Underlying mechanisms of the symptoms and what we may learn from related conditions

Information about underlying mechanisms of the symptoms, treatments and related conditions to COVID-19

Underlying mechanisms for COVID-19 symptoms

Smell loss (1)

Dysfunction of olfaction, anosmia (loss of smell) or hyposmia (reduced sense of smell) is a significant COVID-19 symptom with an incidence of anosmia of 34% to 65% depending on the paper you read. Its incidence can vary due to genetic factors via load, specificities of populations. 13% of COVID-19 patients suffered from hyposmia. Anosmia has served as a key symptom to aid clinical diagnosis. In most cases, the sense of smell recovers after two weeks.

Viral infection of the upper respiratory tract is one of the most common causes of olfactory dysfunction, due to damage to the nerves by the virus. Other causes of anosmia include the presence of nasal polyps, allergies, head trauma, and other factors that lead to the injury to the olfactory nerve. The observation that in most cases the sense of smell in infected individuals is rapidly recovered indicates that the damage occurs in the peripheral olfactory system and that the olfactory epithelium can self-generate in the weeks following the infection. However longer rates of recovery could be because the virus affects the central nervous system.

The distinctive characteristic of the olfactory system is part of the CNS. The functions of the olfactory or Bowman’s glands are still not totally clear. Possible roles include transport of odorants, prevention of infection by microorganisms, protection against xenobiotic compounds through the secretion of biotransformation enzymes.

Anosmia is the consequence of the absence or poor development of the olfactory bulb and olfactory tracts; and the consequences of the gonadal defect of hypothalamic gonadotropin releasing hormone deficiency.


Impaired taste (2)

Dysgeusia is the term used for all types of impaired taste sensation whether qualitative or quantitative. Quantitative taste impairment includes ageusia (total loss of taste) and hypogeusia (reduced taste). Qualitative taste disorders include parageusia (distorted taste sensations; things don’t taste as they used to) or phantogeusia (hallucinatory taste sensations in the absence of external stimuli). All have been reported as symptoms of long COVID.

Neural invasion of the virus to the olfactory and gustatory nerves (neurotropism) is the most likely mechanism. Viruses might cause dysgeusia either by direct damage to cranial nerves responsible for taste or direct damage to the taste buds expressing ACE2 receptors. The binding of virus and ACE2 receptors in oral mucosa may trigger an inflammatory response that could alter taste sensation. Other possible mechanisms included an imbalance in angiotensin II, triggering of proinflammatory cytokines, viral associated changes in saliva, salivary glands and sialic acid. Many of researchers have suggested that direct inflammation of the oral cavity mucosa and damage to the taste buds may be the underlying mechanism that causes dysgeusia associated with COVID-19.

In addition, the COVID-19 virus may infect the salivary glands resulting in changes to the consistency and quantity of salivary secretion, thereby resulting in dysgeusia. This could become an early indicator in asymptomatic COVID-19 patients.

Insufficient oral hygiene or microbial imbalances, excessive exposure to chemicals and disinfectants, and therapeutic drugs in the management of COVID-19, including antibiotic or antipyretics, could also impair smelling and tasting. In addition, since zinc could have a role in antiviral immune responses, zinc could be depleted in gustatory cells (hypozincaemia) and this may result in taste impairment.

For more information, please see:


Immune system and diet (3)

The western diet is typically high in saturated fatty acids and free sugars, which can lead to chronic activation of the image immune system and innovation of the adaptive immune system.

Given that the older adult and African American community have a greater inherent sensitivity to inflammatory modulators, consumption of unhealthy diets by these groups could pose an amplified risk to severe COVID-19 pathology. Indeed, studies show that consuming healthy foods has a rapid anti-inflammatory effect, even in the presence of obesity pathology. In addition to potential lung damage, the possible impacts on neurological function are significant. This is because it is known that peripheral inflammatory events can evoke an exaggerated and persistent neural inflammatory response in vulnerable individuals.

There have been instances of dementia in older adults following viral infection including respiratory viruses such as influenza. High amounts of fruits and vegetables, wholegrain bread and other starchy foods, oily fish etc., boost immune function. 

For more information watch these videos of Professor Philip Calder – an expert in the immune system:


Inflammation

Implementing an anti-inflammatory strategy is challenging, as it is not yet clear if any specific features of the immune response can be inhibited directly without compromising a patient’s overall immune defence. The presence of non-communicable diseases may aggravate the inflammatory pathology, particularly cardiovascular disease.

An effective strategy to reduce risk of developing non-communicable diseases is to control the activities of inflammatory mediators via modifiable risk factors such as diet, exercise, and healthy lifestyle choices.

The complexity of the interaction between nutrition and immune function requires further research in advance of population-based dietary recommendations. At a minimum, the attainment of reference nutrient intakes (RNIs) or recommended daily allowance (RDA) for those nutrients thought to have a role in supporting immune functions is recommended at this time (3).

Long COVID can lead to an increase in chronic medical conditions such as depression, stroke, cardiac injury, chronic renal disease, and type 2 diabetes. It is very similar to Myalgic Encephalomyelitis and resembles chronic fatigue syndrome. Chronic inflammation can exacerbate catabolism and anorexia, hypertension, diabetes, heart disease and renal failure.

Popular treatments with little evidence (probiotics, anti-histamine diets)

Use of Probiotics for long-term symptoms, recovery and immunity (5, 6)

There is still emerging evidence to use probiotics in recovering from COVID-19. Dysbiosis is closely associated with changes in the dynamics of the immune system. Even immunomodulation by signalling pathways of intestinal and immune cells. This route involves intestinal purine metabolism, possibly one of the explanations for the benefits achieved with the use of probiotics. Thus, curiosity and interest in nutritional therapies to promote the reduction of purine intake have increased, whether using probiotics or by dietary restriction advice on source foods, and consequently control of serum uric acid concentrations. This behaviour can positively influence the health of individuals with viral infections.

Probiotics are microorganisms with the ability to modulate the intestinal and systemic immune response could be used in bacterial and viral respiratory infections to improve their outcomes. An important factor that affects both gut microbiota and the immune system is diet being trigger factors for low-grade systemic inflammation and oxidative stress. An unbalanced state of the microbiome, called dysbiosis, is characterised by overgrowth of pathobionts, loss of commensals, and lower diversity. Lactobacillus, for instance, can maintain the ecological balance of the host intestinal microbiota by reinforcing intestinal flora and inhibiting harmful bacteria.

L. gasseri PA3 has demonstrated an ability to reduce purine in foods and beverages. Purines are essential to viral RNA synthesis. Reducing purine availability might slow down virus replication, holding down viral infections.

L. gasseri’s potential to modulate proinflammatory cytokines interferon and interferon-stimulated genes were upregulated. L. gasseri SBT2055 boosted the immune responses in healthy vaccinated subjects that received a trivalent influenza vaccine. This Lactobacillus strain stimulated humoral immunity and total immunity.

IgG and IgA levels in plasma and IgA production in saliva were also higher in the probiotic-treated group. L. gasseri in blocking proinflammatory cytokine production. Therefore, this information might suggest the actions of this lactobacillus strain in COVID-19, improving the innate and adaptive immune systems, and further studies should address this hypothesis.


Anti inflammatory diet BDA statement


Further advice can be found in:

Related conditions to take learning from, which may have a similar course to the ongoing and long effects of COVID-19

Myalgic encephalitis or Chronic Fatigue Syndrome (ME/CFS)

The ME Association provided a booklet with information about post-viral fatigue and post-viral fatigue syndrome (management and monitoring in several aspects including nutrition, mental wellbeing and sleep) following coronavirus infection.

More information on ME/CFS can be found on the Centers for Disease Control and Prevention (CDC) website.


Mast cell disease

Mast cell activation syndrome is a multi-organ multi-symptom disorder characterised by clinical features and responses to medications that block mast cells. There are no diagnostic biomarkers for clinical use, furthermore, lay literature and social media are outpacing science.

Mast cells (MCs) present in submucosa of respiratory tract represent a protection barrier against microorganisms and they can be virus activated to release pro-inflammatory histamine and proteases. Proteases and cytokines modulate angiogenesis, extracellular matrix composition and integrity. This may happen in invasive processes such as cancer. Proteases can also activate or inactivate cytokine function (7). Extensive and uncontrolled release of pro-inflammatory cytokines is termed cytokine storm and clinically it presents inflammation and multiple organ failure. This may be the defining feature of severe COVID-19.

The role of histamine in the guts immune-regulatory pathways has not been fully elucidated. Food derived histamine is associated with non-allergic food intolerance and food poisoning. A reduction in histamine rich foods might be considered if patients exhibit an intolerance to high histamine foods as noted by food and symptom journaling and registered dietitian assessment.

Multiple organ dysfunction is likely attributable to uncontrolled inflammation and cytokine storm release. There is a marked increase in the mutated mass cells in the various tissue compartments including the bone marrow skin and gastrointestinal tract and these are made worse by predictable triggers for instance certain foods, strong sense temperature changes, stress, alcohol, and certain medications. Inflammatory cytokines not only lead to muscle loss but result in decreased muscle function and myalgia (8).

There might be an overlap between mast cell disease and irritable bowel syndrome (IBS) because more than half of patients noted gastrointestinal symptoms from histamine releasing foods or foods rich in biogenic amines. Gastrointestinal symptoms are largely treatable and very common in patients’ morbidity. Half of patients have self-report food allergies some identified milk others cheese and yoghurt others cereal grains such as gluten and preservatives such as sulphides benzoates and nitrates, tomatoes citrus and strawberries.

What differentiates Mast Cell Activation Syndrome (MCAS) from irritable bowel syndrome (IBS) is the presence of symptoms in more than one organ system. Symptoms associated with histamine intolerance mirrored those of mast cell activation disorders including headache, urticaria, hypotension, facial flushing, diarrhoea nausea, vomiting, vertigo, abdominal pain, congestion, asthma.

Chronic symptom disorders that may be confused with MCAS include chronic pain syndrome, chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity syndrome and chronic symptoms syndromes following infections or other exposures (9).

More information can be found on these websites:

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References

(1) Glezer I, Bruni-Cardoso A, Schechtman D, Malnic B. Viral infection and smell loss: The case of COVID-19. J Neurochem. 2020 Sep 24;

(2) Mahmoud MM, Abuohashish HM, Khairy DA, Bugshan AS, Khan AM, Moothedath MM. Pathogenesis of dysgeusia in COVID-19 patients: a scoping review. :21.

(3) Zabetakis I, Lordan R, Norton C, Tsoupras A. COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation. Nutrients. 2020 May 19;12(5):1466.

(4) Mechanick JI, Carbone S, Dickerson RN, Hernandez BJD, Hurt RT, Irving SY, et al. Clinical Nutrition Research and the COVID-19 Pandemic: A Scoping Review of the ASPEN COVID-19 Task Force on Nutrition Research. JPEN J Parenter Enteral Nutr. 2021 Jan;45(1):13–31.

(5) Zhao X, Li Y, Ge Y, Shi Y, Lv P, Zhang J, et al. Evaluation of Nutrition Risk and Its Association With Mortality Risk in Severely and Critically Ill COVID‐19 Patients. Journal of Parenteral and Enteral Nutrition. 2020 Jul 20;jpen.1953.

(6) Morais AHA, Passos TS, Maciel BLL, da Silva-Maia JK. Can Probiotics and Diet Promote Beneficial Immune Modulation and Purine Control in Coronavirus Infection? Nutrients. 2020 Jun 10;12(6):1737.

(7) Breznik B, Motaln H, Turnšek TL. Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumours. Biological Chemistry. 2017 Jul 1;398(7):709–19.

(8) Bauer JM, Morley JE. Editorial: COVID-19 in older persons: the role of nutrition. Curr Opin Clin Nutr Metab Care. 2021 Jan;24(1):1–3.

(9) Hamilton MJ, Scarlata K. Mast Cell Activation Syndrome – What it Is and Isn’t. PRACTICAL GASTROENTEROLOGY. 2020;7.