SummaryBackground
The role of the fungal microbiota in digestive diseases is poorly defined, but is becoming better understood due to advances in metagenomics.

Aim
To review the gastrointestinal fungal microbiota and its relationship with digestive diseases.

Methods
Search of the literature using PubMed and MEDLINE databases. Subject headings including ‘fungal-bacterial interactions’, ‘mycotoxins’, ‘immunity to fungi’, ‘fungal infection’, ‘fungal microbiota’, ‘mycobiome’ and ‘digestive diseases’ were used.

Results
The fungal microbiota is an integral part of the gastrointestinal microecosystem with up to 106 microorganisms per gram of faeces. Next-generation sequencing of the fungal 18S rRNA gene has allowed better characterisation of the gastrointestinal mycobiome. Numerous interactions between fungi and bacteria and the complex immune response to gastrointestinal commensal or pathogenic fungi all impact on the pathophysiology of inflammatory bowel disease and other gastrointestinal inflammatory entities such as peptic ulcers. Mycotoxins generated as fungal metabolites contribute to disturbances of gastrointestinal barrier and immune functions and are associated with chronic intestinal inflammatory conditions as well as hepatocellular and oesophagogastric cancer. Systemic and gastrointestinal disease can also lead to secondary fungal infections. Fungal genomic databases and methodologies need to be further developed and will allow a much better understanding of the diversity and function of the mycobiome in gastrointestinal inflammation, tumourigenesis, liver cirrhosis and transplantation, and its alteration as a consequence of antibiotic therapy and chemotherapy.

Conclusions
The fungal microbiota and its metabolites impact gastrointestinal function and contribute to the pathogenesis of digestive diseases. Further metagenomic analyses of the gastrointestinal mycobiome in health and disease is needed.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/apt.12665

Review article: fungal microbiota and digestive diseases.

Vitamin D (VD) is a fat-soluble steroid essential for life in higher animals. It is technically a pro-hormone present in few food types and produced endogenously in the skin by a photochemical reaction. In recent decades, several studies have suggested that VD contributes to diverse processes extending far beyond mineral homeostasis. The machinery for VD production and its receptor have been reported in multiple tissues, where they have a pivotal role in modulating the immune system. Similarly, vitamin D deficiency (VDD) has been in the spotlight as a major global public healthcare burden. VDD is highly prevalent throughout different regions of the world, including tropical and subtropical countries. Moreover, VDD may affect host immunity leading to an increased incidence and severity of several infectious diseases. In this review, we discuss new insights on VD physiology as well as the relationship between VD status and various infectious diseases such as tuberculosis, respiratory tract infections, human immunodeficiency virus, fungal infections and sepsis. Finally, we critically review the latest evidence on VD monitoring and supplementation in the setting of infectious diseases.

https://www.mdpi.com/2072-6643/9/7/651/pdf

Vitamin D and Infectious Diseases: Simple Bystander or Contributing Factor?

Coccidioidomycosis (or valley fever) is a fungal disease with high morbidity and mortality that affects tens of thousands of people each year. This infection is caused by two sibling species, Coccidioides immitis and C. posadasii , which are endemic to specific arid locales throughout the Western Hemisphere, particularly the desert southwest of the United States. Recent epidemiological and population genetic data suggest that the geographic range of coccidioidomycosis is expanding, as new endemic clusters have been identified in the state of Washington, well outside the established endemic range. The genetic mechanisms and epidemiological consequences of this expansion are unknown and require better understanding of the population structure and evolutionary history of these pathogens. Here we performed multiple phylogenetic inference and population genomics analyses of 68 new and 18 previously published genomes. The results provide evidence of substantial population structure in C. posadasii and demonstrate the presence of distinct geographic clades in central and southern Arizona as well as dispersed populations in Texas, Mexico, South America, and Central America. Although a smaller number of C. immitis strains were included in the analyses, some evidence of phylogeographic structure was also detected in this species, which has been historically limited to California and Baja, Mexico. Bayesian analyses indicated that C. posadasii is the more ancient of the two species and that Arizona contains the most diverse subpopulations. We propose a southern Arizona-northern Mexico origin for C. posadasii and describe a pathway for dispersal and distribution out of this region. IMPORTANCE Coccidioidomycosis, or valley fever, is caused by the pathogenic fungi Coccidioides posadasii and C. immitis . The fungal species and disease are primarily found in the American desert southwest, with spotted distribution throughout the Western Hemisphere. Initial molecular studies suggested a likely anthropogenic movement of C. posadasii from North America to South America. Here we comparatively analyze eighty-six genomes of the two Coccidioides species and establish local and species-wide population structures to not only clarify the earlier dispersal hypothesis but also provide evidence of likely ancestral populations and patterns of dispersal for the known subpopulations of C. posadasii .

