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PURPOSE OF REVIEW: Culturing preservation fluids of solid organs before transplantation is not a standardized procedure. In this review, we aim to describe the state-of-the-art of literature evidence in this debated setting with a special focus on Gram-negative bacteria (GNB). RECENT FINDINGS: Contamination of preservation fluids is frequent, but preservation fluids related infections are rare and most commonly caused by high-risk pathogens, including GNB. GNB preservation fluids related infections are characterized by high morbidity and mortality. Recent studies showed improved outcomes in solid organ transplant recipients receiving antibiotic therapy tailored according to preservation fluids cultures especially when multidrug-resistant GNB are found. A robust procurement network is needed to alert recipients' centers in cases of positivity and the support of transplant infectious diseases specialists is essential to choose the best therapy. SUMMARY: Culturing preservation fluids is a further step into preventing donor-derived infections. Interpreting and managing GNB positivity require a multidisciplinary team with specific skills. Standardized randomized trials are needed for insight into the real utility of preservation fluids cultures, the role of preservation fluids positivity, and the impact of antimicrobial therapy.
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BACKGROUND: The purpose of this study was to understand how transplant infectious disease (TID) physicians assess a potential donor with known or suspected infection and describe posttransplant management. METHODS: We designed a survey of 10 organ offer scenarios and asked questions pertaining to organ acceptability for transplantation and management posttransplant. The survey was distributed to TID clinicians via transplant society listservs and email. Responses were recorded in REDCap, and descriptive statistics were employed. RESULTS: One hundred thirteen infectious disease physicians responded to the survey, of whom 85 completed all cases. Respondents were generally in agreement regarding organ acceptability, although some divergence was seen when evaluating lungs from donors with influenza, tuberculosis, or multidrug-resistant Acinetobacter infection. Posttransplant management showed more variation. Areas of optimization were identified: (1) Further understanding of where risk-mitigation strategies within the donor offer process may improve donor acceptability and therefore organ utilization; (2) importance of recipient considerations in assessing degree of infectious risk; and (3) gaps in evidenced-based data regarding optimal posttransplant management of recipients. CONCLUSION: Evaluation of donor offers by TID clinicians is a complex process. Although the survey does not itself serve to make recommendations regarding best practices, it highlights areas where generation of data to inform acceptance and management practices may allow for improved organ utilization and recipient management.
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Lung transplant recipients (LTRs) respond poorly to vaccination. SARS-CoV-2 pre-exposure prophylaxis (PrEP) with tixagevimab/cilgavimab (TIX/CIL) reduces the incidence of infection and the evolution to severe COVID-19. In vitro data show decreased activity against Omicron variants. We evaluated the clinical efficacy and safety of TIX/CIL in LTRs during the Omicron wave. A prospective observational cohort study was conducted at ISMETT in Palermo (Italy). In June 2022, SARS-CoV-2 PrEP with TIX/CIL 150/150 mg was offered to LTRs. LTRs who received TIX/CIL were compared to LTRs who did not. Logistic regression analysis (adjusted for prior COVID-19, SARS-CoV-2 vaccination, age, years from transplant, and rejection) was performed. The objective of this study was to compare the following among the two populations: prevalence of SARS-CoV-2, length of SARS-CoV-2 positivity, and COVID-19 disease severity. Among 110 eligible LTRs, 79 (72%) received TIX/CIL and 31 (28%) did not. SARS-CoV-2 infections occurred in 6% (n = 5) of patients who received TIX/CIL and 29% (n = 9) of patients who did not (p < 0.001). In both groups, infections were mild/asymptomatic, and no one was hospitalized or died. At multivariate analysis, TIX/CIL was associated with a lower risk of infection (aOR 0.22; 95%CI 0.06-0.78; p = 0.02). TIX/CIL was safe and effective in reducing the risk of SARS-CoV-2 in LTRs during the Omicron wave.
