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J Med Virol . Persistence of SARS-CoV-2 infection and viral intra- and inter-host evolution in COVID-19 hospitalized patients

tetano

Editor, Senior Moderator
J Med Virol


. 2024 Jun;96(6):e29708.
doi: 10.1002/jmv.29708. Persistence of SARS-CoV-2 infection and viral intra- and inter-host evolution in COVID-19 hospitalized patients

Grazia Pavia[SUP] 1 [/SUP], Angela Quirino[SUP] 1 [/SUP], Nadia Marascio[SUP] 1 [/SUP], Claudia Veneziano[SUP] 2 3 [/SUP], Federico Longhini[SUP] 4 [/SUP], Andrea Bruni[SUP] 4 [/SUP], Eugenio Garofalo[SUP] 4 [/SUP], Marta Pantanella[SUP] 1 [/SUP], Michele Manno[SUP] 1 [/SUP], Simona Gigliotti[SUP] 1 [/SUP], Aida Giancotti[SUP] 1 [/SUP], Giorgio Settimo Barreca[SUP] 1 [/SUP], Francesco Branda[SUP] 5 [/SUP], Carlo Torti[SUP] 6 7 [/SUP], Salvatore Rotundo[SUP] 8 [/SUP], Rosaria Lionello[SUP] 8 [/SUP], Valentina La Gamba[SUP] 8 [/SUP], Lavinia Berardelli[SUP] 8 [/SUP], Sara Palma Gullì[SUP] 8 [/SUP], Enrico Maria Trecarichi[SUP] 8 [/SUP], Alessandro Russo[SUP] 8 [/SUP], Camillo Palmieri[SUP] 2 [/SUP], Carmela De Marco[SUP] 2 3 [/SUP], Giuseppe Viglietto[SUP] 2 3 [/SUP], Marco Casu[SUP] 9 [/SUP], Daria Sanna[SUP] 10 [/SUP], Massimo Ciccozzi[SUP] 5 [/SUP], Fabio Scarpa[SUP] 10 [/SUP], Giovanni Matera[SUP] 1 [/SUP]



Affiliations
Abstract

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.

Keywords: SARS‐CoV‐2 immune escape mutations; SARS‐CoV‐2 persistence; inter‐host viral genetic evolution; intra‐host viral genetic evolution; phylodynamic analysis; phylogenetic analysis.

 
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