/pdf/local-population-structure-and-patterns-of-western-3m6s4bv2fq.pdf

Local Population Structure and Patterns of Western Hemisphere Dispersal for Coccidioides spp., the Fungal Cause of Valley Fever

OBJECTIVES The aim of this study was to evaluate miltefosine and four synthetic compounds (TCAN26, TC19, TC106 and TC117) for their in vitro inhibitory activity against Candida albicans planktonic and biofilm cells and investigate whether these compounds are able to inhibit the biofilm formation and to reduce the viability of mature C. albicans biofilm cells. METHODS The XTT reduction assay and transmission and scanning electron microscopy were employed to determine the inhibitory effects of the test compounds in comparison with amphotericin B and fluconazole against both planktonic cells and sessile cells in biofilms. RESULTS C. albicans planktonic cells were susceptible to miltefosine, TCAN26 and TC19, all alkylphospholipid compounds. Miltefosine and TCAN26 present a fungicidal activity with similar values of MIC and minimum fungicidal concentration (MFC), ranging from 2 to 8 mg/L. Cell treatment with sub-inhibitory concentrations of alkylphospholipids induced several ultrastructural alterations. In relation to biofilms, miltefosine reduced formation (38%-71%) and mature biofilms viability (32%-44%), at concentrations of 64 mg/L. TCAN26 also reduced biofilm formation (24%-30%) and mature biofilm viability (15%-20%), at concentrations of 64 mg/L. Although amphotericin B reduced biofilm formation similarly to miltefosine (51%-74%), its activity was lower on mature biofilms (24%-30%). Miltefosine antibiofilm activity was significantly higher than amphotericin B, on both formation and mature biofilms (P<0.05 and P<0.0001, respectively). Fluconazole was the least effective compound tested. CONCLUSION Promising antibiofilm activity was displayed by miltefosine and other alkylphosphocholine compounds, which could be considered a putative option for future treatment of candidaemia associated with biofilm formation, although further evaluation in in vivo systems is required.

/pdf/effect-of-alkylphospholipids-on-candida-albicans-biofilm-3k8iqrqwty.pdf

Effect of alkylphospholipids on Candida albicans biofilm formation and maturation

Epidemiology of acute febrile illness in Latin America

The pathogenic role of invasive fungal infections (IFIs) has increased during the past two decades in Latin America and worldwide, and the number of patients at risk has risen dramatically. Working habits and leisure activities have also been a focus of attention by public health officials, as endemic mycoses have provoked a number of outbreaks. An extensive search of medical literature from Latin America suggests that the incidence of IFIs from both endemic and opportunistic fungi has increased. The increase in endemic mycoses is probably related to population changes (migration, tourism, and increased population growth), whereas the increase in opportunistic mycoses may be associated with the greater number of people at risk. In both cases, the early and appropriate use of diagnostic procedures has improved diagnosis and outcome.