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Unexpected donor-derived fungal infections represent a rare but potentially fatal complication in lung transplant (Tx) recipients. Timely communication of the results of donor cultures and prompt treatment of recipients are crucial to mitigate the consequences of donor-derived transmissions. In this prospective cohort study, all consecutive patients who underwent lung transplantation from 2015 to 2022 were included. In December 2015, a Local Active Surveillance System has been implemented to provide biovigilance of donor culture results and optimize recipients' management. The aim of this study is to investigate the incidence of unexpected, mold-positive cultures among lung donors and the rate of transmission to recipients. Furthermore, management strategies and outcome of recipients with mold transmission are described. In case of isolation of the same mold in donor and recipient cultures, when possible, transmission was confirmed by dendrogram analysis. During the study period, 82 lung Tx were performed from 80 donors. The prevalence of donors with "unexpected" mold isolation from the respiratory tract was 3.75% (3/80). Isolated molds were Aspergillus niger, Rhizopus oryzae, and Aspergillus flavus. Transmissions occurred in all the three cases (100%) with a mean time of 5 days from lung Tx but none of the recipients developed invasive mold disease. Our Local Active Surveillance System allowed prompt recognition of lung donors unexpected mold colonization. Even though transmission occurred, introduction of early targeted antifungal therapy prevented potential catastrophic consequence of mold donor-derived infection in the immediate post-Tx period.
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Immunotherapy has improved survival outcomes of patients with advanced melanoma. Lower gastrointestinal tract immune-related adverse events (irAEs) are common during treatment; however, gastritis is not frequently observed. Herein, we report a case of severe cytomegalovirus (CMV)-related gastritis in a patient treated with ipilimumab and nivolumab for metastatic melanoma. This report presents a 60-year-old woman with stage IV BRAF wild-type melanoma. After the second course of ipilimumab-nivolumab, the patient reported epigastric discomfort after meals, anorexia, and subsequent nausea, vomiting, epigastric pain, and weight loss. Disease staging with PET/CT scan showed very good partial response and diffuse gastroduodenitis. The patient underwent esophagogastroduodenoscopy, showing severe esophageal candidiasis and diffuse hemorrhagic, edematous, and ulcerative mucosa in the whole gastric wall. Biopsies of the gastric wall were obtained. Before receipt of the final pathology report, the patient was empirically started on corticosteroids based on the clinical suspicion of immune-related gastritis, without improvement of symptoms. The hematoxylin-eosin staining demonstrated active gastritis with diffuse nuclear cytopathic viral inclusions in epithelial and interstitial cells; CMV infection was confirmed with immunohistochemical staining. The patient started ganciclovir and fluconazole, with rapid improvement of symptoms. This case presents a rare instance of CMV gastritis in a patient receiving combined anti-PD1 and anti-CTLA4 , in the absence of immune-suppression to manage an irAE. In the case of suggestive symptoms of irAEs, a high index of clinical suspicion is required to rule out concomitant or isolated infective disease. Guidelines for prophylaxis and treatment of these patients are needed, to optimize treatment results.
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Infecciones por Citomegalovirus , Gastritis , Ipilimumab , Melanoma , Nivolumab , Humanos , Melanoma/tratamiento farmacológico , Melanoma/complicaciones , Ipilimumab/efectos adversos , Femenino , Persona de Mediana Edad , Gastritis/inducido químicamente , Nivolumab/efectos adversos , Infecciones por Citomegalovirus/inducido químicamente , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , CitomegalovirusAsunto(s)
Anticuerpos Antivirales , Muerte Encefálica , Donantes de Tejidos , Humanos , Estudios Seroepidemiológicos , Italia/epidemiología , Masculino , Anticuerpos Antivirales/sangre , Femenino , Persona de Mediana Edad , Virus Linfotrópico T Tipo 1 Humano/inmunología , Adulto , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 2 Humano/inmunología , Anciano , Infecciones por HTLV-II/epidemiología , Anticuerpos Anti-HTLV-I/sangreRESUMEN
OBJECTIVE: Solid organ transplant (SOT) recipients have a poorer SARS-CoV-2 vaccine response and higher risk for COVID-19-associated complications. However, there is no consensus on the current management of COVID-19 and data on persistent COVID-19 rates in SOT recipients are lacking. METHODS: An electronic survey concerning the management of COVID-19 in SOT recipients was distributed among all members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) and of the European Society for Organ Transplantation (ESOT). Four major sections were covered: prevention, early COVID-19, late COVID-19, and persistent COVID-19. We developed a structured questionnaire including eight multiple-choice questions with branching logic in case of positive answers and three open-ended questions related to clinical practice. Questions were asked separately for lung and non-lung transplantation. RESULTS: Thirty-two physicians from 24 different centers participated. Most answers (n = 30) were provided by European physicians. Thirty of 32 (93.75%) physicians managed non-lung transplant recipients and 12 of 32 (33.3%) lung transplant recipients. There was a huge variability in practice regarding the treatment of COVID-19, and particularly noticeable when considering lung and non-lung transplant recipients. Main discordances included the use of nirmatrelvir alone or in combination therapy for early COVID-19, the use of immunomodulatory drugs other than steroids for late COVID-19, and the need for treating asymptomatic viral shedding in persistent COVID-19. There was more similarity in terms of prophylaxis recommendations. CONCLUSION: Despite a low number of respondents, this survey shows that there are many differences on how experts manage SARS-CoV-2 infections in SOT recipients.
