Coronavirus (COVID-19) Naturopathic Protocol

Coronavirus (COVID-19) Naturopathic Protocol

This Coronavirus (COVID-19) Naturopathic Protocol is provided as information for patients of HealthMasters Naturopath Kevin Tresize ND as part of a treatment plan to assist patients with understanding of their treatment plan and should not be substituted for medical advise, diagnosis or treatment. It is important to note that this is a summary only and is intended to assist discussion between practitioner and patient as part of consultations. This Coronavirus (COVID-19) Naturopathic Protocol may be changed to suit the individual requirements of the patient and should not be substituted for medical advice, diagnosis or treatment.

HealthMasters Naturopath Kevin Tresize ND

 

Overview:

1.0 Pathophysiology

2.0 Consultation Overview

3.0 Key Drivers

4.0 Monitoring and Responding to COVID

5.0 Treatment Priorities

6.0 Red Flags

7.0 Treatment Recommendations

8.0 Diet and Lifestyle Recommendations

9.0 Clinical Investigation and Pathology

10.0 Pharmaceutical Treatments

11.0 Additional Resources

12.0 Footnotes

13.0 References

While clinical evidence supports the use of natural medicines for immune support and increasing resistance against infections, the below-listed recommendations do not replace medical advice regarding treatment of COVID-19, which is a notifiable condition under Public Health and Wellbeing Regulations. If a patient or Practitioner presents with symptoms, is suspected to have COVID-19, or has come into contact with a confirmed COVID-19 case, individuals must undertake immediate testing and return/stay at home until test results are confirmed. Refer to the Australian Government Department of Health for the latest case numbers, medical advice and information on treatment, as well as hygiene and cleaning practices for healthcare Practitioners and the workplace. Alternatively, call the Coronavirus Health Information Line for advice (ph. 131 450).

 

1.0 Pathophysiology:

  • Coronaviruses (CoVs) are a large family of viruses, seven of which are currently known to infect humans. 
  • Four of these strains cause minor symptoms similar to the common cold, while two are more severe diseases including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). SARS-CoV-2 is the latest strain to have been identified within this family of viruses,[1] with subsequent illness referred to as COVID-19.[2]
  • Due to viral mutation, there are presently[*] six identified variants of the SARS-CoV-2 virus.[3] However, three variants of SARS-CoV-2 (B.1.1.7, B.1.351 and B.1.1.28.1[P1]) have raised concerns and are associated with increased transmissibility and risk of death compared to the parental virus.[4] Refer to the Living Evidence Table for further information on transmissibility, severity and effectiveness of vaccines in relation to these three variants.
  • Once infected, the viral incubation period can range between one to fourteen days after exposure (the average incubation has been shown to last around five days), and up to two weeks for symptom development.[5]
  • SARS-CoV-2 has unusually high pathogenicity. Virulence mechanisms of SARS-CoV-2 have been linked to the function of its structural proteins, which promote viral assembly and release. The four SARS-CoV-2 proteins include the envelope, membrane, nucleocapsid and spike (spikes on the viral surface that link to host receptors).[6],[7]
Each protein serves as an antigen that stimulates antibody response and increases cluster of differentiation 4 (CD4+)/CD8+ T cell responses.[8]
The envelope and membrane proteins have important functions in the viral assembly of a coronavirus, while the nucleocapsid protein is necessary for viral ribonucleic acid (RNA) synthesis.[9]
The spike glycoprotein of SARS-CoV-2 is responsible for virus binding and entry, utilising the spike S1 subunit to bind to their target cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed on the cell surface of epithelial cells of the lung, intestine, kidney, and blood vessels.[10],[11]
  • Viral non-structural proteins (NsP) are also able to block the host innate immune response, reducing immune defences against SARS-CoV-2.[12]

NsPs including Nsp1, Nsp3 and Nsp14, as well as open reading frame (ORF) 3b and ORF6 proteins, and the structural M and N proteins have been associated with impairment of the interferon system, with type I interferon critical to COVID-19 antiviral activity and clearance. Impaired antiviral interferon response, leading to a high viral load, is common in those with severe COVID-19 presentations including cytokine storm[13]

  • Viral entry and cell infection trigger the host’s immune response, with the inflammatory cascade initiated by antigen-presenting cells (APC). The process starts with the APC performing two functions
Presenting the foreign antigen to CD4+ T helper (Th1) cells.[14]
Releasing interleukin-12 (IL-12) to further stimulate the Th1 cell. Th1 cells stimulate CD8+ T killer (Tk) cells, which then target any cells containing the foreign antigen. In addition, activated Th1 cells stimulate B cells to produce antigen-specific antibodies.[15]
  • Patients infected with COVID-19 demonstrate elevated cytokine levels, consistent with an activated Th1 cell response, including IL-1β, interferon gamma (IFNγ), interferon gamma inducible protein 10 (IP10), monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1-α (MIP1-α).[16] Neutrophilia has also been found in both the peripheral blood and lung of patients with SARS-CoV-2.[17] Additionally, patients requiring intensive care unit (ICU) admission have shown higher concentrations of granulocyte colony-stimulating factor (GCSF), IP10, MCP1, MIP1-α, and tumour necrosis factor-α (TNFα) than patients that have not required ICU admission, suggesting that a cytokine storm may be associated with disease severity.[18]
  • SARS-CoV-2 is proposed to trigger NOD-like receptor 3 (NLRP3) inflammasome activation, which forms part of the innate immune response during lung infection. NLRP3 activation amplifies inflammation and exaggerates the immune response, which lead to cytokine storm development and subsequent progression to acute lung injury (ALI) and/or acute respiratory distress syndrome.[19]

