AUTHOR=Rizzello Fernando , Viciani Elisa , Gionchetti Paolo , Filippone Eleonora , Imbesi Veronica , Melotti Laura , Dussias Nikolas Konstantine , Salice Marco , Santacroce Barbara , Padella Antonella , Velichevskaya Alena , Marcante Andrea , Castagnetti Andrea 

TITLE=Signatures of disease outcome severity in the intestinal fungal and bacterial microbiome of COVID-19 patients

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 14 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1352202

DOI=10.3389/fcimb.2024.1352202

ISSN=2235-2988

ABSTRACT=Background: COVID-19, whose causative pathogen is the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was declared a pandemic in March 2020. The gastrointestinal tract is one of the targets of this virus, and mounting evidence suggests that gastrointestinal-related symptoms may contribute to the severity of the disease. The gut-lung axis is involved in the immune responses to SARS-CoV-2, therefore we investigated whether COVID-19 patients’ bacterial and fungal gut microbiome composition was linked to disease clinical outcome. 
Methods: During May 2020, we collected stool samples and patient records from 24 hospitalized patients with laboratory-confirmed SARS-CoV-2 infection. Fungal and bacterial gut microbiome was characterized by amplicon sequencing on the MiSeq, Illumina's integrated next generation sequencing instrument. A cohort of 201 age and sex-matched healthy volunteers from the project PRJNA661289 was used as a control group for bacterial gut microbiota analysis.
Results: We observed that the female COVID-19 patients had a lower gut bacterial microbiota richness compared to the male patients, which was consistent with a different latency in hospital admittance time between the two groups. Both genders in the COVID-19 patients study group displayed multiple positive associations with bacterial opportunistic pathogens like Enterococcus, Streptococcus, and Actinomyces. Of note, Candida genus dominated COVID-19 patients’ gut mycobiota, and the adult patients showed a higher intestinal fungal diversity compared to the elderly patients. We found that Saccharomycetales unassigned fungal genus was positively associated with bacterial short chain fatty acid (SCFA) producers and negatively associated with the proinflammatory genus Bilophila in COVID-19 patients, and we observed that none of the patients who harbored it was admitted to the high intensity unit.
Conclusions: COVID-19 patients were associated with opportunistic bacterial pathogens, along with having Candida as the dominant fungal taxon in the intestine. Together, we found an association between a fungal genus that was present in the intestine of patients who did not experience the most severe outcome of the disease with commensal SCFA-producers. We think that this taxon could have played a role in the disease outcome and that further studies should be addressed to understand the role of fungi in gastrointestinal and health protection.