Prophylactic antibodies inhibit spike-specific T and B cell responses after COVID-19 vaccination.

Active and passive immunization is used in high-risk patients to prevent severe courses of COVID-19, but the impact of prophylactic neutralizing antibodies on the immune reaction to the mRNA vaccines has remained enigmatic. Here we show that CD4 T and B cell responses to Spikevax booster immunization are suppressed by the therapeutic antibodies Casirivimab and Imdevimab. B cell and T cell responses were significantly induced in controls but not in antibody-treated patients. The data indicates that humoral immunity, i. e. high levels of antibodies, negatively impacts reactive immunity, resulting in blunted cellular responses upon boosting. This argues for temporal separation of vaccination efforts; with active vaccination preferably applied before prophylactic therapeutic antibody treatment.

Evaluation of the AltoStar AM16 system for the quantitation of AdV, CMV and HHV-6 DNA from clinical specimens.

The vulnerability of immunocompromised patients to common or opportunistic viral infections is particularly high. The quantitation of viral load in clinical specimens is important for the diagnosis and management of the infection and reactivation in this patient population, particularly transplant recipients. As the new regulation "IVDR" regarding in vitro diagnosis methods is about to come into effect in France, diagnostic laboratories have to implement methods and systems compatible with this new regulation. Technical performance of the AltoStar® Adenovirus (AdV), Cytomegalovirus (CMV) and human Herpesvirus-6 (HHV-6) DNA PCR Kits 1.5 was assessed on the AltoStar Automation system AM16 using reference kits in 146 clinical samples. Overall agreement in clinical specimens was 87.5 % (28/32), 96.8 % (62/64), 100 % (22/22), 100 % (28/28) and 92.8 % (26/28) for AdV, CMV (WB samples and other matrices), HHV-6 A&B respectively. Quantitative results were highly correlated and estimated to be equivalent within a 0.057-0.648 log-amount difference.We found that altona kits on The AltoStar AM16 system are suitable for clinical monitoring of AdV, CMV and HHV-6 in immunocompromised hosts.

Tacrolimus-induced posterior reversible encephalopathy syndrome following liver transplantation.

In this editorial, we talk about a compelling case focusing on posterior reversible encephalopathy syndrome (PRES) as a complication in patients undergoing liver transplantation and treated with Tacrolimus. Tacrolimus (FK 506), derived from Streptomyces tsukubaensis, is a potent immunosuppressive macrolide. It inhibits T-cell transcription by binding to FK-binding protein, and is able to amplify glucocorticoid and progesterone effects. Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES. PRES presents with various neurological symptoms alongside elevated blood pressure, and is primarily characterized by vasogenic edema on neuroimaging. While computed tomography detects initial lesions, magnetic resonance imaging, especially the Fluid-Attenuated Inversion Recovery sequence, is superior for diagnosing cortical and subcortical edema. Our discussion centers on the incidence of PRES in solid organ transplant recipients, which ranges between 0.5 to 5 +ACU-, with varying presentations, from seizures to visual disturbances. The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES. Radiographically evident in the parietal and occipital lobes, PRES underlines the need for heightened vigilance among healthcare providers. This editorial emphasizes the importance of early recognition, accurate diagnosis, and effective management of PRES to optimize outcomes in liver transplant patients. The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks, underlining the necessity for careful monitoring and intervention strategies in this patient population.

Critical considerations for the management of acute abdomen in transplant patients.

