An established virologist specialising in the field of HIV drug-resistance, Ravi Gupta pivoted his expertise to address the COVID-19 pandemic. Over the last 18 months his pioneering research has helped us to stay one step ahead of emerging variants. He talks about his career as an infectious disease specialist and, in celebration of South Asian Heritage Month, what his heritage means to him.
During my late teens I travelled to different countries around the world, including India which is where my parents are from. It was during these trips that I first became interested in diseases of global significance. I began to gain an appreciation of what global health really meant as I contrasted what I saw on my travels with life in the UK.
As part of my undergraduate medical degree at Cambridge, I studied political science. This helped me to consider how the global economy impacts on health care and the disparities that can arise. Later I pursued a master’s in international public health which cemented my interest in infectious diseases.
During my PhD we monitored resistance to the HIV-drugs in Sub-Saharan Africa and Asia. Some of these drugs had previously been thought to be quite robust against resistance. However, we found that due to the fragility of drug combinations, lack of monitoring and erratic implementation of medication this was not the case.
This work highlighted the need for better drug combinations to prevent resistance occurring, especially in Sub-Saharan Africa. We went on to study the effectiveness of integrase inhibitors, a new HIV-drug, in populations in Sub-Saharan Africa.
I established teams at University College London and in Durban, South Africa. For the next ten years we carried out research to aid understanding of HIV treatment and curative strategies. A landmark moment was leading the team demonstrating HIV cure in the ‘London Patient’ – the world’s only living HIV cure, and the second recorded in history. This made global headlines and led to me being named one of Time Magazine’s 100 Most Influential People of the Year.
In 2019 I returned to Cambridge with my research group to take up the position of Professor of Clinical Microbiology at the Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID). Not long after we had arrived in Cambridge the pandemic broke out and we began to consider how we might apply our expertise in infectious diseases to this new virus.
We knew we urgently needed a way of quickly identifying positive COVID-19 cases. At the time diagnostic tests were taking up to two or three days to process as the demand on labs was so great.
I crossed paths with Helen Lee, whom I had worked with previously, and who heads Diagnostics for the Real World, a spin-out company from the University of Cambridge. I learnt that she had adapted a machine designed to monitor HIV viral load to test for COVID-19; however, it needed validation.
My group ran a validation study which demonstrated that the machine, known as the SAMBA II could deliver a result 10 times faster than other diagnostic tools. The machines had an amazing impact at Addenbrookes, our local hospital. We were able to triage patients much more quickly than before which was critical at a time when services were getting overloaded.
During this period we leveraged our expertise in HIV to generate virus particles which, simply put, were HIV on the inside and COVID-19 on the outside. This rendered the particles safe to use but meant that they displayed the properties of COVID-19, meaning we were able to test for antibodies in individuals who had recovered from COVID-19.
We began studying a patient with chronic COVID-19 and realised that the virus was undergoing mutations, meaning it was able to ‘escape’ the antibody treatment. We used our virus particles technique to replicate what we’d seen on the ward, in vitro. We were the first to identify this phenomenon, which paved the way for our next discovery.
On analysing the mutations, we came across a particular variant of COVID-19 – the variant was B1.1.7, which would later be coined the ‘Kent’ or ‘Alpha’ variant. We wondered if this mutation was occurring in other individuals across the population. We searched the COVID-19 Genomics UK Consortium (COG-UK) database and found that it appeared in a number of sequences.
We had essentially stumbled upon the variant which would go on to become the dominant variant in the UK and sweep around the world. Simultaneously Public Health England discovered an outbreak in Kent. It was interesting to see how we’d both arrived at the same place through different routes.
We went on to perform a number of studies investigating the effectiveness of vaccinations against the Alpha variant. The results of these studies were published in the journal Nature and have been widely cited aiding our collective understanding of how we move forward in tackling the virus.
Throughout the course of the year I’d been establishing links with academics and scientists in India. I felt passionate about contributing in this setting and became involved in discussing the emerging Delta variant. We began doing lab work here in the UK to understand more about the Delta variant.
We reported in a preprint, which is currently undergoing review, that the Delta variant is able to escape immunity. We demonstrated that it is able to replicate much faster in cells and artificial organ systems that mimic the lungs. We also have impressive data sets of Indian health workers which show that the Delta variant breaks through vaccinations more effectively than other variants.
This really shows the importance of international collaboration as it’s meant we’ve been able to alert people to what’s around the corner. What we demonstrated is indeed what we are seeing – that vaccines are effective in preventing death and severe disease but you can still get infected, get quite ill and pass it on to other people.
Looking back on the last 18 months I can see how important an organisation like CITTID is which brings together a wide variety of specialisms. For example, many of our studies would not have been possible without the individuals who provided lung organoid cells or the immunologists who are very good at understanding B-cells or those who are experts in genomics. It’s amazing to be working in a place with such a high calibre of individuals.
It’s been a time of real collaboration and communication both in the UK and across the world. It’s been incredible to see the speed at which things can get done when there's a problem to face. It shows humans can overcome all sorts of day to day, political or personal issues to achieve an objective. I think that's been very important for us and hopefully we can take that forward.
My South Asian heritage means a lot to me. It's given me an appreciation of different languages and their importance. I speak English, Spanish, French and Hindi pretty fluently which has been vital when working in different countries.
I have a big extended family in India who I am very close to. Visiting them was a huge part of my upbringing. I learnt about different cultures and philosophies which contributed to a rich set of experiences.
When I was young in this country, I didn’t always feel part of the UK – the eighties were not a particularly good time for ethnic minorities. But as time has gone on, I’ve seen the UK change radically to become a much more inclusive society and one which I am a lot prouder to be a part of than when I was younger.
I think that my less-than-comfortable childhood and rather complex set of experiences gave me strength and fortitude. For me personally it was character building and perhaps made me better able to achieve things. To other people of an ethnic minority background, I’d say: being different is not a disadvantage, it’s your advantage.
This profile is part of This Cambridge Life – stories from the people who make Cambridge University unique.
