We are still living in unprecedented and worrying times, and consequently, factors that can support the proper functioning of the immune system are very much in the spotlight. With no imminent end to the pandemic, we should all aim to support our immune health and to lessen the risks associated with COVID-19, and other infections.
There is a vast amount of evidence available for interventions which support immunity, protect against viral infection, and may possess antiviral activity. In addition, new research has emerged and continues to emerge with regards to interventions that have potential to be beneficial against COVID-19. We are getting many queries about how best to support resilience to infections, so this article aims to take a look at the evidence and discuss the relationship between specific nutrients, immunity, and COVID-19 and other viruses, and will also explore the potential impact that COVID-19 may have on the nutritional status of those who have contracted it. Another key area of focus is inflammation, as the body’s own inflammatory response can sometimes become more dangerous than the infection itself.
As with any intervention, it is important to consider the individual as a whole and use a holistic approach. We know, for instance, that underlying health conditions hold a greater risk of increasing the severity of the illness for some. For example, obesity increases risk for hospitalisation, ICU admission, and death among patients with COVID-19.1 Following a healthy lifestyle is important therefore, not only to support an adequate immune response to the virus, but also for addressing any comorbidities that may affect the response to COVID-19. Dysfunctions including inflammation, leaky gut, dysbiosis and insulin resistance should all be supported as they can help to drive pathologies and potential complications of viral infections.
Published last year, an expert panel wrote a white paper after reviewing the scientific evidence on the role of micronutrients in relation to immune system health and viral infection. The paper states that the ‘role of nutrition, optimal micronutrient status and a well-functioning immune system as a modifiable factor to reduce risk of virus infections and severity is highlighted in several recent scientific publications. These publications address the role of good nutritional status for a well-functioning immune system and report a deficient or low status in some micronutrients among COVID-19 patients’2 The findings of this paper will be addressed throughout.
In addition, EFSA have concluded that there is definitive evidence of the cause–effect relationship between the daily intake of specific vitamins and minerals and the normal, healthy functioning of our immune system.3
Vitamin C 1-6
Vitamin C contributes to immune defence by supporting various cellular functions of both the innate and adaptive immune system. It additionally supports epithelial barrier function against pathogens.
Mechanism of action in immune function: 1–2
- Stimulates Neutrophils –to protect themselves from oxidative damage, neutrophils accumulate millimolar concentrations of vitamins, resulting in improved cellular motility and migration
- Supports lymphocyte production and function – lymphocytes can actively accumulate vitamin C against a concentration gradient
- Increases interferon production – proteins that are made and released in response to pathogens like viruses
- Natural Killer Cells – in clinical studies, vitamin C treatment of healthy subjects promoted and enhanced natural killer cell activity
- Monocytes/macrophages – it has been shown that monocytes contain a high concentration of vitamin C
- Improves chemotaxis – chemotaxis uses cytokines and chemokines to attract macrophages and neutrophils to the site of infection
Function of vitamin C in viral infections2,3
- Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements
- Vitamin C has beneficial immunomodulating properties in patients with viral infections – increasing the production of α/β interferons and down-regulating pro-inflammatory cytokines
- Vitamin C reinforces the maintenance of the alveolar epithelial barrier
- Intravenous vitamin C has been shown to reduce mortality in patients with sepsis induced ARDS
- 3 human trials had reported that there was significantly lower incidence of pneumonia in vitamin C‐supplemented groups
Specific research for vitamin C on COVID-19
As of February 2020, an RCT at the Zhongnan Hospital set out to evaluate the clinical efficacy of vitamin C in viral pneumonia from SARS-CoV-2. Researchers hypothesise that vitamin C infusion can improve the prognosis of severe acute respiratory tract infections. The treatment arm includes a 12g vitamin C infusion for seven days, and the primary outcome measures the ventilation-free days.4 This study is due to end in March 2020
Furthermore, a high dose intravenous vitamin C (HDIVC) cohort study is also in progress in Palermo, Italy. The study includes all patients hospitalised with positive swab tests of SARS-CoV-2 and interstitial pneumonia. 10g of vitamin C will be administered intravenously in addition to conventional therapy. 5
Vitamin C deficiency increases the susceptibility to infections such as pneumonia, and plasma levels decrease during an infection such as pneumonia.6
Zinc is involved in multiple aspects of immune function and a deficiency is associated with reduced:
- T cell and B cell function
- Lymphoproliferative response to mitogens
- Thymic hormone levels
- Cytotoxic activities
Zinc deficiency therefore increases susceptibility to infectious diseases.