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COVID-19 , Trasplante de Órganos , Humanos , Vacunas contra la COVID-19 , SARS-CoV-2 , Encuestas y Cuestionarios , Receptores de TrasplantesRESUMEN
Donor-derived infections (DDIs) caused by carbapenem-resistant gram-negative bacteria (CR-GNB) in solid organ transplant recipients are potentially life-threatening. In this prospective study, we evaluated the incidence, factors associated with transmission, and the outcome of recipients with unexpected CR-GNB DDIs after the implementation of our local active surveillance system (LASS). LASS provides for early detection of unexpected donor CR-GNB infections, prophylaxis of recipients at high risk, and early diagnosis and treatment of DDIs. Whole genome sequencing confirmed DDI. Among 791 recipients, 38 (4.8%) were at high risk of unexpected CR-GNB DDI: 25 for carbapenem-resistant Enterobacterales (CRE) and 13 for carbapenem-resistant Acinetobacter baumannii (CRAB). Transmission did not occur in 27 (71%) cases, whereas DDIs occurred in 9 of 25 of CRE and 2 of 13 of CRAB cases. Incidence of CR-GNB DDI was 1.4%. Recipients of organs with CR-GNB-positive preservation fluid and liver recipients from a donor with CRE infection were at the highest risk of DDI. There was no difference in length of hospital stay or survival in patients with and without CR-GNB DDI. Our LASS contains transmission and mitigates the negative impacts of CR-GNB DDI. Under well-defined conditions, organs from donors with CR-GNB may be considered after a thorough evaluation of the risk/benefit profile.
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Carbapenémicos , Infecciones por Bacterias Gramnegativas , Trasplante de Órganos , Donantes de Tejidos , Receptores de Trasplantes , Humanos , Trasplante de Órganos/efectos adversos , Masculino , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Estudios Prospectivos , Femenino , Persona de Mediana Edad , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/epidemiología , Adulto , Factores de Riesgo , Incidencia , Estudios de Seguimiento , Pronóstico , Anciano , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Complicaciones PosoperatoriasRESUMEN
OBJECTIVES: To retrospectively describe the patterns of use of dalbavancin for treating infections in diabetic patients in Italian and Spanish standard clinical practice. METHODS: DALBADIA [NCT04959799] was a multicentre, observational, retrospective cohort study, conducted in Italy and Spain. The study enrolled 97 adults with type 1 or 2 diabetes mellitus, treated with dalbavancin as per standard clinical practice for a Gram-positive bacterial infection or the Gram-positive component of a mixed infection. RESULTS: Dalbavancin was used to treat cellulitis (18/92 patients, 19.6%), followed by prosthetic joint infection (14 patients, 15.2%), endocarditis (13 patients, 14.1%), and primary bacteraemia (10 patients, 10.9%); 78/92 (84.8%) patients had Gram-positive infections only, and 14 (15.2%) had mixed infections. The most frequently isolated microorganisms were Staphylococcus aureus in 43 (55.8% of the patients with microbial isolation), 25.6% of which methicillin-resistant; Staphylococcus epidermidis in 13 (16.9%), 53.8% of which methicillin-resistant; Enterococcus faecalis in 11 (14.3%). The main reason for the dalbavancin choice was the intent to simplify the antibiotic regimen (81.5% of cases). A multidisciplinary team participated in the treatment choice process for 53 (57.6%) patients. Dalbavancin was given as first-line antibiotic in 34 (37.0%) patients and administered as one infusion in 32 (34.8%), and as two infusions in 39 (42.4%). In total, 57/62 (91.9%) eligible patients with available assessment were judged clinically cured or improved at the end of observation. CONCLUSION: In clinical practice, dalbavancin was used in diabetic patients to treat ABSSSIs and other difficult-to-treat infections with a favourable safety profile and a high rate of positive clinical responses.
