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COVID-19: A once in a generation pandemic

Caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2)

As of the 15th July 2021 total cases world wide 187,827,660, deaths worldwide 4,055,497 and global population who have received at least one vaccination 25.8%.

COVID-19 affects multiple organ systems such as cardiac, endocrine, dermatalogical, thromboembolism, gastrointestinal, hepatic, renal and neurologic. COVID-19 damages multiple organs as a result of

- Direct viral toxicity

- Endothelial cell damage

- Thrombo-inflammation

- Immune system dysfunction

- Renin-angiotensin-aldosterone system dysfunction

The COVID-19 'Cytokine Storm' means an incredible systemic inflammatory process and hits us where we are susceptible and for some us it is in the lungs, others in the heart. Cytokine storm is the reason why people get so ill with COVID-19 infections. There are key inflammatory cytokines that we as practitioners are looking at to evaluate whether or not your inflammatory process is out of control

1). InterLeukin 6

2) TNF a

Understanding what your susceptibility is to these inflammatory markers is incredibly important!

When the virus enters the body it enters our cells thru the spike protein and the ACE2 receptor and it needs this TMPRSS2 to get into the cell. When it does that it has a direct cytotoxic effect and this causes all the viral cell damage. It the can have an effect on the Angiotensin system and this is the cardiovascular side of things when we get tissue injury, inflammation, tightening of the arteries and vascular permeability. So there is fluid leakage into the cells of the vascular system. We can then get cell damage and release of this inflammatory cytokines. The InterLeukin 6 (IL-6) and TNFa are definitely the most important in terms of being able to regulate.

POST-ACUTE COVID-19 SYNDROME ('LONG COVID') is persistent effects of COVID-19 infection lasting 3-4 weeks. Studies in China have shown have shown patients having symptoms 6 months after infection. And alot of people getting these signs and symptoms can go on for a year and some people who got COVID early last year when it first appeared in March they are still having significant issues. When we look at the research a meta-analysis of 45 long COVID-19 studies (approximately 10,000 patients) found that nearly 75% of patients had at least one persistent symptom:

- 40% Fatigue

- 36% Shortness of breath

-24% Loss of sense of smell

-22% Anxiety

- 17% Persistent cough

This can be quite significant the older you get and the more morbidities you have, the more likely you are to have some of these effects.

An interesting hypothesis in April they think the long COVID is a methylation deficiency. When you look at the signs of symptoms of low B12 they are not dissimilar to some of the signs and symptoms you see in COVID. There hypothesis was the COVID infection changes our methylation cycle and the availability of our methyl groups which makes us less likely to deal with the effects and methyl group assault. So the authors of this paper was saying you get oxidative stress that ends up stopping the methionine synthase (this is the enzyme that uses B12, picks up our folate and help makes our S-adenosylmethionine (SAM). SAM really drives our metabolic processes and particularly the availability of SAM and if its been stolen away from our glutathione production it means we have an increase in oxidative stress.

3 hypotheses on the effects of SARS-CoV-2 infection on SAM supply:

  1. COVID 'Cytokine Storm' - causes significant oxidative stress. Oxidative stress inactivates methionine synthase and oxidises cobalamin

  2. Viral Replication- Increased viral replication depletes cellular methyl groups and one-carbon availability

  3. Disrupted remethylation and transsulfuration- SARS-CoV-2 depletes intracellular SAM

Not everyone is affected by COVID-19 the same way. Known risk factors are older co-morbidities such as diabetes, obesity, cardiovascular and cerebrovascular diseases. Genetics plays a pivotal role in determining susceptibility or resilience to viral infections.

Scientists believe there a 3 potential genetic gateways to COVID infection

  1. Polymorphisms or mutations in the Angiotensin-converting enzyme 2 (ACE-2) gene. It is really the ACE-2 that allows the virus to get into the cells and so polymorphisms or mutations in the ACE-2 gene can actually change the way the virus gets into the cell and makes you more susceptible and will also effect the way you deal with inflammation.

