Gut microbiome dynamics and predictive value in hospitalized COVID-19 patients: a comparative analysis of shallow and deep shotgun sequencing

Front Microbiol. 2024 Jun 19:15:1342749. doi: 10.3389/fmicb.2024.1342749. eCollection 2024.

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 has led to a wide range of clinical presentations, with respiratory symptoms being common. However, emerging evidence suggests that the gastrointestinal (GI) tract is also affected, with angiotensin-converting enzyme 2, a key receptor for SARS-CoV-2, abundantly expressed in the ileum and colon. The virus has been detected in GI tissues and fecal samples, even in cases with negative results of the reverse transcription polymerase chain reaction in the respiratory tract. GI symptoms have been associated with an increased risk of ICU admission and mortality. The gut microbiome, a complex ecosystem of around 40 trillion bacteria, plays a crucial role in immunological and metabolic pathways. Dysbiosis of the gut microbiota, characterized by a loss of beneficial microbes and decreased microbial diversity, has been observed in COVID-19 patients, potentially contributing to disease severity. We conducted a comprehensive gut microbiome study in 204 hospitalized COVID-19 patients using both shallow and deep shotgun sequencing methods. We aimed to track microbiota composition changes induced by hospitalization, link these alterations to clinical procedures (antibiotics administration) and outcomes (ICU referral, survival), and assess the predictive potential of the gut microbiome for COVID-19 prognosis. Shallow shotgun sequencing was evaluated as a cost-effective diagnostic alternative for clinical settings. Our study demonstrated the diverse effects of various combinations of clinical parameters, microbiome profiles, and patient metadata on the precision of outcome prognostication in patients. It indicates that microbiological data possesses greater reliability in forecasting patient outcomes when contrasted with clinical data or metadata. Furthermore, we established that shallow shotgun sequencing presents a viable and cost-effective diagnostic alternative to deep sequencing within clinical environments.

Keywords: COVID-19 patients; COVID-19 prognosis; deep shotgun sequencing; gut microbiome; machine learning; shallow shotgun sequencing.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This project was funded by the National Centre for Research and Development (NCBR), Poland (grant no. SZPITALEJEDNOIMIENNE/33/2020). KZ was funded through the NCN Sonata BIS grant number 2020/38/E/NZ2/00598. Publication charges were covered through the NCN Sonata grant number 2019/35/D/NZ2/04353. The funder had no role the study design and collection, analysis, and interpretation of the results.