Can gut microbiome therapies treat Long Covid?

This is the first in my series of blogs giving progress reports on the Long Covid case study programme. To receive email updates, please add your details here.

In the UK alone, there are more than 60,000 people suffering with long term symptoms following Covid, and that number is expected to rise significantly over the coming months.[1] Although COVID-19 is considered to be primarily a respiratory disease, it’s clear that SARS-CoV-2 affects multiple organ systems in the body – including the central nervous system, circulatory system and digestive system – leaving many with persistent symptoms now recognised as post-acute Covid syndrome or Long Covid.

As with other post-viral syndromes and fatigue conditions, medical gaslighting has been common; with some doctors not believing their patients, downplaying their symptoms or dismissing them as psychologically-induced. However Long Covid is taken increasingly seriously by a significant proportion of the medical community and care guidelines have recently been published by the British Medical Journal for GPs and consultants to follow.[2]

To date, the fatality of acute Covid, and the economic and social impacts of lockdown has dominated discourse on the impacts of Covid on our communities, but there is now increasing awareness of the growing numbers of people left with long-term debilitating symptoms. There is urgent need for research into Long Covid and to provide good support, medical investigations and ongoing treatment for Covid Longhaulers. An individualised, integrated approach involving their primary medical care provider and other healthcare practitioners – both conventional and complementary – are likely to be most beneficial for many of these people.

By way of contributing to this effort, I am running a case study programme to investigate the potential for microbiome interventions in treating the symptoms of Long Covid, with a view to publishing the results, so that practitioners and Covid Longhaulers can learn from this study. This is the first of a series of blogs sharing initial findings, and gives the research background to the programme and the questions we are exploring through the study.

What is Long Covid?

A significant proportion of Covid patients don’t recover after their initial illness of 2–3 weeks. Many are left with incapacitating and distressing symptoms, including debilitating fatigue, severely altered smell or taste, recurrent fevers, low oxygen levels, heart symptoms and numerous other painful and troubling symptoms – many of which remain so far without satisfactory medical explanation or effective treatment.

Estimates vary on what proportion of Covid patients develop Long Covid (as many as 1 in 3 or 1 in 10 patients)[3] with many unable to return to their work or responsibilities many weeks and months after falling ill. Recent UK data suggest that as many as 1 in 50 are still unwell after 3 months[4], while a study in the Netherlands found 1 in 3 people were still dependent on carers after 3 months.[5] With more than 46 million people having had Covid worldwide so far, this could mean millions suffering longterm symptoms, with an unknown prognosis. Given the long-term nature of post-viral syndromes and the current poor medical understanding of Covid in general, many people are understandably concerned their new health difficulties may be lifelong, or even life-threatening.

What role does the microbiome play in Long Covid?

One of the leading medical theories explaining Long Covid symptoms is the proposed breakdown in the regulation of the body’s inflammatory processes, leading to excessive inflammation in certain tissues (including blood vessels) and more widely through the body. For example, studies have shown people have signs of heart inflammation and injury months after Covid.[6]

As well as the inflammatory symptoms (such as the cytokine storm) now known to make acute Covid so dangerous, the neurological manifestations of Sars-CoV-2 are becoming more widely recognised. These include anosmia (loss of smell), headaches and neuropathy (nerve pain) that are now known to be common symptoms of acute Covid. Many of the Long Covid symptoms are also consistent with a breakdown in the regulation of aspects of the nervous system that supports rest and recovery from illness (known as autonomic nervous system dysregulation).

Both excessive inflammation and autonomic nervous system dysregulation are thought to underlie other chronic fatigue conditions, including ME/CFS, Postural Tachycardia Syndrome (POTS) and Post Viral Syndrome, although all these conditions are seriously under-researched. Previous viral outbreaks such as MERS, Ebola, H1N1 and the Spanish flu have all been associated with long-term symptoms and the mechanism may be similar. Research into Long Covid may prove beneficial for many people with post-viral fatigue conditions.

The gut microbiome has a well-recognised role in inflammation – with some species contributing to inflammation locally in the gut, and elsewhere in the body, and others reducing inflammation. Some species produce substances that reduce inflammation, while others interact directly with immune cells involved in the body's inflammatory processes. Some bacterial species are known to interact with our autonomic nervous system too and affect its function. So it makes sense to investigate the role of the gut microbiome in Long Covid symptoms – as well as other fatigue conditions.

Further research is of course needed on Covid and the microbiome specifically, but for more on what we know so far, please see my earlier blog on the proposed role of the microbiome in Covid symptom severity, and I will be writing another blog with more detail on the potential role of the microbiome and Long Covid soon.

What is this case study investigating?

This case study programme includes six participants treated over a period of up to three months, and will investigate the potential for microbiome interventions in treating the symptoms of Long Covid.

The study is exploring the following questions:

· Is a pro-inflammatory microbiome associated with Long Covid symptoms?

· Is a diminished anti-inflammatory capacity of the microbiome associated with Long Covid symptoms?

· Can the use of individualised treatment protocols employing probiotics, prebiotics and dietary changes diminish the pro-inflammatory capacity of the microbiome and restore the balance anti-inflammatory bacterial species in people with Long Covid?

· Is the restoration of the anti-inflammatory capacity of the microbiome associated with a decrease in symptoms and an improvement in quality of life for people who have Long Covid?

The case study programme is now underway, and I was excited to receive the first sets of results back from microbiome stool tests a couple of weeks ago. Analysis of each person’s unique gut microbiome has informed my decisions on which prebiotics, probiotics and dietary changes I have recommended to four of the six participants so far. The next blog will cover the design of this case study, and detail how the participants were selected and the Long Covid symptoms they are suffering, as well as share the initial findings from my analysis of their gut microbiomes at the start of the study.

Acknowledgements

With grateful thanks to Biomesight for sponsoring this programme with free and reduced-price test kits, and to my microbiome colleagues Erin O’Meara, Jan Goldberg, Deborrah Wall Cisneros, Patricia Kaufman and Joanne Hyde Lipsinki for their support, encouragement and sign-posting to useful resources and research in devising this study.

[1] Guardian article on the Covid Symptom Study report 8 September 2020 [2] Greenhalgh et al (11 August 2020). Management of post-acute covid-19 in primary care  BMJ  2020;  370 :m3026 [3] BBC article on Long Covid 5 October 2020 [4] Sudre et al ( 21 October 2020) Attributes and predictors of Long-COVID: analysis of COVID cases and their symptoms collected by the Covid Symptoms Study App medRxiv 2020.10.19.20214494

[5] Vaes et al (7 September 2020) Care Dependency in Non-Hospitalized Patients with COVID-19, J. Clin. Med. 9(9) 2946 [6] Puntmann et al (27 July 2020) Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19), JAMA Cardiology

Viola Sampson BSc is a microbiome analyst practising in London, UK and online. To book an appointment, please see www.violasampson.com/bookonline