Function of zinc in viral infections
Zinc deficiency impairs antiviral immunity, particularly to herpes simplex, common cold, hepatitis C, and the human immunodeficiency virus (HIV). A meta-analysis of oral zinc supplementation studies suggested beneficial effects on the shortening of symptom duration and duration of common cold infection.
It has been shown that intracellular levels of zinc may play a role in the prevention of viral infections, as increasing levels can efficiently impair the replication of a variety of RNA viruses, including poliovirus and influenza virus. Other in vitro studies have demonstrated reduced viral replication of viruses including severe acute respiratory syndrome (SARS) coronavirus.
Specific research on Coronaviruses
Positive-stranded RNA viruses include many important pathogens, including SARS CoV coronaviruses. They have evolved a variety of replication strategies but are unified in the fact that an RNA-dependent RNA polymerase (RdRp) functions as the core enzyme of their RNA-synthesizing machinery. Coronaviruses utilise the enzyme SARS-CoV RdRp where elongation of which was inhibited, and template binding reduced by the presence of zinc in vitro. Zinc ionophore also demonstrated to block replication of SARS CoV in cell culture (in vitro).
Research suggests SARS-Cov-2 virus enters cells via ACE2 by binding to zinc metalloproteases. Coronavirus viral replication downregulates ACE2. Zinc is an essential component of ACE2 receptors, and therefore may help to normalise ACE2 receptor function. In institutionalised elderly, a higher status of zinc is associated with lower incidence of, and faster recovery from pneumonia.
Vitamin D is known to support healthy immune function and has been shown to be deficient in the majority of the population, particularly over the winter months. Observed differences in COVID-19 mortality between the northern and southern hemispheres support the case for vitamin D having a role in the pathogenesis of COVID-19.
Role of Vitamin D in immunity
As the vitamin D receptor is expressed on immune cells, vitamin D has the capability of acting in a milieu of immunological functions. It can modulate both the innate and adaptive immune responses and a deficiency is associated with increased autoimmunity as well as an increased susceptibility to infection.4
Research on efficacy against infections
Vitamin D is known to mitigate the scope of acquired immunity and regenerate endothelial lining.5 This may be beneficial in minimising the alveolar damage caused in ARDS.
Vitamin D3 in relation to COVID-19
- Research suggests SARS-Cov-2 virus enters cells via ACE2. Coronavirus viral replication downregulates ACE2 dysregulating the renin-angiotensin system (RAS) and leads to a cytokine storm in the host, causing ARDS
- Research shows that Vitamin D acts to rebalance RAS and attenuates lung injury
- Vitamin D deficiency is strongly associated with ARDS and poor mortality outcomes, as well as being associated with many comorbidities associated with COVID-19 case fatalities
- High dose oral Vitamin D has been shown to improve mortality in patients with severe vitamin D deficiency
- Chronic vitamin D deficiency induces lung fibrosis through activation of the RAS
Since the coronavirus pandemic more than 1500 scientific papers have been published in relation to COVID-19, which address the potential roles of vitamin D for the immune system.1
For instance, a systematic review and meta-analysis carried out in November 2020 analysed the association between vitamin D deficiency and COVID-19 severity, via an analysis of the prevalence of vitamin D deficiency and insufficiency in people with the disease. It was found that a vitamin D concentration insufficiency increased hospitalization and mortality from COVID-19, and hence researchers observed a positive association between vitamin D deficiency and the severity of the disease.13
There are also more than 30 human studies that are evaluating the benefit of vitamin D in relation to COVID-19.1 For example, researchers from Queen Mary University London launched a new clinical trial in October 2020. The trial named CORONAVIT has enrolled over 5000 participants to see if a test and treat approach to correct vitamin D deficiency reduces Covid-19 severity risk. This is due to end later this year.
In short, scientific evidence now shows that:
- Higher vitamin D blood levels are associated with lower rates of SARS-CoV-2 infection
- Higher D levels are associated with lower risk of a severe case (hospitalization, ICU, or death)
- Intervention studies (including RCTs) indicate that vitamin D can be a highly effective treatment
- Many papers suggest several biological mechanisms by which vitamin D influences COVID-19
The government recommends supplementing 10ug of vitamin D all year round although requirements may increase depending on vitamin D status. Public health England have recently increased the recommended level to 25ug/day during the current pandemic. The UK’s Health Secretary has now encouraged people to supplement with vitamin D based on recent evidence.