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Antibacterianos , Diabetes Mellitus , Teicoplanina , Adulto , Humanos , Italia , Estudios Retrospectivos , España , Teicoplanina/análogos & derivadosRESUMEN
BACKGROUND: Performance of active screening for multidrug-resistant Gram-negative bacteria (MDR-GNB) and administration of targeted antibiotic prophylaxis (TAP) in colonized patients undergoing liver (LT) and/or kidney transplantation (KT) are controversial issues. METHODS: Self-administered electronic cross-sectional survey disseminated from January to February 2022. Questionnaire consisted of four parts: hospital/transplant program characteristics, standard screening and antibiotic prophylaxis, clinical vignettes asking for TAP in patients undergoing LT and KT with prior infection/colonization with four different MDR-GNB (extended-spectrum cephalosporin-resistant Enterobacterales [ESCR-E], carbapenem-resistant Enterobacterales [CRE], multidrug-resistant Pseudomonas aeruginosa [MDR-Pa], and carbapenem-resistant Acinetobacter baumannii [CRAb]). RESULTS: Fifty-five respondents participated from 14 countries, mostly infectious disease specialists (69%) with active transplant programs (>100 procedures/year for 34.5% KT and 23.6% LT), and heterogeneous local MDR-GNB prevalence from <15% (30.9%), 15%-30% (43.6%) to >30% (16.4%). The frequency of screening for ESCR-E, CRE, MDR-Pa, and CRAb was 22%, 54%, 17%, and 24% for LT, respectively, and 18%, 36%, 16%, and 11% for KT. Screening time-points were mainly at transplantation 100%, only one-third following transplantation. Screening was always based on rectal swab cultures (100%); multi-site sampling was reported in 40% of KT and 35% of LT. In LT clinical cases, 84%, 58%, 84%, and 40% of respondents reported TAP for prior infection/colonization with ESCR-E, CRE, MDR-Pa, and CRAb, respectively. In KT clinical cases, 55%, 39%, 87%, and 42% of respondents reported TAP use for prior infection/colonization with ESCR-E, CRE, MDR-Pa, and CRAb, respectively. CONCLUSION: There is a large heterogeneity in screening and management of MDR-GNB carriage in LT and KT.
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Infecciones por Bacterias Gramnegativas , Trasplante de Riñón , Humanos , Profilaxis Antibiótica , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/prevención & control , Trasplante de Riñón/efectos adversos , Estudios Transversales , Bacterias Gramnegativas , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Hígado , Carbapenémicos , Encuestas y CuestionariosRESUMEN
This cohort study compares outcomes for patients with hematologic malignant tumors who prophylactically received tixagevimab-cilgavimab against SARS-CoV-2 with those who did not.
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Anticuerpos Monoclonales , Neoplasias Hematológicas , Humanos , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , PacientesRESUMEN
PURPOSE OF REVIEW: Human cytomegalovirus (CMV) continues to be the most important infectious complication following solid organ transplantation (SOT). RECENT FINDINGS: Universal prophylaxis and preemptive therapy are the most adopted strategies for prevention of CMV disease globally. Prophylaxis with valganciclovir is the most widely used approach to CMV prevention, however leukopenia and late onset CMV disease after discontinuation of prophylaxis requires new strategies to prevent this complication. The use of assays detecting CMV-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. Letermovir has been recently approved for prophylaxis in kidney transplant recipients. CMV-RNAemia used together with CMV-DNAemia in the viral surveillance of CMV infection provides accurate information on viral load kinetics, mostly in patients receiving letermovir prophylaxis/therapy. The development of refractory and resistant CMV infection remains a major challenge and a new treatment with maribavir is currently available. In the present paper we will review the most recent advances in prevention and treatment of CMV diseases in SOT recipients. SUMMARY: Recent findings, summarized in the present paper, may be useful to optimize prevention and treatment of CMV infection in SOT.
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Acetatos , Infecciones por Citomegalovirus , Trasplante de Órganos , Quinazolinas , Humanos , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/prevención & control , Valganciclovir/uso terapéutico , Receptores de Trasplantes , Trasplante de Órganos/efectos adversosRESUMEN
CASE PRESENTATION: A pregnant woman developed hepatitis due to a herpes simplex virus 2 primary infection with a severe systemic inflammatory response. Treatment with acyclovir and human immunoglobulin was given and both mother and baby survived. PURPOSE: We provide the first description of the inflammatory response associated with herpetic hepatitis in pregnancy.
