COVID-19: ARDS, CYTOKINE STORM, and GLUTATHIONE

My good friend Dr. Deborah Gordon recently sent me a terrific article on an Integrative Medicine Approach to Covid-19. It confirmed much of what I have discussed about COVID-19 and provides 383 scientific references (many of which were cited in my previous posts). Thank you Dr. Deborah!

In my last post I promised to write about glutathione and cytokine storm.

Cytokines are proteins made by our immune system. When our body suffers an infection, cytokines act as essential signaling proteins that produce a defensive inflammatory response. In a cytokine storm the usual regulatory process that helps resolve inflammation becomes disturbed and self destruction can occur.

With COVID-19 this can happen in any organ of the body but frequently starts in the lungs, resulting in ARDS (Acute Respiratory Distress Syndrome).

In most clinical contexts the mortality rate of ARDS is 40-45%. In the context of COVID-19 it is 80-90 % lethal in most clinical reports (twice the usual mortality rate for ARDS). However, the ICU doctors in the Northwell Hospital system in NYC have been using NAC (n-Acetylcysteine).

While using NAC as part of their treatment protocol of COVID-19 associated ARDS, they are getting 50% of patients off the ventilator with a significant reduction in mortality rates compared to previous reports (personal communication with a Northwell physician and also mentioned in the Review Article cited above.)

This drug (also available as a dietary supplement) has been used for decades to treat acetaminophen (APAP) overdose (Tylenol brand name, also called paracetamol in Europe). If not treated early APAP overdose commonly causes death from liver failure.

Chronic acetaminophen toxicity is the most common cause of liver failure leading to liver transplant in the US.

How does this treatment  with NAC work in the setting of APAP overdose?

“When paracetamol is taken in large quantities, a minor metabolite called N-acetyl-p-benzoquinone imine (NAPQI) accumulates within the body. It is normally conjugated by glutathione, but when taken in excess, the body’s glutathione reserves are not sufficient to deactivate the toxic NAPQI. This metabolite is then free to react with key hepatic enzymes, thereby damaging liver cells. This may lead to severe liver damage and even death by acute liver failure.”

NAC (n-acetylcysteine) provides cysteine, one of the three amino acids that make up glutathione.

“glutathione synthesis is primarily controlled by the cellular level of the amino acid cysteine, the availability of which is the rate-limiting step.”

So by providing a source of cysteine, the body produces more glutathione which can detoxify the liver damaging metabolites of APAP.

Glutathione is our MASTER ANTI-OXIDANT. Since a cytokine storm involves an overwhelming amount of oxidative stress, glutathione is obviously important.

Clinical research in the 1990s established that the lungs of patients with ARDS are very deficient in glutathione.

A profound 20 fold reduction was confirmed in this study.

“Glutathione is a tripeptide that is able to react with and effectively neutralize oxidants, such as hydrogen peroxide. The present study found that the alveolar epithelial lining fluid of patients with ARDS was deficient in total glutathione compared with that of normal subjects (31.5 ± 8.4 versus 651.0 ± 103.1 µM, p = 0.0001) and patients with cardiogenic pulmonary edema (31.5 ± 8.4 versus 154.1 ± 52.4 µM, p = 0.001). In addition, a greater percentage of total glutathione was in the oxidized form in patients with ARDS compared with normal subjects (30.6 ± 6.1 versus 6.4 ± 2.9%, p = 0.03). This deficiency of reduced glutathione in the alveolar fluid may predispose these patients to enhanced lung cell injury.

Subsequent studies of humans with ARDS on ventilators showed clinical benefit by increasing glutathione levels with NAC.

“In our controlled clinical trials with NAC we found that patients with ARDS have depressed plasma and red cell glutathione concentrations, that these levels are substantially increased by therapy with intravenous NAC and there are measurable clinical responses to treatment with regard to increased oxygen delivery, improved lung compliance and resolution of pulmonary edema.”

Despite these findings decades ago, the use of NAC for ARDS has not been widely adopted. But it would make sense to employ this inexpensive medication, widely used for APAP overdose, for ARDS and in particular for cytokine storm caused by COVID-19.

Oxidative stress decreases glutathione levels and if these levels reach a critically  low level in tissues, organ damage can ensue rapidly. Cytokine storm is the extreme example.

Chronic alcohol abuse also decreases protective glutathione levels in the lung.

In my recent posts on COVID-19 I have pointed out that alcohol (even 2 drinks) suppresses the immune system for at least a few days. Alcohol consumption is a double hit, first as an immune suppressant, then as a major source of oxidative stress and reduction in protective glutathione levels. Two glasses of wine tonight followed by a COVID-19 sneeze in your face the next day could be the difference between an effective immune response (mild symptoms) versus an overwhelming life threatening infection!

Likewise, one night of inadequate sleep (which immediately suppresses immunity) followed by a COVID sneeze in your face the next day could have the same deleterious effect.

Below is a chart from the review article mentioned at the start of this post. Notice the top line states “ADDRESS SLEEP, STRESS, DIET, SUGAR, ALCOHOL

If you have been reading my posts on COVID-19, you have heard this before.

integrative medicine chart

Notice the second row in the chart with escalating doses of NAC as intensity of disease increases. When cytokine storm hits NAC dose recommendations peak and glutathione (available for IV administration) is recommended. IV glutathione surprisingly is not part of most hospital formularies and I have never seen it used in a hospital setting. Functional medicine physicians sometimes use it outside of the hospital setting. IV glutathione has become a sexy and lucrative office procedure in some functional medicine practices.

NAC has high bioavailability, meaning it is absorbed well in our gut. So oral supplementation can rapidly and effectively increase levels of glutathione in the body. IN FACT, treatment of acetaminophen overdose in the ER typically begins with oral NAC (often administered through a naso-gastric feeding tube, passed through the nose and into the stomach) Doses are often calculated by the regional poison control center (available by phone 24/7/365) and subsequent doses follow a standard protocol based on weight.

I would encourage you to read through this COVID-19 INTEGRATIVE MEDICINE review article.

It is thick with science but you might be surprised by how much you understand and learn.

In the chart above there is specific mention of Vitamin C supplementation in escalating doses as degree of illness increases. Vitamin C is an important anti-oxidant and in that sense is a glutathione sparing agent helping to mitigate glutathione depletion.

Other important factors mentioned in the article and the chart above include items mentioned here in previous posts: ZINC, ZINC IONOPHORES, phytochemicals (quercitin, EGCg, curcumin), Vitamin D, exercise, sleep, stress reduction, sunshine.

So I will close this post the way I have closed on many posts related to COVID-19.

Support your immune system.

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. Follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system
  8.  Eliminate sugar-added foods and beverages from your diet, sugar increases inflammation, contributes to metabolic dysfunction and impairs immunity.

In a future post I will describe my PERSONAL approach to dietary supplements in the context of COVID-19. I will also discuss the issue of an ADVANCED DIRECTIVE, in case you are hospitalized.

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

Glutathione review links are below:

Glutathione!

Mitochondrial Glutathione, a key survival antioxidant

Glutathione: overview of its protective roles, measurement, and biosynthesis

 

 

 

COVIDS 19: Drugs vs Food and Supplements, Part II

Today we discuss the many ways curcumin might defend us against COVID-19.

A Google Scholar Search for  “curcumin and virus” will yield over 43,000 results.

Narrow that down to a search for  “curcumin and corona virus” and you will get 1500 results.