  2. Human Leukocyte antigen (HLA) genes are responsible for our ability to fight our immune system.

  3. Activation of Toll-like receptors and complement pathways which actually controls our inflammation and immune activation.

Therefore, need a very good level of Vitamin D to deal with immune system.

MTHFR regulates homocysteine levels in the body. MTHFR predisposes people to having an elevation an homocysteine levels in the body and therefore we are working to try and get this under control. The theory is because MTHFR effects homocysteine. Homocysteine unable to be recycled, the homocysteine builds up and when it builds up, it causes systemic inflammation and that will accelerate the viral infection. So it is absolutely critically important that everyone is evaluating there homocysteine levels. It is a risk factor for cardiovascular issues and so at worst we need to be making sure we keep it under good levels. Another research study looked at 273 patients with mild COVID-19. If your homocysteine levels was greater than 15.4 umol/L you were 3 times more likely to progress to a more problematic form of COVID. So it is important to check homocysteine levels whether you have been vaccinated or not. Some countries where there are high percentages of MTHFR polymorphisms there are more deaths eg. Latino, European (non-Finnish), East Asian, South Asian and African.

New evidence shows that COVID-19 may be airborne, not droplet transmission!

One of the things we do need to accept now it is an airborne transmission, it is droplet and therefore we need to take precautions that will allow us to avoid droplets. The difference between droplet and airborne transmission.

- Droplet Transmission- Coughs and sneezes can spread droplets of salvia and mucus

- Airborne Transmission- Tiny particles, possibly produced by talking, are suspended in the air for longer and travel further

As a result vaccinations become more crucial.

There are 19 different vaccines and as time progresses we will have more and more vaccines as the virus changes. Some vaccines have been approved, others are waiting approval. Many vaccines need to be evaluated before a successful candidate is found.

How are Vaccines made?

There are 3 main approaches to making a vaccine.

  1. Whole- microbe- Inactivated, live-attenuated, viral vector- triggers an immune response.

  2. Subunits- parts of the vaccine used to trigger an immune response

  3. Genetic approach- nuclei acid vaccines uses genetic material from the virus that provides instructions for certain proteins to be made

Currently available vaccines and mechanisms of action

1. Viral Vector Viruses eg.Astra Zeneca, Johnson & Johnson, Sputnik v

Viral Vector Viruses is inserting the DNA in a virus to exploit the viruses ability to infect the MRNA. In the case of Astra Zeneca they use a chimpanzee adenovirus. They believe this has less cross reactivity with human cells, if they don't use a human adenovirus. Johnson & Johnson and Sputnik V, both use human adenoviruses.

A viral vector vaccine- instructions for the COVID-19 spike protein is placed inside adenovirus (Chimpanzee). Stimulates our body to produce surface spike proteins, priming the immune system to attack the virus if exposed later. Phase 1 clinical trials started on April 2020 in the UK and Brazil. Authorized in Europe on January 12 2021. Requires 2 doses, 28 days apart. Johnson and Johnson not as effective. Astra Zeneca has been tarred with the blood clot incidences and the European Medicines Agency (EMA) in March decided it was enough to suspend the vaccine and we need to do a little bit more research. As a result it is important to look at inflammatory markers and clotting agents and what your clotting may or maybe especially if you have a family history and your homocysteine levels. We also have to remember that COVID-19 the virus does increase the risk of clotting. Triggers a hyperinflammatory response, activates platelets, having a direct effect on clotting.

2. Messenger RNA vaccines eg. Pfizer, Moderna

The MRNA vaccines Pfizer and Moderna are 2 inactivated virus vaccines.

3. Inactivated Virus Vaccines eg. Sinovac, Sinopharm, Bharat Biotech

These are the vaccines based on killed microorganisms, but they are inactivated.

