This week we talked to Dr. Benjamin Krishna from the Cambridge Institute of Therapeutic Immunology & Infectious Disease. He was part in a study led by the University of Cambridge that has discovered that the protein interferon gamma (IFN-γ) might be a key indicator of Long COVID fatigue. This finding could help develop treatments and offer a clear diagnosis for some patients.

“We saw really big differences between the patients and our controls in the way that the muscle is able to generate energy using mitochondria. We know that that normally exercise is good for you and the exercise improves the mitochondrial function, but in our patients we saw the opposite happening - that it worsens.”

“We are seeing viral persistence in tissues over many years after initial infection and the immune system is not able to completely clear this out. And so now we have to figure out how either we a) can get the immune system to clear this all out, or can we use other modalities - antivirals, monoclonal antibodies, immune-boosting modification, things like that, that will actually help purge these kind of persistent infected cells that we're observing in tissue.”

“The first year of this was recognising the problem and getting people to buy into that... The second year of this was describing who was most likely to get this condition. The third year of this was laying out potential biology. The current era of this now needs to be proving that each of those mechanisms is or is not driving this and… you actually have to intervene on those pathways to see if you can change either a biological measurement or change how people feel. What that means to us is doing trying to do these intense proof of concept, experimental medicine type studies, where we identify a target pathway that we think it is contributing, then we try to alter it by giving an investigational treatment and we see what happens and whether our hypothesis was correct.”

“If we’ve learned anything, this is not something anyone wants to get… The fact that there's a genomics that underlie Long Covid tells you how real it is, right? And then the fact that we will get treatments to people, all these things reinforce how big an issue.”

“Our reward system is - how many papers, how many citations, how many grants… and what enamoured me as I got started in my career was the idea that none of that really matters if you haven't made a difference in people's lives. So the question really is - what's the value of the information you're producing? And how can you do it in a way that that makes a difference?”

“The conventional model is trying to identify what disease does this person have, and then you treat the disease. Well, that may work in some situations… but there are many situations involving chronic illness in which that doesn't work. And I've evolved and taught other approaches to diagnosis, something that I call person-centred diagnosis.”

“We’re trying to develop clinical trials ourselves, to look at this combination of clinical point testing, where we can actually do that very robust analysis of saying, what's going on in terms of blood gases, what's going on in terms of bicarbonate, what's going on in terms of pH? How is that affecting patients at rest and in movement, and how does that correlate with symptoms?”

“I would word this as a massive public health problem… crisis that most of the world is yawning through and sleepwalking through. I think people are sleepwalking through this because it's too invisible.”

Publishing in scientific journals is a challenging process due to fierce competition, limited resources, lack of networks and mentorship, bias and subjectivity in peer review, leading to high rejection rates. Addressing these obstacles requires collective efforts to foster inclusivity, collaboration, and support systems for all researchers.

Dr Jim Jackson, research professor of Medicine and Psychiatry at Vanderbilt University Medical Centre, does not believe that Long Covid is all in your mind, but he has found that treating the brain, as if it has a brain injury, can help Long Covid recovery. In this week’s episode Dr Jackson explains his clinical experience of the neurological impact of Long Covid from brain fog to anxiety, PTSD to OCD. He discusses the power of cognitive rehabilitation (which should be viewed as physiotherapy for the brain) and tells us about his book “Clearing the Fog: A practical guide to surviving and thriving with Long Covid”. And he talks us through the power of talking to others within the community: his support groups have been a hugely impactful for sufferers enabling them to learn from each other, learn how to advocate for themselves, and give them hope.

“We have always been focusing to find something which is detectable and when we talk about something detectable we are actually talking about something which is produced more - this is called as gain of function. But…sometimes loss of function is also important.. there is one switch which is where we are actually losing something from ourselves.”

“when people say what's the magic recipe for treating people well, there is no magic recipe you actually have to individualise you know, because Because Because one treatment for one person will actually totally backfire for the other person. So I do think it's, it's, you know, we're learning a lot about this is a very complex condition.”

“This is a systemic illness. MECFS is a systemic illness. It is a systemic illness. These are all connected, and that's part of the reason why post viral illness is basically impossible to treat.”

“There are so many questions that are unanswered about Long Covid. We're just scratching the surface of this disease.. that's why it's dangerous to come to a conclusion at this stage - because we know so little. It doesn't mean that we aren't looking. We're looking very hard. I'm obsessed about trying to understand this disease, and many scientists are, so hopefully will chip away at this disease. But we need to be open minded and humble about what's going on.”

“So what's really very different about it is its novelty. And I definitely feel that that one of the things that this pandemic taught us is that viruses can lead to long term manifestations.”

“As I expected SARS COV-2 has produced its own mini epidemic of chronic fatigue syndrome.”

“We're tracking heart rate variability, heart rates, and we're also tracking posture as well. It's a really important one. We know that underlying these conditions is some level of dysautonomia, I think 70% or so people with Long Covid would qualify, or would fail the NASA lean test.”

“There are still people out there trying to pitch their one supplement or their one medicinal or their one device that is curing all Long Covid. There’s at least 10 or 15 mechanisms that we're chasing right now. And each one needs a precision approach.”

“I think we will end up in a position that we accept that Long Covid is multiple different conditions that are triggered by the same virus, but result in different consequences.”