Here is a picture of the many ways curcumin has been shown to interfere with various kinds of viruses:

curcumin anti viral multiple effects

This review article discusses (in-vitro and animal in-vivo) studies that show the following targets for curcumin interfering with one or more kinds of viruses:

  1. viral attachment to the cell
  2. viral penetration of the cell
  3. viral replication inside the cell
  4. viral activation of inflammatory genes
  5. direct anti-inflammatory effects of curcumin

Blocking any one or combination of steps 1 through 4 would attenuate damage to the host (us) by limiting spread and replication of the virus within our body (steps 1-3) and by limiting the virus ability to induce inflammatory damage (steps 4 and 5). From the review article:

“Accumulated evidence indicated curcumin plays an inhibitory role against infection of numerous viruses. These mechanisms involve either a direct interference of viral replication machinery or suppression of cellular signaling pathways essential for viral replication, such as PI3K/Akt, NF-κB.”

Curcumin has been studied and found to be effective in vitro against:

  • COVID-19
  • SARS VIRUS
  • INFLUENZA A VIRUS
  • HIV
  •  Hepatitis C virus
  •  Respiratory Syncytial Virus
  •  Hemorrhagic Fever
  •  Rift Valley Fever
  •  Dengue Virus
  •  Japanese Encephalitis
  • Epstein Barr Virus
  •  Human Papilloma Virus
  •  Coxsackie Virus

Links to articles related to all of these viruses appear below.

The multiple anti-inflammatory effects of curcumin (blocking chemical and gene signaling pathways of inflammation) would be expected to help mitigate the frequently lethal cytokine storm. 

A cytokine storm occurs when an excessive inflammatory response by the immune system causes self-destruction of the human host, mediated by chemicals called cytokines, produced by our immune cells. Although the human body has feedback systems designed to regulate our immune response, those systems do not always work adequately. The result can be severe organ damage and eventually death. This often begins in the lungs, presenting as Acute Respiratory Distress Syndrome or ARDS but then spreads to other organs creating multi-organ dysfunction syndrome (also referred to as multi-organ failure).

Of all the phytochemicals derived from our foods and spices, curcumin is arguably the most studied relative to a variety of disease categories.

 

.curcumin clinical studies

Here we are interested in Corona Viruses (in general, since they share many commonalities) and COVID 19 in particular.

In my last post I presented data on how strongly EGCg, quercitin, curcumin, and other phytochemicals bind to the COVID-19 spike protein, which attaches to the ACE-2 receptor on human cells as the first step in gaining entry into the cell. EGCg in one study had the greatest binding strength, exceeding that of both Remdesivir and Chloroquine (prescription drugs now being studied for COVID-19). CURCUMIN was second only to EGCg in binding strength in that study.

By attaching to the spike protein on the outer membrane of the virus, it prevents the virus from attaching (or docking) to the human cell, thus blocking the first step of entry into the cell. The virus must enter the cell to replicate, no entry = no replication = no infection.

In studies of the Influenza A virus (IAV) in mice:

“The results showed that curcumin could directly inactivate IAV, blocked IAV adsorption and inhibited IAV proliferation.”

Curcumin worked through several mechanisms, blocking not only viral entry and replication but also reducing  oxidative stress (which contributes to cytokine storm). It increased the survival rate of mice, reduced levels of virus and inflammatory cytokines in the lungs, and reduced lung injury.

Curcumin had similar effects against Respiratory Syncytial Virus (RSV) in human nasal epithelial cells (the same place that COVID-19 first strikes).

curcumin inhibits RSV in human nasal cells

The red lines show the many places curcumin was found to interfere with the RSV infection of human nasal (nose) cells.

Their have been multiple studies that have demonstrated that curcumin (and other phytochemicals) specifically interfere with the docking/binding of COVID-19 by binding to and therefore disabling the effects of, the crucial Spike Protein.

In fact  this study demonstrated that Curcumin and Catechin (EGCg mentioned in the last post) bind not only to the spike protein on the COVID-19 virus, but they also bind to the ACE-2 receptor on the cell surface that receives the virus (like a lock and key), blocking both the lock and the key.

 “Here, through computational approaches we have reported two polyphenols, Catechin and Curcumin which have dual binding affinity i.e both the molecule binds to viral S-protein and as well as ACE2.”

curcumin AND catechin bind COVID19 S protein and ACE-2

In my series of posts on COVID-19 I have discussed the importance of Vitamin D3, zinc, zinc ionophores (such as quercetin and EGCg), Curcumin, and other phytochemicals.  The authors of  this article present multiple lines of evidence and study supporting the notion that supplementation with Vitamin D3, Curcumin and Vitamin C in combination would be beneficial in fighting COVID-19.

Curcumin has a very low absorption rate in the gut. Used as a spice with food, any form of fat in the meal will enhance the absorption of turmeric and it’s phytochemical curcumin (which includes various curcuminoids). Various supplement forms add other substances or encapsulate the curcumin in a manner that increases the absorption rate. Some preparations add Piperine, a black pepper extract. Piperine increases intestinal permeability, thereby enhancing absorption of curcumin. Meriva is a licensed brand of curcumin supplement that uses a phospholipid to enhance absorption of the curcumin. It has been studied to treat osteoarthritis of the knee in humans, effectively reducing pain by an amount equivalent to a prescription dose of ibuprofen. Many other brands are available with enhanced absorption and good safety profiles.

Unfortunately there have been no human randomized controlled trials of curcumin or any other phytochemical or micronutrient in the prevention or treatment of COVID-19. There likely will never be such a study because of our medical system’s orientation to drugs.

Yet, a great deal of scientific evidence has described multiple mechanisms through which vitamins, minerals, phytochemicals and other micronutrients found in foods, beverages, spices and supplements can be beneficial in fighting COVID-19.

Examples discussed so far have included

  • Zinc in combination with Zinc ionophores (which open up channels so that zinc can enter the cell where it is known to block virus replication),
  • Vitamin D3 (which supports immune function and immune regulation in addition to numerous other vital physiologic functions),
  •  curcumin, which blocks viral entry, replication, and the inflammatory response
  • quercitin, which blocks viral entry, replication, the inflammatory response and also functions as a zinc ionophore
  • EGCg, which blocks viral entry, replication, inflammation, and also functions as a zinc ionophore

Vitamin C has not been discussed much here but there is mounting evidence that high doses of Vitamin C (which have been used by some ICU doctors for COVID 19 patients) may have beneficial effects by scavenging free radicals, reducing oxidative stress, and mitigating against depletion of GLUTATHIONE, the master anti-oxidant in the human body.

Glutathione, Vitamin C, and supplements that increase the production of glutathione in the human body will be discussed in the next post, Part III of this series on supplements/foods and COVID-19.

REMEMBER THE BASICS. SUPPORT YOUR IMMUNE SYSTEM.

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. Follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Below you will find links to multiple scientific studies on curcumin and protection against many kinds of virus.

