These updated AST‐IDCOP guidelines provide information on epidemiology, diagnosis, and management of Aspergillus after organ transplantation. Aspergillus is the most common invasive mold infection in solid‐organ transplant (SOT) recipients, and it is the most common invasive fungal infection among lung transplant recipients. Time from transplant to diagnosis of invasive aspergillosis (IA) is variable, but most cases present within the first year post‐transplant, with shortest time to onset among liver and heart transplant recipients. The overall 12‐week mortality of IA in SOT exceeds 20%; prognosis is worse among those with central nervous system involvement or disseminated disease. Bronchoalveolar lavage galactomannan is preferred for the diagnosis of IA in lung and non‐lung transplant recipients, in combination with other diagnostic modalities (eg, chest CT scan, culture). Voriconazole remains the drug of choice to treat IA, with isavuconazole and lipid formulations of amphotericin B regarded as alternative agents. The role of combination antifungals for primary therapy of IA remains controversial. Either universal prophylaxis or preemptive therapy is recommended in lung transplant recipients, whereas targeted prophylaxis is favored in liver and heart transplant recipients. In these guidelines, we also discuss newer antifungals and diagnostic tests, antifungal susceptibility testing, and special patient populations.

Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity (CMI), the determinants of CMI in humans are poorly understood. Here we demonstrate that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence CMI in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered CMI in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and CMI. These results identify CCL3L1 and CCR5 as major determinants of CMI and demonstrate that these host factors influence HIV pathogenesis through their effects on both CMI and other viral entry-independent mechanisms.

Severe acute respiratory virus syndrome 2 (SARS-CoV-2) has led to a worldwide pandemic. Early studies in solid organ transplant (SOT) recipients suggested a wide variety of presentations, however, there remains a paucity of robust data in this population. We conducted a systematic review and meta-analysis of SOT recipients with SARS-CoV-2 infection from January 1 st t October 9 th , 2020. Pooled incidence of symptoms, treatments and outcomes were assessed. Two hundred and fifteen studies were included for systematic review and 60 for meta-analysis. We identified 2,772 unique SOT recipients including 1,500 kidney, 505 liver, 141 heart and 97 lung. Most common presenting symptoms were fever and cough in 70.2% and 63.8% respectively. Majority (81%) required hospital admission. Immunosuppressive medications, especially antimetabolites, were decreased in 76.2%. Hydroxychloroquine and interleukin six antagonists were administered in59.5% and 14.9% respectively, while only few patients received remdesivir and convalescent plasma. Intensive care unit admission was 29% from amongst hospitalized patients. Only few studies reported secondary infections. Overall mortality was 18.6%. Our analysis shows a high incidence of hospital admission in SOT recipients with SARS-CoV-2 infection. As management of SARS-CoV-2 continues to evolve, long-term outcomes among SOT recipients should be assessed in future studies.

The basis for the extensive variability seen in the reconstitution of CD4 + T cell counts in HIV-infected individuals receiving highly active antiretroviral therapy (HAART) is not fully known. Here, we show that variations in CCL3L1 gene dose and CCR5 genotype, but not major histocompatibility complex HLA alleles, influence immune reconstitution, especially when HAART is initiated at <350 CD4 + T cells/mm 3 . The CCL3L1-CCR5 genotypes favoring CD4 + T cell recovery are similar to those that blunted CD4 + T cell depletion during the time before HAART became available (pre-HAART era), suggesting that a common CCL3L1-CCR5 genetic pathway regulates the balance between pathogenic and reparative processes from early in the disease course. Hence, CCL3L1-CCR5 variations influence HIV pathogenesis even in the presence of HAART and, therefore, may prospectively identify subjects in whom earlier initiation of therapy is more likely to mitigate immunologic failure despite viral suppression by HAART. Furthermore, as reconstitution of CD4 + cells during HAART is more sensitive to CCL3L1 dose than to CCR5 genotypes, CCL3L1 analogs might be efficacious in supporting immunological reconstitution.HIV-1 infection is characterized by extensive variability in the degree of depletion or recovery in CD4 + T cell (abbreviated as CD4 + ) counts before or after receipt of HAART, respectively. Variability in CD4 + depletion cannot be attributed solely to the extent of viral replication (as reflected by the viral load) 1,2 , as host factors can influence HIV disease course independently of viral load 2,3 . Similarly, variability in the depth of HAART-induced suppression of viral replication cannot be the sole factor underlying intersubject differences in recovery of CD4 + counts. For example, the majority of HIV-positive subjects who initiate therapy with a low CD4 + nadir during untreated disease (<200 cells/mm 3 ) do not fully recover peripheral or mucosal CD4 + counts, despite HIV-suppressive HAART 4-12 . Conversely, some HIV-positive individuals show sustained recovery of CD4 + counts in the face of incomplete viral suppression 5,10,13-20 . However, the host factors that mediate this variable CD4 + recovery are largely unknown.Here we tested the hypothesis that CD4 + depletion and recovery reflect a dynamic balance between pathogenic and reparative processes integrally linked by specific common genetic pathways programmed during early stages of HIV disease. The importance of events occurring within the initial phases of HIV disease is highlighted by the observation that the magnitude of early immune damage determines the development and durability of virus-specific immunity, which dictates, in part, steady-state viral load, initial CD4 + loss and, subsequently, HIV disease course 1,3,21-23 . However, once host genetic factors skew the balance toward pathogenic processes (CD4 + depletion) during early untreated infection, it is unclear whether this imbalance can be fully reversed, even in the presence of HAART-induced viral suppression....

