS-CoV-2 infection in lung transplant recipients in the Omicron era

Lung Transplant Recipients and COVID-19: Report of Two Cases.

Although the WHO has declared the end of the pandemic emergency, COVID-19 still poses a threat to immunocompromised patients. The COVID-19 pandemic has spread throughout the world over the last two years, causing a significant number of deaths. After three years, SARS-CoV-2 has lost its initial lethality but has shown a significantly worse prognosis for immunocompromised patients, especially those who have undergone lung transplantation, compared with the general population. This paper presents two compelling case studies that highlight the complex challenges of COVID-19 infection in lung transplant recipients. The first case involves a patient who received a bilateral lung transplant for pulmonary artery hypertension in 2009, followed by a kidney transplant in 2022. Surprisingly, despite an initially favorable clinical course after contracting COVID-19, the patient deteriorated rapidly and died within a few days due to extensive lung involvement. This case highlights the unpredictable nature of COVID-19 and its potentially devastating impact on lung transplant recipients. The second case involves a patient who underwent bilateral lung transplantation five years earlier for chronic obstructive pulmonary disease (COPD). This individual also contracted COVID-19 and had pre-existing complications, including chronic lung allograft rejection (CLAD) and diffuse bronchial stenosis. Following viral infection, the patient's clinical condition deteriorated rapidly, with worsening bronchial stenosis. This case highlights the ability of COVID-19 to exacerbate pre-existing pulmonary complications in transplant recipients. These cases highlight the urgent need for increased vigilance and tailored management strategies when dealing with COVID-19 in lung transplant recipients. The unpredictable and detrimental course of the disease observed in these patients highlights the importance of implementing stringent preventive measures, such as vaccination and strict adherence to infection control protocols, in this vulnerable population. Further research is essential to gain a full understanding of the unique dynamics of COVID-19 in lung transplant recipients and to develop targeted interventions to improve their outcomes.

Diagnostic difficulties in non-tuberculous mycobacterial infection in lung transplant recipients.

Despite antimicrobial prophylaxis, 34% to 59% of lung transplant recipients experience severe life-threatening opportunistic infections, sometimes caused by Nontuberculous Mycobacteria (NTM) and Nocardia. Although differentiating these infections is of utmost importance for effective treatment, it can be challenging as they share morphological and growth characteristics. Therefore, culture remains the gold standard for laboratory confirmation. With the aid of novel molecular methods performed on the cultured organisms, diagnosis may be accomplished rapidly and precisely. We present a case of a lung transplant recipient with a pulmonary infection where long, thin, beaded, branching filamentous organisms were seen with Acid-Fast Bacilli (AFB) and Modified Gomori's Methenamine Silver (GMS) stains in bronchoalveolar lavage sample. Cytological characteristics led to the suspicion of a Nocardia species infection. However, culture and the PCR-restriction fragment length polymorphism analysis (PRA) identified M. fortuitum. Additionally, antibiotic resistance was detected, which aided in choosing the appropriate treatment. Therefore, to overcome such diagnostic difficulties to differentiate NTM and Nocardia, a multidisciplinary approach including culture, molecular methods, and cytology is needed to enhance clinical outcomes.

Rarely Encountered Gram-Negative Rods and Lung Transplant Recipients: A Narrative Review.

The respiratory tract of lung transplant recipients (LTR) is likely to be colonized with non-fermentative Gram-negative rods. As a consequence of the improvements in molecular sequencing and taxonomy, an increasing number of bacterial species have been described. We performed a review of the literature of bacterial infections in LTR involving non-fermentative Gram-negative rods with exclusion of Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Achromobacter spp. and Burkholderia spp. Overall, non-fermenting GNR were recovered from 17 LTR involving the following genera: Acetobacter, Bordetella, Chryseobacterium, Elizabethkinga, Inquilinus, and Pandoraea. We then discuss the issues raised by these bacteria, including detection and identification, antimicrobial resistance, pathogenesis, and cross-transmission.

Diagnosis and Treatment of Fungal Infections in Lung Transplant Recipients.

Fungal infections are a significant source of morbidity in the lung transplant population via direct allograft damage and predisposing patients to the development of chronic lung allograft dysfunction. Prompt diagnosis and treatment are imperative to limit allograft damage. This review article discusses incidence, risk factors, and symptoms with a specific focus on diagnostic and treatment strategies in the lung transplant population for fungal infections caused by Aspergillus, Candida, Coccidioides, Histoplasma, Blastomyces, Scedosporium/Lomentospora, Fusarium, and Pneumocystis jirovecii. Evidence for the use of newer triazole and inhaled antifungals to treat isolated pulmonary fungal infections in lung transplant recipients is also discussed.