Doctor Bob

A cost-effective preventative approach to potentially save lives in the coronavirus pandemic, jointly using Vitamin D, Curcumin, and Vitamin C,(with updated dosage …

Destabilizing the Structural Integrity of SARS-CoV2 Receptor Proteins by Curcumin Along with Hydroxychloroquine: An Insilco Approach for a Combination Therapy

Identification of potent COVID-19 Main Protease (Mpro) inhibitors from Curcumin analogues by Molecular Docking Analysis

Virtual Screening of Curcumin and Its Analogs Against the Spike Surface Glycoprotein of SARS-CoV-2 and SARS-CoV

Catechin and Curcumin interact with corona (2019-nCoV/SARS-CoV2) viral S protein and ACE2 of human cell membrane: insights from Computational study and …

 Molecular Docking Study of the Structural Disruption of the Viral 3CL-Protease of COVID19 Induced by Binding of Capsaicin, Piperine and Curcumin Part 1: A …

Effects of Vitamin C, Curcumin and Glycyrrhizic Acid Potentially Regulates Immune and Inflammatory Response Associated with Coronavirus Infections: A Perspective from …

Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus

Antiviral potential of curcumin

Inhibition of curcumin on influenza A virus infection and influenzal pneumonia via oxidative stress, TLR2/4, p38/JNK MAPK and NF-κB pathways

Curcumin prevents replication of respiratory syncytial virus and the epithelial responses to it in human nasal epithelial cells

Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF‐κB signaling pathway

Inhibition of curcumin on influenza A virus infection and influenzal pneumonia via oxidative stress, TLR2/4, p38/JNK MAPK and NF-κB pathways

Synergic effect of curcumin and its structural analogue (Monoacetylcurcumin) on anti-influenza virus infection

Identification of regulators of the early stage of viral hemorrhagic septicemia virus infection during curcumin treatment

Synergistic antiviral effect of curcumin functionalized graphene oxide against respiratory syncytial virus infection

Inhibition of human immunodeficiency virus type-1 integrase by curcumin

Curcumin inhibits influenza virus infection and haemagglutination activity

Curcumin and curcumin derivatives inhibit Tat-mediated transactivation of type 1 human immunodeficiency virus long terminal repeat

Curcumin inhibits herpes simplex virus immediate-early gene expression by a mechanism independent of p300/CBP histone acetyltransferase activity

Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding

Curcumin inhibits hepatitis C virus replication via suppressing the Akt‐SREBP‐1 pathway

An in vitro study of liposomal curcumin: stability, toxicity and biological activity in human lymphocytes and Epstein-Barr virus-transformed human B-cells

Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells

Curcumin inhibits ultraviolet light induced human immunodeficiency virus gene expression

Curcumin inhibits hepatitis B virus via down‐regulation of the metabolic coactivator PGC‐

Curcumin inhibits Rift Valley fever virus replication in human cells

Inhibitory effects of curcumin on dengue virus type 2-infected cells in vitro

Curcumin protects neuronal cells from Japanese encephalitis virus-mediated cell death and also inhibits infective viral particle formation by dysregulation of ubiquitin …

Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infection

The chemopreventive compound curcumin is an efficient inhibitor of Epstein‐Barr virus BZLF1 transcription in Raji DR‐LUC cells

Structure–activity relationship analysis of curcumin analogues on anti‐influenza virus activity

Effect of antioxidant (turmeric, turmerin and curcumin) on human immunodeficiency virus

Curcumin as a multifaceted compound against human papilloma virus infection and cervical cancers: A review of chemistry, cellular, molecular, and preclinical …

Dysregulation of the ubiquitin-proteasome system by curcumin suppresses coxsackievirus B3 replication

 

 

COVID 19: Drugs vs Food and Supplements, Part 1.

There are several drug studies underway for treating COVID-19. Millions of dollars will be spent on drug studies. Yet there are several dietary supplements that are known to have anti-viral activity through several mechanisms. Some phytochemicals act as zinc ionophores. They facilitate entry of zinc into cells where zinc can block virus replication. Some phytochemicals (including those that act as zinc ionophores) can bind to the critical spike protein on the surface of COVID-19 which allows the virus to enter the cell. In addition there are many anti-inflammatory phytochemicals that could potentially mitigate the lethal cytokine storm that leads to multi-organ failure in the ICU, resulting in death. Some phytochemicals might have all three effects.

Despite the basic science that would support the potential use of these phytochemicals in the treatment of COVID-19, no clinical studies have been funded. They likely never will. The culture of medical research and practice in the US remains oriented towards drug interventions and surgery. Without a patent there is little profit in finding clinically effective, inexpensive and safe alternatives to drugs.

I have previously discussed EGCg (green tea extract) and quercitin as zinc ionophores. If you have not already read that discussion please go here.

Lets look at the second mechanism of action mentioned above, binding to the COVID-19 spike protein that facilitates cell entry.

Recently several NATURALLY occurring phytochemicals, found in vegetables, fruits, and tea, have been compared to two drugs under study for COVID-19 in terms of their ability to bind to the COVID-19 spike protein. The results are noteworthy.

“The computed activity of EGCG was found to be higher than that of both reference drugs, Remdesivir and Chloroquine”

So a naturally occurring substance found in green tea has greater binding affinity for the critical spike protein on COVID-19 then two leading drug candidates.

The image below shows the binding affinity of various phytochemicals for several COVID-19 surface protein domains (domains are areas on the protein where drugs and phytochemicals might bind and work). The phytochemicals appear in rank order. EGCg found in green tea and available as an extract in supplement form, binds to the viral protein more strongly than the drugs Remdesivir and Chloroquine.

EGCg also functions as a zinc ionophore, as does quercitin, which also binds to the critical COVID-19 spike protein. Remember, the virus must first enter the cell before it can replicate. If the virus cannot enter the cell, it cannot replicate. COVID-19 enters the cell when the surface spike protein on the virus binds to the ACE-2 receptor on human cells. These receptors are found in abundance in the nose, throat, and lung. (They are present on many other types of human cells as well) This binding/docking and entry process represents a major target for drug interventions.

docking sites and polyphenols.png

Curcumin, which has anti-inflammatory activity (potentially mitigating a cytokine storm) has the second strongest binding among the many phytochemicals studied. And quercitin (another zinc ionophore) is not far behind.

You can read this study (a preprint which means it has not yet been peer-reviewed) here.

So both EGCg and quercitin have potential benefit by  blocking the virus from entering the cell as well as facilitating zinc’s ability to block virus replication once the virus is inside the cell.

But that’s not all. Both of these supplements have anti-inflammatory activity.

“Dietary plant polyphenols such as the flavonoids quercetin (QCT) and epigallocatechin-gallate act as antioxidants and as signaling molecules.”

And the cytokine storm that can be lethal with COVID-19 is an inflammatory reaction.

Quercitin is the most abundant polyphenol found in foods:

FOODS QUERCETIN
(MG/100G)
capers, raw 234[6]
capers, canned 173[6]
dock like sorrel 86[6]
radish leaves 70[6]
carob fiber 58[6]
dill 55[8]
cilantro 53[6]
Hungarian wax pepper 51[6]
fennel leaves 49[6]
onion, red 32[6]
radicchio 32[6]
watercress 30[6]
kale 23[6]
chokeberry 19[6]
bog blueberry 18[6]
cranberry 15[6]
lingonberry 13[6]
plums, black 12[6]

EGCG is found in green tea but has low bioavailability.

EGCG in very high doses can cause liver toxicity. From WIKIPEDIA:

A 2018 review showed that excessive intake of EGCG may cause liver toxicity.[15] In 2018, the European Food Safety Authority stated that daily intake of 800 mg or more could increase risk of liver damage.[16] The degree of toxicity varies by person, suggesting that it is potentiated by genetic predisposition and the diet eaten during the period of ingestion, or other factors.[17]

A typical 400 mg capsule of green tea extract contains 200 mg of EGCg, so if you decide to take some, read the labels carefully to avoid taking too much. If you like to drink green tea:

A single cup (8 ounces or 250 ml) of brewed green tea typically contains about 50–100 mg of EGCG.