Vitamin K 1,2
In one study, researchers proposed an association between low levels of vitamin K and the enhanced breakdown of tissue fibres, such as elastin, which is involved with pulmonary disease. It was found that dp-ucMGP (inactive Matrix Gla-protein – which is a vascular calcification inhibitor that needs vitamin K for its activation) was significantly lower in COVID-19 patients compared to controls. The findings suggest that improved vitamin K levels may play a role in improving the body’s natural ability to cope with the novel virus.1
Furthermore, a systematic review suggested that Vitamin K metabolism maybe the potential missing link between lung damage and thromboembolism in COVID-19.2 Thrombosis is a manifestation of COVID-19 that often causes poor outcomes in the patient. Researchers made observations that elastic fibre pathologies were associated with health conditions that increased the likelihood and severity of COVID-19 symptoms. Elastic fibres are critical components in the extracellular matrix of dynamic tissues and provide deformability to lungs and arteries, which facilitates respiration and circulation.2
It was found that extrahepatic vitamin K status was extremely low in COVID-19 patients, which could have been a result of low vitamin K status prior to infection or in combination with accelerated depletion after infection. The researchers of the study hypothesised that given the importance of vitamin K-dependent proteins in coagulation as well as elastic fibre metabolism, deficiency of vitamin K maybe implicated in poor COVID-19 outcomes.
Vitamin A is important for the function of neutrophils, macrophages, and natural killer cells. Deficiency can impair innate immunity by impeding normal regeneration of mucosal barriers damaged by infection. Vitamin A is also required for adaptive immunity and plays a role in the development of T both-helper (Th) cells and B-cells. It is also essential for the maintenance and repair of epithelial tissue and therefore helps to maintain the integrity of the respiratory and gastrointestinal lining.1,2
Research on vitamin A and viral infections
Vitamin A deficiency is strongly involved in measles, which can become severe in vitamin A‐deficient children. The mechanism by which vitamin A and retinoids inhibit measles replication is upregulating elements of the innate immune response in uninfected bystander cells, making them refractory to productive infection during subsequent rounds of viral replication.3
Research shows that the effect of infection with infectious bronchitis virus, a kind of coronavirus, was more pronounced in chickens fed a diet marginally deficient in vitamin A than in those fed a diet adequate in vitamin A.4
From a pulmonary perspective, retinoic acid has been implicated in modulating the pathogenesis of ARDS, influencing the production of IL1-β and IL-1 receptor antagonist by alveolar macrophages, and the subsequent pulmonary infiltration of neutrophils.5 In light of its pulmonary and immunological roles, oral supplementation of vitamin A is currently being investigated in the treatment of COVID-19 alongside many other antioxidants.6
Selenium is an essential antioxidant and supports the production of the master intracellular antioxidant, glutathione. Dietary selenium deficiency that causes oxidative stress in the host can alter a viral genome so that a normally benign or mildly pathogenic virus can become highly virulent in the deficient host under oxidative stress.1
Selenium has an important role in the modulation of the inflammatory response and cytokine production.2 Researchers found that supplementation with selenium improves the immune system response to viruses in deficient individuals. COVID-19 patients with low selenium status have been shown to have higher mortality rates.2,3
Role in viral infections: 4-7
- Selenium deficiency has been associated with the pathogenicity of several viruses
- In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains
- Replication of a mild strain of influenza virus in selenium-deficient mice resulted in a novel virulent strain that causes severe lung pathology, even when passed into selenium-adequate mice
- These studies demonstrate that selenium status of the host can profoundly influence the genome of viral pathogen, leading to a new viral strain.
