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COVID-19: the long and short of it

Dr Nyarie Sithole talks us through his work at Addenbrooke’s – from the first COVID patient in ICU to a new clinic for long COVID sufferers.

Dr Sithole is a Hughes Hall Research Associate, a Clinical Research Fellow with the Department of Medicine and a Consultant in Infectious Diseases and Acute Medicine, working at Addenbrooke’s. After completing his Medicine MBChB degree in Zimbabwe, he completed an MSc in Infectious Diseases and Tropical Medicine at London School of Hygiene and Tropical Medicine and went on to obtain a PhD from the University of Cambridge. He is a member of the Royal College of Physicians.

He has been heavily involved in the response to the pandemic. I spoke to Dr Sithole to find out more about his work from the early days on the emergency wards to his recent efforts establishing a coordinated and informed national response to long COVID. In May 2020, Dr Sithole set up a clinic in the Department of Infectious Diseases at Addenbrooke’s Hospital to assess patients referred by their GPs, who suspected they had had COVID-19 and were experiencing ongoing symptoms.

Tell us a little about the first days of the disease and what you’ve learned

In the early days, before we knew much about COVID as a disease and how it presented, I was one of the first doctors at Addenbrooke’s to look after a COVID-positive patient. We had just one patient, but we were aware what was happening in Italy. And of course, as the days passed, the patient numbers increased and before we knew it wards were filling up.

What I vividly remember about the very first cohort of patients is how deceptive the disease was – and is. They appeared well yet deteriorated so suddenly. It is one of the striking things about COVID that a stable patient suddenly requires moving to ICU: tragically, the change is very rapid. We have become far more confident, with the second wave, in predicting if and when patients are likely to deteriorate, enabling us to get them to an intensive care bed at the right time and ensure the best possible outcome. Everything we learn is shared through best practice guidelines to help clinicians. The infectious disease doctors split up to support other less specialised physicians to ensure patients receive the best care.

How has your focus changed in terms of tackling the disease?

Although I am still involved in supporting acute patients at Addenbrooke’s, my focus on caring for COVID patients has changed. Since the end of May, I have become very interested in what are now known as long COVID cases – patients that go on to have prolonged symptoms for more than 12 weeks after the acute phase. We still don’t know why there is a group of patients who seem not to recover when we expect them to.

From the clinical perspective, I am now focused on these cases and was the first to establish a clinic in the UK for long COVID patients to receive referrals from GPs. Typically, patients come in with symptoms including fatigue, fever, chest pains and shortness of breath which they are struggling to get rid of. As there were no swab tests during the first wave, they may not know whether they had COVID. From the clinical aspect, I am interested in looking after these patients.

What does this new study entail?

From the research aspect, we first have to establish whether or not they had COVID and therefore need to learn how to make a retrospective diagnosis in those who didn’t have a swab test and were not in hospital, but who have a history of symptoms suggestive of COVID. The immune response in COVID is very interesting. If we look at antibody response there are patients with an antibody response and patients who are antibody negative, but this does not mean they didn’t have COVID. Therefore, my study looks at the T-cell response in this latter group of patients. This ‘other arm’ of immune response – the T-cell response – can be looked at retrospectively for evidence of infection, even 12 months down the line.

Once patients have consented to the study, we take samples to analyse their blood, looking for a T-cell response. If the response shows evidence of infection it means the patient was infected, even in the absence of an antibody response. The T-cell response is more representative of what we expect to see in a post-infection period.

What is your current understanding of long COVID and how can you improve patient outcomes?

We know from the wider infectious disease field that, for other diseases, patients rarely have symptoms that continue like this long after the initial infection. We could expect some fatigue or general malaise but we have never seen what we are seeing with long-COVID in terms of both the severity and the variety of symptoms. Every system in the body can be involved whether it is the lungs, heart, liver, bowels, muscles, or the nervous system. It can be a great wave of symptoms that comes and goes and can significantly affect their long-term health. This is new.