Part 2 of this series will discuss the cytokine storm, glutathione our body’s major anti-oxidant, and potential strategies to mitigate the lethal excessive inflammatory spiral of a cytokine storm.

But remember, there are many lifestyle choices we make that can protect us against any viral infection:

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. You must follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

 

COVID 19: Link to Vitamin D status. Should doctors prescribe sunshine?

Preliminary (not yet peer reviewed) data on mortality rates with COVID-19 infection from Indonesia show a dramatic increase in death rates associated with low vitamin D status.

Relative Risk of DEATH Corrected for age, sex, and co-morbidities

Vitamin D level (ng/ml)

 

10.1 <20
7.6

21-29

 

1

 

>= 30

Prabowo, Patterns of COVID 19 Mortality and Vitamin D, Indonesian Study, Ap 26, 2020 BMJ

This study was a retrospective cohort study of 780 cases of laboratory confirmed COVID-19 in Indonesia. Age, sex, co-morbidity (hypertension, diabetes, obesity etc.) and Vitamin D levels were extracted from medical records. The differences between patients with various levels of vitamin D were statistically significant and CLINICALLY SIGNIFICANT.

If there were a drug that reduced mortality by 10 fold it would be a best-seller/blockbuster drug.

“When controlling for age, sex, and comorbidity, Vitamin D status is strongly associated with COVID-19 mortality outcome of cases.”

Association does not equal causation but this profound degree of association warrants further consideration. Is it possible that Vitamin D insufficiency could cause such a profound influence on death rates with a viral infection?

Before we answer that question let’s look at some other data. Risk of death with COVID-19 dramatically changes with latitude (sunlight exposure reflecting Vitamin D making capability):

Latitudes Hospitalizations COVID-19 Deaths COVID-19
Northern 22% 5.2%
Equator 9.5% 3.1%
Southern 8.7% 0.7%

You can read about this data here.

The authors state:

“Although it is more likely that any protective effect of vitamin D against
Covid19 is related to suppression of cytokine response and reduced severity/risk for ARDS, there is also evidence from a meta-analysis that regular oral vitamin D2/D3 intake (in doses up to 2000 IU/d without additional bolus), is safe and protective against acute respiratory tract infection, especially in subjects with vitamin D deficiency. It therefore seems plausible that Vitamin D prophylaxis (without over-dosing) may contribute to reducing the severity of illness caused by SARS-CoV-2, particularly in settings where hypovitaminosis D is frequent. This will include people currently living in Northern countries and those with underlying gastroenterological conditions where vitamin D deficiency is more prevalent. This may become even more important with absence of sunlight exposure as a consequence of “shut-down” measures to control the spread of Covid19. For this to be effectively implemented will require worldwide government guidelines, and further studies looking at possible impacts of vitamin D deficiency on Covid-19 outcomes are urgently needed.”

Plenty of references are provided for their discussion so I encourage you to not only read the publication but further explore their references.

The importance of Vitamin D for proper immune function has been well studied and known for a long time.

“Vitamin D metabolizing enzymes and vitamin D receptors are present in many cell types including various immune cells such as antigen-presenting-cells, T cells, B cells and monocytes. In vitro data show that, in addition to modulating innate immune cells, vitamin D also promotes a more tolerogenic immunological status. In vivo data from animals and from human vitamin D supplementation studies have shown beneficial effects of vitamin D on immune function, in particular in the context of autoimmunity”

“Especially in the field of human immunology, the extra-renal synthesis of the active metabolite calcitriol—1,25(OH)2D—by immune cells and peripheral tissues has been proposed to have immunomodulatory properties similar to locally active cytokines”

Now consider this startling fact. At the turn of the century (2001-2004) 70% of the US population over age 12 had 25 Hydroxy-Vitamin D levels LESS THAN 30 ng/ml. 

And the situation has not improved since that study. In the chart above that places 70% of the US population in the groups with 7.6 to 10.1 times increased risk of death from COVID 19 compared with those having “normal” levels (>30 ng/ml).

Conclusions

“National data demonstrate a marked decrease in serum 25(OH)D levels from the 1988–1994 to the 2001–2004 NHANES data collections. Racial/ethnic differences have persisted and may have important implications for known health disparities. Current recommendations for vitamin D supplementation are inadequate to address the growing epidemic of vitamin D insufficiency.”

Multiple studies on COVID-19 have shown higher mortality rates amongst blacks. Although this is likely related to many socio-economic and nutritional factors, blacks have consistently shown significantly lower Vitamin D levels in the US compared with other ethnic/racial groups.

During the 2009 Viral Pandemic, death rates were observed to increase with distance from the equator, similar to the COVID-19 observations.

Death rates from COVID-19  in ITALY, where Vitamin D status is much lower compared to the rest of Europe, have been higher than other countries in Europe.

And a large report on Vitamin D status in Europe and the Middle East states:

“A low vitamin D status was also associated with increased mortality risks as extensively reviewed”  with references (327206209).

A brilliant video podcast on the relationship between Vitamin D and COVID-19 can be viewed here.

And if you wish to further explore the health effects of Vitamin D you can watch this:

Insufficient Vitamin D levels are associated with almost every risk factor for Morbidity and Mortality with COVID-19 including Diabetes, Insulin Resistance, Obesity, Hypertension and Cardiovascular Disease.

Many of the concerns covered in Ivor Cummin’s podcast above have been covered in previous posts here including the importance of Vitamin K2 and other fat soluble vitamins, the importance of SUNSHINE for general health and immune function, and the importance of a nutrient dense whole food diet rich in wild seafood and grass fed animal sources of protein. Almost every cell in the body has receptors for Vitamin D. The most beneficial sources of Vitamin D include sunshine and food sources. Supplementation is often necessary to achieve levels above 30 ng/ml, especially during the winter months (when respiratory viruses strike) and increase with distance from the equator.

The deleterious effects of inadequate Vitamin D cannot be overstated. The consequences below only address the effects of Vitamin D insufficiency on bone health but the causes and prevention are important to understand. Vitamin D deficiency = Immune Deficiency and is likely strongly and causally related to increased risk of death with COVID-19.

Vit D status, sources.jpeg

 

Here is an image that links Vitamin D deficiency to Diabetes, inflammation and oxidative stress:

inflamation, PTH, Oxidative stress, calcium, IR, DM2.png

And here is a good description of the consequences of inadequate Vitamin D.

vitamin-d-deficiency-causes and consequences.png

So what do you think? Is it possible that Vitamin D insufficiency could cause such a profound influence on death rates with a viral infection? Lets look a little closer.

The Public Health system in UK has been concerned about Vitamin D deficiency:

 

 

vitamin-d-deficiency-symptoms UK Public Health.jpg

And once again here is how inadequate Vitamin D interacts with the co-morbidities that are unequivocally associated with increased death rates associated with COVID-19 infection.

Vit D and inflammation.jpg

PTH is parathyroid hormone. The RAAS above refers to the renin-angiotensin system hypertension effects mediated through the kidney. The chronic inflammation associated with inadequate Vitamin D leads to atherosclerosis and cardiovascular events, diabetes, insulin resistance, metabolic syndrome which all have positive feedback effects on each other. They all increase risk of death with COVID-19.

Again I ask, what do you think? Is it possible that Vitamin D insufficiency could cause such a profound influence on death rates with a viral infection?

