RT Journal Article SR Electronic T1 Recurrent emergence and transmission of a SARS-CoV-2 Spike deletion ΔH69/V70 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.12.14.422555 DO 10.1101/2020.12.14.422555 A1 SA Kemp A1 WT Harvey A1 RP Datir A1 DA Collier A1 IATM Ferreira A1 AM Carabelli A1 DL Robertson A1 RK Gupta YR 2020 UL http://biorxiv.org/content/early/2020/12/21/2020.12.14.422555.abstract AB SARS-CoV-2 Spike amino acid replacements in the receptor binding domain (RBD) occur relatively frequently and some have a consequence for immune recognition. Here we report recurrent emergence and significant onward transmission of a six-nucleotide deletion in the S gene, which results in loss of two amino acids: H69 and V70. Of particular note this deletion, ΔH69/V70, often co-occurs with the receptor binding motif amino acid replacements N501Y, N439K and Y453F. One of the ΔH69/V70+ N501Y lineages, B.1.1.7, is comprised of over 1400 SARS-CoV-2 genome sequences from the UK and includes eight S gene mutations: RBD (N501Y and A570D), S1 (ΔH69/V70 and Δ144/145) and S2 (P681H, T716I, S982A and D1118H). Some of these mutations have possibly arisen as a result of the virus evolving from immune selection pressure in infected individuals and possibly only one chronic infection in the case of lineage B.1.1.7. We find the ΔH69/V70 enhances viral infectivity, indicating its effect on virus fitness is independent to the N501Y RBM change. Enhanced surveillance for the ΔH69/V70 deletion with and without RBD mutations should be considered as a priority. Such “permissive” mutations have the potential to enhance the ability of SARS-CoV-2 to generate vaccine escape variants that would have otherwise significantly reduced viral fitness.Competing Interest StatementRKG has received consulting fees from UMOVIS lab, Gilead Sciences and ViiV Healthcare, and a research grant from InvisiSmart Technologies.