TY - JOUR
T1 - Persistence of SARS-CoV-2 infection and viral intra- and inter-host evolution in COVID-19 hospitalized patients
AU - Pavia, Grazia
AU - Quirino, Angela
AU - Marascio, Nadia
AU - Veneziano, Claudia
AU - Longhini, Federico
AU - Bruni, Andrea
AU - Garofalo, Eugenio
AU - Pantanella, Marta
AU - Manno, Michele
AU - Gigliotti, Simona
AU - Giancotti, Aida
AU - Barreca, Giorgio Settimo
AU - Branda, Francesco
AU - Torti, Carlo
AU - Rotundo, Salvatore
AU - Lionello, Rosaria
AU - La Gamba, Valentina
AU - Berardelli, Lavinia
AU - Gullì, Sara Palma
AU - Trecarichi, Enrico Maria
AU - Russo, Alessandro
AU - Palmieri, Camillo
AU - De Marco, Carmela
AU - Viglietto, Giuseppe
AU - Casu, Marco
AU - Sanna, Daria
AU - Ciccozzi, Massimo
AU - Scarpa, Fabio
AU - Matera, Giovanni
PY - 2024
Y1 - 2024
N2 - Severe 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.
AB - Severe 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.
KW - SARS‐CoV‐2 immune escape mutations
KW - SARS‐CoV‐2 persistence
KW - inter‐host viral genetic evolution
KW - intra‐host viral genetic evolution
KW - phylodynamic analysis
KW - phylogenetic analysis
KW - SARS‐CoV‐2 immune escape mutations
KW - SARS‐CoV‐2 persistence
KW - inter‐host viral genetic evolution
KW - intra‐host viral genetic evolution
KW - phylodynamic analysis
KW - phylogenetic analysis
UR - http://hdl.handle.net/10807/303900
U2 - 10.1002/jmv.29708
DO - 10.1002/jmv.29708
M3 - Article
SN - 1096-9071
VL - 96
SP - N/A-N/A
JO - Journal of Medical Virology
JF - Journal of Medical Virology
ER -