The number of solid organ transplantations performed annually is increasing and are increasing in the following order: Kidney, liver, heart, lung, pancreas, small bowel, and uterine transplants. However, the outcomes of transplants are improving (organ survival > 90% after the 1st year). Therefore, there is a high probability that a general surgeon will be faced with the management of a transplant patient with acute abdomen. Surgical problems in immunocompromised patients may not only include graft-related problems but also nongraft-related problems. The perioperative regulation of immunosuppression, the treatment of accompanying problems of immunosuppression, the administration of cortisol and, above all, the realization of a rapidly deteriorating situation and the accurate evaluation and interpretation of clinical manifestations are particularly important in these patients. The perioperative assessment and preparation includes evaluation of the patient's cardiovascular system and determining if the patient has hypertension or suppression of the hypothalamic-pituitary-adrenal axis, or if the patient has had any coagulation mechanism abnormalities or thromboembolic episodes. Immunosuppression in transplant patients is associated with the use of calcineurin inhibitors, corticosteroids, and antiproliferation agents. Many times, the clinical picture is atypical, resulting in delays in diagnosis and treatment and leading to increased morbidity and mortality. Multidetector computed tomography is of utmost importance for early diagnosis and management. Transplant recipients are prone to infections, especially specific infections caused by cytomegalovirus and Clostridium difficile, and they are predisposed to intraoperative or postoperative complications that require great care and vigilance. It is necessary to follow evidence-based therapeutic protocols. Thus, it is required that the clinician choose the correct therapeutic plan for the patient (conservative, emergency open surgery or minimally invasive surgery, including laparoscopic or even robotic surgery).

Mycobacterium genavense infections in immunocompromised patients with HIV: A clinical case report.

Key Clinical Message: It is essential to consider non-tuberculosis mycobacterium in HIV-positive patients with fever, abdominal pain, weight loss, and splenomegaly. Abstract: Mycobacterium genavense is an opportunistic slow-growing nontuberculous mycobacterium in patients with immunocompromised backgrounds, especially HIV-positive patients. In this study, we present two cases of Mycobacterium genovese infection in HIV-positive patients with a good clinical response to accurate treatment.

Risk of fungal exposure in the homes of patients with hematologic malignancies.

BACKGROUND: Patients with hematological malignancies are at a high risk of developing invasive fungal infections (IFI) because they undergo several cycles of treatment leading to episodes of neutropenia. In addition, they alternate between hospital stays and periods spent at home. Thus, when an IFI is diagnosed during their hospital stays, it is highly challenging to identify the origin of the fungal contamination. The objective of this study was to analyze at home fungal exposure of 20 patients with leukemia by taking air and water samples in their living residence. METHODS: Air was sampled in 3 rooms of each home with a portable air system impactor. Tap water was collected at 3 water distribution points of each home. For positive samples, fungi were identified by mass spectrometry or on the basis of their morphological features. RESULTS: 85 % of homes revealed the presence in air of Aspergillus spp. and those belonging to the section Fumigati presented the highest concentrations and the greatest frequency of isolation. Concerning mucorales, Rhizopus spp. and Mucor spp. were isolated in air of 20 % and 5 % of dwellings, respectively. In 4 homes, more than 70 % of the fungal species identified in air were potential opportunists; these were mainly Aspergillus spp. with concentrations greater than 20 cfu/m3. The water samples revealed the presence of Fusarium in 3 dwellings, with concentrations up to 80 cfu/L. Finally, for one patient, fungal species isolated during a period of hospitalization were phenotypically similar to those isolated in samples taken at home. For a second patient, a PCR Mucorale was positive on a sample of bronchoalveolar fluid while air samples taken at his home also revealed also the presence of mucorales. CONCLUSION: The presence of opportunistic fungal species in the air of all the explored homes suggests the need for strengthened preventive measures in the home of immunocompromised patients. It would be interesting to compare the fungi isolated (from patients and from their environment) by genotyping studies aimed at specifying the correspondence existing between fungal species present in the patients' homes and those responsible for IFI in the same patients.

Engineered HCMV-infected APCs enable the identification of new immunodominant HLA-restricted epitopes of anti-HCMV T-cell immunity.

