Recurrent SARS-CoV-2 mutations in immunodeficient patients
Wilkinson SAJ., Sparks N., Kele B., Peacock TP., Robson SC., Connor TR., Loman NJ., Golubchik T., Martinez Nunez RT., Bonsall D., Rambaut A., Snell LB., Livett R., Ludden C., Corden S., Nastouli E., Nebbia G., Johnston I., Lythgoe K., Estee Torok M., Goodfellow IG., Prieto JA., Saeed K., Jackson DK., Houlihan C., Frampton D., Hamilton WL., Witney AA., Bucca G., Pope CF., Moore C., Thomson EC., Harrison EM., Smith CP., Rogan F., Beckwith SM., Murray A., Singleton D., Eastick K., Sheridan LA., Randell P., Jackson LM., Ariani CV., Gonçalves S., Fairley DJ., Loose MW., Watkins J., Moses S., Nicholls S., Bull M., Amato R., Smith DL., Aanensen DM., Barrett JC., Aggarwal D., Shepherd JG., Curran MD., Parmar S., Parker MD., Williams C., Glaysher S., Underwood AP., Bashton M., Pacchiarini N., Loveson KF., Byott M., Carabelli AM., Templeton KE., de Silva TI., Wang D., Langford CF., Sillitoe J., Gunson RN., Cottrell S., O’Grady J., Kwiatkowski D., Lillie PJ., Cortes N., Moore N., Thomas C., Burns PJ., Mahungu TW., Liggett S., Beckett AH., Holden MTG., Levett LJ., Osman H., Hassan-Ibrahim MO., Simpson DA., Chand M., Gupta RK., Darby AC., Paterson S., Pybus OG., Volz EM., de Angelis D., Robertson DL., Page AJ., Martincorena I., Aigrain L.
Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COVID-19 Genomics UK (COG-UK) dataset. The spike gene receptor-binding domain and N-terminal domain (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, T30I was determined to be the second most frequent recurrently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation.There is an apparent selective pressure for mutations that aid cell–cell transmission within the host or persistence which are often different from mutations that aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted.