Multi-omics Evaluation Of Microbial Co-infection As Marker Of Covid-19 Severity (CO-INFECTOMICS)

Since March 11 2020, the world is facing a large-scale pandemic with the COVID-19 outbreak affecting more than 1.7 million individuals globally. The SARS-CoV-2 fatality rate has been maintained at a low level thanks to countermeasures established in many countries, in particular, physical distancing to limit the infection rate and the enormous effort of nursing staff. Yet there is a major risk of overwhelming health care systems, which would lead to a dramatic increase in morbidity. Several risk factors for developing a severe pathology have been identified to date: sex, age, obesity, diabetes, hypertension and cardiovascular disease. Co-infections have been reported in several Chinese studies, but have not been examined systematically. In the frame of the PREDICOVID study, the CO-INFECTOMICS project aims to understand if apart from SARS-CoV-2, co-infections are a predictive marker of disease severity in COVID-19 positive patients in Luxembourg. To achieve this, our project will compare the taxonomic microbial composition as well as the functional potential and transcriptional activity of the respiratory and intestinal tract microbiota of 60 mild and 60 severe COVID-19 patients with a non-targeted approach. Nucleic acids will be extracted from sputum, nasal/oropharyngeal swabs, and stool samples using in-house established protocols, which will be optimised for bacteria, fungi and for virus detection at once. To examine co-infection or potential co-carriage, metagenomic and metatranscriptomic analyses will be performed using our multi-omic computational pipelines, i.e. the Integrated Meta-Omic Pipeline (IMP) and PathoFact, amongst others. Multi-omic microbial profiles, covering viruses, bacteria, and fungi, will be generated and compared between mild and severe patients. Furthermore, the taxonomic composition as well as the functional potential and transcriptional activity of the upper and lower respiratory tract will be compared, using sputum and nasal/oropharyngeal swabs derived from the same patients, at two time points. The respiratory and intestinal microbial profiles will be associated to the immune response and clinical data to detect links between co-infection and disease severity. CO-INFECTOMICS aims to determine microbial markers which could be used in clinics and, thus, to support the stratification of high-risk patients.