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An evolving problem with an extensive impact

We just over one year on since the COVID-19 pandemic has started and you may have heard or read the name ‘Long Covid’ or ‘Post-COVID-19 syndrome’ in the news. In this short article we would like to explain the symptom picture (i.e. condition) these terms refer to.

Long Covid is a term that describes the effects of Covid-19 disease that continue for months beyond the active infection. This infection usually starts in the lungs but the virus can find its way into any and every organ and tissue, as post-mortem studies have shown. As a result, it can affect many organs (even simultaneously), including the blood vessels, heart, brain, digestive system and skin, and can lead to serious conditions such as chronic fatigue, chronic pain and depression. 

It is acknowledged that there are still many uncertainties concerning the long-term effects of COVID-19 but there is a UK-wide guideline that is being developed by the National Institute for Health and Care Excellence (NICE), the Scottish Intercollegiate Guidelines Network (SIGN) and The Royal College of General Practitioners (RCGP) on request from the NHS England and the Chief Medical Officer of the Scottish Government. This guideline is still ‘being developed’ because it is necessary to use a ‘living approach’, where everything is continuously reviewed and updated based on the developing and emerging evidence base. 

There may be over a million Long Covid sufferers in the UK by now, and therefore it is important to understand the potential medical, psychological, and rehabilitation needs for this patient group to support their recovery.

Long Covid is not contagious. Symptoms of Long Covid are caused by your body's response to the virus continuing beyond the initial illness. It has been found that women are affected more than men, in a 5:1 ratio.

Current case definitions

Below are some current case definitions developed by medical consensus:

Acute COVID -19 infection
Signs and symptoms of acute COVID-19 infection that may last up to 4 weeks. 

Ongoing symptomatic COVID-19
Signs and symptoms of COVID-19 infection from 4 weeks up to 12 weeks.  

Post-COVID-19 syndrome or ‘Long Covid’
Signs and symptoms developed during or following COVID-19 infection that continue for more than 12 weeks after the acute phase of COVID-19 ended, and are not explained by an alternative diagnosis. Currently, there are over 200 symptoms associated with Long Covid, and it is common to have 1 or more ongoing symptoms, which can affect any system in the body.

Diagnosis of COVID-19: A person may be diagnosed with COVID-19 based on clinical symptoms WITH OR WITHOUT a positive SARS-CoV-2 test (PCR, antigen or antibody), and this diagnosis can be made retrospectively based on symptoms alone (for those who self-managed their acute illness).

Findings of the largest known study to date of patients with symptoms of ‘Long Covid’

The largest known report to date of patients with symptoms consistent with ‘Long COVID’ examined 3,762 respondents from 56 countries (age range: age 18-39 31.5%, age 40-49 31%, and age 50+ 37.7%). 2,330 were tested for SARS-CoV-2 but only 1,020 had tested positive (RT-PCR, antigen, or antibody test). 92% of the respondents were not hospitalized. (Davis et. al., 2020. Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact)

Researchers found that the symptom picture was similar between those who had been tested positive for SARS-CoV-2 test and those who had not. They also found that 10 organ systems were affected over a 7 months period. 

The most prevalent and persistent symptoms by week 28 were:

  • fatigue (80% of respondents)
  • brain fog/memory issues and neurological problems (60%)
  • headaches, insomnia, shortness of breath and palpitations ( near 40%)

The top three most debilitating symptoms were: 

  • fatigue
  • breathing issues
  • cognitive dysfunction

The worst symptoms with the most improvement were reported to be:

  • fatigue
  • breathlessness
  • headaches
  • palpitations
  • brain fog 

It was reported that with time people learned to manage their symptoms better, and most of them felt notable rates of improvement in symptoms after 6 months and 10 months. 

Interestingly, the researchers found no difference in symptoms in different age groups. 

In fact, younger cohorts were affected more severely in the following categories:

  • attention
  • thinking
  • executive function
  • problem-solving
  • confusion

Other notable and concerning findings: 

  • 73% of responders were not able to work in the same way as pre-Covid
  • 93% were unable to work full time without risking their well-being or relapse
  • After 6 months, most patients still had most symptoms, however, some improvement was noticed

This is a great and insightful study that helps us understand how the symptoms of  ‘Long Covid’ may affect people. However, there are some limitations of this study, which are important to mention and these include:

  • data were based on self-reported symptoms and COVID-19 testing results
  • participants self-selected into the study, which limits generalisability
  • responders were primarily white and female, which is not representative of the larger population
  • most participants did not receive a positive RT-PCR, antigen, or antibody test for COVID-19, so other conditions may have contributed to the symptoms experienced

As mentioned above, this virus (SARS-CoV-2) can find its way into any and every organ and tissue in the body, and hence can affect multiple systems, including the cardiovascular system, digestive system, skin and brain. Currently, there are over 200 symptoms associated with Long covid, of which the topmost reported symptoms are:

  • fatigue
  • poor exercise tolerance/post-exertional malaise
  • cognitive dysfunction, brain fog  (not being able to think straight or focus) 
  • shortness of breath
  • tightness of chest
  • headaches
  • IBS symptoms (diarrhea)
  • insomnia
  • anxiety and depression
  • palpitations
  • joint or muscle pain
  • heart palpitations
  • dry cough

When managing patients with symptoms of ‘Long Covid’, it is important to ask about the right symptoms because practitioners often miss questions related to neurological, especially cognitive function, post-exertional malaise and questions on relapses. This may particularly be true when using algorithms, which will be biased without a representative patient and symptom dataset.

