RR:C19 Evidence Scale rating by reviewer:
In this publication, the authors report a case of the persistence of SARS-CoV-2 infection in an HIV patient with antiretroviral treatment failure. The authors obtained the SARS-CoV-2 genomic sequences from the patient at seven different sampling points before the HIV viral load was reduced by switching the antiretroviral treatment. The authors showed an increase in the intra-host diversity of SARS-CoV-2 as a consequence of the persistence of the infection. Several of the mutations that arose in the quasispecies are related to the escape from neutralizing antibodies, for example, E484K and K417N.
The strength of evidence for this work is strong. The publication makes a clear description of the methodologies and results. The cited literature corresponds to the current knowledge in the topic. The results are consistent with previous publications that show a rapid evolution of the intra-hots diversity of SARS-CoV-2 and the emergence of mutations related to the escape from neutralizing antibodies in immunosuppressed patients. I have a suggestion. In the discussion, the authors suggest that the emergence of 501Y.V2 is a product of the accelerated intra-host evolution during persistent infection. However, another piece of work stated that antigenic evolution could offer an alternative explication to the origin of this lineage. 1 The authors could provide a more important argumentative support to their hypothesis. For example, the authors could specify the epidemiological particulars of South Africa that would allow the diversity generated at the level of a persistent infection to lead to the emergence of a new and better adapted viral lineage. Similarly, the authors could discuss if their hypothesis can be extrapolated to the emergence of other lineages related to an improved infective capacity, as is the case of B.1.525, P.2, and P.1.
This work reinforces the evidence around the role played by the quasispecies in the generation of diversity related to the response of the virus to the host immune pressure. A policy of permanent monitoring of intra-host diversity could lead to early detection of adaptive variants before combinatorial events occur that improve the viral fitness.
1. Tegally, H. et al. Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. medRxiv 2020.12.21.20248640 (2020) doi:10.1101/2020.12.21.20248640.