Res-Ipsa-Loquitur.jpg

(The thing speaks for itself)

RX from the doctor could read:

Sunbath for 15 minutes daily between 1100 AM and 1 PM (wear a hat, sunglasses, bathing suit optional depending on circumstances and privacy)

Eat fatty fish frequently.

Get your 25 hydroxy-vitamin D levels checked, if < 30 ng/ml increase the above.

Supplement in the winter.

Further reading can be found here:

Vitamin D Insufficiency is Prevalent in Severe COVID-19

The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients

Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-2019)

 

Latitude Dependence of the COVID-19 Mortality Rate—A Possible Relationship to Vitamin D Deficiency?

 

Vitamin D supplementation could prevent and treat influenza, coronavirus, and pneumonia infections

 

low population mortality from COVID19 in countries south of latitude 35 degrees North–supports vitamin D as a factor determining severity

 

Covid19, and vitamin D

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

 

 

 

 

 

 

ZINC, ionophores, supplements and COVID-19

ZINC is an essential mineral present in many foods. It is also available as a dietary supplement. Zinc in combination with a zinc ionophore (which helps zinc enter human cells) can inhibit viral replication in human cells. It does this by blocking RNA POLYMERASE, which is necessary for replication of the CORONA VIRUS.

Zinc is required for proper functioning of more than 300 important enzymes in our bodies and plays an essential role in:

Immune Function

Protein Synthesis

Wound Healing

DNA Synthesis

Normal Growth and Devlopement During Pregnancy, Childhood and Adolescence

A daily intake of ZINC IS REQUIRED because the human body has no specialized storage system.

“Zn is an essential trace element for all organisms. In human subjects body growth and development is strictly dependent on Zn. The nervous, reproductive and immune systems are particularly influenced by Zn deficiency, as well as by increased levels of Zn. The relationship between Zn and the immune system is complex, since there are four different types of influence associated with Zn. (1) The dietary intake and the resorption of Zn depends on the composition of the diet and also on age and disease status. (2) Zn is a cofactor in more than 300 enzymes influencing various organ functions having a secondary effect on the immune system. (3) Direct effects of Zn on the production, maturation and function of leucocytes. (4) Zn influences the function of immunostimulants used in the experimental systems.”

Zinc deficiency is very common amongst the elderly which may contribute to the high death rate for COVID-19 for folks 65 and older.

From the NIH:

“some evidence suggests that zinc intakes among older adults might be marginal. An analysis of NHANES III data found that 35%–45% of adults aged 60 years or older had zinc intakes below the estimated average requirement of 6.8 mg/day for elderly females and 9.4 mg/day for elderly males. When the investigators considered intakes from both food and dietary supplements, they found that 20%–25% of older adults still had inadequate zinc intakes

You can read more about Zinc here.

Here is a list of zinc levels in various foods:

Table 2: Selected Food Sources of Zinc [11]
Food Milligrams (mg)
per serving
Percent DV*
Oysters, cooked, breaded and fried, 3 ounces 74.0 673
Beef chuck roast, braised, 3 ounces 7.0 64
Crab, Alaska king, cooked, 3 ounces 6.5 59
Beef patty, broiled, 3 ounces 5.3 48
Lobster, cooked, 3 ounces 3.4 31
Pork chop, loin, cooked, 3 ounces 2.9 26
Baked beans, canned, plain or vegetarian, ½ cup 2.9 26
Breakfast cereal, fortified with 25% of the DV for zinc, 1 serving 2.8 25
Chicken, dark meat, cooked, 3 ounces 2.4 22
Pumpkin seeds, dried, 1 ounce 2.2 20
Yogurt, fruit, low fat, 8 ounces 1.7 15

When CNN discussed the importance of ZINC relative to COVID-19, zinc supplements disappeared from the shelves in pharmacies and health food stores. Zinc supplements are still out of stock in most on-line supplement sites.

Hydroxychloroquine and Chloroquine are anti-malarial drugs (also used to treat Lupus, Rheumatoid Arthritis) that act as Zinc Ionophores.

So far, all the studies on the use of anti-malarial drugs for COVID-19 have been disappointing with no randomized/controlled trials demonstrating clinical benefit (no reduction in death rates). But NONE OF THESE STUDIES CHECKED ZINC LEVELS OR PROVIDED ZINC SUPPLEMENTATION!!!

In addition, as discussed before, these anti-malarial drugs can cause significant (and rarely lethal) side effects.

There are dietary sources of zinc ionophores that do not require a prescription.

Quercitin and EGCG (Epigallocatechin-gallate) both act as zinc ionophores in-vitro (in cell cultures).

“Dietary plant polyphenols such as the flavonoids quercetin (QCT) and epigallocatechin-gallate act as antioxidants and as signaling molecules. Remarkably, the activities of numerous enzymes that are targeted by polyphenols are dependent on zinc. We have previously shown that these polyphenols chelate zinc cations and hypothesized that these flavonoids might be also acting as zinc ionophores, transporting zinc cations through the plasma membrane. To prove this hypothesis, herein, we have demonstrated the capacity of QCT and epigallocatechin-gallate to rapidly increase labile zinc in mouse hepatocarcinoma Hepa 1-6 cells as well as, for the first time, in liposomes.”

Quercitin is the most abundant dietary polyphenol.

Foods Quercetin
(mg/100g)
capers, raw 234[6]
capers, canned 173[6]
dock like sorrel 86[6]
radish leaves 70[6]
carob fiber 58[6]
dill 55[8]
cilantro 53[6]
Hungarian wax pepper 51[6]
fennel leaves 49[6]
onion, red 32[6]
radicchio 32[6]
watercress 30[6]
kale 23[6]
chokeberry 19[6]
bog blueberry 18[6]
cranberry 15[6]
lingonberry 13[6]
plums, black 12[6]

It is also available as a dietary supplement.

EGCG is found in green tea but has low bioavailability.

EGCG in very high doses can cause liver toxicity. From WIKIPEDIA:

A 2018 review showed that excessive intake of EGCG may cause liver toxicity.[15] In 2018, the European Food Safety Authority stated that daily intake of 800 mg or more could increase risk of liver damage.[16] The degree of toxicity varies by person, suggesting that it is potentiated by genetic predisposition and the diet eaten during the period of ingestion, or other factors.[17]

Zinc is an essential mineral but can be toxic when taken at high doses.

From the NIH:

“Zinc toxicity can occur in both acute and chronic forms. Acute adverse effects of high zinc intake include nausea, vomiting, loss of appetite, abdominal cramps, diarrhea, and headaches [2]. One case report cited severe nausea and vomiting within 30 minutes of ingesting 4 g of zinc gluconate (570 mg elemental zinc) [84]. Intakes of 150–450 mg of zinc per day have been associated with such chronic effects as low copper status, altered iron function, reduced immune function, and reduced levels of high-density lipoproteins [85]. Reductions in a copper-containing enzyme, a marker of copper status, have been reported with even moderately high zinc intakes of approximately 60 mg/day for up to 10 weeks [2]. The doses of zinc used in the AREDS study (80 mg per day of zinc in the form of zinc oxide for 6.3 years, on average) have been associated with a significant increase in hospitalizations for genitourinary causes, raising the possibility that chronically high intakes of zinc adversely affect some aspects of urinary physiology [86].

The FNB has established ULs for zinc (Table 3). Long-term intakes above the UL increase the risk of adverse health effects [2]. The ULs do not apply to individuals receiving zinc for medical treatment, but such individuals should be under the care of a physician who monitors them for adverse health effects.”