Long COVID

  • Long COVID presents with a variety of symptoms, which can wax and wane over an extended period beyond infection resolution. Symptoms include fatigue, shortness of breath, body aches and pains, and cognitive deficits.[20],[21],[22]
  • Development of long COVID is not influenced by initial disease severity, pre-existing health condition or age.[23] In Australia, patients aged 20 to 39 years make up 40% of long COVID cases.[24]
  • Findings suggest that long COVID is caused by unchecked pro-inflammatory cytokine activity, rather than by the virus itself, resulting in ongoing neuroinflammation, central nervous system damage and neurological changes.[25] This can lead to mitochondrial and neuroendocrine dysfunction, explaining the presence of chronic fatigue and postural orthostatic tachycardia (POTs)[†] experienced by many patients with long COVID.[26] Comparisons have also been made between long COVID and mast cell activation syndrome (MCAS).[27]

 

2.0 Consultation Overview:

2.1 Identify Risk Factors

In Clinic Investigations- Refer to Key Drivers and the Clinical Investigation and Pathology sections below for further guidelines:

  • Use the decision tree (refer to Figure 1 in Identify Signs of COVID-19 section) or online symptom checker to determine if patient is suspected of having COVID-19 or presenting with signs of the condition. If infection is suspected, advise patient to seek immediate guidance from a medical professional or call the Coronavirus Health Information Line for advice (ph. 131 450).
  • Investigate travel history to determine if patient has recently travelled to an international high-risk area or visited local state and territory hotspots.
  • Assess if patient has recently been in contact with a confirmed case of COVID-19.
  • Avoid contact with potentially infected patient and implement appropriate personal hygiene and workplace sanitisation procedures to prevent viral spread (refer to Diet and Lifestyle Recommendations section and the Australian Government Department of Health guidelines).
  • If patient is confirmed as having COVID-19, you may be required to isolate yourself from the general population for up to 14 days to stop viral spread. Contact a medical professional or the Coronavirus Health Information Line for further advice (ph. 131 450).
  • To assess MCAS as a differential diagnosis for long COVID, use the MCAS Screening Questionnaire along with the MCAS treatment protocol.

2.2 Pathology Investigations- Refer to Key Drivers and the Clinical Investigation and Pathology sections below for guidelines:

If COVID-19 infection is suspected, immediately advise patient to contact a medical professional to arrange appropriate testing using the COVID-19 test kit. Practitioners that have come into contact with a confirmed COVID-19 case must also undertake immediate testing. Patients and Practitioners awaiting test results must return/stay at home until test results are confirmed.

 

2.3 Identify Signs of COVID-19

Symptom severity of COVID-19 varies, with mixed reports of severe flu-like symptoms in addition to milder presentations. Refer to Figure 1 for symptomatic comparisons between COVID-19, the common cold and the flu. Primary symptoms of COVID-19 to be aware of include:

  • Fever
  • Cough
  • Shortness of breath/breathing difficulties

Affected individuals may also experience additional flu-like symptoms including: 

  • Headache
  • Muscular stiffness and pain
  • Loss of appetite
  • Malaise/extreme generalised fatigue
  • Chills
  • Confusion
  • Dizziness
  • Rash
  • Night sweats
  • Gastrointestinal upset

 

Figure1 Common symptoms associated with COVID-19, the common cold and flu HealthMasters

Figure 1: Common symptoms associated with COVID-19, the common cold and flu.[28]

Individuals who have recently travelled to an international high-risk area, local hotspots or who have recently been in contact with a confirmed case are at an increased risk of developing COVID-19 and are advised to contact a medical professional for assistance. Refer to the Australian Government Department of Health for local state and territory outbreak information and travel restrictions.

 

