Temporal changes in fecal microbiota of patients infected with COVID-19: a longitudinal cohort
Authors: Galperine Tatiana , Choi Yangji , Pagani Jean-Luc , Kritikos Antonios , Papadimitriou-Olivgeris Matthaios , Méan Marie , Scherz Valentin , Opota Onya , Greub Gilbert , Guery Benoit , Bertelli Claire ,   the RegCOVID Study Group, Bochud Pierre-Yves , Desgranges Florian , Filippidis Paraskevas , Haefliger David , Kampouri Eleftheria-Evdokia , Manuel Oriol , Munting Aline , Regina Jean , Rochat-Stettler Laurence , Suttels Veronique , Tadini Eliana , Tschopp Jonathan , Van Singer Mathias , Viala Benjamin , Vollenweider Peter 
Published: August 2023

Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a multifaceted disease potentially responsible for various clinical manifestations including gastro-intestinal symptoms. Several evidences suggest that the intestine is a critical site of immune cell development, gut microbiota could therefore play a key role in lung immune response. We designed a monocentric longitudinal observational study to describe the gut microbiota profile in COVID-19 patients and compare it to a pre-existing cohort of ventilated non-COVID-19 patients.

Methods
From March to December 2020, we included patients admitted for COVID-19 in medicine (43 not ventilated) or intensive care unit (ICU) (14 ventilated) with a positive SARS-CoV-2 RT-PCR assay in a respiratory tract sample. 16S metagenomics was performed on rectal swabs from these 57 COVID-19 patients, 35 with one and 22 with multiple stool collections. Nineteen non-COVID-19 ICU controls were also enrolled, among which 14 developed ventilator-associated pneumonia (pneumonia group) and five remained without infection (control group). SARS-CoV-2 viral loads in fecal samples were measured by qPCR.

Results
Although similar at inclusion, Shannon alpha diversity appeared significantly lower in COVID-19 and pneumonia groups than in the control group at day 7. Furthermore, the microbiota composition became distinct between COVID-19 and non-COVID-19 groups. The fecal microbiota of COVID-19 patients was characterized by increased Bacteroides and the pneumonia group by Prevotella. In a distance-based redundancy analysis, only COVID-19 presented significant effects on the microbiota composition. Moreover, patients in ICU harbored increased Campylobacter and decreased butyrate-producing bacteria, such as Lachnospiraceae, Roseburia and Faecalibacterium as compared to patients in medicine. Both the stay in ICU and patient were significant factors affecting the microbiota composition. SARS-CoV-2 viral loads were higher in ICU than in non-ICU patients.

Conclusions
Overall, we identified distinct characteristics of the gut microbiota in COVID-19 patients compared to control groups. COVID-19 patients were primarily characterized by increased Bacteroides and decreased Prevotella. Moreover, disease severity showed a negative correlation with butyrate-producing bacteria. These features could offer valuable insights into potential targets for modulating the host response through the microbiota and contribute to a better understanding of the disease's pathophysiology.

Trial registration
CER-VD 2020–00755 (05.05.2020) & 2017–01820 (08.06.2018).