Critically ill patients with COVID-19 show lung fungal dysbiosis with reduced microbial diversity in patients colonized with Candida spp.

Abstract

Objectives The COVID-19 pandemic has intensified interest in how the infection impacts the lung microbiome of critically ill patients and contributes to acute respiratory distress syndrome (ARDS). We aimed to characterize the lower respiratory tract mycobiome of COVID-19 critically ill patients in comparison to COVID-19-negative patients. Methods We performed an Internal transcribed spacer 2 (ITS2) profiling, with the Illumina MiSeq platform, on 26 respiratory specimens from COVID-19 positive patients as well as from 26 patients with non-COVID-19 pneumonia. Results COVID-19+ patients were more likely to be colonized with Candida spp. and ARDS was associated with lung dysbiosis characterised by a shift to Candida species colonisation and a decrease of fungal diversity. We also observed higher bacterial phylogenetic distance among taxa in COVID-19+ colonized patients. In COVID-19+ patients non-colonized with Candida spp , ITS2 amplicon sequencing revealed an increase of Ascomycota unassigned spp. and one Aspergillus spp positive specimen. Then, we found that corticosteroid therapy was frequently associated with positive Galactomannan cell wall component of Aspergillus spp among COVID-19+ patients. Conclusions Our study underpins that ARDS in COVID-19+ patients is associated with lung dysbiosis and that an increased density of Ascomycota unassigned spp. is present in patients not colonized with Candida spp .

Alterations in the respiratory tract microbiome in COVID-19: current observations and potential significance

“…and an increase in Pseudomonas spp . A study from the same hospital by Viciani et al found increased colonization by Candida species in intubated COVID-19 patients relative to patients with non-COVID-19 pneumonia [ 71 ]. Sulaiman et al found Candida glabrata enriched in the lungs of intubated patients with longer hospital stays [ 69 ], suggesting an altered fungal microbiome as well.…”

“…Two metagenomic studies found Candida spp. increased in the lower airway in more severe COVID-19 patients [ 69 , 71 ]. Contrary to the bacterial microbiome, Hoque et al found increased alpha diversity in the fungal microbiome of nasopharyngeal swabs in COVID-19 relative to healthy controls [ 84 ].…”

“…Sputum meta-transcriptomes from COVID-19 patients also showed lower alpha diversity compared to a large cohort of non-COVID-19 pneumonia patients, suggesting that the consistent signature of low airway diversity seen in many COVID-19 studies is not necessarily common to all severe respiratory infections [ 93 ]. Additionally, Viciani and colleagues found increased Candida colonization in COVID-19 lower airways relative to non-COVID-19 pneumonia patients, again suggesting that previously discussed associations are not general to all pneumonias [ 71 ].…”

Role of Microbiota in Viral Infections and Pathological Progression

“…These observations are transient, and the involvement of the microbiota in disease progression has not been fully established; however, positive correlations between inflammation [ 64 , 67 ] or disease severity and the gut microbiota have been reported [ 60 , 67 , 76 ]. Recent reports described changes in the fungal microbiota of the lungs of patients with COVID-19 [ 77 ]. In addition, an increasing number of reports using a shotgun analysis of patients’ stool specimens described the correlation among the changes in the gut microbiota, immune responses, and metabolic pathway [ 67 , 78 , 79 , 80 ].…”

Association of SARS-CoV-2 and Polypharmacy with Gut–Lung Axis: From Pathogenesis to Treatment

“… 47 Recently, a study proposing fungal dysbiosis seen in COVID-19 patients has been related to the overgrowth of Candida albicans , while a few reports have seen COVID-19-associated pulmonary aspergillosis. 48 According to another meta-analysis, Candida species like Candida albicans have been frequently isolated fungi present in severely affected COVID-19 patients. 49 The serious imbalance of the mycobiome in lungs attributed to the wide use of antibiotics and corticosteroids, along with COVID-19 severity, may also lead to the invading of internal organs, thereby causing deep systemic infection.…”