References 

  1. Davis, H. et al. 2020. Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact. doi: https://doi.org/10.1101/2020.12.24.20248802
  2. Callard F & Perego E. How and why patients made Long Covid. Soc Sci Med. 2021 Jan;268:113426. doi: 10.1016/j.socscimed.2020.113426. Epub 2020 Oct 7.
  3. Dani M et al. Autonomic dysfunction in 'long COVID': rationale, physiology and management strategies. Clin Med (Lond). 2021 Jan;21(1):e63-e67. doi: 10.7861/clinmed.2020-0896. Epub 2020 Nov 26.
  4. Deng H, Carlson J & Price L. Nrf2 and the Nrf2-Interacting Network in Respiratory Inflammation and Diseases. Nrf2 and its Modulation in Inflammation. 2020; 85: 51–76. Published online 2020 May 22.
  5. Doykov I et al. 'The long tail of Covid-19' - The detection of a prolonged inflammatory response after a SARS-CoV-2 infection in asymptomatic and mildly affected patients. F1000Res. 2020 Nov 19;9:1349. doi: 10.12688/f1000research.27287.2. eCollection 2020.
  6. Gorna R. Long COVID guidelines need to reflect lived experience. Lancet. 2021 Feb 6;397(10273):455-457. doi: 10.1016/S0140-6736(20)32705-7. Epub 2020 Dec 23.
  7. Halpin S, O'Connor R, Sivan M. Long COVID and chronic COVID syndromes. J Med Virol. 2020 Oct 30: 10.1002/jmv.26587.
  8. Huang C et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021 Jan 16;397(10270):220-232.
  9. The Lancet. Facing up to long COVID. Lancet. 2020 Dec 12; 396(10266): 1861. Published online 2020 Dec 10.
  10. Mandal S et al. 'Long-COVID': a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19. Thorax. 2020 Nov 10;thoraxjnl-2020-215818.
  11. Mendelson M et al. Long-COVID: An evolving problem with an extensive impact. S Afr Med J. 2020 Nov 23;111(1):10-12.
  12. Nunn AVW et al. SARS-CoV-2 and mitochondrial health: implications of lifestyle and ageing. Immun Ageing. 2020; 17: 33. Published online 2020
  13. Oronsky B et al. A Review of Persistent Post-COVID Syndrome (PPCS). Clin Rev Allergy Immunol. 2021 Feb 20;1-9.
  14. Saita Y. Risk/caution of vitamin D insufficiency for quarantined athletes returning to play after COVID-19. BMJ Open Sport Exerc Med. 2020; 6(1): e000882. Published online 2020 Oct 19.

How Your Gut Bacteria Can Influence Your Weight

Obesity is one of the most prevalent health issues and leading risks for global death of the 21st century. It is a major risk factor for serious metabolic disorders, including type 2 diabetes, cardiovascular disease and various cancers. Obesity is often defined as being the net result of a long-term imbalance between energy intake and expenditure. Although excess calorie intake and lack of physical activity are leading causes of its development, obesity is a rather complex condition, which is influenced by several factors including genetic, biological, social, cultural, behavioural and environmental. Obesity prevention and treatment is currently problematic and unfortunately remains unresolved.

In the meantime, emerging evidence in the last 10 years suggests that the composition and functionality of the gut microbiota may be an important causal factor in the development of obesity and related metabolic diseases. Recent animal and human studies suggest that dietary supplementation of particular species of probiotic bacteria (e.g. Lactobacillus and Bifidobacterium species) may also help to improve weight management, by acting as regulators of energy metabolism in the body. However, at present, the impact of probiotic and prebiotic supplementation on the individual’s energy regulation is insufficiently explored and conflicting results can be misleading.

Gut microbiota: opportunity or hype?

There has been an unprecedented explosion of scientific knowledge and advances in human microbiome research over the last few years. The term human microbiome refers to the population of microorganisms, including bacteria, viruses and fungi, and their genetic material that live on and inside the human organisms (skin, mucous membranes, intestinal tract, etc.).