4. Protein Subunit eg. Novavax

They are just starting novavax now and these vaccines are based on the proteins present on the surface of microbes. In the case of novavax, they have a protein carrried by nano particles and the protein is made using moth cells and angiovan which is a tree bark. It is an ingredient in the vaccine which makes it have a greater immune response and that's how alot of the vaccines typically work.

The hypothesis is some sort of autoimmune pathology that is causing immune cells to react aberrantly and it could also be those people who have exposed to the virus already maybe the ones more at risk. Absolute risk according to the statistics in vaccinated individuals is 4.1 million (Pfizer, Moderna), 5 millon had CVST (AZ) and with the COVID virus itself it jumps up to 39 million. The risk is there either way, whether you get the virus or vaccinated. But greater in the virus itself.

Why are COVID-19 variants significant?

More than 4000 variants have been identified. Not are all clinically.

The Alpha, Beta, Gamma and Delta variants are variants of concern, implying that they:

- Have increased transmissibility

- Causes more severe disease

- Significantly reduce ability of antibodies acquired previously during infection or vaccination to neutralize them

- Reduce effectiveness of treatment or vaccines

- May not be detected with current methods

Pfizer is 89.5% effective against Alpha variant. 75% effective against BETA variant and 88% effective against Delta variant.

AZ is 66% effective against the Alpha variant. 10.4% effective against the BETA variant and 59.8% effective against the Delta variant.

As of 20th July 2021 the DELTA variant has been reported in over 124 countries. The DELTA variant is prevalent in >75% of sequenced cases in several countries around the world including Australia. Currently in NZ there are no community cases.

Why is the Delta Variant significant?

- Viral load for Delta variant 1200x higher

- Delta variant replicates faster and is more infectious

- 120% increase in risk of hospitalization, ICU admission and death

- Increased risk of reinfection

Vitamin D is a known immune response regulator. Enhances both the innate and adaptive immune systems. Vitamin D may suppress chronic immune activation. Limits dendritic cell mutation. Switches T cell profile from pro- (Th1, Th17) to anti-inflammatory (TH2, Treg)

Other Herbs to Consider:

- Tumeric (curcumin) and ginger- anti-inflammatory

- Licorice- show to be more effective than common antivirals in inhibiting the replication of the SARS virus.

- Ashwaganda (withania) has a natural phytochemical which will effect on viral receptor binding domain and host ACE2 receptor complex and therefore may be good to curb COVID.

- Studies comparing hydroxychloroquine, quercetin, hispidulin, artemisia and curcumin show that these compound have better potential inhibition than hydroxychloroquine.

Important Treatment Strategies

- Reduce the cytokine storm and regulate CD4+ and CD8+ regulation- decreases in these are associated with severe COVID 19- Vitamin D

- Reduce IL-6, TNF-@, IL-8, Leptin and adiponectin as these exacerbate the inflammatory response. (Vitamin D also inhibits IL-6)

- Assess homocysteine levels

- Assess MTHFR

- Take key nutrients that reduce inflammation- quercetin, zinc, selenium if low, Vit D

- Melatonin if you get COVID

- Nasal spray

- Masks, social distancing and handwashing


- Elderly more prone- decreases ability to fight infection, diminished response to the vaccine, increased prevalence of autoimmunity and low grade inflammation

- Microbiota- it shapes the immune system in the gut. Respiratory tract microbiota influences the host immune responses to the virus

- Diet- higher anti-inflammatory vs pro inflammatory nutrients (polyphenolics in fruit and vegetables)

- Vitamins- D,A,C, Selenium, Zinc ( deficiency impairs immunity, antiviral immunity)


-COVID-19 infections have the potential to cause severe long term effects even after apparent recovery

- Vaccinations avoiding hospitalizations particularly with the new variants like Delta

- Getting a vaccine does not stop you getting the virus

- Long term MRNA effects still unknown

- Fertility risks unknown

- If you get the vaccine and if you don't you need to do your due diligence.

- Inflammation is key.

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