 

Table 3: Tolerable Upper Intake Levels (ULs) for Zinc [2]
Age Male Female Pregnant Lactating
0–6 months 4 mg 4 mg
7–12 months 5 mg 5 mg
1–3 years 7 mg 7 mg
4–8 years 12 mg 12 mg
9–13 years 23 mg 23 mg
14–18 years 34 mg 34 mg 34 mg 34 mg
19+ years 40 mg 40 mg 40 mg 40 mg
 

 

Most zinc supplements come in doses of 25-50 mg of elemental zinc.

There are potential interactions between medications and zinc. The following medications decrease the absorption of zinc.

Quinolone antibiotics (including Cipro)

Tetracycline antibiotics.

Penicillamine (used to treat Rheumatoid Arthritis, a known risk factor for bad outcomes in COVID-19)

Thiazide diuretics (chlorthalidone, hydrochlorthiazide) and these can lead to chronic zinc deficiency. They are used to treat hypertension which is a known risk factor for bad outcomes in COVID-19.

In the setting of COVID-19, a Paleo/Ancestral TYPE anti-inflammatory diet is VERY IMPORTANT.

There are many reasons including the following benefits of such a diet:

  1.  High intake of zinc and foods containing quercetin and EGCG
  2.  Avoidance of foods high in phytic acid which blocks the absorption of zinc and many other essential minerals such as magnesium, calcium, and iron.
  3.  Improved blood sugar control (diabetes and insulin resistance increase the risk of death from COVID-19)
  4.  Improved blood pressure (hypertension increases the risk of death from COVID-19)
  5.  Avoidance of alcohol which increase risk of death from COVID-19 by impairing immune function.

A physician friend and colleague recently wrote a post that documents the benefits of a carbohydrate restricted, whole foods diet, with elimination of processed and sugar-added foods and beverages. I highly recommend you read it here.

With regards to maintaining a properly functioning immune system a few simple lifestyle habits are essential,

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. You must follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system

Finally, think about ZINC and ZINC IONOPHORES  relative to diet and personal habits. While there have not been studies using zinc in combination with zinc ionophores (and there likely will never be) relative to COVID-19, all available scientific information about the relationship between corona virus replication and these two items indicates that in combination they might provide benefit. It is a shame that the studies in progress have not considered zinc status in patients receiving the anti-malarial drugs.

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

 

 

 

 

 

 

Stanford Study on Santa Clara County: Very questionable conclusions

My last post discussed a study from Stanford that suggested 50-85 times greater Infection Rate (IR) compared to the Case Rate (CR) in Santa Clara County. The Wall Street Journal published a discussion of this Study (which has not yet been peer reviewed) claiming that it was good evidence of a much lower fatality rate for COVID-19. Turns out that study was deeply flawed. The test used likely had a false positive rate of 13%, not 0.5% assumed by the authors. That alone makes the conclusions completely bogus. In addition, the study population was not truly a random sample and likely had significant selection bias. For a complete expose watch this:

One would expect something better from Stanford, but like I said, this was not yet peer reviewed.

“This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.”

But the Wall Street Journal reported on it in a favorable way, not revealing that one of the authors of the study was also the author who wrote the WSJ article!

A brief note about false positives and false negatives.

Suppose you are looking at a population of 1,000,000 people with an infection rate of 1% (990,000 do not have the disease)

Assume a sensitivity of 93% (the test is positive in 93% of true positives)

Assume a specificity of 96% (false positive rate of 4%)

If you test everyone, 9300 of the 10,000 true cases will be detected, 700 of the cases will not be detected.

BUT 40,000 false positives will be found for a total of 49,300 positives. You will publish an infection rate of 4.93% while the real infection rate is only 1%.

Statistics are tricky. The sensitivity and specificity of a test are extremely important.

Be careful about what you read. We all would like to be reassured that it would be safe to relax restrictions but we still do not yet know  the true IFR. The true infection rate depends on widespread testing with an accurate test and we have not yet done that.

Besides the economic downturn associated with shelter in place, there are valid clinical concerns about the damage being caused (depression, anxiety, suicide, spousal abuse, child abuse, reluctance to call 911 for a real emergency, etc..) We will need to return to less restrictions in an incremental way based on regional circumstances (NYC not the same as Northern California).

For a detailed discussion about how and when we should relax restrictions read this.

There has been allot of comparing apples with oranges in the social media. People keep trying to compare COVID-19 to the flu. They are very different with respect to the fatality rate and ease of transmission. (In addition, whereas we have had a vaccine for Influenza A and B, we do not have one for COVID-19 or any other Corona Virus)

Review:

Case Rate (CR) is the # of known cases based on nasal swab PCR test divided by population.

Infection Rate (IR) is the actual # of cases divided by population. This is estimated by performing a reliable serology test on a large random sample of people, testing for infection by measuring antibodies (there are a few tests available but their sensitivity and specificity remain controversial and crucial)

A recent analysis comparing the 2009 H1N1 influenza A pandemic to COVID 19 suggested this:

Case Fatality Rate Infection Fatality Rate
2009 H1N1 Virus (flu) 0.1% to 0.2% 0.02%
COVID-19 New York 8% 0.50%

Some folks on social media have been comparing the CFR of the flu to the IFR of COVID-19. That is comparing apples to oranges.

The data in the table above are based on what appears to be the most recent and reliable information from New York City. The data on 2009 H1N1 is reported here.

In the old news clip below, 2920 adult deaths associated with 12 million cases of H1N1 calculates out to a 0.02% IFR which is exactly the same IFR described in the study linked above..

In this same report and in other discussions of H1N1 it was clear that children were more severely effected compared to COVID-19.

The table above would indicate that the IFR (infection fatality rate) of COVID-19 IS 25 TIMES GREATER than the IFR of the 2009 H1N1 Influenza A pandemic. The CFR of COVID-19 IN NEW YORK CITY is 40 times greater. This represents a much greater difference than the relative fatality rates suggested by the highly questionable conclusions of the Stanford Study of Santa Clara County.

There is a possibility that the New York City strain of COVID-19 might be more lethal than the strain of COVID-19 on the West Coast. That suggestion is PURELY SPECULATIVE and so far there is no data to support it. This possibility has been suggested because  NYC and New Jersey hospitals are much closer to capacity with COVID-19 compared to the West Coast experience and there are portable refrigerator truck morgues outside of hospitals in NYC and New Jersey where the local morgues filled up weeks ago. Again I would point to the major differences of the apparent CFRs between various countries and regions within countries which have not yet been explained (as discussed in my last post).

We have much more to learn, we need more testing (both nasal PCR and blood serology) to understand the spread and lethality of this disease. Those in the social media who claim we already have herd immunity are spewing nonsense. Herd immunity requires > 80% infection rate. Our measured IRs are highest in NYC (about 15%) and much lower in other areas where “reliable” serology has been performed.

One great failure in our country has been the prolonged lack of adequate testing. Shelter-in-place should have been a time-out to collect data and access where we are. That can only happen with reliable wide-spread testing. To AVOID overwhelming our hospitals and health care workers we must identify cases, trace contacts, isolate positives and isolate contacts. Isolation would ideally not be at home where the disease could easily spread to the entire household. Isolation at home is only reasonable when that home has a separate bedroom and bathroom for the infected person AND the household follows strict isolation and hygiene.

