Researching Infectious Diseases: From HIV to COVID-19

Hello! Who are you and what are you working on?

I am a medical doctor, graduating from Trinity College Dublin in 2013. I am currently specializing in the area of Infectious Diseases and will complete my training in 2023. I am also doing a Ph.D. as part of my training. This has been facilitated by the Irish Clinical Academic Training Programme, funded by the Wellcome Trust and Health Research Board in Ireland, aiming to develop academic clinicians.

I began this Ph.D. program in 2018, and aim to complete it in mid-2021. My research is centered on the effects of viral infection on the host, looking at immunological changes and the translation of these to the clinical phenotype seen in daily medical practice. I initially began by studying the effects of HIV on the development of chronic low-grade inflammation leading to premature ageing/frailty. However, given the emergence of a global viral pandemic, I have began studying the effects of SARS-CoV-2 on the immune system and clinical phenotype in both acute and convalescent infection.

In addition to my PhD work, I remain clinically active. I provide clinical hours in the outpatient department, as well as performing on-call duties. I was also seconded back to full-time clinical work on the inpatient service during the height of the pandemic in Ireland.

What’s your backstory and how did you come up with the idea?

I studied medicine as an undergraduate from 2008 – 2013, and have been working as a full-time clinician since graduation. I have always had a keen interest in the area of Infectious Diseases; it sits at the intersection of immunology, environment, and socioeconomic effects. HIV management in particular has been transformed in the last 30 years. It is a testament to the work of HIV research that almost every HIV patient I have met since starting my career has well-controlled infection with well-tolerated medications.

However, what I did begin to note was the increase in conditions traditionally associated with ageing, occurring at a much younger age in people living with HIV. There was a growing body of evidence that this was as a result of chronic low-grade inflammation, despite the use of anti-retroviral therapy. I developed a research plan in conjunction with my supervisors to investigate frailty in our HIV patients, while also assessing systemic inflammation.

The arrival of the COVID-19 pandemic presented a novel infection whose clinical severity was most common in old and frail individuals. Furthermore, it also appeared to lead to the development of post-infectious syndromes with many characteristics shared with the traditional frailty phenotype. We devised a clinical and immunological study similar to that which we wee using our HIV patients and applied it to SARS-CoV-2 infection.

Please describe the process of learning, iterating, and creating the project

This is by no means an easy process! The learning curve is incredibly steep, especially as I was coming from a clinical background with no laboratory experience. Through trial and multiple errors, I developed our lab pathways and flow cytometry panels, as well as designing the clinical data capture and recruitment tools. This process took the best part of a year to develop robust reproducible results.

At the time of the COVID-19 pandemic, I was fortunate to be in a position where I had managed to develop these skills. I was also well-situated in a translational research lab, co-located on the site of our hospital. Furthermore, I was lucky to have collaborators and mentors that were eager to support, contribute and develop the project. This meant that what had taken me almost 12 months to develop was translated very quickly by our clinical and diagnostic colleagues into a rapid robust process that facilitated detailed immunophenotyping and clinical characterisation of COVID-19 patients.

Please describe the process of launching the project

As I was undertaking this project as part of the ICAT programme, they have excellent mechanisms in place to promote the work of their fellows. This includes promoting the projects via traditional platforms such as scientific conferences as well as social media such as Twitter.

My university (Trinity College, Dublin) and specifically Trinity Translational Medicine Institute have also been very supportive in promoting the study.

Since launch, what has worked to make your project grow/successful?

The single most important element that has helped this project is the incredible goodwill and commitment of all the collaborators involved. This has allowed recruitment, sample processing, data curation and analysis to take place smoothly. The novel nature of the SARS-CoV-2 virus meant that many highly-skilled collaborators will eager to contribute, lead and donate their time and resources. Furthermore, we had an incredibly willing patient group who were happy to take part in any COVID-related research in order to help us further understand this virus. We also had the advantage of having a clinical research facility co-located on our hospital site to allow for prompt recruitment and sample processing.

How is everything going nowadays, and what are your plans for the future?

Things are busy! From what was a single PhD project idea has grown into multiple different related pieces of work. A disease registry for older HIV patients has been established, as has a COVID-19 bioresource. The large amount of clinical and immunological data has required significant upskilling in statistics on my part, as well as collaborations with data scientists.

Over the course of the next few years I would like to expand on the collaborative network that we have built so far. There is the potential for large-scale immunological and genomic studies to be conducted across multiple countries into the pathogenesis of post-COVID syndrome. We are well placed in Ireland given our strong global reputation in the field of immunology to contribute and lead in this area.

Through your science, have you learned anything particularly helpful or advantageous?

Failure is inevitable. Experiments don’t work, then do work, then don’t work again.

Celebrate the successes when they happen. This doesn’t mean publications alone. A success can be an experiment or protocol consistently producing reproducible results, or reaching an intermediate milestone in your study.

