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 (Glezer et al., 2020)

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 (Mahmoud et al., 2021)

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 (Zabetakis et al., 2020)

The western diet is typically high in saturated fatty acids and free sugars, which can lead to chronic activation of the immune system and inhibition of the adaptive immune system. Obesity also prompts lower response to viral infections as it is a maintained state of inflammation (Calder, 2020).

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 (mostly Zabetakis et al., 2020)

“Hyper-activation of the immune system and the ‘cytokine storm’ is a key component of COVID-infection, and inflammation is a fundamental component of CVD. Thus approaches to reduce chronic inflammation (through decreasing adiposity, promoting physical activity and making healthier food choices) should be a priority for the long-term health of the population” (Butler et al., 2020)

Some cultures use foods and plants to help decrease inflammation across various health issues, such as by using oregano tea to relieve menstrual cramps. Antioxidants also have a benefit in preventing inflammatory disorders, as do foods high in omega-3 fats and antioxidants (e.g. yellow, orange and red vegetables, dark leafy greens, citrus fruits, black and green tea and allium vegetables), foods high in fibre and spices with anti-inflammatory compounds (e.g. ginger, rosemary, turmeric, oregano, cayenne, cloves and nutmeg). Although this diet can solve many issues related to inflammation, effects may take six weeks to six months in delivering benefits, which may be problematic in this fast-paced society (Sanders and Sanders-Gendreau, 2007).

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. There is a review that focuses on mapping elements in people with obesity that can lead to a higher risk of producing pro-inflammatory compounds that negatively affect the immune system through a cytokine shock, endothelial inflammation and other mechanisms (De Bandt and Monin, 2021).

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.

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.

Gut microbiome (Segal et al., 2020)

The gut microbiome and bile acids have been recognised to play an important role in vitamin K production and absorption. This becomes particularly important for patients who had COVID-19 given the potential use of antibiotics to treat co-existing lung infections. This affects the vitamin K’s pool in the gut microbiome.

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

Use of Probiotics for long-term symptoms, recovery and immunity (Morais et al., 2020; Zhao et al., 2020)

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. Another example is Lactoferrin, which is a key component of maternal milk and has been proven to reduce the severity and frequency of viral infections (Naidu, Pressman and Clemens, 2021).

A Cochrane review suggested that probiotics in general aid mechanisms against gut pathogens and can prevent antibiotic associated diarrhoea. There is no evidence yet to support probiotics improving COVID-19 symptoms (Lockyer, 2020). Probiotics may be helpful in the gut-lung axis and reducing the risk of “cytokine storm”. However, strains, posology and duration of interventions need to be better defined. Most studies have been conducted in paediatric populations using lactobacillus or Bifidobacterium or a mixture with variable duration as well (Costagliola et al., 2021). However, plant derived carbohydrates (prebiotics) increase beneficial bacteria especially galacto-ollisaccarides or olifructose such as Bifidobacteria, Lactobacillus, Roseburia (Rishi et al., 2020).

Currently, avoid recommending probiotics as a treatment for COVID-19. The role of the microbiota in COVID-19 has not been fully understood. However, at the end of 2020, there were 11 clinical trials registered (on clinicaltrials.gov) on the use of probiotics for the treatment of COVID-19 (Segal et al., 2020). New evidence is emerging all the time.

The following provides an overview of clinical studies (in humans, particularly adults) to show what hypotheses and evidence are available for COVID-19 recovery:

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 (Morais et al., 2020).

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 (Morais et al., 2020).

IgG and IgA levels in plasma and IgA production in saliva were also higher in the probiotic-treated group, as L. gasseri helped to block 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 (Morais et al., 2020).

L. rhamnosus, L. plantarum and B. longum were found effective in reducing risk of ventilator-associated pulmonia (Singh and Rao, 2020).

L. rhamnosus GG and B. lactis Bb-12 have shown to improve quality of life in patients who had upper respiratory infections (Singh and Rao, 2020).

L. paracasei N1115 was effective in preventing upper respiratory infections (Singh and Rao, 2020).

We advise HCP access the original studies and clinical trials, including adverse effects reports, before making any suggestions to patients or clients.

Examples of weak studies are shown next:

A protocol conducted in the U.S. trialled the lactobacillus rhamnosus GG for preventing COVID-19 transmission and symptom development on healthy home based participants (not immunosuppressed or with another underlying condition that affected swallowing or risk of infections) from 1 year old onwards (Tang et al., 2021). Researchers however do not plan to collect or analyse data excluding cofounders such as BMI, level of physical activity or type of diet.

A RCT in Mexico trialled the probiotic formula Lactiplantibacillus plantarum stains KABP022, KABP023 and KABP033 plus Pediococcus acidilactici strain KABP021 in 300 symptomatic COVID-19 patients, with almost half of them had underlying risk factors such as obesity and diabetes but were all Hispanic (ethnicity which has been relater to higher mortality due to COVID-19) and younger than 60 years old. Adjusting by these variables, the probiotic had a significant effect on improving remission rate as compared to the placebo group, as well as shorter duration of intestinal and non-intestinal symptoms (Gutiérrez-Castrellón et al., 2022). Weaknesses included that diet was not assessed, that they had a small population sample, and that funding was provided by a private company, which means a potential conflict of interest.