3.0 Key Drivers:

  • Inadequate hygiene: Transmission of COVID-19 occurs when infected droplets are distributed via human-to-human contact, usually when a sick person coughs or sneezes. It may also spread via contact with contaminated objects, as human coronaviruses can remain infectious on inanimate surfaces for up to nine days.[29] Airborne spread has not been reported for COVID-19 and it is not believed to be a major driver of transmission.[30]
  • Immunocompromised: Individuals with compromised immunity/impaired immune response are at an increased risk of chronic or critical infections inducing multiple systemic effects, which elevates the risk of morbidity and mortality.[31] Increased antibody-secreting cells, follicular helper T cells, activated CD4+ and CD8+ T cells, and immunoglobulin M (IgM) and IgG antibodies during the early phase of infection are associated with clinical resolution.[32]Although there is limited information available regarding the impact of COVID-19 on immunocompromised individuals, experience from other respiratory viral infections, in particular influenza, suggests that persons with COVID-19 may shed detectable viral material and potentially infectious virus for an extended period of time, including beyond recovery.[33] Patients with cancer are more susceptible to infection due to their immunocompromised status caused by malignancy and anticancer treatments, such as immunosuppressive agents.[34] Additional immuno­com­pro­mised persons include those with congen­ital immunity deficien­cies, poorly controlled human immunodeficiency virus (HIV), solid-organ or stem cell trans­plant and autoim­mune disor­ders.[35]
  • Chronic medical conditions: Chronic illness can compromise immune function, increasing the susceptibility and severity of infection. In particular, people with heart disease and diabetes are at an increased risk of COVID-19 infection, in addition to poorer prognosis if they become infected. The expression of ACE2 receptor (the binding target of SARS-CoV-2) is substantially increased/upregulated in patients with type 1 or type 2 diabetes, and in those who are treated with angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type-I receptor blockers (ARBs). ACE2 expression can also be increased by thiazolidinediones and ibuprofen, often prescribed to patients with chronic illness. Consequently, the increased expression of ACE2 would facilitate infection with COVID-19 by increasing the number of viral entry points, thereby increasing viral load.[‡][36]
  • Immune exhaustion: T cell exhaustion is a hallmark of severe COVID-19,[37] with up to 85% of patients in this category present with lymphopaenia.[38] In this instance, the immune system is unable to mount an effective adaptive immune response against pathogenic infection, causing alterations in the T cell phenotype that diminish cytotoxic capacity.[39] ‘Exhausted’ T cells display increased levels of inhibitory receptors, including programmed cell death protein 1 (PD-1), leading to apoptosis and subsequent reduction in T cell numbers,[40] creating immune dysfunction that increases susceptibility and severity of COVID-19. T cell activity is essential for viral clearance and the subsequent inhibition of the innate immune system’s inflammatory state, as such, T cell exhaustion underpins the COVID-19 cytokine storm.[41] Comparatively, patients with mild presentations of COVID-19 display a robust adaptive response complete with T cell expansion.[42]
  • Microbiome disruptions: Functional changes in the microbiome, as well as the presence of opportunistic pathogens have been identified in COVID-19 patients, with up to 10% presenting with gastrointestinal symptoms.[43] Faecal metabolomics analysis has detected amino acid-related pathways that associate gut microbiota with inflammation and COVID-19 severity, with increased low-grade inflammation related to lower bacterial diversity. Complications of COVID-19 are more frequent in people with a pro-inflammatory condition.[44]
  • Stress: Long-term stress alters the hypothalamic-pituitary-adrenal (HPA) axis response and promotes an excessive release of pro-inflammatory cytokines. Chronic secretion of catecholamines, noradrenalin, adrenalin, and dopamine enhances the growth of pathogens[45]while also lowering natural killer (NK) cell activity,[46] thereby compromising viral immune defences.
  • Poor sleep quality: Sleep dysregulation is associated with increased C-reactive protein (CRP) and IL-6, reduced NK cell activity and cytotoxicity, lowered neutrophil phagocytosis, increased superoxide production, and diminished CD4+ T cell levels.[47],[48] These factors compromise the immune system and may lead to the development of critical and chronic infections.
  • Ageing: Older age is also associated with declined immune competence, increasing the susceptibility to infection. Impaired immune functions include reduced dendritic cell and T cell communication (lowering interferon secretion in response to viruses), diminished phagocytic capacity of neutrophils, reduction of new naïve T cells from thymus atrophy, and dysregulation in the differentiation of T cells into CD4+ and CD8+ memory T cells.[49],[50] 

 

4.0 Monitoring and responding to COVID-19:

  • If COVID-19 infection is suspected, advise patient to self-isolate from the general population for up to 14 days and seek immediate guidance from a medical professional. Refer to the above disclaimer for additional guidelines.
  • Avoid contact with potentially infected patient and implement appropriate personal hygiene and workplace sanitisation procedures to prevent viral spread (refer to Diet and Lifestyle Recommendations section and the Australian Government Department of Health guidelines).
  • If patient is confirmed as having COVID-19, you may be required to isolate yourself from the general population for up to 14 days to stop viral spread. Contact a medical professional or the Coronavirus Health Information Line for further advice (ph. 131 450).

 

5.0 Treatment Priorities:

  • Provide patient with immune-enhancing herbs and nutrients to stimulate immune defences, including innate and adaptive immune responses, and increase resistance against pathogenic virulence, infectious occurrence, and/or infection severity.
Please note, while clinical evidence supports the use of natural medicines for immune support, the below-listed recommendations are not intended to replace medical advice regarding treatment of COVID-19 and are not positioned to control infectious disease.
Caution: Immune-stimulating herbs are not recommended in severe cases of COVID-19 (which has been associated with immune system hyperactivation) or in instances of cytokine storm syndrome. For further information regarding possible interactions, please contact your practitioner.
  • Provide antioxidant and anti-inflammatory support to reduce airway tissue damage associated with COVID-19 respiratory pathogenesis, which can lead to long-term respiratory complications.
  • Ensure nutrient precursors for mitochondrial adenosine triphosphate (ATP) generation are replete to support energy levels and prevent viral-associated fatigue.
  • Support stress adaptation by minimising sympathetic nervous system activation and excessive glucocorticoid production, to minimise infectious susceptibility associated with maladaptive stress.
  • Provide patient with dietary and lifestyle interventions that promote rest and illness recovery.

 