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Hepatitis A , Hepatitis , Herpes Simple , Complicaciones Infecciosas del Embarazo , Embarazo , Femenino , Humanos , Herpesvirus Humano 2 , Herpes Simple/diagnóstico , Herpes Simple/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/complicaciones , Aciclovir/uso terapéutico , Hepatitis/complicacionesRESUMEN
Patients can be immunocompromised from a diverse range of disease and treatment factors, including malignancies, autoimmune disorders and their treatments, and organ and stem-cell transplantation. Infections are a leading cause of morbidity and mortality in immunocompromised patients, and the disease treatment landscape is continually evolving. Despite being a critical but preventable and curable adverse event, the reporting of infection events in randomised trials lacks sufficient detail while inconsistency of categorisation and definition of infections in observational and registry studies limits comparability and future pooling of data. A core reporting dataset consisting of category, site, severity, organism, and endpoints was developed as a minimum standard for reporting of infection events in immunocompromised patients across study types. Further additional information is recommended depending on study type. The standardised reporting of infectious events and attributable complications in immunocompromised patients will improve diagnostic, treatment, and prevention approaches and facilitate future research in this patient group.
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Trasplante de Células Madre Hematopoyéticas , Humanos , Consenso , Huésped InmunocomprometidoRESUMEN
Promoting the optimal use of antibiotics through evidence-based recommendations should be regarded as a crucial step in the global fight against antimicrobial resistance. Within this scope, several guidelines and guidance documents for antibiotic therapy have been published in recent years. All documents underline the limitations of existing evidence and remark on the need for tailoring recommendations at the national level, based on local epidemiology, availability of diagnostics and drugs, and antimicrobial stewardship principles. The GRADE-ADOLOPMENT methodology is an evidence-based methodology that allows the adoption, adaptation, and update of existing recommendations to specific settings without performing de novo systematic reviews and grading of the evidence. However, procedures to integrate this evidence with stewardship principles, countries' surveillance data, and capacity in terms of diagnostics and antibiotics' availability have never been defined. This Personal View provides the first example of a country's calibration of international evidence-based guidance documents on treating infections caused by multidrug-resistant bacteria. A panel of experts convened by the Italian Medicine Agency (AIFA) used the GRADE methodology for systematically extracting and evaluating 100 recommendations on the treatment of infections due to multidrug-resistant Gram-negative bacteria from 11 guidance documents and 24 systematic reviews. The ADOLOPMENT procedure was used to calibrate the existing recommendations to the national context, leading to the adoption of 64, the adaptation of 27, and the rejection of nine recommendations. We discuss the technical details of the GRADE-ADOLOPMENT application, the calibration process, and the human resources required to support such an effort. This Personal View also covers the challenges of integrating antibiotic stewardship principles in evidence-based recommendations for treating infections with very limited therapeutic and diagnostic options. The details presented here could support the easy transferability of the methodology to other countries and settings, particularly where the incidence of antibiotic-resistant infections is high.
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Programas de Optimización del Uso de los Antimicrobianos , Humanos , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana MúltipleRESUMEN
PURPOSE OF REVIEW: Skin and soft tissue infections (SSTI) in solid organ transplant (SOT) recipients may be a great challenge for clinicians caring for SOT due to the involvement of both common and opportunistic pathogens associated with a blunted immune response. The purpose of this review is to outline current literature and describe open issues on the management of SSTI in this special population. RECENT FINDINGS: Clinical presentation in SOT recipients can manifest as isolated skin lesions after primary inoculation or be the sign of a disseminated infection. Tissue samples for microscopy and histopathology are crucial to making an accurate diagnosis given the nonspecific and heterogeneous appearance of skin lesions. Multidisciplinary teams are required for a comprehensive diagnosis and management. SUMMARY: SSTI are frequent contributors to morbidity and mortality in SOT. Specific research focused on the clinical presentation, risk factors and management in this special population is needed.
