Longitudinal Fecal Microbiota Profiles in A Cohort of Non-Hospitalized Adolescents and Young Adults with COVID-19: Associations with SARS-CoV-2 Status and Long-Term Fatigue

Adolescents most often experience mild acute COVID-19, but may still face fatigue and persistent symptoms such as post-COVID-19 condition (PCC) and post-infective fatigue syndrome (PIFS). We explored the fecal microbiota of SARS-CoV-2 positive and negative non-hospitalized adolescents and young adults (12-25 years of age) in the "Long-Term Effects of COVID-19 in Adolescents" (LoTECA) project, a longitudinal observational cohort study. With a targeted qPCR approach, the quantities of 100 fecal bacterial taxa were measured at baseline (early convalescent stage) in 145 SARS-CoV-2-positive and 32 SARS-CoV-2 negative participants and after six months in 107 of the SARS-CoV-2-positive and 19 of the SARS-CoV-2 negative participants. Results: <i>Faecalibacterium prausnitzii M21.2</i> and <i>Gemmiger formicilis</i> (both <i>p</i> < 0.001) were enriched in the SARS-CoV-2-positive participants compared to negative controls at baseline. In SARS-CoV-2-positive participants, lower baseline abundance of <i>Faecalibacterium prausnitzii M21/2</i> (<i>p</i> = 0.013) and higher abundance of <i>Clostridium spiroforme</i> (<i>p</i> = 0.006), <i>Sutterella wadsworthensis</i> (<i>p</i> < 0.001), and <i>Streptococcus thermophilus</i> (<i>p</i> = 0.039) were associated with six-month fatigue. <i>Sutterella wadsworthensis</i> and <i>Streptococcus thermophilus</i> enrichment was additionally associated with PCC in the SARS-CoV-2-positive group (<i>p</i> < 0.001 and 0.042 respectively). Conclusions: Adolescents and young adults with mild acute COVID-19 infection had increased fecal abundance of the beneficial <i>Faecalibacterium prausnitzii M21/2</i> and <i>Gemmiger formicilis</i> compared to SARS-CoV-2 negative controls in the early convalescent stage. Additionally, the abundance of both known (<i>Faecalibacterium prausnitzii, Streptococcus thermophilus</i>) and new (<i>Clostridium spiroforme, Sutterella wadsworthensis</i>) bacteria were associated with persistent symptoms such as fatigue in the COVID-19 infected group, warranting further exploration of the role of these bacteria in COVID-19 disease and PCC pathophysiology.