Objectives-There is an enrichment of immune response genes that are subject to copy number variations (CNVs). However, there is limited understanding of their impact on susceptibility to human diseases. CC chemokine ligand 3 like-1 (CCL3L1) is a potent ligand for the HIV coreceptor, CC chemokine receptor 5 (CCR5), and we have demonstrated previously an association between CCL3L1-gene containing segmental duplications and polymorphisms in CCR5 and HIV/AIDS susceptibility. Here, we determined the association between these genetic variations and risk of developing systemic lupus erythaematosus (SLE), differential recruitment of CD3+ and CD68+ leukocytes to the kidney, clinical severity of SLE reflected by autoantibody titres and the risk of renal complications in SLE.Methods-We genotyped 1084 subjects (469 cases of SLE and 615 matched controls with no autoimmune disease) from three geographically distinct cohorts for variations in CCL3L1 and CCR5.Results-Deviation from the average copy number of CCL3L1 found in European populations increased the risk of SLE and modified the SLE-influencing effects of CCR5 haplotypes. The CCR5 human haplogroup (HH)E and CCR5-32-bearing HHG*2 haplotypes were associated with an increased risk of developing SLE. An individual's CCL3L1-CCR5 genotype strongly predicted the overall risk of SLE, high autoantibody titres, and lupus nephritis as well as the differential Conclusion-CCR5haplotypes HHE and HHG*2 strongly influence the risk of SLE. The copy number of CCL3L1 influences risk of SLE and modifies the SLE-influencing effects associated with CCR5 genotypes. These findings implicate a key role of the CCL3L1-CCR5 axis in the pathogenesis of SLE.

Background: One year into the pandemic, published data on hematopoietic cell transplantation (HCT) recipients with coronavirus disease 2019 (COVID-19) remain limited. Methods: Single-center retrospective cohort study of adult HCT recipients with polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Results: Twenty-eight consecutive transplantation and cellular therapy patients (autologous, n = 12; allogeneic, n = 15; chimeric antigen receptor T-cell therapy [CAR-T], n = 1) with COVID-19 were identified. The median age was 57 years. The median time from HCT to COVID-19 diagnosis was 656 days (interquartile range [IQR], 33-1274). Patients were followed for a median of 59 days (IQR, 40-88).Among assessable patients (n = 19), 10 (53%) had documented virological clearance; median time to clearance was 34 days (range, 21-56). Out of 28, 12 (43%), 6 (21%), and 10 (36%) patients had mild, moderate, and severe/critical disease, respectively.Overall mortality was 25%, nearly identical for autologous and allogeneic HCT, and exclusively seen in hospitalized patients, older than 50 years of age with severe COVID-19. None of the patients with mild (n = 12) or moderate (n = 6) COVID-19 died whereas 7/10 patients (70%) with severe/critical COVID-19 died (P = .0001). Patients diagnosed with COVID-19 within 12 months of HCT exhibited higher mortality (57% vs 14%; P = .04). All-cause 30-day mortality (n = 4) was 14%. A higher proportion of patients who died within 30 days of COVID-19 diagnosis (3/4) were receiving ≥2 immunosuppressants, compared with patients who survived beyond 30 days after COVID-19 diagnosis (2/24; 75% vs. 8%; P = .01). Conclusions:Mortality in COVID-19 HCT patients is higher than that of the agecomparable general population and largely dependent on age, disease severity, timing from HCT, and intensity of immunosuppression.

Influence of the timing of antiretroviral therapy on the potential for normalization of immune status in human immunodeficiency virus 1-infected individuals.

Protective immunity against Aspergillus depends on a highly coordinated interaction between the innate and adaptive arms of the immune system. Fungal recognition via pattern recognition receptors, such as pentraxin 3, dectin-1, and Toll-like receptors, leads to complement activation, phagocytosis, and killing of ingested fungi. Aspergillus-specific T-helper 1 and 17 cells produce cytokines such as interferon γ and interleukin 17, which facilitate macrophage activation and neutrophil recruitment, respectively. Genetic (or drug-induced) defects in components of these networks of antifungal immunity result in increased risk of invasive aspergillosis after chemotherapy or transplantation. We review the most important genetic, immunological, and pharmacological factors that influence human susceptibility to Aspergillus and discuss the potential role of immune biomarkers in risk stratification strategies that facilitate individualized antifungal therapy/prophylaxis in immunocompromised hosts.