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Trasplante de Órganos , Infecciones de los Tejidos Blandos , Trasplantes , Humanos , Infecciones de los Tejidos Blandos/diagnóstico , Infecciones de los Tejidos Blandos/epidemiología , Infecciones de los Tejidos Blandos/etiología , Trasplante de Órganos/efectos adversos , Receptores de TrasplantesRESUMEN
OBJECTIVES: To describe the dynamics and factors related to natural and hybrid humoral response against the SARS-CoV-2 and risk of reinfection among first-wave patients. METHODS: A prospective longitudinal study with periodic serological follow-up after acute onset of all recovered patients with SARS-CoV-2 infection cared in Udine Hospital (March-May 2020). Nucleocapsid (N) protein and spike receptor-binding domain (S-RBD) antibody tests were used to distinguish natural and vaccine-induced response. RESULTS: Overall, 153 patients (66 men, mean age 56 years) were followed for a median of 27.3 (interquartile range 26.9-27.8) months. Seroreversion was 98.5% (95% CI: 96.8-99.4) for SARS-CoV-2-N IgM at 1 year and 57.4% (95% CI: 51.5-63.5) for SARS-CoV-2-N IgG at 2 years. Initial serological response (hazard ratio [HR]: 0.99, 95% CI: 0.99-0.99, p 0.002 for IgM and HR: 0.97, 95% CI: 0.97-0.98, p < 0.001 for IgG) and severity of acute infection (HR: 0.62, 95% CI: 0.39-0.96, p 0.033 for IgM and HR: 0.60, 95% CI: 0.37-0.99, p < 0.001 for IgG) were independently associated with persistent SARS-CoV-2-N IgM/IgG response. Older age and smoker status were associated with long-term SARS-CoV-2-N IgM and SARS-CoV-2-N IgG, respectively (HR: 0.75, 95% CI: 0.57-0.98, p 0.038; HR: 1.77, 95% CI: 1.19-2.61, p 0.004 respectively). All patients maintained SARS-CoV-2-S-RBD IgG response at 24-month follow-up. Reinfections occurred in 25 of 153 (16.3%) patients, mostly during the omicron circulation. Reinfection rates did not differ significantly between SARS-CoV-2-N IgG seronegative and seropositive patients (14/89, 15.7% vs. 10/62, 16.1%, p 0.947). Unvaccinated patients had higher risk of reinfection (4/7, 57.1% vs. vaccinated 21/146, 14.4%, p 0.014). DISCUSSION: First-wave patients had durable natural humoral immunity in 40% and anti-S-RBD response in 100% up to 2 years after infection. Natural humoral response alone was not protective against reinfections with omicron SARS-CoV-2 variants, whereas vaccination was effective to reduce the risk of a new infection.
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COVID-19 , Masculino , Humanos , Preescolar , COVID-19/epidemiología , Formación de Anticuerpos , Reinfección/epidemiología , SARS-CoV-2 , Estudios Longitudinales , Estudios Prospectivos , Anticuerpos Antivirales , Inmunoglobulina G , Inmunoglobulina MRESUMEN
INTRODUCTION: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. METHODS: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. RESULTS: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. CONCLUSIONS: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51.
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BACKGROUND: Since November 2020, Italy was the first country to carry out a protocol and use liver from COVID-19 donors. We aimed to evaluate the medium-term outcome of patients who underwent liver transplant (LT) with those grafts. METHODS: We consecutively enrolled 283 patients who underwent first LT from November 2020 to December 2022 in our Center (follow-up 468 days). Twenty-five of 283 (8.8%, study population) received a graft from donors with previous (4%) or active (96%) SARS-CoV-2 infection, and 258/283 (91.2%, control group) received a graft from COVID-19-negative donors. SARS-CoV-2-RNA was tested on graft tissue of COVID-19 donors and their recipients underwent weekly evaluation of SARS-CoV-2-RNA in nasal swabs for the first month after LT. RESULTS: One-year and 2-year patient survival was 88.5% and 88.5% in study group versus 94.5% and 93.5% in control group, respectively (p = .531). In study population there was no evidence of donor-recipient virus transmission, but three (12%) patients (vs. 7 [2.7%] of control group, p = .048) developed hepatic artery thrombosis (HAT): they were SARS-CoV-2-RNA negative at LT and 1/3 grafts tested SARS-CoV-2-RNA positive on liver tissue. COVID-19 donor was independently associated with HAT (odds ratio (OR) = 4.85, 95% confidence interval (CI) 1.10-19.15; p = .037). By comparing study population with control group, acute rejection and biliary complication rates were not significantly different (16% vs. 8.1%, p = .26; 16% vs. 16.3% p = .99, respectively). CONCLUSIONS: Our 1-year results of transplant strategy including liver grafts from COVID-19 donors were favorable. HAT was the only complication with significantly higher rate in patients transplanted with COVID-19 donors compared with control group.