Complications due to HCMV infection or reactivation remain a challenging clinical problem in immunocompromised patients, mainly due to insufficient or absent T-cell functionality. Knowledge of viral targets is crucial to improve monitoring of high-risk patients and optimise antiviral T-cell therapy. To expand the epitope spectrum, genetically-engineered dendritic cells (DCs) and fibroblasts were designed to secrete soluble (s)HLA-A*11:01 and infected with an HCMV mutant lacking immune evasion molecules (US2-6 + 11). More than 700 HLA-A*11:01-restricted epitopes, including more than 50 epitopes derived from a broad range of HCMV open-reading-frames (ORFs) were identified by mass spectrometry and screened for HLA-A*11:01-binding using established prediction tools. The immunogenicity of the 24 highest scoring new candidates was evaluated in vitro in healthy HLA-A*11:01+/HCMV+ donors. Thus, four subdominant epitopes and one immunodominant epitope, derived from the anti-apoptotic protein UL36 and ORFL101C (A11SAL), were identified. Their HLA-A*11:01 complex stability was verified in vitro. In depth analyses revealed highly proliferative and cytotoxic memory T-cell responses against A11SAL, with T-cell responses comparable to the immunodominant HLA-A*02:01-restricted HCMVpp65NLV epitope. A11SAL-specific T cells were also detectable in vivo in immunosuppressed transplant patients and shown to be effective in an in vitro HCMV-infection model, suggesting their crucial role in inhibiting viral replication and improvement of patient's outcome. The developed in vitro pipeline is the first to utilise genetically-engineered DCs to identify naturally presented immunodominant HCMV-derived epitopes. It therefore offers advantages over in silico predictions, is transferable to other HLA alleles, and will significantly expand the repertoire of viral targets to improve therapeutic options.

A Comparison of the Immunogenicity and Safety of an Additional Heterologous versus Homologous COVID-19 Vaccination among Non-Seroconverted Immunocompromised Patients after a Two-Dose Primary Series of mRNA Vaccination: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to compare the immunogenicity and safety of an additional heterologous (viral vector) versus homologous (mRNA) COVID-19 vaccine dose among non-seroconverted immunocompromised patients after a two-dose primary series of mRNA vaccine. We searched studies published up to 21 June 2023 in PubMed, Scopus, and Embase. The meta-analysis was conducted to compare the seropositivity rates based on anti-SARS-CoV-2 spike protein IgG (anti-S IgG) and SARS-CoV-2-specific T-cell immune response rates, assessed by interferon-γ release assay at 4 weeks, and the incidences of serious adverse events (SAEs) within 28 days between the two vaccine regimens. In four included randomized controlled trials (RCTs), there were no statistically significant differences in the seropositive rate of anti-S IgG (risk ratio [RR]: 0.79, 95% CI: 0.48-1.29) and the concentration of SARS-CoV-2 interferon-γ (RR: 1.19, 95% CI: 0.96-1.48) between heterologous and homologous regimens. The heterologous regimen exhibited a significantly lower incidence of injection pain (RR: 0.55, 95% CI: 0.45-0.69), but a higher incidence of headache (RR: 1.44, 95% CI: 1.02-2.02) compared with the homologous regimen. No vaccine-related SAEs were reported within 28 days following vaccination. An additional heterologous or homologous COVID-19 vaccine dose was well tolerated and demonstrated a comparable vaccine immunogenicity among non-seroconverted immunocompromised patients who were initially vaccinated with a two-dose COVID-19 mRNA vaccine. This finding supports the recommendations of an extended primary series of COVID-19 vaccination in immunocompromised persons.

Severe Legionnaires' disease.