6.0 Red Flags:

  • Acute respiratory distress syndrome (ARDS): In serious cases of infection, SARS-CoV-2 invades the cells that line the respiratory tract and lungs, causing pneumonia (Figure 2). Severe lung damage from pneumonia can result in ARDS, which in turn can cause septic shock – a leading cause of death in patients.[51] The severity of lung damage correlates with extensive pulmonary infiltration of neutrophils and macrophages, in addition to higher numbers of these cells in the peripheral blood in patients.[52] Individuals with COVID-19 pneumonia who develop ARDS demonstrate significantly higher neutrophil counts than patients without ARDS.[53] Patients with ARDS are likely already under hospital care however, if ARDS is suspected, call the Coronavirus Health Information Line for advice (ph. 131 450) or call triple zero (000) in an emergency (notify attendant of COVID-19 infection). 
  • Cytokine storm: SARS-CoV-2 can stimulate a cytokine storm in the lung, leading to ARDS, acute cardiac injury, secondary infection and/or death. This mechanism occurs via immune system hyperactivation in an attempt to neutralise the COVID-19 infection, producing a number of inflammatory mediators including IL-2, IL-6, IL-7, GCSF, IP10, MCP1, MIP1-α, and TNFα. An inflammatory cytokine storm can lead to oedema, dysfunction of air exchange and multiple organ failure.[54] Patients experiencing a cytokine storm will likely already be under the care of a medical Practitioner however, if a cytokine storm is suspected, call the Coronavirus Health Information Line for advice (ph. 131 450) or call triple zero (000) in an emergency (notify attendant of COVID-19 infection). Avoid contact with infected patient and implement appropriate sanitisation procedures (refer to Diet and Lifestyle Recommendations section) of skin and contaminated objects to prevent viral spread.

 

Figure2 Spectrum of severity and stages of COVID-19 HealthMasters

Figure 2: Spectrum of severity and stages of COVID-19.[55]

Key: ARDS: Acute respiratory distress syndrome; CS: Cytokine storm; LRTI: Lower respiratory tract infection; URTI: Upper respiratory tract infection; D8: Day 8; D16: Day 16.

 

7.0 Treatment Recommendations:

7.1 Core Recommendations

 

7.1.1 NK Cell Regulation

Dosage: Take 2 tablets daily with food.

Andrographis, green tea, zinc, and vitamins C and D to lower symptom severity and duration of acute respiratory tract infections via immune modulation, inflammatory regulation and viral control.

Mechanism of Action/Clinical Research:

  • Andrographis supports antiviral immunity via anti-inflammatory and antioxidant activities.[56],[57] Recent studies show that andrographis restricts inflammasome activation and IL-1b concentrations in tissues, while up-regulating the expression of nuclear factor erythroid 2–related factor 2 (Nrf2), therefore inducing protective intracellular antioxidant pathways.[58] Andrographolides are also shown to beneficially regulate pro-inflammatory cytokines, IL-2, IL-4 and IFN-g.[59],[60]
A meta-analysis concluded that andrographis significantly reduced cold and influenza symptoms and shortened illness by up to three days.[61]
Preliminary investigations indicate that 180 mg/d of andrographis (with unspecified andrographolides content) administered within 72 hours of a COVID-positive test result enhanced symptom improvement within three days without complications.[62] As such, andrographis may lessen symptoms associated with acute respiratory conditions.
  • Andrographis has been shown to stimulate both the antigen-specific and non-specific immune response, as well as increase NK cell activity, antibody-dependent cellular cytotoxicity and antibody-dependent complement-mediated cytotoxicity,[63] thereby supporting host immune defences.
  • Epigallocatechin-gallate (EGCG) from green tea has been found to improve the intracellular uptake of zinc through the formation of zinc ionophores,[64] leading to increased intracellular zinc concentrations, which inhibit the replication of several RNA viruses including rhinoviruses, influenza and coronaviruses.[65]
  • Zinc deficiency is associated with inflammasome activation and the expression of inflammatory cytokines.[66] Zinc is also integral for interferon production[67]; both key targets for COVID-19.
Evidence suggests that zinc deficiency correlates with higher rates of complications in COVID-19 patients including acute respiratory distress syndrome and mortality.[68]
A Cochrane review recognised that zinc supplementation, when taken for at least five months, reduced the incidence of colds.[69]

  

7.1.2 Cordyceps, Coriolus and Reishi for Immune Stimulation

Dosage: Add 1 level metric teaspoon (2.7 g) to 125 mL of water daily or as directed by your practitioner.

Medicinal mushrooms to stimulate cellular and humoral immunity, providing antiviral actions while increasing resistance to virulent infections and preventing infectious reoccurrence.

Mechanism of Action/Clinical Research:

  • Cordyceps, coriolus, reishi and shiitake activate the innate immune system, triggering the production of NK cells, lymphocytes, neutrophils, macrophages, and inflammatory cytokines.[70] Cytokine synthesis prompts adaptive immune processes to take effect, through the promotion of B cells for antibody production, and stimulation of T cells, which mediate cellular and humoral immunity.[71]
  • Cordycepin, from cordyceps, stimulates host defence mechanisms such as macrophage and phagocytic activity, up-regulates TNF-α, IL-6, IL-10, IL-12 and inducible nitric oxide synthase (iNOS), involved in the cellular immune response.[72]
  • Coriolus’ active constituent, polysaccharopeptide (PSP), initiates immune cell activation and pathogenic recognition, phagocytic activity of macrophages, expression of cytokines and chemokines including TNF-α, IL-1β, IL-6, and prostaglandin E2 (PGE2) production, and filtration of dendritic cells.[73]
  • Reishi has been shown to bind to cell surface receptors of immune cells, leading to alteration in the activities of macrophages, T helper cells and NK cells,[74] activate peripheral blood mononuclear cells,[75] promote lymphocyte proliferation and differentiation,[76] and inhibit viral replication.[77]

 

ALTERNATIVELY, if patient is in a high-risk population group:

7.1.3 AHCC and Ginger

Dosage: Take 2 capsules twice daily.

Active hexose correlated compound (AHCC) and ginger enhance immune function and surveillance, to support the immune system at times of chronic and serious infection.

Mechanism of Action/Clinical Research:

  • AHCC supplementation has been shown to improve T cell release of interferon,[78],[79] and improve viral clearance in humans[80] and animal models.[81],[82]
  • AHCC has been used in over 20 human clinical trials with results demonstrating enhanced dendritic cell populations,[83] increased cytokine expression of CD4+ and CD8+ T lymphocytes[84] and improved antibody synthesis in elderly patients to the influenza B virus.[85]
  • AHCC has been shown to increase interferon gamma (IFN-γ)-producing T cells and splenic T cell populations,[86] and enhance splenic natural killer NK cell cytotoxicity.[87],[88] AHCC lowers local cortisol levels and systemic levels of noradrenalin and cortisol,[89] while also intensifying local immune infiltration but lowering systemic leukocyte activity for a more controlled immune response.[90]

 

7.1.4 Vitamin D3

Dosage: Take 1 capsule daily with food or as directed by your practitioner.

Vitamin D to modulate the innate and adaptive immune responses, supporting immune function during infection.

Mechanism of Action/Clinical Research:

  • A significant negative correlation between vitamin D levels and COVID-19 cases was established in European countries.[91]
  • It is well known that vitamin D plays an important role in regulating immune function, with deficiency impacting the activity of T regulatory (Treg) cells,[92],[93] as well as the production of antibodies and regulation of dendritic cell function.[94]
  • Vitamin D enhances the adaptive immune response by increasing the differentiation of monocytes to macrophages and stimulating white blood cell proliferation, essential to the neutralisation or viral infections.[95]

A systematic review and meta-analysis investigating vitamin D supplementation (between 800 IU/d and 2,000 IU/d for periods spanning months to years) demonstrated a reduced risk of all acute respiratory tract infections.[96]

  • With receptors expressed on a wide variety of cell types, vitamin D is involved in the modulation of activated T and B lymphocytes.[97]
  • Vitamin D has been shown to regulate T helper cell function.[98]

 

7.1.5 Lactobacillus plantarum HEAL9, Lactobacillus paracasei 8700:2 and Lactobacillus rhamnosus LGG to Boost Immunity

Dosage: Take 1 capsule daily.

Strain specific probiotics, with proven human health benefits, to boost and regulate immunity.

Mechanism of Action/Clinical Research:

  • Studies have demonstrated Lactobacillus plantarum (HEAL9), Lactobacillus paracasei (8700:2) and Lactobacillus rhamnosus (LGG) all have the capacity to induce IL-10, a key anti-inflammatory and immunoregulatory cytokine, which is expressed by Tregs and T helper 2 cells.[99]
In a clinical trial, 898 participants who were frequently sick with colds were allocated to receive either 500 million colony forming units (CFU)/d each of Lactobacillus plantarum HEAL9 and Lactobacillus paracasei 8700:2 or a placebo for 12 weeks throughout winter. Compared to the placebo, the probiotic group experienced significantly fewer colds overall, as well as a 30% reduction in the incidence of repeated colds.[100]
A randomised, parallel, double-blind, placebo-controlled study involving 272 subjects supplemented with either 500 million each of HEAL 9 and 8700:2 or placebo for 12 weeks demonstrated a 28% reduction in the duration of their cold and a reduction in total symptom scores by 24%.[101]
  • LGG has been shown to protect against viral infection, including influenza, by stimulating respiratory NK cell activity, and upregulating antiviral IFN-γ.[102],[103]
  • L. plantarum (HEAL9) and L. paracasei (8700:2) have been shown to stimulate the innate immune responses.[104]

 

7.1.6 High Bioavailability Zinc with Vitamin C

Dosage:

Children 4 to 8 years: Acute: Add ¼ metric teaspoon (0.95 g) to 100 mL water once daily with food;

Children 9 to 13 years: Acute: Add ¼ metric teaspoon (0.95 g) to 100 mL water twice daily with food;

Children 9 to 13 years: Maintenance: Add ¼ metric teaspoon (0.95 g) to 100 mL water once daily with food.

Adults and children over 14 years: Acute: Add ½ metric teaspoon (1.9 g) to 200 mL water twice daily with food;

Adults and children over 14 years: Maintenance: Add ½ metric teaspoon (1.9 g) to 200 mL water once daily with food.

Zinc and vitamin C to support the development, function and mediation of immune cells required for viral defence.

Mechanism of Action/Clinical Research:

  • Vitamin C supplementation has been shown to reduce the duration and severity of colds[105] and is increasingly efficacious when combined with zinc, with deficiencies of vitamin C and zinc both severely suppressing immune responses.[106]
  • Vitamin C stimulates white blood cell production and function, enhances NK cell activity and chemotaxis, supports clearance of spent neutrophils from sites of infection, increases serum levels of antibodies, and augments lymphocyte differentiation and proliferation, facilitating innate and adaptive immune responses.[107]
  • Zinc is involved in several aspects of immunological function, including the development, function and mediation of immune cells, such as neutrophils, monocytes and NK cells. Zinc also affects the development of acquired immunity and T lymphocyte function.[108]

 

7.1.7 Specialised Pro-Resolving Mediators[§] 

Dosage: 1 capsule twice daily.

Specialised Pro-resolving Mediators (SPMs) to support antiviral immunity and manage underlying systemic inflammation, which is associated with delayed viral clearance and prolonged inflammation.

Mechanism of Action/Clinical Research:

  • SPMs encourage resolution by regulating macrophage polarisation. SPMs trigger the switch from pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages, reducing inflammation and tissue damage, and promoting resolution. Additionally, M2 macrophages have been shown to inhibit polymorphonuclear neutrophils (PMNs) and promote efferocytosis and tissue repair.[109]
  • SPMs inversely correlate with biological activity and dissemination of viral cells.[110]
  • The resolvin E1 receptor (ERV1) has been shown to contribute to antiviral immunity and recognition of impaired lung responses to viral pneumonia.[111]

 

7.2 Additional Considerations:

If presenting with long COVID:

7.2.1 BCM-95 Turmeric and Saffron for Depression

Dosage: Take 1 capsule twice daily with food.

Anti-inflammatory herbs, BCM-95 turmeric and saffron, to combat neuroinflammation, which drives long-COVID associated neurological changes.

Mechanism of Action/Clinical Research:

  • Saffron and BCM-95 Turmeric impede the activity of transcription factors, including mitogen activated protein kinase (MAPK) and the master controller of inflammation, nuclear factor kappa B (NFκB),[112],[113] therefore modulating inflammation.
  • Saffron and turmeric inhibit pro-inflammatory cytokines including TNF-α, IL-1β and IL-6, which can disrupt neurotransmitter metabolism, leading to dysfunction within neurotransmitter systems that contributes to neuroinflammation.[114],[115]
  • Active constituents found in saffron, including crocin-1, crocin-2, crocin-3, crocin-4 and crocin-5, enhance neuroprotection via down-regulation of microglial activation and proliferation.[116]

 

7.2.2 Enhanced Bioavailability Ubiquinol for Energy and Cardiovascular Health

Dosage: Take 1 capsule daily with food.

Active ubiquinol (CoQ10) to support ATP production, enhancing cellular energy to reduce viral-associated fatigue.

Mechanism of Action/Clinical Research:

  • CoQ10, in both its reduced (ubiquinol) and oxidised forms (ubiquinone), is involved in oxidative phosphorylation, facilitating ATP production within the mitochondria.[117],[118]

CoQ10 (100 mg/d for three months) prescribed to women with chronic fatigue significantly improved fatigue and exercise tolerance in 90% of supplemented participants,[119] while 150 mg/d of CoQ10 over 12 weeks demonstrated improvements in autonomic nervous function, cognitive function, sleep quality and depressive symptoms.[120]

  • CoQ10 also functions as a membrane antioxidant, therefore protecting the mitochondrial membrane from oxidation and lipid peroxidation.[121],[122]

 

7.2.3 Mental and Physical Energy Powder

Dosage: Add 2 level scoops (9.5 g) to 200 mL of water, twice daily.

A magnesium and B vitamins required for energy production and oxidative phosphorylation, to reduce the effects of physical and mental fatigue.

Mechanism of Action/Clinical Research:

  • Magnesium is a critical cofactor for ATP manufacture within the electron transport chain, which generates phosphorylation reactions. Magnesium ions support cellular bioenergetics through interactions with phosphorylated molecules and by influencing the kinetics of ion transport across plasma membranes.[123]
  • Phosphate (-PO43-) is required for the generation of ATP (adenosine combined with three phosphate groups), providing high-energy phosphate bonds that, when hydrolysed, release energy required for cellular processes.[124]
  • Carnitine assists in the transport of fatty acids across cell membranes, particularly in muscle tissues, for use as an energy source. It is essential for mitochondrial fatty acid oxidation, the primary fuel source for the heart and skeletal muscle.[125]

4 g/d of carnitine has been shown to reduce both physical and mental fatigue in a randomised, double-blind, clinical trial involving 96 subjects prescribed acetyl-L-carnitine for 180 days.[126]

  • Nicotinamide (vitamin B3) is essential for many biosynthetic pathways including oxidative phosphorylation.[127]
  • Pantothenic acid (vitamin B5), as part of coenzyme A, participates in the metabolism of carbohydrates, lipids and protein. It also plays a role in cellular respiration, the oxidation of fatty acids and acetylation of other molecules.[128]
  • Mecobalamin (vitamin B12) has several key roles, including cell growth and replication; metabolism of carbohydrates, lipids and proteins; nucleic acid synthesis and red blood cell production.[129]

 

7.2.4 Vitamins B5, B6 & C for Stress and Adrenal Health

Dosage: Take 1 tablet twice daily with food.

Activated B vitamins combined with vitamin C to support neurotransmission and steroid hormone synthesis, regulate HPA axis activity (adrenaline, noradrenaline and cortisol synthesis) and modulate the sympathetic and parasympathetic arms of the stress response in fatigued individuals.

Mechanism of Action/Clinical Research:

  • Vitamin B5 forms part of coenzyme A (CoA), which is essential for the production of acetylcholine[130] (a neurotransmitter involved in brain and muscle function). CoA is also required for the synthesis of steroid hormones including cortisone.[131]
  • Vitamin B6, is a vital cofactor for transaminase enzymes, which are fundamental in the creation of gamma-aminobutyric acid (GABA), dopamine, histamine and serotonin.[132] Research also suggests that vitamin B6 diminishes sympathetic output and acts peripherally to blunt the physiological impact of corticosteroids.[133]
  • Biotin (vitamin B7) is an important cofactor for the enzyme pyruvate carboxylase, which is involved in cortisol production.[134]
  • Vitamin C is involved in dopamine production and is a necessary cofactor for the activity of enzyme, dopamine B-hydroxylase (dBh).[135]

 

If presenting with symptoms of gastrointestinal dysfunction:

7.2.5 Glutamine & Boswellia (Bospure® Boswellia) for Intestinal Integrity

Dosage: Add 2 level scoops (7.7 g) to 200 mL water twice daily with food, or as directed by your healthcare professional.

Anti-inflammatory herbs, boswellia and aloe vera, glutamine, arabinogalactan and zinc to support gut integrity, protect the gastrointestinal mucosa and assist microbiome health, enhancing the mucosal immune response and increasing infection resistance.

Mechanism of Action/Clinical Research:

  • Aloe has been shown to promote the rapid repair of damaged membranes in the gastrointestinal tract.[136]
  • Boswellic acid compound, acetyl-11-keto-beta-boswellic acid (AKBA), acts as a potent antibacterial against gram-positive pathogens, with an ability to disrupt the permeability barrier of microbial membrane structures. AKBA has also demonstrated an inhibitory effect against the growth of microbial biofilms, particularly the growth of staphylococcus-containing biofilms.[137]
  • Glutamine serves as a precursor for nucleotide synthesis in rapidly dividing cells, including intestinal cells, therefore supporting healthy cellular reproduction and decreasing intestinal permeability.[138]
  • Larch arabinogalactans act as a prebiotic, enhancing beneficial gut microflora such as bifidobacteria and lactobacilli. Arabinogalactans are fermented by intestinal bacteria to create short-chain fatty acids (SCFAs), particularly butyrate, which act as a fuel source for epithelial cells, aiding their replication and integrity, while supporting intestinal health and barrier function.[139]
  • Zinc is involved in the initial step of epithelial wound healing, a process called epithelial cell restitution.[140]

 

If presenting with stress or anxiety:

7.2.6 Herbal Support for Hyper HPA and Stress

Dosage: Take 1 tablet three times daily. 

Zizyphus, passionflower, kudzu and magnolia to enhance GABA activity and work against glutamate-mediated excitability in the brain,alleviating anxiety, nervous tension and agitation. These symptoms, associated with a dysfunctional HPA axis response, compromise immune defences and increase infectious susceptibility and severity.

Mechanism of Action/Clinical Research:

  • Zizyphus has been shown to modify the GABAα receptor subunits expressional levels,[141] which opposes glutamate-mediated excitability in the brain, contributing to its anxiolytic effects.[142]
  • Passionflower has been found to modulate the GABA system, demonstrating an affinity for both GABAα and GABAβ receptors, increasing its inhibitory effects.[143]

A clinical trial involving 154 participants with prolonged nervous tension were treated with 1,020 mg/d of passionflower for 12 weeks. Passionflower significantly improved stress-associated symptoms including restlessness, sleep disturbances, exhaustion, anxiety, poor concentration, nausea, tremors, and palpitations.[144]

  • Kudzu has demonstrated β-adrenoceptor blocking activity[145],[146] similar to pharmacological beta-blockers, which are used to reduce the physical effects of anxiety and stress such as palpitations, high blood pressure, tremor and sweating.
  • Magnolia exhibits muscle relaxing effects via GABAergic mechanisms,[147] as well as neuroprotective properties.[148],[149]

 

8.0 Diet and Lifestyle Recommendations:

8.1 Lifestyle

Practising good hand and sneeze/cough hygiene provides the best defence against viral infections. These include:

  • Washing your hands frequently with soap and water, before and after eating, and after going to the toilet.
  • Covering your mouth and nose when coughing and sneezing, immediately disposing of tissues and using alcohol-based hand sanitiser.
  • If unwell, seek immediate guidance from a medical professional. You may be advised to isolate yourself from the general population for up to 14 days to stop viral spread.

The World Health Organisation (WHO) have issued the following general recommendations:

  • The most important strategy for the populous to undertake is to frequently wash their hands, use portable hand sanitiser and avoid contact with their face and mouth after interacting with a possibly contaminated environment.[150]
  • Avoid close contact with subjects suffering from acute respiratory infections.[151]
  • Avoid unprotected contact with farm or wild animals.[152]
  • People with symptoms of acute airway infection should keep their distance, cover coughs or sneezes with disposable tissues or clothes, and wash their hands.[153]
  • Individuals that are immunocompromised should avoid public gatherings.[154]
  • Healthcare workers caring for infected individuals should utilise contact and airborne precautions to include personal protective equipment (PPE) such as N95 or FFP3 masks, eye protection, gowns, and gloves to prevent transmission of the pathogen.[155]
  • Adequate sleep is essential to optimal immune function, required to prevent/overcome infection. Refer to Figure 3 for guidelines regarding sleep requirements relative to age.

Figure3 Sleep requirements across the lifespan HealthMasters

Figure 3: Sleep requirements across the lifespan.[156]

 

8.2 Diet

  • If suffering from viral infection, nutrient-rich foods consistent with a wholefood diet, such as high intake of fruits and vegetables, lean protein, quality essential fatty acids, and wholegrains (limiting starchy grains and vegetables), may optimise immune function by increasing protection against inflammation and immune activation.[157]
  • Dietary patterns high in refined starches, sugar, and saturated and trans-fatty acids, poor in natural antioxidants and fibre from fruits, vegetables, and whole grains, and poor in omega-3 fatty acids may cause an activation of the innate immune system, most likely by excessive production of pro-inflammatory cytokines associated with a reduced production of anti-inflammatory cytokines.[158]
  • Current evidence suggests that the Mediterranean diet provides protection against several diseases associated with inflammation and immune activation.[159]
  • The Metagenics Wellness Diet reflects the wholefood principles of the Mediterranean diet and also provides a simple guide to moderate portion size and the overall balance of macronutrients.
  • Increase intake of microbiome-enhancing foods to nourish commensal gut flora and enhance gut-associated immunity. Refer to the Metagenics Microbiome Enhancing Foods list for dietary recommendations.
  • Supplement diet with easily digestible foods with high nutritional value such as soup, stew and bone broth.

