• Alterations in Fecal Fungal Microbiomes of Patients With COVID-19

Alterations in Fecal Fungal Microbiomes of Patients With COVID-19

Patients hospitalized with COVID-19 have alterations in their fecal mycobiomes, including enrichment of fungal pathogens from the genera Candida and Aspergillus, compared with controls researchers report in the October issue of Gastroenterology. Unstable gut mycobiomes and prolonged dysbiosis persisted in a subset of patients with COVID-19 for as long as 12 days after nasopharyngeal clearance of SARS-CoV-2.

SARS-CoV-2 infects the intestinal epithelium and is detected in feces and anal swabs from patients with COVID-19. Bacterial and fungal infections are common complications of viral pneumonia, and associate disease course and outcomes. The intestinal bacterial microbiome is significantly altered in patients with COVID-19, with a significant expansion of pathogens and associated with disease severity and fecal content of SARS-CoV-2.

The gastrointestinal tract also contains many fungi, which affect microbiome assembly and immune development. Although the number of fungal cells is smaller than that of the bacteria in the gut, they regulate health and development of severe infectious diseases. It has been unclear whether the gut mycobiome is altered and whether fungal pathogens expand in patients with COVID-19.

Tao Zuo et al performed deep shotgun metagenomic sequencing analysis of fecal samples from 30 patients with COVID-19 in Hong Kong, from February 5 through May 12, 2020. The authors compared mycobiome compositions of fecal samples from patients with COVID-19, collected from time of hospitalization until clearance of SARS-CoV-2 from nasopharyngeal samples, with fecal samples from 9 subjects with community-acquired pneumonia and 30 healthy individuals (controls).

Zuo et al found that patients with COVID-19 had significant alterations in their fecal mycobiomes compared with controls, characterized by enrichment of Candia albicans and a highly heterogeneous mycobiome configuration, at time of hospitalization. Although fecal mycobiomes of 22 patients with COVID-19 did not differ significantly from those of controls during times of hospitalization, 8 of 30 patients with COVID-19 had continued significant differences in fecal mycobiome composition, through the last sample collected.

The diversity of the fecal mycobiome of the last sample collected from patients with COVID-19 was 2.5-fold higher than that of controls (P < .05). Samples collected at all timepoints from patients with COVID-19 had increased proportions of opportunistic fungal pathogens, C albicansC auris, and Aspergillus flavus compared with controls.

Two respiratory-associated fungal pathogens, Aspergillus flavus and Aspergillus niger, which cause pulmonary aspergillosis and respiratory illnesses (particularly cough), were detected in fecal samples from 6 and 4 patients with COVID-19, respectively, even after clearance of SARS-CoV-2 from nasopharyngeal samples and resolution of respiratory symptoms. Two of the 3 patients who had both fungal species (A flavus and A niger) in their fecal samples presented with critical COVID-19 and were admitted to intensive care unit; the third case had high fever and moderate COVID-19 severity.

The authors propose the expansion of opportunistic fungal pathogens, Candida species and Aspergillus species, in the gut of patients with COVID-19 over the disease course. Their presence after nasopharyngeal clearance of SARS-CoV-2 could pose a long-term health threat, even after clearance of SARS-CoV-2 infection.

How might COVID-19 lead to changes in the intestinal microbiome? SARS-CoV-2 infection is associated with significant reductions in T cells, which could compromise immune homeostasis and the stability of the microbial communities in the gut. Mechanistic studies are needed.

Zuo et al state that prospective studies are needed of asymptomatic and unhosptialized patients with SARS-CoV-2 infection, and of symtomatic patients followed from disease onset until after recovery, to associate changes in gut fungi with disease progression and long-term outcomes. Studies are also needed to determine whether alterations in intestinal fungi contribute to or result from SARS-CoV-2 infection.