Margaret Rayman, a professor of Nutritional Medicine at the University of Surrey hypothesised that selenium status was associated with COVID-19 disease outcome in China. She proposed that the appearance of COVID-19 in China could be linked to the belt of selenium deficiency that runs from the north-east to the south-west of the country. Her team of researchers subsequently examined data from provinces and municipalities with more than 200 cases, and cities with more than 40 cases. In the city of Enshi in Hubei Province, which has the highest selenium intake in China, the cure rate was almost three-times higher than the average for all the other cities in Hubei Province. By contrast, in Heilongjiang Province, where selenium intake is among the lowest in the world, the death rate from COVID-19 was almost five-times as high as the average of all the other provinces outside of Hubei. They found that areas with high levels of selenium were more likely to recover from the virus.8
The inhalation of pathogens is the primary route for infections that affect the respiratory system. Viruses are spread via tiny droplets or particles and have the potential to live on surfaces long enough to penetrate the mucosal epithelium. The epithelium of the respiratory tract provides a physical barrier to viruses and is therefore one of the first lines of defence utilised by the body to ward off infectious agents. An effective defence is reliant on many factors such as communication with the adaptive immune system and the secretion of epithelial defence molecules.
Lactoperoxidase (LPO) is an enzyme that is found in our exocrine secretions and is well known for its antimicrobial activity. Glands that secrete LPO include the mammary, salivary, and mucosal glands, thus making LPO present in milk, saliva, tears, and the epithelial surfaces of the respiratory and gastrointestinal tract.
Mechanisms of Action in Immune Function
- LPO is a natural antimicrobial agent and one of the body’s first lines of defence against pathogens
- The LPO system is a combination of lactoperoxidase, thiocyanate (or iodine) and hydrogen peroxide and makes up part of the humoral immune response
- The mechanism of action is the oxidation of thiocyanate ions with the use of hydrogen peroxide to form hypothiocyanite ions
- Hypothiocyanite exerts a wide spectrum of activity against bacteria, viruses, yeasts, and moulds. It does so by oxidizing the thiol groups of amino acid residues of microbial proteins, leading to impaired function, inhibition of cell division or death of the microorganism1
- LPO also plays an important role in protecting the respiratory and digestive tract
How well the innate system functions, however, is heavily dependent on our nutritional status and can be compromised if our diet is poor.
LPO is an iron containing glycoprotein and therefore dependent on adequate levels of iron in the body. Iron deficiency is the most common nutritional disorder in the world, therefore having widespread potential implications on innate system competence.
LPO uses either thiocyanate or iodine as its substrate of which it oxidises.
Thiocyanate is found in plant foods such as kale, cabbage, cauliflower, Brussel sprouts and turnips. It can also be derived from plants containing cyanogenic glycosides such as almonds, linseed, and beans.
Iodine deficiency is common and is often related to poor soil quality, and hence lower levels in natural foods or dairy, or where little seafood is eaten.
- Hypothiocyanite has powerful anti-viral capabilities as it has been shown to oxidize the sulfhydryl groups often present on the outer structure of viruses rendering them damaged or destroyed
- By oxidizing free thiol radicals of proteins and creating disulfide bonds hypothiocyanite seems capable to alter the surface proteins of respiratory viruses, contrasting their binding with the airway epithelium
- It is also argued that hypothiocyanite might interfere with the synthesis and assemblance of viral proteins and nucleic acids, thereby interfering with the release of viruses from infected cells
- One study showed that the H1N2 influenza virus was inactivated by human and rat tracheal epithelial cells. The LPO system which produced hypothiocyanite showed a potent anti-influenza mechanism which inactivated the virus prior to infection of the epithelium
- More recently, another study showed that LPO was capable of inactivating 12 different influenza strains when tested in vitro
- A recent laboratory experiment also demonstrated that the hypothiocyanite ion inactivated viral activity in vitro against the 2009 H1N1 pandemic influenza virus
Specific research against Coronaviruses
Research findings have shown hypothiocyanite to be an important and active molecule against a range of viruses and an important participant in the antiviral defences of the innate immune system. This may suggest its wider potential application for newly emergent strains such as the SARS-CoV-2.
In a recent study, to test virucidal activity of hypothiocyanite and lactoferrin against SARS-CoV-2 researchers conducted an in-vitro study. They showed a dose-dependent virucidal activity of hypothiocyanite at micromolar concentrations, slightly improved by the presence of lactoferrin. 12
Lysine is an essential amino acid and must be included in the diet as the body is unable to synthesise it. It is important for carrying out many roles in the body including ones related to the immune system.
Mechanism of Action in Immune Function
- Amino acids, including lysine, are building blocks for proteins, which are needed for the production of immune cells
- Studies have demonstrated an important role for amino acids in immune responses
- Research has shown that lysine can strengthen the immune system and exhibits anti-viral properties. It has been shown to have positive effects on the herpetic family of viruses which include Herpes (HSV-1), Epstein Barr and Kaposi’s sarcoma herpesvirus
Function of Lysine in Viral Infections
Lysine & Arginine
- It is essential to look at the relationship that exists between lysine and arginine to gain a better understating of the function of lysine on viral infection
- Lysine and arginine share the same biological pathway, and both compete for entry into the cell
- Many studies have demonstrated that some viruses rely on arginine for their survival and that arginine is an essential requirement for their replication and progression
- Lysine is thought to be effective against some viruses as it blocks arginine and hence viral replication
- When arginine is not available, herpes viruses are unable to complete a single replication cycle and cell damage is evident in infected cells
- A study showed that Lysine had a positive effect on HSV-1 infection, symptoms, and occurrence
It has been well documented that the severity of COVID-19 is often due to a cytokine storm, where inflammation runs away, and the body’s own inflammatory response becomes more dangerous than the infection itself. SARS-CoV2 has been shown to activate the NLRP3 inflammasome, which is strongly involved in hyper-activation of the innate immune response. The NLRP3 inflammasome is a protein complex that initiates an inflammatory form of cell death and triggers the release of proinflammatory cytokines. The NLRP3 inflammasome has been implicated in a wide range of diseases, including infectious disease.
The body requires an appropriate inflammatory response to react to the initial infection. However, many people already have a heightened inflammatory response as it is a driver of many chronic conditions (CVD, diabetes type 2). Many suggested interventions are to normalise the inflammatory response to help support resilience and help to prevent activation of the NLRP3 inflammasome.
Omega-3 fatty acids help to regulate inflammation and are also likely deficient in a typically Western diet. Omega-3 has been shown to reduce inflammatory cytokines and there have been some trials using omega-3 in response to ARDS. Increasing the ratio of omega-3 to omega-6 can help move away from a hyper-inflammatory response to infection. The omega-3 fatty acids, EPA and DHA present at the site of inflammation are enzymatically converted to specialized pro-resolving mediators known as resolvins, protectins, and maresins. These molecules work together to orchestrate the resolution of inflammation and to aid healing, including in the respiratory tract. Notably, nutritional deficiencies in these essential fatty acids can result in delayed or suboptimal resolution of inflammation.1 This could be crucial in the context of severe COVID-19, which presents as uncontrolled inflammation.
Addressing oxidative stress and increasing antioxidant intake maybe also be beneficial here in the context of inflammation. Oxidative stress produces harmful free radicals and can increase inflammation. Reinforcing the body’s antioxidant levels by including plenty of antioxidant-rich plant foods can reduce the impact of oxidative injury and help to control inflammation.
Flavonoids are one of the largest groups of phytonutrients and are rich in antioxidant properties. They have several subgroups, which include chalcones, flavones, flavanols, and isoflavones.
Studies have suggested:
- Flavonoids from Pterogyne Nitens could inhibit the entry of the hepatitis C Virus
- Anti‐coronavirus activity of some flavonoids (herbacetin, rhoifolin and pectolinarin) was due to the inhibition of 3C‐like protease
- Other flavonoids (herbacetin, isobavachalcone, quercetin 3‐β‐d‐glucoside, and helichrysetin) were found to be able to block the enzymatic activity of MERS‐CoV/3CLpro
- Bioflavonoids from Torreya nucifera also brought inhibition effect of SARS‐CoV/3CL
- Data shows the possibility that TGG and luteolin may achieve their antiviral activity by interfering with the virus-cell fusion process against SARS-CoV. Quercetin is an analogue of luteolin, which is structurally related, and is FDA approved and has additionally demonstrated anti-viral properties potentially via the same mechanism
- Several flavonoids were tested for their potential to regenerate and promote the hypothiocyanite production by LPO with positive results
Quercetin has been shown to have antiviral effects against both RNA and DNA viruses. Quercetin has a pleiotropic role as an antioxidant and anti-inflammatory, modulating signalling pathways that are associated with post-transcriptional modulators affecting post-viral healing.
Studies have shown quercetin:
- promotes viral eradication or inactivation
- favourably modulates viral-induced pathological cellular processes – modulation of NLRP3 inflammasome activation
Curcumin is a lipid-soluble polyphenol and the main active ingredient of Curcuma longa (turmeric). It has powerful anti-inflammatory effects and is a strong antioxidant.
Mechanism of Action in Immune Function 2-7
Curcumin enhances the immune system, helps decrease viral growth and can reduce symptoms. Accumulated research has suggested that curcumin can play an inhibitory role against numerous viruses. These mechanisms involve either a direct interference of viral replication machinery or suppression of cellular signalling pathways, which are essential for viral replication.
COVID-19 and other Viral Infections 8,9
Curcumin has been shown to reduce inflammation and decrease viral activity for COVID-19. A preprint suggests that curcumin can target the COVID-19 main protease to reduce viral replication. Researchers successfully crystallised the COVID-19 main protease (Mpro), which is a potential drug target. The Mpro in CoV is essential for the proteolytic maturation of the virus and has been examined as a potential target protein to prevent the spread of infection by inhibiting the cleavage of the viral polyprotein. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 Mpro inhibitors, using a molecular docking study.
In another study, researchers found that nano-curcumin, as an anti-inflammatory herbal-based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients.
The diverse intestinal microbiota shapes the immune system and promotes the host well-being. It is therefore important to keep it nourished with the necessary nutrients it needs. The respiratory tract microbiota also influences the host immune responses to viruses. Acute respiratory viral infections disrupt the host-microbiota interactions and creates the intestinal dysbiosis with the post-viral immune responses that contribute to pneumonia development by the secondary bacterial infection. The healthy, diverse intestinal and respiratory tract microbiota is then another critical determinant for supporting immunity.
Research has demonstrated that there have been significant differences in the microbiota of free-living older adults and those residing in residential care.1 In addition, an abnormal gut microbiota is seen in obesity and in individuals with chronic age-related conditions.2 In one study researchers noted that some Chinese patients with COVID-19 showed intestinal dysbiosis with low numbers of lactobacilli and bifidobacteria.3
There is evidence that probiotic bacteria can modify the microbiota, modulate the immune response and protect against infections, including of the respiratory tract.2
Beta glucans are not synthesised by the human body and therefore are recognised as foreign. As they are found in the cell walls of fungi and bacteria, the innate immune system recognises them as a potential pathogen, although they themselves do not possess the ability to cause an infection. The recognition of these specific molecules triggers the upregulation of the immune system.
- There are increasing problems with antibiotic and anti-viral resistance. Priming the innate immune system with 1-3, 1-6 beta glucan has repeatedly been shown to increase resistance to bacteria and viruses in humans, fish, poultry, Guinea pigs, pigs, and honeybees
- A study looking at 49 adults aged 50 to 70 showed that daily oral β-1-3, 1-6 glucan may protect against URTIs and reduce the duration of URTI symptoms in older individuals once infected
- Beta glucan supplementation maintains immune function in endurance athletes
- Beta glucan supplementation reduces post-exercise URTIs in marathon runners
- A study in healthy subjects showed a 20-25% reduction in common cold episodes with supplementation of yeast beta glucan 1-3, 1-6. It concluded that the yeast beta glucan preparation increased the body’s potential to defend against invading pathogens
Acetylcysteine is a derivative of the amino acid cysteine, which is required for the production of glutathione. As glutathione is the body’s most powerful antioxidant, N-acetylcysteine (NAC) is valued primarily for its antioxidant role in the body.
COVID-19 and other Viral Infections
NAC promotes glutathione production, which has been shown to be protective in mice infected with influenza. This activity is thought to be the basis for the protective effect of NAC administration in both influenza patients and in mouse models of the disease.
In human studies, a randomised double-blind trial was carried out on a total of 262 elderly subjects who received 600 mg NAC twice daily, as opposed to those receiving placebo. The group that received NAC experienced fewer influenza-like symptoms and days of bed confinement.
Other research has indicated that in immune-compromised situations such as the flu, NAC may hamper the virus’s ability to replicate, potentially reducing the symptoms and lifespan of the illness.
It is the potential antioxidant mechanism of NAC that has generated interest with the current COVID-19 pandemic. In a preprint, patients with COVID-19 had a clear increase of glutathione reductase levels, occurring in around 40% of patients.
Several studies have researched the anti-viral activity of NAC against influenza A strains. Both In-vitro and in vivo experiments show that NAC enhances glutathione levels, which reduce viral load by inhibiting viral replication in several viruses e.g., influenza A (H3N2 and H5N1).
As reactive oxygen species play a crucial role in inflammatory responses and viral replication, antioxidants that exert antiviral and anti-inflammatory effects have been suggested as candidates for the treatment of a cytokine storm induced by severe influenza. NAC was shown to inhibit both H5N1 replication and H5N1-induced production of pro-inflammatory molecules in lung epithelial cells.
Glutathione levels decrease with age, and as a result of certain disease states. These disease states should be supported, particularly in the case of viral assault. Low levels of glutathione are virtually universal among patients with chronic disease.
The oil extracted from oregano leaves has a long history of medicinal uses and has been traditionally used to treat respiratory disorders such as asthma, coughs and bronchitis for many years.
Mechanism of Action in Immune Function
Oregano is rich in antioxidants due to a high content of phenolic acids and flavonoids and helps to fight the damage from free radicals. It has also shown antibacterial, antifungal, and anti-inflammatory qualities.
Viral Infections 1-6
To date, there have been several studies that have looked at the health benefits of oregano in relation to viral infection. One study demonstrated that participants with URTIs, who used a throat spray containing oregano oil, experienced reduced hoarseness, sore throat and coughing and had significant and immediate improvement in symptoms.
In a further study, researchers investigated the antiviral activity of oregano oil and found that it inhibited both human and animal viruses in vitro. Carvacrol alone exhibited high antiviral activity against the human rotavirus.
In an animal study, the antiviral efficacy of oregano oil and its primary active component, carvacrol, was investigated against the nonenveloped murine norovirus (MNV) and was found to be effective in inactivating MNV within one hour of exposure, by acting directly on the viral capsid and subsequently the RNA.
Oregano essential oil has also exhibited strong antiviral activity against several nonenveloped RNA and DNA viruses such as adenovirus type 3, poliovirus, and coxsackievirus B1.
Some evidence suggests that following infection, immunity to COVID-19 may be reasonably short lived. Is it a novel mechanism of this virus or is it immune dysfunction that inhibits complete immunity? It is not currently known how long immunity may last following COVID-19 infection. However, it is important that the immune system maintains its “memory” of previous infections, allowing it to produce antibodies effectively in the event of a second infection. Compromised or dysfunctional immunity is more likely to result in a less adequate response to a second infection than if the immune system is primed and ready. Therefore, supporting a healthy immune and inflammatory response is essential for optimising prolonged immunity as much as possible.
- COVID-19 is caused by a strain of corona virus known as SARS-CoV2. This enters the body via ACE2 receptors and utilises enzymes including SARS-CoV 3C-like protease (3CLpro) to replicate. Individuals who have had severe symptoms of COVID-19 have experienced a cytokine storm where inflammatory molecules have run away with inflammation.
- Interventions for supporting immune function, inhibiting viral replication and modulating inflammation may all be useful in supporting protection against severity of infection.
- Nutrients with immune supporting functions include vitamin c, vitamin D, vitamin zinc, selenium and beta glucans.
- Zinc, iron and manganese are all co-factors for enzymes and have been implicated in inhibiting viral replication.
- Research suggests SARS-Cov-2 virus enters cells via ACE2 by binding to zinc metalloproteases Coronavirus viral replication downregulates ACE2, zinc is an essential component of ACE2 receptors, therefore may help to normalise ACE2 receptor function.
- Vitamin D is an important immune modulator and support lung epithelial tissue, countries which have been most severely affected by COVID-19 are those that have a higher incidence of Vitamin d deficiency as they have just come out of winter and are above 20 degrees latitude in the northern hemisphere.
- Data shows the possibility that TGG and luteolin may achieve their antiviral activity by interfering with the virus-cell fusion process against SARS-CoV. Quercetin is an analogue of luteolin, which is structurally related, and is FDA approved has additionally demonstrated anti-viral properties potentially via the same mechanism.
- Curcumin has been shown to modulate the NLRP3 inflammasome therefore helping to prevent the cytokine storm.
- The gut microbiome plays an essential role in supporting the immune system, 70% of immune tissue is found in the gut.
If you have questions regarding the topics that have been raised, or any other health matters, please do contact Helen or Amanda by phone or email at any time.
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Helen Drake, Amanda Williams and the Cytoplan Editorial Team
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