When it comes to numbers, well, current estimates arrive at a ratio of 1.3 bacterial cells for every human cell. However, the actual number may be much higher if the viruses and fungi are also taken into account. Similarly, our microbial cells contain far more, about 100-times more genes (2,000,000) than our own human genome (20,000). Interesting question: based on human microbiome research, if half of our cells are not Homo Sapiens cells, what does it mean to be an individual human being? The answer may be that we might need to reconceptualise the human being as a superorganism, rather than being a single individual. What I wanted to demonstrate in this section is the magnitude and importance of our microbiome. In fact, it is now scientific consensus that the microbiome affects our health and disease significantly.

What is the role of the microbiome in healthy metabolism?

The gut microbiota (GM) is an extremely complex and diverse functional system and has coevolved with the human species to help perform certain physiological functions that the host would have been unable to manage on its own. Their mutualistic relationship allows the bacteria to extract energy from non-digested food, while the host benefits from vital functions carried out by the microbes.

These functions include but not limited to:

  • vitamin production
  • the repair of the intestinal wall
  • amino acid synthesis (building blocks of protein)
  • harvesting energy from otherwise indigestible carbohydrate and protein sources
  • nutrient absorption and metabolism (via mediating the intestinal barrier function)
  • mediating susceptibility to illness and infection

Fascinatingly, the gut microbiota is also able to interfere with how your genes are expressed, and hence can ultimately change, for example, your metabolism and weight. Therefore, theoretically, host energy extraction from the diet may be regulated by the manipulation of the composition of the gut microbiota.

What is the connection between the gut microbiome and body weight?

It is estimated that approximately 10% of the total dietary energy supply in humans is provided by the microbiota-generated short chain fatty acids (SCFA), such as acetate and butyrate. These SCFAs are the metabolic end products of bacterial carbohydrate fermentation, and they possess key roles in regulating host metabolism. For example, acetate has been shown to suppress body fat accumulation by multiple mechanisms.

Studies also demonstrated that the microbiota can directly and/or indirectly influence how much energy is spent and/or stored by the host. It has also been discovered that the microbiome can influence leptin (a signalling hormone that is made by fat cells and reduces hunger) concentrations in humans, and hence can influence appetite. These suggest that the complex host-microbe interactions can easily interfere with body weight and adiposity.

What can influence the composition of the microbiome?

As our microbiome feeds on the types of food that are ingested, diet is a major determinant of its composition, diversity, and richness. However, the picture is a lot more complex because the microbiome is a living ecosystem, and consequently undergoes fluctuations due to various factors apart from the diet, including:

  • genetic background
  • early colonization (e.g. vaginal birth vs. C-section, nursing vs. formula feeding)
  • infections
  • antibiotics (especially in early life, they can have a profound effect that may result in the later development of obesity and other disorders)
  • aging
  • exercise
  • chronic physical and psychological stress
  • sleep deprivation
  • cohabitation with pets, such as dogs

For example, it has been found that Western-type diets may function as an environmental factor that predispose toward energy storage and obesity.

What you can do to support a healthy gut bacteria?

It is now well-recognised that an altered microbiota composition (aka. dysbiosis) may be strongly associated with obesity and related metabolic disturbances. As mentioned above, diet is recognised as having a major effect on regulating microbial diversity, and, as a consequence, greatly impacting the final metabolic potential of the host. Fortunately, there is a lot of general support that we can recommend, which can yield quick results.

Tips

  • Keep to a mealtime routine
  • Eat with others whenever you can, at a table, mindfully, away from distractions
  • Eat slowly and chew every bite properly
  • Daily moderate exercise can have a positive effect
  • If stress is an issue: a few deep breaths before eating can stimulate the parasympathetic nervous system, which is essential for proper digestion. Practicing stress-management techniques (e.g. meditation, yoga) will be essential
  • Keep a food diary and note problematic foods that may cause reflux, digestive problems, headaches, and immune reactions. Find potential alternative foods or at least minimise the ones causing trouble
  • Avoid being too restrictive with your diet unless you have to (e.g. due to an allergy)
  • A positive 80/20 rule (80% healthy foods and 20% ‘unhealthy’ foods) can be a good long-term strategy that encourages a good relationship with food while also ensuring sufficient nourishment. Note: ideally, the 20% proportion should consist of whole/real foods
  • Always discuss it with your health care practitioner if you would like to supplement with probiotics and/or prebiotics
  • Avoid inflammatory-type diets (e.g. high refined carbohydrates, high sugar, low-fibre high-protein, and high-fat) as these can alter the composition of gut microbiota towards a more inflammatory type).
  • Higher proportions of dietary fibre in the diet contribute to microbiota richness
  • Low fibre intakes are associated with reduced microbial diversity, or may lead to permanent extinction of important microbial species

In summary, it is undeniable that the gut microbiota is a metabolically very active interface, and thus plays a vital role in host metabolism and weight.

Nature Medicine, 2018 Apr 10;24(4):392-400.
J Clin Invest. 2008 Dec; 118(12):3817.
Protein Cell. 2018 May; 9(5): 404–415
The American journal of clinical nutrition, 2011. 94(1), pp.58–65.
The Journal of nutrition, 2013. 143(4), pp.417–23.

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