Association Between Severe SARS-CoV-2 Infection and De Novo HLA Donor Specific Antibody Production in Lung Transplant Recipients: Single-center study

The COVID-19 pandemic has led to significant morbidity and mortality in lung transplant recipients (LTR). Respiratory viral infections may be associated with de-novo HLA donor-specific antibody (DSA) production and impact lung transplant outcome. Since one of the immunomodulation strategies post-SARS-CoV-2 infection in LTR include decreasing or holding anti-metabolites, concerns have been raised for higher incidence of de-novo DSA production in LTR. We performed a retrospective chart review of 80 consecutive LTR diagnosed with COVID-19 to investigate this concern. COVID-19 disease severity was divided into 3 groups: mild, moderate, and severe. Mild disease was defined as patients with COVID-19 diagnosis who were stable enough to be treated as out-patients. Moderate disease was defined as patients who required admission to the hospital and were on less than 10 liters of oxygen at rest. Severe disease was identified as patients who required hospitalization and were on more than 10 liters of oxygen with or without mechanical ventilation or extra corporal membrane oxygenation (ECMO). Groups were compared using the Kruskal-Wallis test. A total of 23, 47, and 10 LTR were diagnosed with mild, moderate, and severe COVID-19 respectively. De-novo HLA DSAwere detected in 0/23 (0%), 3/47 (6.3%), and 4/10 (40%) LTR with mild, moderate, and severe COVID-19 respectively (p = 0.0007) within 6 months post-COVID-19 diagnosis. Severe COVID-19 may be associated with increased risk of de novo HLA DSA production resulting in allograft dysfunction.

Changes in HCMV immune cell frequency and phenotype are associated with chronic lung allograft dysfunction.

Human cytomegalovirus (HCMV) infection is common and often severe in lung transplant recipients (LTRs), and it is a risk factor associated with chronic lung allograft dysfunction (CLAD). The complex interplay between HCMV and allograft rejection is still unclear. Currently, no treatment is available to reverse CLAD after diagnosis, and the identification of reliable biomarkers that can predict the early development of CLAD is needed. This study investigated the HCMV immunity in LTRs who will develop CLAD. This study quantified and phenotyped conventional (HLA-A2pp65) and HLA-E-restricted (HLA-EUL40) anti-HCMV CD8+ T (CD8 T) cell responses induced by infection in LTRs developing CLAD or maintaining a stable allograft. The homeostasis of immune subsets (B, CD4T, CD8 T, NK, and γδT cells) post-primary infection associated with CLAD was also investigated. At M18 post-transplantation, HLA-EUL40 CD8 T responses were less frequently found in HCMV+ LTRs (21.7%) developing CLAD (CLAD) than in LTRs (55%) keeping a functional graft (STABLE). In contrast, HLA-A2pp65 CD8 T was equally detected in 45% of STABLE and 47.8% of CLAD LTRs. The frequency of HLA-EUL40 and HLA-A2pp65 CD8 T among blood CD8 T cells shows lower median values in CLAD LTRs. Immunophenotype reveals an altered expression profile for HLA-EUL40 CD8 T in CLAD patients with a decreased expression for CD56 and the acquisition of PD-1. In STABLE LTRs, HCMV primary infection causes a decrease in B cells and inflation of CD8 T, CD57+/NKG2C+ NK, and δ2-γδT cells. In CLAD LTRs, the regulation of B, total CD8 T, and δ2+γδT cells is maintained, but total NK, CD57+/NKG2C+ NK, and δ2-γδT subsets are markedly reduced, while CD57 is overexpressed across T lymphocytes. CLAD is associated with significant changes in anti-HCMV immune cell responses. Our findings propose that the presence of dysfunctional HCMV-specific HLA-E-restricted CD8 T cells together with post-infection changes in the immune cell distribution affecting NK and γδT cells defines an early immune signature for CLAD in HCMV+ LTRs. Such a signature may be of interest for the monitoring of LTRs and may allow an early stratification of LTRs at risk of CLAD.

(701) Use of Tixagevimab and Cilgavimab (Evusheld) and Subsequent Outcomes of SARS-CoV-2 Infections in Lung Transplant Recipients

(701) Use of Tixagevimab and Cilgavimab (Evusheld) and Subsequent Outcomes of SARS-CoV-2 Infections in Lung Transplant Recipients

(705) Risk Factors for Death and Hospitalisation in COVID-19 Infection in Lung Transplant Recipients; a Single Australian Centre Experience

(705) Risk Factors for Death and Hospitalisation in COVID-19 Infection in Lung Transplant Recipients; a Single Australian Centre Experience