Having collaborators makes dealing with the failures easier, and makes the celebrating the successes far more enjoyable.

We’d like to know more about you, could you please let us know what is your morning routine like?

I get up a little after 6 and have a very quick snack at home, usually a yoghurt and an espresso, before cycling to work. Between 7 and 07:30 I check my emails and any patient results from the previous day. I answer any emails that can be done quickly, and then at half 7 go to the work canteen for breakfast. Over breakfast (coffee, toast and eggs, I’m a creature of habit!) I check my calendar for the day, including scheduling time to address any issues that have arisen from the morning emails. I’m back at my desk for 8 ready to start the day.

And how does a typical day look for you?

Prior to COVID, most of my days were spent obtaining patient samples in the morning and then bringing them to the lab. I would process the blood and run flow cytometry on the samples on the day of collection. I would usually do PCR or ELISA tests on days when recruitment wasn’t scheduled.

Since COVID, my day has changed a lot. My number of Zoom calls has exploded; it is seldom I would have a day without any. At the start of the pandemic, much of my time was spent recruiting patients, obtaining samples, and inputting the clinical and immunological data into spreadsheets.

Now, much of my day is spent wrestling with the data in Stata, as well as trying to write manuscripts based on our findings. My clinical commitments are in the post-COVID outpatient clinic, which rounds my week off on a Friday afternoon.

What does your workstation look like?

My workstation is a little bit chaotic. I’ve my desktop computer and my laptop; having two screens makes life so much easier. I’ve a copy of Mandell’s Principles and Practice of Infectious Diseases, which is every ID doctor’s Bible. There are sheets of paper scattered all over the place; some have thoughts and notes jotted down, others belong in the recycling bin but just haven’t made it that far yet! On the wall is an A4 sheet with my current short-term projects, I strike them off as they are completed. There are blood bottles, alcohol swabs and other items for phlebotomy so that I am ready to go if a participant is recruited. Finally, there’s my coffee pot and mug, which are probably the most important parts of my workstation.

What platform/tools do you use for your professional life?

Most of my tools are based around data analysis. I spend most of my time ensuring my Excel sheets are clean and easy to import into Stata, which is where I do most of my analysis. I use GraphPad for visualisation of the Stata outputs. At the start of my PhD I was using FlowJo a lot to analyse flow cytometry data.

What secondary software and apps do you use daily?

Gmail is constantly open on a tab, and I always have Spotify playing.

Zoom has become more and more central to my daily life as the pandemic has progressed.

How do you stay up to date on News and resources?

I tend to use a combination of print, online and social media platforms to stay up to date. I get weekly PubMed updates based on keywords such as COVID, frailty, and immunology. I also get weekly MedScape email updates.

I find Twitter an excellent platform for keeping track of new papers, as well as analysis of the papers. All of the papers that catch my eye end up in my Endnote library so that I can find them easily in the future.

What have been the most influential podcasts, or other resources?

I tend to steer clear of work-based podcasts. The only ones I listen to are my Mark Crislip, an Infectious Diseases doctor in Oregon. He releases a fortnightly Puscast, which is a review of the key infectious diseases publications during that period. He also releases Gobbets of Pus, which are short case vignettes with evidence-based therapy.

What tools do you use in your personal life? Cook? Self Care? Hobbies?

I find cooking a great way to destress and take my mind off work. My wife is an excellent baker, so I look after the savoury side of things. I think if my house was on fire the griddle pan would be the only thing I’d grab as I ran out the door.

We’re also very lucky to have a couple of parks on our doorstep, so we can easily escape for a walk. There’s also a market there at weekends, so when we don’t feel like cooking we can grab something there. Other than that, it’s the usual combination of reading fiction and watching Netflix to unwind in the evenings.

Prior to the pandemic, I held a season ticket for our local rugby team with my parents and brother, and it was a great way to meet up and relax. I’m looking forward to spectator restrictions being lifted so we can return to doing that.

Advice for other scientists who want to get started or are just starting out?

Luck is a huge part of science. You need to be in the right place at the right time. Therefore, failure is inevitable, and it is not necessarily your fault. So keep trying. As Samuel Beckett said, Ever tried. Ever failed. No matter. Try again. Fail again. Fail better.

Collaborate. You have a better chance of being in the right place at the right time if there are more of you. You will also be able to achieve far more, reach a wider audience, and derive more satisfaction from working with others than you will working alone.

Continue to develop new skills. It is important to be able to identify your own areas of weakness, and work on improving those. This may be learning a new laboratory technique, improving your statistical knowledge, or developing your scientific writing skills. The better and wider your skillset, the greater the chance of success.

Thank you very much for your time, Liam. Where can we go to learn more?

My twitter handle is @LiamT_Tweets

My ORCID ID is 0000-0002-7089-0665

I’m also on ResearchGate