BACKGROUND: Legionnaires' disease (LD) is a common but under-diagnosed cause of community-acquired pneumonia (CAP), although rapid detection of urine antigen testing (UAT) and advances in molecular testing have improved the diagnosis. LD entails intensive care unit (ICU) admission in almost one-third of cases, and the mortality rate ranges from 4% to 40%. This review aims to discuss recent advances in the study of this condition and to provide an update on the diagnosis, pathogenesis and management of severe LD. RESULTS: The overall incidence of LD has increased worldwide in recent years due to the higher number of patients with risk factors, especially immunosuppression, and to improvements in diagnostic methods. Although LD is responsible for only around 5% of all-cause CAP, it is one of the three most common causes of CAP requiring ICU admission. Mortality in ICU patients, immunocompromised patients or patients with a nosocomial source of LD can reach 40% despite appropriate antimicrobial therapy. Regarding pathogenesis, no Legionella-specific virulence factors have been associated with severity; however, recent reports have found high pulmonary Legionella DNA loads, and impairments in immune response and lung microbiome in the most severe cases. The clinical picture includes severe lung injury requiring respiratory and/or hemodynamic support, extrapulmonary symptoms and non-specific laboratory findings. LD diagnostic methods have improved due to the broad use of UAT and the development of molecular methods allowing the detection of all Lp serogroups. Therapy is currently based on macrolides, quinolones, or a combination of the two, with prolonged treatment in severe cases. CONCLUSIONS: Numerous factors influence the mortality rate of LD, such as ICU admission, the underlying immune status, and the nosocomial source of the infection. The host immune response (hyperinflammation and/or immunoparalysis) may also be associated with increased severity. Given that the incidence of LD is rising, studies on specific biomarkers of severity may be of great interest. Further assessments comparing different regimens and/or evaluating host-directed therapies are nowadays needed.

Fusarium, Scedosporium and Other Rare Mold Invasive Infections: Over Twenty-Five-Year Experience of a European Tertiary-Care Center.

Invasive mold infections (IMD) are an emerging concern due to the growing prevalence of patients at risk, encompassing but not limited to allogeneic hematopoietic stem cell transplant recipients, hematological malignancies patients, solid organ transplant recipients and intensive care unit patients. In contrast with invasive aspergillosis and mucormycosis, other hyalohyphomycoses and phaeohyphomycoses remain poorly known. We conducted a retrospective analysis of the clinical, biological, microbiological and evolutive features of 92 IMD having occurred in patients in our tertiary-care center over more than 25 years. A quarter of these infections were due to multiple molds. Molds involved were Fusarium spp. (36.2% of IMD with a single agent, 43.5% of IMD with multiple agents), followed by Scedosporium spp. (respectively 14.5% and 26.1%) and Alternaria spp. (respectively 13.0% and 8.7%). Mortality at day 84 was higher for Fusarium spp., Scedosporium spp. or multiple pathogens IMD compared with Alternaria or other pathogens (51.7% vs. 17.6%, p < 0.05). Mortality at day 84 was also influenced by host factor: higher among hematology and alloHSCT patients than in other patients (30.6% vs. 20.9% at day 42 and 50.0% vs. 27.9% at day 84, p = 0.041). Better awareness, understanding and treatments are awaited to improve patient prognosis.

Pre-Exposure Prophylaxis and Treatment with Tixagevimab/Cilgavimab for COVID-19 among Immunocompromised Pediatric Patients.

Background: Patients treated with hemato-oncological malignancies (HO) or undergoing cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cells (CAR-T) were significantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the success of SARS-CoV-2 vaccination, immunocompromised patients remain at increased risk for severe coronavirus disease (COVID-19), rendering this group of population a high priority for additional prevention and treatment options. Tixagevimab and Cilgavimab (TIXA/CILGA, AZD7442, Evusheld®) is a combination of two fully human, long-acting monoclonal antibodies. TIXA/CILGA have been approved as pre-exposure prophylaxis and treatment in patients at risk of severe disease with impaired vaccine response. Our objective was to describe the efficacy and safety among immunocompromised pediatric patients. Methods: This was an observational multicenter cohort study of immunocompromised pediatric patients receiving TIXA/CILGA conducted at nine Polish centers of Pediatric Oncology, Hematology and Bone Marrow Transplantation. We analyzed patients in two groups; those treated with HO and those undergoing cellular therapies: HSCT or CAR-T cells. In addition, two other cohorts were identified: patients given TIXA/CILGA as pre-exposure prophylactic and therapeutic intervention. Results: A total of 78 patients were evaluated during the study period: 69 (88.5%) received TIXA/CILGA as pre-exposure prophylaxis and 9 (11.5%) as a treatment strategy. A total of 52 (66.6%) patients were treated with standard chemotherapy at HO departments; 21 (27%) underwent HSCT, and 5 (6.4%) received CAR-T cell therapy. All children with COVID-19 receiving TIXA/CILGA presented a mild degree of severity. The most common clinical manifestations were fever, cough and coryza. At least one adverse event (AE) was reported in two (3.8%) patients excluding standard injection site reactions. Reported AEs were mild or moderate in intensity. One child reported mild myalgia and one reported moderate bone pain and weakness. Conclusions: In our observational multicenter cohort study, we explored the use of TIXA/CILGA as pre-exposure prophylaxis and treatment for COVID-19 among immunocompromised pediatric patients. While our findings suggest a potential benefit in preventing and managing COVID-19 in this vulnerable population, it is important to note the study's non-comparative design. Our results highlight the need for well-designed clinical trials to confirm these observations and further assess the efficacy and safety of TIXA/CILGA in immunocompromised children.

Photodynamic Therapy for the Treatment of Bowen's Disease: A Review on Efficacy, Non-Invasive Treatment Monitoring, Tolerability, and Cosmetic Outcome.

Bowen's disease represents the in situ form of cutaneous squamous cell carcinoma; although it has an excellent prognosis, 3-5% of lesions progress to invasive cutaneous squamous cell carcinoma, with a higher risk in immunocompromised patients. Treatment is therefore always necessary, and conventional photodynamic therapy is a first-line option. The aim of this review is to provide an overview of the clinical response, recurrence rates, safety, and cosmetic outcome of photodynamic therapy in the treatment of Bowen's disease, considering different protocols in terms of photosensitizers, light source, and combination treatments. Photodynamic therapy is a valuable option for tumors at sites where wound healing is poor/delayed, in the case of multiple and/or large tumors, and where surgery would be difficult or invasive. Dermoscopy and reflectance confocal microscopy can be used as valuable tools for monitoring the therapeutic response. The treatment is generally well tolerated, with mild side effects, and is associated with a good/excellent cosmetic outcome. Periodic follow-up after photodynamic therapy is essential because of the risk of recurrence and progression to cSCC. As the incidence of keratinocyte tumors increases, the therapeutic space for photodynamic therapy will further increase.

Baseline immune status and the effectiveness of response to enteral nutrition among ICU patients with COVID-19: An observational, retrospective study.

OBJECTIVES: This study aimed to compare how immunocompromised and immunocompetent patients responded differently to enteral nutrition (EN) support in intensive care units (ICUs) during the COVID-19 pandemic, including serum nutritional biomarkers, inflammatory biomarkers, gastrointestinal (GI) intolerance symptoms, and clinical outcomes. METHODS: An observational, retrospective study was conducted in the ICUs of a teaching hospital in southwest China. We recruited a convenience sample of 154 patients between December 2022 and February 2023. We defined immunocompromise as primary immunodeficiency diseases, active malignancy, receiving cancer chemotherapy, HIV infection, solid organ transplantation, hematopoietic stem cell transplantation, receiving corticosteroid therapy with a target dose, receiving biological immune modulators, or receiving disease-modifying antirheumatic drugs or other immunosuppressive drugs. We conducted a Mann-Whitney U test, χ2 test, or generalized estimation equation model to explore the differences between immunocompromised and immunocompetent patients. RESULTS: Among the 154 study participants, 41 (27%) were defined as immunocompromised. The immunocompromised patients were younger than the immunocompetent patients. There were no statistically significant differences between the two groups with respect to serum nutritional biomarkers, inflammatory biomarkers, incidence of GI intolerance symptoms, and in-hospital mortality. However, the immunocompromised patients exhibited a longer hospitalization duration than the immunocompetent patients. CONCLUSION: We found that the immunocompromised patients spent more time in the hospital. These findings may help us to standardize the participants before EN interventional studies better and better individualize EN supports based on patients' immunity status.