8.3 Long COVID

Pacing is recommended for patients experiencing long COVID symptoms to help manage energy, reduce fatigue and post-exertional malaise (PEM).

There are two elements of pacing:

  • Pre-emptive rest: Involves planned rest periods to minimise drops in energy.
  • Reduced activity/pacing intervention: Where individuals are lying still with their eyes closed, not engaged in any activities or distractions around them.

In addition to the above strategies, it is important for individuals to stay below their anaerobic threshold to prevent overexertion and PEM. Methods of calculating individual anaerobic threshold include:

  1. Estimated maximum heartrate, measured by subtracting age from 220 (e.g. 220 – 50 years = 170 beats per minute). Use a heart rate monitor or a smartwatch to ensure patient remains below maximum heart rate.
  2. Treadmill stress test. Refer patient to a General Practitioner for assessment if a stress test is indicated.
  3. Monitor/prevent increases in resting heart rate, which can be assessed by using a heart rate monitor/smartwatch or by counting the number of beats in 15 seconds and multiplying by four (measure before getting out of bed in the morning).

8.4 Additional tips to assist with managing energy:

  • Be mindful of activities associated with PEM (Figure 4).
  • Prioritise activities.
  • Delegate tasks.
  • Break activities into smaller chunks.
  • Ensure ergonomic support to prevent poor posture, which can lead to muscle tension and use of unnecessary energy.
  • Create resting stations in instances that require long-distance travel or physical exertion (e.g. climbing flights of stairs).
  • Use mobility aids.

 Figure4 Top triggers of post-exertional malaise in long COVID patients. HealthMasters

Figure 4: Top triggers of post-exertional malaise in long COVID patients.[160]

 

9.0 Clinical Investigation and Pathology:

Clinical Screening

  Rationale

Case Taking If patient presents with fever, cough and shortness of breath/breathing difficulties, has recently travelled to an international high-risk area or local state and territory hotspot or has recently been in contact with a confirmed case, consider possibility of COVID-19 infection and advise patient to seek immediate guidance from a medical professional.
Metagenics MCAS Screening Questionnaire The MCAS Screening Questionnaire is based on peer-reviewed research that identifies and calculates the likelihood of MCAS based on clinical signs, triggering factors, laboratory parametres, imaging methods and medical history.

 

Pathology Testing

Ideal Reference Range

Rationale

COVID-19 Test Kit

Refer to laboratory reference ranges If COVID-19 infection is suspected, advised patient to immediately contact a medical professional to arrange appropriate testing.

 

10.0 Pharmaceutical Treatments:

*Contact your practitioner to ensure product recommendations are suitable for use in conjunction with pharmaceutical medications.

  • Oxford-AstraZeneca vaccine: A viral vector vaccine that uses a modified, low-pathogenic virus, such as adenoviruses, parvoviruses or paramyxoviruses, to function as a vector that shuttles the COVID antigen into host cells, inducing an immune response against the target pathogen.[161]

  • Pfizer vaccine: A nucleic acid-based vaccine (genetic vaccine) consisting of messenger ribonucleic acid (mRNA) sequences, which translate proteins that induce an immune response and code for a COVID-specific antigen.[162],[163]

Analysis of data from Israel suggests that the Pfizer vaccine is up to 90% effective by day 21, with a corresponding reduction in new COVID-19 infections and decreased moderate to severe presentations.[164]

While side effects are common with any vaccination, the majority of those associated with Oxford-AstraZeneca and Pfizer vaccines have been transient and an expected result of immune activation, including injection site pain, fatigue, headache and myalgia, with serious side effects being extremely rare.[165],[166] Refer to the Vaccination Support treatment protocol for general information regarding vaccination.

  • Corticosteroids: Corticosteroids are utilised for treatment of patients with severe illness/ARDS, reducing inflammatory-induced lung injury. However, current evidence in patients with SARS and MERS suggests that receiving corticosteroids has no effect on mortality, but rather delays viral clearance.[167]

 

11.0 Additional Resources:

  • Support groups for long COVID include:
Body Politic COVID-19 Support Group - https://www.wearebodypolitic.com/covid19
Long COVID Facebook group - https://www.facebook.com/groups/longcovid
COVID-19 Recovery Awareness – https://www.c19recoveryawareness.com
Long COVID Support - https://www.longcovid.org/
  • Research and data collection:
Survivor corps - https://www.survivorcorps.com/
COVID Symptom study - https://covid.joinzoe.com/

 

12.0 Footnotes:

[*] At the time of writing: March 2021

[†] POTs is a disorder of the autonomic nervous system characterised by an abnormal increase in heart rate that occurs when sitting upright or standing up (caused by excessive pooling of blood below the level of the heart when upright). Associated symptoms include severe fatigue, lightheadedness, brain fog, heart palpitations, nausea/vomiting, headaches, and excessive sweating.

[‡] At the time of writing, the Therapeutic Goods Administration (TGA) has issued an alert that states there is currently no published, peer-reviewed scientific evidence tying severe presentations of COVID-19 with ibuprofen.

[§] Ensuring patients maintain an omega-3 index above 8% is essential to SPM production. Omega-3 status can be evaluated/monitored using the Omega-3 Index Test (refer to Pathology Testing section). In the instance of deficiency, consider co-prescribing High Purity, Low Reflux, Concentrated Fish Oil Liquid or Capsules.

 

13.0 References:

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Monitoring and responding to COVID-19

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