Regarding the study’s aims, I am interested to answer what is the driving force behind the small number not recovering when expected. For instance, is it their immune response which continues to be in a highly active state, thereby causing ongoing symptoms, or is it some other dysregulated function within that patient’s body? There are theories still being tested as to the mechanisms behind it, but once we have an answer to that we can develop a basis for a therapeutic intervention for these patients.

This is our goal. If we can find the cause of long COVID, we hope we will find the treatment.

We predict there will be a great number of patients suffering from long-COVID way beyond this current pandemic, and possibly for years to come. Perhaps millions of people around the world will be affected. We are trying to find the time and resources to prepare for this, whilst also treating those with acute symptoms of COVID now.

We must contain and curtail the current pandemic, but we must balance this with finding ways to intervene in incidences of long-COVID and help patients recover more quickly. Our work will need scaling up to manage patients numbers in the long term.

Is this work joined up nationally, or globally?

There is some government money for research into long COVID and the establishment of clinics. A number of UK centres are doing this and we are looking to collaborate with these other centres in future, clinically and research-wise.

Regarding the international situation, I think we will have an impact globally. My aim, with time, is to expand our work into Africa, because these areas will not have the facilities that have been set up on this side of the world. They will have lots of patients whose recovery we can support. They will also have lots of cases that we can compare notes with – looking at genetic or racial differences between African and UK patients in terms of the pathophysiology will help us determine the causes and the differing influences on the disease within different demographics.

Looking back, have there been any turning points for?

When I started the long COVID clinic, I didn’t know how it would pan out. I was hesitant and there was a lot of negativity around me. A real turning point for me was receiving a card from a patient I had seen in the clinic: Thank you so much for your time, for looking after me and giving me the space and time to express the symptoms and feelings I am experiencing. You will never know what a difference it made. Listening to me was all that I needed to begin to feel better. I can believe I will recover now.

Her message really affected me. I remember going home and sharing it with my wife. I didn’t remember doing much to help her but even when there is no pharmacological intervention, sometimes we can help just by understanding and believing. Many long COVID sufferers have felt ignored and dismissed – I hope I can change that. Our jobs are not just about scribbling prescriptions, but about being there for people in a wider sense. She reminded me that I am working for the greater good and helped me believe in what I am trying to achieve.

What do you think your days will look like in 12 months?

I think in 12 months, we will be very busy clinically with long COVID patients and the services treating them will need to expand beyond a makeshift team. This translates to the research aspect because the more clinical patients we are addressing, the more scientific interest and relevance grows, and therefore the more funding is attracted, so this will be a busy field going forward, probably throughout the world.

At the moment, resources are focused on containing the acute phase – tackling the pandemic itself – but when the dust has settled, all nations will need to look at the clinical after-effects.

Given your frontline role, have you felt vulnerable to the disease?

I have not had COVID and even from day one I have never felt vulnerable. I just felt comfortable with the very first patients despite the fear and nervousness amongst some hospital staff. For me it was a challenge I just had to meet.

Of course, we have seen cases of healthcare workers infected before, such as with SARS and MERS, and this time, the scale is so daunting, but it is what it is. It is why we are here for this moment and we just have to get on with it.

How are you coping personally on the frontline of a pandemic?

I suppose it has been a rollercoaster, and there is a lot of pressure. It is easy to get carried away and never give yourself a break. I have realised I have to be more proactive about stepping back otherwise I can never recharge. There can be a significant psychological impact too for those of us looking after COVID patients.

At the same time, every day is a learning experience. There is so much that is new and I am surrounded by people with a similar appetite for learning – so many highly rated scientists and clinicians. So, I am learning from people every day – colleagues and patients – and I am happy to be in this inspiring environment.

With many thanks to Nyarie for sharing details of his work and experiences during the pandemic.

If you would like to share your research or other news, please email: comms@hughes.cam.ac.uk.