MHC class II genes mediate susceptibility and resistance to coronavirus infections in bats.

Understanding the immunogenetic basis of coronavirus (CoV) susceptibility in major pathogen reservoirs, such as bats, is central to inferring their zoonotic potential. Members of the cryptic Hipposideros bat species complex differ in CoV susceptibility, but the underlying mechanisms remain unclear. The genes of the major histocompatibility complex (MHC) are the best understood genetic basis of pathogen resistance, and differences in MHC diversity are one possible reason for asymmetrical infection patterns among closely related species. Here, we aimed to link asymmetries in observed CoV (CoV-229E, CoV-2B and CoV-2Bbasal) susceptibility to immunogenetic differences amongst four Hipposideros bat species. From the 2072 bats assigned to their respective species using the mtDNA cytochrome b gene, members of the most numerous and ubiquitous species, Hipposideros caffer D, were most infected with CoV-229E and SARS-related CoV-2B. Using a subset of 569 bats, we determined that much of the existent allelic and functional (i.e. supertype) MHC DRB class II diversity originated from common ancestry. One MHC supertype shared amongst all species, ST12, was consistently linked to susceptibility with CoV-229E, which is closely related to the common cold agent HCoV-229E, and infected bats and those carrying ST12 had a lower body condition. The same MHC supertype was connected to resistance to CoV-2B, and bats with ST12 were less likely be co-infected with CoV-229E and CoV-2B. Our work suggests a role of immunogenetics in determining CoV susceptibility in bats. We advocate for the preservation of functional genetic and species diversity in reservoirs as a means of mitigating the risk of disease spillover.

Central Nervous System Cryptococcosis due to Cryptococcus gattii in the Tropics.

Purpose of Review: Cryptococcosis of the central nervous system due to Cryptococcus gattii species complex is a serious mycosis with worldwide distribution but of great importance in the tropics. This article aims to review the progress made in these regions in the knowledge of this disease and its etiological agent. Recent Findings: They can be summarized in the presence in apparently immunocompetent patients of autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), which is a hidden risk factor for acquiring C. gattii infection; this finding strengthens the concept that C. gattii is an opportunistic pathogen. A greater knowledge of the clinical and molecular epidemiology of C. gattii infection and of the different environmental niches of this fungus in the tropics. The discovery of a new lineage of C. gattii, VGV, in environmental samples from Africa. Until now, the COVID-19 pandemic has not meant an increase in cryptococcosis cases. Summary: Advances have been made in the identification of risk factors for cryptococcosis due to C. gattii as well as in the knowledge of its etiological agent and its relationship with the environment. Remarkably, there have been no significant achievements in diagnosis and treatment notwithstanding the documented importance.

Characteristics and Outcomes in Hospitalized Patients with Covid-19 Complicated by Fungemia: A Single Center Retrospective Study

Background. Covid19 caused by SARS-CoV2 can lead to significant morbidity and mortality. Fungemia is a rare hospital-associated infection and there are limited data regarding its association with Covid19. We reviewed all cases of fungemia in our Covid19 cohort at Stony Brook University Hospital (SBUH). Methods. We conducted a retrospective medical record review of patients admitted with Covid19 in a 3-month interval. We reviewed positive blood cultures for fungi and recorded co-morbidities, co-infections, length of stay, treatments, and outcomes (survival vs death). There were 60 positive blood cultures for fungi in 25 unique patients (Table 1);in prior years < 30 per year reported at SBUH. Collation of each unique identified fungal species from fungal blood cultures in patients hospitalized with Covid-19 Results. During a 3 month interval at the local peak of the pandemic 1398 patients hospitalized with Covid19 at SBUH, 25 cases of fungemia were detected;C. albicans (CA) n=8,32%, non C albicans species (nCA) n=16,64%, and C. neoformans n=1,4%, 17/25 (68%) also with bacteremia during same hospitalization. In same 3 months there were 264 cases of bacteremia and Covid19 co-infection. Demographics and medical co-morbidities of fungemic patients are in Table 2. Majority were men (76%). No difference between fungaemic (FC) and total cohort (TC) in median age (62 vs 62), DM p=0.31, HTN p=1.0, COPD p=0.12. Within FC, DM was higher in nCA group (58.8%) vs CA group (37%). Mortality was 40% in FC vs 15% in TC, p< 0.001. Within FC mortality was 56% in nCA and 25% in CA group. C. parapsilosis was the most common nCA species isolated with 43% mortality. FC more likely to require ICU and mechanical ventilation (88% vs 15%, p< 0.0001) and had longer median length of stay 42 days vs 22 days. The median time from admission to fungaemia was 21d, from central line placement 19d, Table 3. Of FC 21 (84%) were treated with steroids/Tocilizumab concurrently. Of note, no mortality was recorded in the 4 patients that did not receive steroids/Tocilizumab. PCT and WBC were significantly higher at time of fungemia as compared to admission, Table 3. Relevant patient characteristics and laboratory parameters in patients hospitalized with Covid19 and fungemia Conclusion. Fungemia in hospitalized patients with COVID-19 is associated with higher mortality. We observed higher fatality in non C. albicans infections. Prolonged use of central line catheters and concurrent treatment with steroids/tociluzimab are likely high-risk factors for development of fungemia.

Prevalence, Genetic Structure, and Antifungal Susceptibility of the Cryptococcus neoformans/C. gattii Species Complex Strains Collected from the Arboreal Niche in Poland.

Fungi belonging to the Cryptococcus neoformans/C. gattii species complex (CNGSC) are etiological agents of serious and not infrequently fatal infections in both humans and animals. Trees are the main ecological niche and source of potential exposition concerning these pathogens. With regard to epidemiology of cryptococcosis, various surveys were performed worldwide, enabling the establishment of a map of distribution and genetic structure of the arboreal population of the CNGSC. However, there are regions, among them Central and Eastern Europe, in which the data are lacking. The present study shows the results of such an environmental study performed in Wroclaw, Poland. The CNGSC strains were detected in 2.2% of the tested trees belonging to four genera. The obtained pathogen population consisted exclusively of C. neoformans, represented by both the major molecular type VNI and VNIV. Within the tested group of isolates, resistance to commonly used antimycotics was not found, except for 5-fluorocytosine, in which about 5% of the strains were classified as a non-wild type.