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 (Breznik, Motaln and Turnšek, 2017). 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 (Bauer and Morley, 2021).

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 (Hamilton and Scarlata, 2020).

More information can be found on these websites:

Deconditioning in older adults in the context of COVID-19 (Public Health England, 2021)

There was an increase of 5% of older people who were inactive during the first lockdown. The average duration of strength and balance activity decreased from 126 to 77 minutes. Older people in the most deprived groups were more likely to be inactive. The reduction of strength in the age group 70 to 74 was 45% for males and 49% for females. Because of these, almost 40% more older adults are projected to have at the least one fall per year as a result of reduced strength and balance during the pandemic. This can be higher for males (6%) than for females (4%). It is recommended to increase activity in order to reduce risk and enable the confident participation of older adults, including those who shielded, or with multimorbidity, with dementia, in social care settings and from more deprived backgrounds. Around half of older adults did not seek medical advice about a healthcare condition during the pandemic.

Deconditioning is the syndrome of physical, psychological and functional decline that occurs as a result of prolonged inactivity and associated loss of muscle strength. In healthy adults, three days of immobility was sufficient to significantly decrease muscle mass, tone and force.

Immediate impacts of this decline are:

  • cardiovascular, respiratory, and metabolic deconditioning
  • loss of strength and balance
  • insulin resistance and increased fat mass
  • increased social isolation
  • worse mental health and wellbeing (e.g. motivation, energy levels, anxiety, memory and confidence issues).

Medium and long-term impacts include:

  • falls
  • depression
  • type 2 diabetes
  • cardiovascular disease
  • musculoskeletal problems.

Recommendations for addressing deconditioning in the context of COVID-19

The approach to post-COVID-19 syndrome recovery will be similar to the approach to deconditioning recovery in patients (i.e. gradually increasing levels of light exercise). However, it is important to note that some individuals with post-COVID-19 syndrome will require specialised treatment, and it is unclear whether individuals with severe COVID-19 related fatigue may benefit from evidence-based structured strength and balance exercise.

Referral to post-COVID-19 syndrome clinics should be necessary only where individuals have severe symptoms or experience significant functional impact, or in cases deemed clinically complex by the appropriate healthcare professional. Approximately 10% of adults aged 70 years and over are estimated to experience fatigue five weeks after COVID-19 infection. It is important to consider the functional levels of the individual and signpost to the most appropriate local or online programmes available.

Increases in physical activity can become integrated into daily life. This may mean a ‘triage’ type system locally that knows all the available services in the area (e.g. online, face to face, evidence-based fall prevention and more health promotion strength and balance sessions). Those at highest risk of falls should be seen by a multi-disciplinary team and offered evidence-based falls prevention programmes (e.g. Falls Management Exercise [FaME] and Otago exercise programme) delivered by appropriately qualified individuals (e.g. physiotherapists, trained rehabilitation assistants, postural stability instructors and Otago exercise programme leaders). Others, who have not transitioned into frailty but need to work on their strength and balance so they are confident in increasing their general physical activity, can be directed to community-based face-to-face and online options delivered by personal trainers and other qualified exercise instructors. For individuals with long-term conditions, increasing physical activity from levels seen during the pandemic should be considered as part of a general approach to supporting individuals to manage their own conditions. 

Finally, it is important to note some of the differences in activity levels between different groups of older adults, with the largest reductions in physical activity seen in males aged 65 to 74 and females aged 65 to 84, suggesting that efforts aimed at encouraging resumption of past physical activity should be particularly focused on these groups. 

Some apps and websites have been scientifically analysed and peer reviewed and are thus recommended for more active older adults. Many organisations recommend ‘Make Movement Your Mission’, which runs 15-minute movement ‘snacks’ three times a day, seven days a week on Facebook and YouTube. It is important to consider the functional levels of the individual and signpost to the most appropriate local or online programmes available.

Whole population recommendations

  • Older adults should participate in daily physical activity to gain health benefits. Some physical activity is better than none; even light activity brings some health benefits compared to being sedentary.
  • Older adults should break up prolonged periods of being sedentary with light activity when physically possible, or at least with standing, as this has distinct health benefits for older people.
  • Older adults should maintain or improve their physical function by undertaking activities aimed at improving or maintaining muscle strength, balance and flexibility on at least two days a week.
  • Each week, older adults should aim to accumulate at least 150 minutes (2½ hours) of moderate intensity aerobic activity, building up gradually from current levels.

For a specific table with each recommendation and relevant resources/considerations, as week as targeted recommendation for addressing deconditioning, see Public Health England: Wider impacts of COVID-19 on physical activity, deconditioning and falls in older adults (PDF)

Contact us

This knowledge hub is constantly being reviewed and updated. We welcome your comments or feedback about it.

Please contact abigail.troncohernandez@plymouth.ac.uk and we will get back to you promptly.


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Breznik, B., Motaln, H. and Turnšek, T.L. (2017) ‘Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumours’, Biological Chemistry, 398(7), pp. 709–719. doi:10.1515/hsz-2016-0283.

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Why we created this page

In creating the knowledge hub we worked with expert panels to form a consensus on the nutritional care for people recovering from COVID-19 infection. Each section of the knowledge hub includes a consensus statement produced by the relevant expert panel. For information on the background of the Nutrition and COVID-19 recovery knowledge hub project visit the 'about us' page.