Impact of next-generation sequencing on antimicrobial treatment in immunocompromised adults with suspected infections.

BACKGROUND: Prompt pathogen identification can have a substantial impact on the optimization of antimicrobial treatment. The objective of the study was to assess the diagnostic value of next-generation sequencing (NGS) for identifying pathogen and its clinical impact on antimicrobial intervention in immunocompromised patients with suspected infections. METHODS: This was a retrospective study. Between January and August 2020, 47 adult immunocompromised patients underwent NGS testing under the following clinical conditions: 1) prolonged fever and negative conventional cultures; 2) new-onset fever despite empiric antimicrobial treatment; and 3) afebrile with suspected infections on imaging. Clinical data, including conventional microbial test results and antimicrobial treatment before and after NGS, were collected. Data were analyzed according to documented changes in antimicrobial treatment (escalated, no change, or de-escalated) after the NGS results. RESULTS: The median time from hospitalization to NGS sampling was 19 d. Clinically relevant pathogens were detected via NGS in 61.7% of patients (29/47), more than half of whom suffered from fungemia (n=17), resulting in an antimicrobial escalation in 53.2% of patients (25/47) and antimicrobial de-escalation in 0.2% of patients (1/47). Antimicrobial changes were mostly due to the identification of fastidious organisms such as Legionella, Pneumocystis jirovecii, and Candida. In the remaining three cases, NGS detected clinically relevant pathogens also detected by conventional cultures a few days later. The antimicrobial treatment was subsequently adjusted according to the susceptibility test results. Overall, NGS changed antimicrobial management in 55.3% (26/47) of patientst, and conventional culture detected clinically relevant pathogens in only 14.9% of patients (7/47). CONCLUSION: With its rapid identification and high sensitivity, NGS could be a promising tool for identifying relevant pathogens and enabling rapid appropriate treatment in immunocompromised patients with suspected infections.

Safety and antibody response of the BNT162b2 SARS-CoV-2 vaccine in children aged 5-11 years with underlying diseases: A prospective observational study.

BACKGROUND: Data on the safety and antibody response of the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in children aged 5-11 years with underlying diseases are limited. Thus, our study aimed to address this gap. METHODS: This prospective observational study investigated the antibody titers for SARS-CoV-2 spike protein receptor-binding domain (S-IgG) and nucleocapsid protein (N-IgG) in patients aged 5-11 years with chronic underlying diseases following two doses of BNT162b2. Additionally, a questionnaire was used to assess adverse events (AEs) arising within 7 days after each dose. Data on severe AEs arising within 28 days after each dose were extracted from the patients' electronic medical records. RESULTS: Among 122 patients, 24.6% (30/122) were immunocompromised. Furthermore, 79 patients experienced at least one AE following vaccination, but all recovered without sequelae, including one severe case after the first dose. The seropositivity rate after the second dose was 99.1% (116/117). Excluding 19 N-IgG-positive patients, the geometric mean antibody titer (GMT) was significantly higher in immunocompetent patients than in immunocompromised patients (1496 U/mL [95% confidence interval 1199-1862] vs. 472 U/mL [200-1119], p = 0.035). Additionally, the GMT of S-IgG was higher in N-IgG-positive patients than in N-IgG-negative patients (8203 [5847-11482] U/mL vs. 1127 [855-1486] U/mL, p < 0.001). CONCLUSIONS: BNT162b2 is acceptably safe and immunogenic for children aged 5-11 years with underlying diseases. Although seroconversion was satisfactory in immunocompromised patients, the titers were lower than in immunocompetent patients.

Management of Cytomegalovirus Infections in the Era of the Novel Antiviral Players, Letermovir and Maribavir.