We must all recognize that the primary objective of shelter in place is to avoid overwhelming the health care system. Eventually, unless a treatment or vaccine becomes available, the disease will infect most of our population before we reach herd immunity. To return to economic activity and a more “normal life” we will necessarily accept a large number of deaths, primarily but not exclusively amongst the elderly and infirm. Generally it would seem reasonable to begin incrementally relaxing restrictions in areas of low impact, wearing masks, working from home where possible, avoiding public gatherings especially in confined spaces, and following good personal hygiene. So far the best information on risk (of death) appears to be in the table above, stratifying for age and risk factors.

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

 

 

COVID 19, Conflicting DATA EMERGES ON MORTALITY RATES. We need more data (testing)

Testing remains inadequate to determine how we should be addressing this virus. But recent data suggests that the IFR (infection fatality rate) is lower than originally thought. To understand this you must understand the difference between the CR (Case Rate) and the IR (Infection Rate) as well as the difference between the CFR (Case Fatality Rate) and the IFR (Infection Fatality Rate).

Case Rate: # Positive tests/ population

Infection Rate: # actual people infected/ population

Case Fatality Rate= #deaths/ # positive tests (# deaths/known cases)

Infection Fatality Rate= # deaths from the virus/ # infected (# deaths/ known and unknown cases)

Ideally everyone would be tested with a perfect test. A perfect test would be positive for everyone infected ( no false negatives-whether symptomatic or without symptoms) and it would be negative if the virus is not present (no false positives).

No test is perfect, but even with imperfect tests we would know much more with greater numbers of people tested, including those without symptoms.

To calculate an accurate estimate for the Infection Fatality Rate, we must widely test people without symptoms in a hard hit area such as New York City. Only then will we understand whether this virus is significantly more lethal than other viruses such as the flu. Early estimates were based on very imperfect data. Remember, Fauci stated before congress that COVID 19 is “ten times worse than the flu” based upon all the information available at the time. Fauci is arguably the most informed/knowlegable/reasonable professional we have to help guide us through this very uncertain time. The more data (testing) we obtain, the better-informed will be our plans going forward.

Shelter-in-place is most effective when started early, before the disease spreads widely and buys time to let hospitals prepare and expand capacity so that the system is not over-whelmed. Flattening the curve is important. It buys time and saves lives primarily by avoiding a situation where health care capacity is exceeded by demand (when that happens people who could have been saved do not stand a chance). But during the time-bought, we should have implemented widespread testing of people with and without symptoms to gain a better understanding of the epidemic. We did not do that. Testing remains inadequate for proper assessment of when and how we might begin to return to “the new normal”. Testing remains inadequate for understanding the risks of lifting various restrictions.

Early in an epidemic, lives are saved by testing, contact tracing, and isolation in combination with social distancing measures and the extreme measure of shelter in place. Unfortunately, we still do not know where we stand, primarily because of inadequate testing.

Below is the link to a long interview with a respected epidemiologist who explains that his recent study suggests the IFR for Covid 19 is similar to the Flu. This does not mean that shelter-in-place did not provide benefit. COVID 19 is clearly much more contagious than the Flu. But it does mean that provided we INCREASE TESTING and follow closely the impact of GRADUAL REDUCTION OF SOCIAL RESTRICTIONS, we may soon be able to allow the return of certain activities in an incremental fashion. The ideal strategy will depend on the specific local and regional circumstances (rates of infection and deaths, availability of hospital beds, ICU beds, PPE, health care workers, rural vs urban, reliance on public transportation (subways/buses vs cars), population density,  degree of at-risk population, etc.)

If you choose to watch this long interview, be careful to take everything with a grain of salt. One study of IR (infection rate) in one community does not automatically translate into national policy implications. The difference between Santa Clara County CA and the New York Metropolitan area is enormous for many reasons. This should not lead to anyone dropping their cautions, throwing away masks, and resuming activity with abandon. But it should lead to understanding the completely inadequate data that we presently have to make decisions AND the great need for caution as we move forward.

The person conducting this interview clearly is biased, believing that stay-at-home was not necessary. He is constantly pressing Dr. Ioannidis to draw that conclusion. Remember, one small epidemiologic study is not enough to draw conclusions about the fatality rate of infection. We need more data. But there is a glimmer of hope.

This data has not been peer-reviewed yet.

“This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.”

Excerpts from the study referenced in this interview:

We report the prevalence of antibodies to SARS-CoV-2 in a sample of 3,330 people, adjusting for zip code, sex, and race/ethnicity. 

Under the three scenarios for test performance characteristics, the population prevalence of COVID-19 in Santa Clara ranged from 2.49% (95CI 1.80-3.17%) to 4.16% (2.58-5.70%). These prevalence estimates represent a range between 48,000 and 81,000 people infected in Santa Clara County by early April, 50-85-fold more than the number of confirmed cases.

Here is the link.

 

Now, whether you chose to sit through that very long interview, here is another quote from a study by the same author, also a “Pre-Print” not yet peer-reviewed.

Individuals with age <65 account for 5%-9% of all COVID-19 deaths in the 8 European epicenters, and approach 30% in three US hotbed locations. People <65 years old had 34- to 73-fold lower risk than those ≥65 years old in the European countries and 13- to 15-fold lower risk in New York City, Louisiana and Michigan. The absolute risk of COVID-19 death ranged from 1.7 per million for people <65 years old in Germany to 79 per million in New York City. The absolute risk of COVID-19 death for people ≥80 years old ranged from approximately 1 in 6,000 in Germany to 1 in 420 in Spain. 

So there are huge differences in mortality rates from country to country and region to region, including for different age groups.

WE DO NOT YET UNDERSTAND THESE DIFFERENCES NOR CAN WE SAFELY EXTRAPOLATE THESE NUMBERS TO MAKE PUBLIC HEALTH DECISIONS.

WE NEED MORE DATA.

OK, now here is an update to this post. The Stanford Study described above and discussed in the video of Dr. Ionnidis SHOULD BE WITHDRAWN. I have read serious methodological criticisms of this study. Here are a few of the major problems.

  1. The study assumed a test specificity of 99.5% ( false positive rate of 0.5%) BUT an independent test of the test that was likely used (Chinese lab test vendor:Hangzhou Biotest Biotech) revealed 87% specificity (13% false positive rate). That is a huge problem as described in this analysis.
  2.  The sample was not truly a random population, they advertised on facebook for participants at a time when testing was not very available in Santa Clara County. If you had symptoms or had been exposed and heard about a free test would you enroll in the study? (you bet).

Very thoughtful and knowledgeable scientists have been analyzing how America can return incrementally to less restricted activity. It is very complicated, will vary from region to region, locality to locality, and will need constant assessment and modification. You can read one excellent report here.

That report, prepared by Johns Hopkins School of Public health, is titled Public Health Principles for a Phased Reopening During COVID-19: Guidance for Governors.

Here is an important excerpt.

The majority of models have shown that, in the absence of social distancing, COVID-19 has a reproduction rate of between 2 and 3 (though some models have shown it to be higher). This means that every person with the disease will spread it to 2 to 3 others, on average. To end an epidemic, control measures need to drive that number as far below 1 as possible. A vaccine can do that if and when it becomes available. But in the meantime, social distancing measures, combined with case-based interventions, are the key tools to maintaining the reproduction rate below 1. If the reproduction rate rises above 1, this means that epidemic growth has resumed. If that occurs, it may be necessary to reinitiate large-scale physical distancing. It is important to recognize that states will need to actively manage COVID-19 cases with great vigilance for the entire duration of the pandemic until a safe and effective vaccine is widely available.

