Affiliation:
1. Unit of Clinical Microbiology, Department of Health Sciences “Magna Græcia” University Hospital Catanzaro Italy
2. Department of Experimental and Clinical Medicine “Magna Graecia” University of Catanzaro Catanzaro Italy
3. Interdepartmental Center of Services (CIS), Molecular Genomics and Pathology “Magna Græcia” University of Catanzaro Catanzaro Italy
4. Unit of Anesthesia and Intensive Care, Department of Medical and Surgical Sciences “Magna Graecia” University Catanzaro Italy
5. Unit of Medical Statistics and Molecular Epidemiology Università Campus Bio‐Medico di Roma Rome Italy
6. Dipartimento di Scienze di Laboratorio e Infettivologiche Fondazione Policlinico Universitario “A. Gemelli” IRCCS Rome Italy
7. Dipartimento di Sicurezza e Bioetica Università Cattolica del Sacro Cuore Rome Italy
8. Unit of Infectious and Tropical Disease, Department of Medical and Surgical Sciences “Magna Græcia” University Hospital Catanzaro Italy
9. Department of Veterinary Medicine University of Sassari Sassari Italy
10. Department of Biomedical Sciences University of Sassari Sassari Italy
Abstract
AbstractSevere acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) persistence in COVID‐19 patients could play a key role in the emergence of variants of concern. The rapid intra‐host evolution of SARS‐CoV‐2 may result in an increased transmissibility, immune and therapeutic escape which could be a direct consequence of COVID‐19 epidemic currents. In this context, a longitudinal retrospective study on eight consecutive COVID‐19 patients with persistent SARS‐CoV‐2 infection, from January 2022 to March 2023, was conducted. To characterize the intra‐ and inter‐host viral evolution, whole genome sequencing and phylogenetic analysis were performed on nasopharyngeal samples collected at different time points. Phylogenetic reconstruction revealed an accelerated SARS‐CoV‐2 intra‐host evolution and emergence of antigenically divergent variants. The Bayesian inference and principal coordinate analysis analysis showed a host‐based genomic structuring among antigenically divergent variants, that might reflect the positive effect of containment practices, within the critical hospital area. All longitudinal antigenically divergent isolates shared a wide range of amino acidic (aa) changes, particularly in the Spike (S) glycoprotein, that increased viral transmissibility (K417N, S477N, N501Y and Q498R), enhanced infectivity (R346T, S373P, R408S, T478K, Q498R, Y505H, D614G, H655Y, N679K and P681H), caused host immune escape (S371L, S375F, T376A, K417N, and K444T/R) and displayed partial or complete resistance to treatments (G339D, R346K/T, S371F/L, S375F, T376A, D405N, N440K, G446S, N460K, E484A, F486V, Q493R, G496S and Q498R). These results suggest that multiple novel variants which emerge in the patient during persistent infection, might spread to another individual and continue to evolve. A pro‐active genomic surveillance of persistent SARS‐CoV‐2 infected patients is recommended to identify genetically divergent lineages before their diffusion.