Professor Carolyn Williamson, Ph.D., is head of the division of medical virology at the University of Cape Town and co-founder of the Network for Genomic Surveillance in South Africa (NGS-SA). In the first CoVICIS blogpost, Prof Williamson joins us to discuss the impressive surveillance work being conducted in South Africa and some of the insights into future work to investigate the role of the HIV epidemic in the emergence of variants of concern.  

Why is the research being conducted in South Africa so important?

The COVID-19 pandemic unfolded in the face of a longstanding HIV epidemic in South Africa where more than 7.5 million people are living with HIV. While almost 7 million of those individuals know their status, only 5.5 million are on antiretroviral treatment, of whom 5.1 million are virally suppressed. This means more than 2.4 million people living with HIV in South Africa are not virally suppressed and risk becoming immunocompromised. People who are immunocompromised face greater risks of adverse outcomes from infection with SARS-CoV-2. This includes chronic SARS-CoV-2 infection, which itself may be one source of viral evolution that could lead to the next instance of viral resurgence.

What is the focus of the work being conducted in South Africa?

SARS-COV-2 genomic surveillance is supported by the South African Medical Research Council, Department of Science and Innovation, Wellcome Centre Infectious Diseases Research in Africa, and the National Health Laboratory Service. In addition to ongoing surveillance, we are conducting a retrospective observational study using samples from routine diagnostic testing to understand the evolution of SARS-CoV-2 in the context of the HIV epidemic in South Africa. This is based on the hypothesis that novel SARS-CoV-2 variants emerge in immunocompromised individuals with persistent SARS-CoV-2 infections. In particular, we aim to investigate how commonly intra-host SARS-CoV-2 evolution is detected in individuals with HIV/SARS-CoV-2 co-infection who also have low CD4 T cell counts (less than 200 cells/µl) compared to those with high CD4 counts (>500/µl).  

What sort of techniques are you using in this work?

We are implementing a range of techniques to solicit in-depth insights into the samples tested. This will include cutting-edge approaches to conduct whole genome amplification and sequencing, genome assembly, and phylogenetic analysis and to assess intra-host diversity and patterns in SARS-CoV-2 genetic profiles in different individuals and populations.

What are some of your findings so far?

By looking at individuals who have multiple SARS-CoV-2 positive samples and/or are immunocompromised, we have been able to investigate intra-host heterogeneity, including the identification of unique spike variants, and cases of reinfection. For example, in one HIV-positive individual infected with the SARS-CoV-2 variant B.1.1, the infection persisted for about 6 months, and we found mutations that are present in variants of concern such as Omicron, Mu, and Lambda, as well as signature mutations present in Beta. In a second individual infected with B.1.1.459, the infection persisted for about 8 months, and we also detected the emergence of mutations present in variants of concern such as Beta, Delta, and Kappa. Importantly, we identified an increased number of private mutations in sequences from these individuals, indicative of intra-host evolution.

What is next for this study?

As part of the SARS-CoV-2/HIV study we are establishing and optimizing pipelines and data harmonization to ensure that we can conduct the most in-depth and efficient surveillance possible. This includes but is not limited to harmonization of contextual data, and the establishment of a study-specific database to enable automated data analyses as well as validating the bioinformatics tools required to achieve the study objectives. We are currently expanding our sample number of HIV-positive samples. We hope to have completed the data analyses of the re-infection/persistent infection study and have a publication available by February 2023.