https://link.springer.com/content/pdf/10.1007%2Fs12281-011-0081-7.pdf

Epidemiology of Invasive Fungal Infections in Latin America

Abstract Background Post-COVID-19 syndrome occurs usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis (WHO definition, 2021). Our objective was to describe the prevalence, type, and duration of symptoms and their impact on the quality of life of patients hospitalized for COVID-19. Methods A cross-sectional descriptive study was done, digital informed consent was obtained. Patients with a history of hospitalization for COVID-19 between March 2020 and October 2021 were invited to answer electronically an adaptation of the questionnaire for the identification of post-COVID-19 syndrome and the instrument EuroQol-5D (quality of life). Both were performed at 3, 6, 9 and 12 months after the initial evaluation for COVID-19. Results We included 246 patients, of whom 76% (187/246) met the definition of post-COVID-19 syndrome, 54% were men, with a median age of 50 years (IQR 41-63). Sixty-three percent (117/187) of post-COVID-19 syndrome patients described a worse health status (OR 9.2, 95% CI 4.1-22.6, p=< 0.0001). The median time to symptoms onset after hospital discharge was 1 day (IQR 1-20), and the median duration of symptoms was 150 days (IQR 90-225). The most frequent symptoms were dyspnea 75% (141), arthralgia 71% (132), fatigue 68% (127), hair loss 60% (112), myalgia 53% (99), sleep disturbances 52% (97), dizziness 47% (88), and palpitations 41% (76) (Figure 1). Regarding quality of life, the post-COVID-19 syndrome patients presented a lower visual analog scale of the EQ-5D versus the group without syndrome (80mm [IQR 70-90] vs. 89.5mm [IQR 75-90], p=0.05). All five dimensions of the quality of life were affected in the post-COVID-19 syndrome group; and dimensions of pain/discomfort, usual activities, and anxiety/depression showed a statistical difference (Fig 2). Figure 1. Frequency of symptoms in Post-COVID-19 syndrome.Figure 2. Distribution of the EQ-5D dimensions affected. Euroqol (EQ)-5D:Specific instrument to describe and value health-related quality of life. Conclusion Post-COVID-19 syndrome occurred in 76% of hospitalized patients, with prolonged duration and quality of life impairment. Dyspnea was the most frequent symptom. Timely diagnostic and therapeutic intervention is required. Disclosures All Authors: No reported disclosures.

283. Post COVID-19 syndrome and quality of life impairment in a cohort of severe COVID-19


 
 
 In March 2020 our Institution was designated a COVID-19 unit, since the start of 2021 conventional medical attention has been reinstalled and it became a hybrid hospital. Our objective was to compare the outcome of patients with Invasive Aspergillosis (IA) without COVID-19 during the COVID-19 pandemic, compared with past controls from a historical cohort, and describe their clinical characteristics. As a secondary objective, we described the characteristics of other Invasive Fungal Infections (IFI) in a similar patient group.
 
 
 
 Retrospective and descriptive study. The information was obtained from the electronic file. For IFI diagnosis, the EORTC/MSG criteria for proven and probable infection were considered, including the AspiCU modified criteria. The main outcome was death at 6 weeks, time from symptom onset to diagnosis/treatment, and having received antifungal treatment as secondary outcomes. Outcomes were compared to historical IA controls (2:1) from a pre-COVID-19 cohort. The study was approved by the local research and ethics committee.
 
 
 
 From March 2020 to December 2021, 50 IFIs were diagnosed in non-COVID-19 patients, of which 27 (54%) were Invasive Aspergillosis, 10 (20%) Cryptococcosis, 8(16%) histoplasmosis, 4 (8%) mucormycosis, and 1 (2%) Fusariosis. The median age was 44 years (IQR 33-58) and 67% were men. Forty three percent (22/51) had immunosuppression and 35% (18/51) had hematological malignancy, the median time from symptom onset to IFI diagnosis was 30 days (IQR 11-90) and 38% died within 6 weeks. During the pandemic, in Invasive Aspergillosis non COVID-19 patients, the median number of days from symptom onset to start antifungal was 21 (IQR 6-68) vs 5 (IQR 3-10) of IA historic controls (p=0.0005), 81.5% (22/27) vs 93% (50/54) received antifungal treatment (OR 0.88 , 95% CI 0.72-1.0,p=0.13), and IA cases had a mortality of 44% (12/27) vs 41% (22/54) in the historical cohort (p=0.75). We show the IA characteristics in Table 1. Table 1.Clinical characteristics of Patients with Invasive aspergillosis without COVID-19 during COVID-19 pandemic vs historic controlsFigure 1.Invasive fungal infections in non-COVID-19 patients during COVID-19 pandemicFigure 2.Invasive aspergillosis diagnosis methods in non-COVID-19 patients during COVID-19 pandemic
 GM: Galactomannan antigen
 
 
 
 During the COVID-19 pandemic, patients with IA withouth COVID-19 were diagnosed significantly later. Also, a trend towards increased mortality and lower proportion of antifungal treatment was observed. It is likely a consequence of hospital reconversion during the start of the pandemic.
 
 
 
 All Authors: No reported disclosures.


L. Alfredo Ponce-de-León

Papers

Epidemiology of Invasive Fungal Infections in Latin America

283. Post COVID-19 syndrome and quality of life impairment in a cohort of severe COVID-19

355. Outcome of patients with non-COVID-19 related Aspergillosis during the COVID-19 pandemic