Cytomegalovirus (CMV) infections may increase morbidity and mortality in immunocompromised patients. Until recently, standard antiviral drugs against CMV were limited to viral DNA polymerase inhibitors (val)ganciclovir, foscarnet and cidofovir with a risk for cross-resistance. These drugs may also cause serious side effects. This narrative review provides an update on new antiviral agents that were approved for the prevention and treatment of CMV infections in transplant recipients. Letermovir was approved in 2017 for CMV prophylaxis in CMV-seropositive adults who received an allogeneic hematopoietic stem cell transplant. Maribavir followed four years later, with an indication in the treatment of adult and pediatric transplant patients with refractory/resistant CMV disease. The target of letermovir is the CMV terminase complex (constituted of pUL56, pUL89 and pUL51 subunits). Letermovir prevents the cleavage of viral DNA and its packaging into capsids. Maribavir is a pUL97 kinase inhibitor, which interferes with the assembly of capsids and the egress of virions from the nucleus. Both drugs have activity against most CMV strains resistant to standard drugs and exhibit favorable safety profiles. However, high-level resistance mutations may arise more rapidly in the UL56 gene under letermovir than low-grade resistance mutations. Some mutations emerging in the UL97 gene under maribavir can be cross-resistant with ganciclovir. Thus, letermovir and maribavir now extend the drug arsenal available for the management of CMV infections and their respective niches are currently defined.

COVID-19 in immunocompromised patients after hematopoietic stem cell transplantation: a pilot study.

Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients at early stage of immune reconstitution after hematopoietic stem cell transplantation (HSCT) are limited. In the present study, we retrospectively investigated the incidence and clinical features of SARS-CoV-2 infection in patients who underwent HSCT in 2022. Patients (allo-HSCT, n = 80; auto-HSCT, n = 37) were consecutively included in the study. The SARS-CoV-2 infection rate was 59.8%, and the median interval of HSCT to coronavirus disease 2019 (COVID-19) was 4.8 (range: 0.5-12) months. Most patients were categorized as mild (41.4%) or moderate (38.6%), and 20% as severe/critical. No deaths were attributable to COVID-19. Further analysis showed that lower circulating CD8+ T-cell counts and calcineurin inhibitor administration increased the risk of SARS-CoV-2 infection. Exposure to rituximab significantly increased the probability of severe or critical COVID-19 compared with that of mild/moderate illness (P < .001). In the multivariate analysis, rituximab use was associated with severe COVID-19. Additionally, COVID-19 had no significant effect on immune reconstitution. Furthermore, it was found that Epstein-Barr virus infection and rituximab administration possibly increase the risk of developing severe illness. Our study provides preliminary insights into the effect of SARS-CoV-2 on immune reconstitution and the outcomes of allo-HSCT recipients.

Prevention of legionella infections from toilet flushing cisterns.

INTRODUCTION: Immunocompromised patients are at an increased risk of severe legionella infections. We present the results of an outbreak investigation initiated following a fatal case of hospital-acquired legionellosis linked to contaminated water from a toilet-flushing cistern. Additionally, we provide experimental data on the growth of Legionella spp. in flushing cisterns and propose a straightforward protocol for prevention. METHODS: We monitored the growth of Legionella spp. in the building's hot- and cold-water systems using quantitative bacterial culture on selective agar. Molecular typing of Legionella pneumophila isolates from the infected patient and the water system was conducted through core-genome multi-locus sequence typing (cgMLST). RESULTS: Legionella contamination in the hospital building's cold-water system was significantly higher than in the hot-water system and significantly higher in toilet flushing cistern's water compared with cold water from bathroom sinks and showers. Isolates from the patient and from the flushing cistern of the patient's bathroom were identical by cgMLST. In an experimental setting, daily toilet flushing for a period of 21 days resulted in a 67% reduction in the growth of Legionella spp. in the water of toilet flushing cisterns. Moreover, a one-time disinfection of cisterns with peracetic acid, followed by daily flushing, decreased legionella growth to less than 1% over a period of at least seven weeks in these setting. CONCLUSIONS: One-time disinfection of highly contaminated cisterns with peracetic acid and daily toilet flushing as short-term measure can significantly reduce legionella contamination in flushing cisterns. These measures may aid in preventing legionella infection among immunocompromised patients.