Association of nasopharyngeal Dolosigranulum pigrum and Corynebacterium species with post-acute sequelae of SARS-CoV-2 (PASC) in a longitudinal cohort
This longitudinal study investigated the differential composition of the nasopharyngeal microbiome in patients presenting different COVID-19 infectious phenotypes and its evolution during convalescence, with a focus on post-acute sequelae of SARS-CoV-2 (PASC) and its potential microbiome-related mechanisms.  Microbiota composition was assessed for a cohort of healthy participants (n=25), influenza patients (n=24), and patients with moderate (n=50) and severe (n=57) COVID-19. Samples were collected at two time points: during the acute infection phase and at approximately at three-month follow-up. From collected nasopharyngeal swab samples, metagenomics using shotgun sequencing was performed and the microbiota composition was analysed.  Alpha and beta diversity analyses revealed no significant differences in overall community diversity between patient groups across visits. However, differential abundance testing identified specific species, such as Dolosigranulum pigrum and various Corynebacterium species, whose profiles correlated with PASC development. Furthermore, the analysis of microbial co-associations identifies commensal species, including D. pigrum and Corynebacterium species, that are less abundant in patients who develop PASC, consistent with a potential protective role suggested by experimental studies but not proven by our observational data. Antibiotic use was associated with lower levels of key protective taxa, which may increase susceptibility to PASC in case of superinfection.  These findings highlight the potential importance of the nasopharyngeal microbiome in acute COVID-19 disease outcomes and suggest that preserving or restoring a balanced respiratory microbiome could mitigate the risk of COVID-19 persistent symptoms and PASC development. Our results may set the stage for future clinical interventions involving probiotics or microbial-derived metabolites to promote respiratory health post-COVID-19.