UNRAVELING THE MICROBIOME DIVERSITY AND DYNAMICS IN DIFFERENT SAMPLE TYPES DURING CORONAVIRUS INFECTIONS

Abstract

Background: Mucosal immunity and gut microbiome influence respiratory diseases like those caused by coronaviruses (HCoV). This study explores the relationship between HCoV infection and the respiratory and gut microbiome. Methods: The study included two cohorts: MERS AND SARS-CoV- two patients. For the MERS patients, we collected bronchoalveolar lavage fluid (BAL), urine, and fecal samples from two acutely infected patients at different time points. Next-generation sequencing (NGS) was used to profile 16S rRNA (bacteria) and 18S rRNA (eukaryotes) genes. For the SARS-CoV-2 infected patients (n=100), nasal swab samples (50 per variant (n=50) were analyzed using the ONT platform. Microbiome alterations were analyzed in relation to IgA levels against the SARS-CoV-2 S1 as well as co-infections with other respiratory viruses. Results and Discussion: MERS patients displayed diverse bacterial communities in BAL samples across time points. 16S revealed the most abundant phyla are Bacillota (Firmicutes), Pseudomonadota, Campylobacterota, and Mycoplasmatota. Microbiome patterns changed during disease progress to be dominated by Staphylococcus at a later disease stage. A similar pattern was observed in mycobiome as Candida was the most abundant across. These findings were associated with antibiotic admission. Only samples from BA.4 and BA.5 yielded 16S PCR products that were subsequently sequenced and analyzed. We found no significant differences in phylum and genus level between BA.4 and BA.5 variants infection. Surprisingly, co-infection prevalence was 94.5%, where co-infection with sHCoV (229E, OC43, HKU1, NL63) was prevalent across variants. Notably, BA.4 infected patients show a significant increase in IgA levels compared to NC and BA.5 infected. Conclusions: This study highlights the dynamic nature of the respiratory microbiome in HCoV patients. Further research, including other SARS-CoV-2 variants, is needed to understand the effect of infection with different variants and microbiomes and to explore the interplay between the microbiome and immune response in HCoV infection.