And another:

There are still many gaps in scientific understanding about the transmission dynamics of SARS-CoV-2. But initial published data suggest that transmission of SARS-CoV-2 occurs primarily through prolonged, close contact. In studies that have monitored people with a known exposure to a confirmed case, household members, those who report frequent contact, and people who have traveled together or shared a meal are found to be at highest risk of infection. Other studies that attempt to reconstruct transmission chains among confirmed cases have also found that prolonged close contact is the source of most new infections. Some special settings have also been identified. Superspreading events have been linked to religious services, choir practice, and large family gatherings, among others. Congregate settings like cruise ships, institutions of incarceration, and long-term care facilities have also been the source of large outbreaks. These findings suggest that settings where close contact is minimal will be lower risk than settings with prolonged close contact.

The precursor to the report cited above can be read here.

Clearly, at-risk individuals (elderly, anyone with chronic illness) will need to have greater restrictions for longer periods of time. Everyone will need to be careful to follow guidelines to prevent infecting themselves and others. People living in densely populated areas that rely heavily on public transportation (example: New York Metropolitan area) have suffered the most and will continue to be hot zones until herd immunity is achieved. Large gatherings of people, particularly in confined areas with close proximity, remain high risk for contracting the illness. Remember, sitting at a table and eating or playing cards with an asymptomatic but infected person can result in everyone at the table getting infected. Remember the choir rehearsal in Washington where everyone likely became infected.

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

 

 

 

 

Bill Evans, Jazz Pianist, Genius, Interview worth watching and hearing

Today I depart from my usual topic of health and lifestyle to present a fascinating recorded interview with Jazz Pianist, innovator, genius, Bill Evans. Bill was born in Plainfield NJ, close to my hometown. He was arguably the most influential Jazz Pianist of the 20th century. This interview was with his brother, also a Jazz Pianist and Professor, and includes commentary by Steve Allen.

In this interview Bill relates classical music, originally an improvisational art form, to Jazz and discusses improvisation with incredibly beautiful demonstrations at the piano.

During our stay-at-home confinement due to COVID 19 I recommend you spend time watching and listening to this genius. I hope you will be inspired to further explore the music and creativity of Bill Evans. It is rare that we can experience the insight and work of such a remarkable genius.

Bill died tragically from complications of heroin abuse. I had only one opportunity in my life to attend Bill’s concert at the Jazz Workshop in Boston shortly before his untimely death. His hands and face were swollen from the ravages of heroin-related liver disease. I will never forget that evening of magic some 40+ years ago. I mourned his death which occurred while I was in medical school and was deeply grateful that I had a chance to experience his improvisational genius. I rank that evening along with a live performance of Segovia at Symphony Hall in Boston, as two of the most amazing live performances of my lifetime.

Here is the link:

 

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

 

Summer Relief from COVID19 not likely, study suggests.

“Although some pundits have suggested that the COVID-19 pandemic will dissipate with coming warm temperatures and high humidity in the Northern Hemisphere, the virus is unlikely to be seasonal in nature, according to a paper published yesterday by the National Academy of Sciences, Engineering, and Medicine.”

Countries in summer climates (Australia, Iran) are presently experiencing rapid virus spread.

MERS and SARS (both corona viruses) did not show a seasonal pattern.

Flu pandemics have not demonstrated seasonal patterns.

“There have been 10 influenza pandemics in the past 250-plus years—two started in the northern hemisphere winter, three in the spring, two in the summer and three in the fall,” they said. “All had a peak second wave approximately six months after emergence of the virus in the human population, regardless of when the initial introduction occurred.”

The study admits many limitations and caution is advised in drawing firm conclusions. Nevertheless, we should not depend on an assumption of summer bringing relief.

In the meantime, stay-at-home, social distancing, careful shopping habits, masks in public, frequent dis-infection of surfaces and handwashing, all make sense.

Remember, simply breathing can transmit virus without a cough or sneeze. Singing and yelling may simulate a cough (Washington choir experience reported previously). Asymptomatic individuals can be carriers (estimated 25% of carriers do not exhibit symptoms.)

Symptoms are extremely variable.

covid-19-symptoms-FREQUENCY.jpg

And the incubation period (time from viral transmission to appearance of symptoms) is highly variable.

 

incubation various viruses.gif

Many folks presume you must have many symptoms, but only one or two may be present. Fever alone is enough. GI problems alone is consistent with one  of the many presentations. Sudden death due to myocarditis (inflammation of the heart) has been reported.

corona-virus-symptoms 2.jpg

Besides the well known precautions that should be taken, remember to support your immune system with adequate restorative sleep.

Other lifestyle considerations that support your immune system include:

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

 

COVID19 treatment breakthrough

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I just listened to an  NSPR interview with Dr. Jacob Glanville, an immuno-engineer, who has developed anti-bodies against the COVID19 virus. Dr. Glanville was featured in a Netflix movie “PANDEMIC’ which ironically aired in late January, after news of the novel corona virus had caught the public’s attention.

HISTORY: Dr. Glanville attended a “BIOTHREATS MEETING” in Washington DC in January 2020. Dr. Fauci (NIH Director of Allergy and Infectious Diseases) gave a talk at the conference in which he stated that COVID19 was “NO LONGER CONTAINABLE” and NIH was commissioning bio-tech companies to develop treatments. (mind you this was January 2020, Fauci already perceived a serious health threat to the USA and the world)

Several larger companies were in line ahead of Glanville’s to obtain federal funding for this project. Because of the critical nature of the problem Glanville decided on the spot to discuss with his colleagues at Distributed Bio an effort to develop antibodies against COVID 19 without funding. His company assigned researchers to work at night and on weekends to develop “high affinity” antibodies against COVID19. They used “superhuman”, a process and tool developed by his company, to access a “library” in a test tube with 76 billion human antibodies.

Following the SARS virus pandemic in 2003, the public domain had 5 “high affinity” antibodies against SARS. Because SARS and COVID19 are similar (both viruses enter human cells through the ACE2 receptor protein, both are forms of corona virus and can cause respiratory distress syndrome) , they took the 5 known SARS antibodies and “evolved” each one to work against COVID19. The weekend after Governor Newsome ordered a statewide shelter-at-home strategy in California, Dr. Glanville’s volunteer researchers made the breakthrough (working day and night). They found that the “evolved” antibodies from each of the 5 SARS antibodies offered high-affinity for the COVID19 virus. Each one of the five had been a success.

We took a series of five antibodies from around 2002 that were able to neutralize SARS. We were able to use technology in our laboratories to evolve those antibodies against SARS to adapt them to recognize COVID-19.

We tried with five different antibodies because we weren’t sure which one would work the best. All five worked so we have a pretty powerful tool chest available to us right now to produce a final therapeutic.

 From the interview:

What is the next step?

We are sending [the antibodies] to the military for confirmation testing and to Charles River Laboratories for safety and tox characterization. We’ve partnered with two different companies that will help us scale up large batches of the antibody for production. We’re in discussions to start human phase one/two trials that would happen at the end of the summer.

The earliest this could possibly reach clinical application would be September 2020 under  the  compassionate use act if everything goes smoothly and efficiently and red-tape is overcome.

The story of this rapid response by volunteers working after hours and on weekends, long before the Whitehouse started taking action, represents a remarkable effort undertaken by a private company with no public funding. Many hurdles must be overcome to bring this bio-therapeutic to patients. Once this becomes available it offers great hope for an effective treatment.

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob