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COVID-19, Lifestyle interventions more effective than drugs.

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So far drug intervention trials for treating COVID-19 have been disappointing. No studies have shown benefit for hydroxychloroquine, with or without azithromycin. This topic has been covered in previous posts. Remdesivir has been FDA approved based upon one study that showed reduction in duration of symptoms. The mortality rate with Remdesivir, however, did not demonstrate a statistically significant difference when compared to “usual care”. https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19

Another study published in Lancet failed to show any clinical benefit from Remdesivir.

“No statistically significant benefits were observed for remdesivir treatment beyond those of standard of care treatment. Our trial did not attain the predetermined sample size because the outbreak of COVID-19 was brought under control in China. Future studies of remdesivir, including earlier treatment in patients with COVID-19 and higher-dose regimens or in combination with other antivirals or SARS-CoV-2 neutralising antibodies in those with severe COVID-19 are needed to better understand its potential effectiveness.”

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext

But we do know that certain underlying conditions such as obesity, diabetes, pre-diabetes (insulin resistance) and hypertension significantly increase risk of DEATH AND COMPLICATIONS with COVID-19. Since there are lifestyle interventions that can quickly and effectively mitigate these problems (diet, exercise, sleep, stress reduction….) now would seem like a good time to take our epidemics of obesity and diabetes in hand with aggressive lifestyle interventions to decrease the mortality rate of COVID-19 infection. Such measures do not require expensive drugs or expensive drug trials, they simply require knowledge, guidelines and the will to implement change in our daily habits. Yet there has been little discussion about this in the media or on the part of public health officials.

Lets look at obesity in the US.

From 1999–2000 through 2017–2018, the age-adjusted prevalence of obesity increased from

30.5% to 42.4%, and the prevalence of severe obesity increased from 4.7% to 9.2%.

Click to access db360-h.pdf

The most effective tool for addressing obesity and diabetes is a very low carbohydrate diet.

Effects of the Low Carbohydrate, High Fat Diet on Glycemic Control and Body Weight in Patients With Type 2 Diabetes: Experience From a Community-Based Cohort

https://pubmed.ncbi.nlm.nih.gov/32193200/

This study was a done in a community-based program, not an academic practice setting. That is significant since it demonstrates feasibility outside of academic centers with standard community resources. The results of this study confirmed the results of many previous studies done in academic settings including better blood sugar control, reduction or elimination of diabetic medications, and significant weight loss.

“All patients following the LCHF diet who initially took
insulin had either a reduction or discontinuation of
this therapy by their healthcare provider when clinically
indicated, compared with less than a quarter of
those receiving usual care.“

In another study done in Italy, significant weight reduction (7 kg), waistline reduction (7 cm.), fat mass reduction (3.8%) and systolic blood pressure reduction (10.5 mmHg) were achieved in 3 months with a Very Low Carbohydrate diet.

Middle and Long-Term Impact of a Very Low-Carbohydrate Ketogenic Diet on Cardiometabolic Factors: A Multi-Center, Cross-Sectional, Clinical Study (https://pubmed.ncbi.nlm.nih.gov/25986079/

Nina Teicholz had an opinion piece published in the Wall Street Journal on May 30, discussing the USDA dietary guidelines that have largely ignored a massive body of evidence supporting a Very Low Carbohydrate Diet for obesity and diabetes. She cites many studies that have been ignored by the USDA dietary guidelines committee. Here is here opening statement.

“Americans with obesity, diabetes, heart disease and other diet-related diseases are about three times more likely to suffer worsened outcomes from Covid-19, including death. Had we flattened the still-rising curves of these conditions, it’s quite possible that our fight against the virus would today look very different.”

You can read the full article here:

https://www.wsj.com/articles/a-low-carb-strategy-for-fighting-the-pandemics-toll-11590811260

But think about that simple statement, THREE TIMES MORE LIKELY TO SUFFER WORSENED OUTCOMES FROM COVID-19. Yet these conditions are highly responsive to lifestyle interventions that not only mitigate obesity, insulin resistance and high blood pressure, but also enhance immune function.

More from Teicholz’s opinion piece:

“Other studies have found that dietary changes can rapidly and substantially improve cardiovascular risk factors, including conditions like hypertension that are major risk factors for worsened Covid-19 outcomes. A 2011 study in the journal Obesity on 300 clinic patients eating a very low-carbohydrate diet saw blood pressure quickly drop and remain low for years. And a 2014 trial on 148 subjects, funded by the National Institutes of Health, found a low-carb diet to be “more effective for weight loss and cardiovascular risk factor reduction” than a low-fat control diet at the end of the 1-year experiment.“

In a recent letter to the editor published in the journal METABOLISM, Dr. Casey Means points out:

A diagnosis of diabetes has been a key indicator of the severity of
COVID-19, and in this regard, the virus has relentlessly highlighted our
global Achilles heel of metabolic dysfunction, and points to a prime opportunity
to fight back.
That fight, however, is not going to be won with Clorox, Purell,
masks, or anti-IL-6 drugs. The fight will only be won through a serious
commitment to improving everyone’s foundational metabolic health,
starting with the lowest hanging evidence-based fruit: dietary and lifestyle
interventions.

Read the full letter here: https://www.metabolismjournal.com/article/S0026-0495(20)30118-9/pdf

In 2 pages the letter describes multiple benefits of better glucose control relative to COVID -19 infection and the immune system as well as reduction of factors that lead to cytokine storm (terminal event for many COVID-19 patients). The letter also discusses the benefit of reducing environmental toxins (discussed in previous posts about COVID-19 and other health problems) that would likely benefit COVID-19 patients.

Research published April 18th, 2020 found that patients exposed to
highest amount of environmental nitrogen dioxide (NO2) had increased
risk of death fromCOVID-19, and that long-term exposure to this pollutant
may be one of the most important contributors to fatality by
compounding lung inflammation [20].

Minimizing exposure to environmental
pollutants may serve a role in quelling the underlying pro-inflammatory
state that characterizes metabolic disease and COVID-19 associated
cytokine storms.

Other environmental toxins, including persistent organic pollutants
(POPs) found in air, water, and food generated from pesticides
and industrial chemicals, are also strongly implicated in the pathogenesis
of metabolic syndrome; promoting “clean living,” toxin-avoidant
strategies for patients as simple as emphasizing organic foods, home
air purification, and non-toxic home supplies could be considered, although
the clinical utility of these measures in the acute setting is unknown
[21].

In discussing the white elephant in the room he states:

What is starkly missing is the clear, simple, and strong recommendation for no added
sugar or ultra-refined carbohydrates, both of which are known drivers
of postprandial hyperglycemia and inflammation. As a medical community, we must not miss the opportunity to serve patients with straightforward, evidence-based nutritional and lifestyle strategies to assist in glycemic control.

I would encourage you to follow the link and read the 2 pages supported by multiple peer-reviewed references.

Evidence based nutritional and lifestyle strategies, so often discussed on this website include:

  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. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

If you have obesity, diabetes or pre-diabetes the Very Low Carbohydrate version of the anti-inflammatory diet linked above would be the fastest and most effective intervention you can immediately employ to reduce your risk of succumbing to COVID-19. (Of course wear a mask, follow good hygiene with hand-washing frequently, and practice social distancing)

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

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COVID-19: Hydroxychloroquine and Chloroquine, BAD NEWS.

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The most comprehensive study on the use of these 2 drugs, including 96,032 patients in multiple hospitals and multiple countries shows increased risk of death with either of these two drugs in patients hospitalized with COVID-19. This was a retrospective study but offers the most amount of data to date on the issue of clinical efficacy and risk. You can read the full article https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext.

TreatmentDeath rateventricular arrhythmia
No drug9.30%0.30%
Hydroxychloroquine18%6.10%
Hydroxychloroquine plus Macrolide23.80%8.10%
Chloroquine16.40%4.30%
Chloroquine plus Macrolide22.20%6.50%
Macrolide is an antibiotic like Zithromax.
Differences between no drug and all drug treatment categories statistically significant.

This was not a randomized prospective controlled clinical trial. However the data were adjusted for:

age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity.

So far it is the best information we have available.

There have been many physicians who have supported the use of these drugs without randomized controlled trials based on anecdotal reports in the medical literature. Given the desparate situation without a known effective drug that is understandable.

The authors note:

The absence of an effective treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led clinicians to redirect drugs that are known to be effective for other medical conditions to the treatment of COVID-19. Key among these repurposed therapeutic agents are the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for the treatment of autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis.

However, the use of this class of drugs for COVID-19 is based on a small number of anecdotal experiences that have shown variable responses in uncontrolled observational analyses, and small, open-label, randomised trials that have largely been inconclusive.

 The combination of hydroxychloroquine with a second-generation macrolide, such as azithromycin (or clarithromycin), has also been advocated, despite limited evidence for its effectiveness.

This study is an important milestone, disappointing but illustrative of a common phenomenon in medicine.

Previous warnings about potential lethal heart rhythm issues were viewed with skepticism by armchair pundits claiming that there was not much data on sudden death related to use of these widely used drugs. Those pundits failed to understand that sudden death caused by prolonged QT interval (effect of these and many other drugs) cannot be diagnosed without an EKG during the event. When this occurs outside the hospital setting, or even in the hospital without a continuous EKG monitor on the patient, it goes unrecognized.

An important dictum in medicine is “first do no harm” (primum non nocere).

In the meantime, we do know what reduces risk:

Test/Trace/Isolate, social distance, MASKS4ALL, wash hands frequently, disinfect surfaces, show consideration for others. To understand why and how these measures can make a big difference you can go to this website. https://www.erinbromage.com/

In addition you can read a great article about the same topic here. https://www.newyorker.com/science/medical-dispatch/amid-the-coronavirus-crisis-a-regimen-for-reentry

I will close with the sermon on lifestyle and COVID-19.

  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
  8. Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.

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

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COVID-19 Sweden vs Other Countries

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5/21/2020 deaths/ million 7 day running average doubling time
cumulative deaths/million/day days
SWEDEN 379 3.3 46
Norway 43.6 0.13 241
Finland 54.9 0.52 138
Denmark 95.6 0.49 120
USA 282 4.02 49
NZ 4.3 0 598
stay home test-trace leadership
isolate example
SWEDEN no yes ?
Norway yes yes good
Finland yes yes good
Denmark yes yes good
USA late/variable POOR poor
New Zealand yes excellent excellent

Sweden was a source of controversy for the choice against instituting a stay-home policy. As you compare Sweden with other Scandinavian countries above you will see a dramatic difference in deaths per million (cumulative), running 7 day average deaths per million per day, and doubling time. The higher the doubling time (in days) the more a country has slowed the spread. New Zealand is the obvious winner. Early and aggressive action, effective test/trace/isolate, excellent leadership and example by the president are the hallmarks of success in New Zealand. Of course New Zealand is a small island with minimal international business and tourism so the comparison is not fair. HOWEVER, their success and strategy are obvious.

The US failed (and continues to fail) on test/trace/isolate despite the bluster and misrepresentations from the Whitehouse. California and Washington instituted early measures with respect to stay-home but without adequate test kits all of US states have been unable to execute the test/trace/isolate strategy proven effective in other countries. President Trump promised California 100,000 nasal swabs per week three weeks ago. They have not arrived. (California Department of Public Health)

Thus comparing USA to Sweden we see that with adequate social distancing, test/trace/isolate, Sweden did almost as well (or as poorly) as the US where stay at home was employed on a variable time line and to different degrees between the states.

You can review worldwide data, download spreadsheets, choose countries for comparison here.

Test/Trace/Isolate + Social distance + Masks4all + cooperation = SUCCESS

Had the US responded early and effectively, stay-home could have ended very quickly and safely with much less economic disruption.

Poor Management = inadequate Test/Trace/Isolate and other measures.

The New England Journal of Medicine published an article discussing the failure of the
USA relative to Test/Trace/Isolate.

Failing the Test — The Tragic Data Gap Undermining the U.S. Pandemic Response

 

The importance of  Reviving the US CDC after annual cuts by the Trump Administration is discussed here.

On March 25 the NEJM published an editorial on responding to the pandemic.

We did not follow the recommendations.

The AMERICAN ENTERPRISE INSTITUTE, a conservative think-tank, published a comprehensive Roadmap to Reopening.

Unfortunately we have not followed that roadmap.

So boost your immune system and meet the challenge with your personal behavior. Be smart.

  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
  8. Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.

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

 

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COVID-19: ARDS, CYTOKINE STORM, and GLUTATHIONE

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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

 

 

 

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ZINC, ionophores, supplements and COVID-19

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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

 

 

 

 

 

 

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Stanford Study on Santa Clara County: Very questionable conclusions

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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

 

 

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Follow up to Letter from Front Line Doctor post and more

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After posting the letter from an ER doc who eloquently expressed the danger, concerns, and most importantly, call for action I realized that some explanation for the lay person is necessary.

Intubation is the placement of a breathing tube into the windpipe for a person in respiratory failure. During the procedure the doctor and all providers in the immediate area are in a very high risk situation because the droplets filled with billions of virus can become aerosolized. I previously explained the difference between spread by droplet vs aerosol. Droplets fall to the floor and surfaces where virus can be infectious for hours. But when aerosolized, the virus remains suspended in the air for hours and anyone entering the area can become infected by simply breathing the air.

During intubation the doctor has his/her face inches from the patients mouth and nose. During this procedure droplets can become aerosolized. Even wearing a perfectly fitting N95 mask, goggles, gown, gloves the doctor (and those assisting) is/are not completely protected.

I received a warning letter from an ENT surgeon at Stanford, warning colleagues about cases of ENT and Neuro-surgery (endoscopic surgery through the nose) where despite FULL PPE, all practitioners in the operating room became infected and  surgeons have died. The ENT surgeon warned that PPE with N-95 mask was not fully protective and recommended PAPRs be used (Powered, Air Purifying Respirators.) Here is what the surgeon reported he received from his international colleagues:

“All 14 people who came in and out of the OR during that case became infected. He saw this repeat with other endoscopic cases

He has also shared that a significant number of doctors who died in China were ENTs and Ophthalmologists, possibly due to the high viral shedding from the nasal cavity. This has now been confirmed in the media as well.[i]

[i] https://www.bloomberg.com/news/articles/2020-03-17/europe-s-doctors-getting-sick-like-in-wuhan-chinese-doctors-say?fbclid=IwAR2ds9OWRxQuMHAuy5Gb7ltqUGMZNSojVNtFmq3zzcSLb_bO9aGYr7URxaI”

All 14 people who entered and left the operating room during the surgery became infected despite wearing PPE!!!!!!!!!!

“we have additionally heard from Iran that at least 20 ENTs are currently hospitalized with COVID-19, with 20 more in isolation at home.” 

Although SARs had a higher mortality rate, IT WAS NOT AS CONTAGIOUS.

This demonstrates how contagious this virus can be, and that was early on in China and Iran, before it mutated. Mutations can make the virus more contagious and more lethal. There has already been a SECOND STRAIN IDENTIFIED.

In my career I have performed more than 10,000 intubations. Many under emergency circumstances. Donning full PPE correctly takes time and when in a hurry the N95 mask may not be perfectly fitted. (WATCH THE VIDEO BELOW)

Although I have intubated people with sepsis and TB under emergency conditions, I have never been exposed to the level of danger that doctors and other providers around the world are now experiencing. The PPE (personal protection equipment) is already running short in hot zones. Many hospitals are a few days away from running out. MANY PROVDERS are reusing PPE that is not meant to be reused.

AS more doctors, nurses, and techs become infected (which is inevitable) there will be less personnel to care for patients so MORTALITY RATES WILL INCREASE.

This has not been factored into the epidemiologic models and projections.

Temporary emergency hospital tents are great, but useless without personnel. There is a limited # of ICU and ER doctors, nurses and techs. And they all need PPE.

That is why flattening the curve is so important.

That is why folks who ignore the behavioral guidelines are reckless and endangering others in the community and in hospitals.

We need to hear this every day from Doctors like FAUCI.

Misinformation from uninformed and anti-science politicians is tragically harmful.

EASTER WILL NOT BE MAGICAL.

Ventilators are useless without doctors, nurses and respiratory therapists to manage them. So production of ventilators is futile unless PPE are prioritized, WHICH HAS NOT YET HAPPENED. Shortages abound and the executive branch has not coordinated the private sector in addressing production and distribution. Instead leaving it up to the MARKET!

This has been described as a WAR, but we are not mobilizing the way we did during WW2. Mobilization requires central coordination, not bidding wars between states and hospitals for PPE, bleach and other sanitizers.

Here is the link to AN instructional video on donning PPE. Watch how long it takes and the steps required to achieve proper fit and seal for the N95 mask. Now imagine doing that while a patient is blue/hypoxic, or in cardiac and/OR respiratory arrest.

 

 

Later I will post practical precautions for groceries, mail, gas stations etc. A separate page on this website will document that.

I will also create a COVID 19 page with cut and pasted excerpts from documents as well as links to informative documents, videos and websites.

STAY SAFE.

I do not wish to create or contribute to panic, if you follow the recommendations of shelter in place and social distancing and follow good hygiene you and everyone around you will be MUCH SAFER. I merely want to emphasize why flattening the curve and following recommendations are so important. The more people comply, the shorter will be the time when we can prudently start to return incrementally to normal activity.

Testing still remains inadequate with backlogs of 10 days in hot zones. So the information we are getting on # of cases is almost 2 weeks behind what is out there and even if we had 45 minute turn around, the testing kits are being rationed. So we are just seeing the tip of the iceberg. And that will be the UNFORTUNATE situation for a while.

Although we have seen TOO LITTLE TOO LATE, we can still flatten the curve by following recommended practices. We can still save lives, prevent disability and suffering, and get to a point where we can return to a more “normal” life. The longer we wait for every state to institute necessary measures (Florida is an example of inadequate measures) the longer will be our restrictions.

Remember, you can boost your immune system by getting adequate restorative sleep, rest, exercise, sunshine, stress reduction and eating an anti-inflammatory diet. Avoid alcohol (which impairs your immune system) and quit smoking. You can help prepare your body to mitigate a cytokine storm by increasing in your cell membranes, the omega 3 marine fats (EPA and DHA) which are the precursors for RESOLVINS that help regulate the inflammatory response. The inflammatory response is protective but when out of control it can be lethal in the ICU or on your way to the hospital. Your body’s defense systems can be optimized by eating an anti-inflammatory diet rich in nutrients that support immunity and regulate inflammation. A healthy diet can only be beneficial. All of these measures can be practiced while sheltering in place and practicing social distancing.

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

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COVID19 UPDATE, UCSF CONFERENCE REPORTS FRIGHTENING INFORMATION

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On March 10 a panel discussion/conference of Infectious Disease and PANDEMIC experts convened at UCSF (University of California San Francisco). Here are the panelists.

  • Panelists
    • Joe DeRisi:  UCSF’s top infectious disease researcher.  Co-president of ChanZuckerberg BioHub (a JV involving UCSF / Berkeley / Stanford).  Co-inventor of the chip used in SARS epidemic.
    • Emily Crawford:  COVID task force director.  Focused on diagnostics
    • Cristina Tato:   Rapid Response Director.  Immunologist.
    • Patrick Ayescue:   Leading outbreak response and surveillance.  Epidemiologist.
    • Chaz Langelier:   UCSF Infectious Disease doctor

Unless bracketed, these are direct quotes of the panelists. This was forwarded to me by a physician friend whose colleague prepared it. The “I” refers to that colleague.

University of California, San Francisco BioHub Panel on COVID-19

March 10, 2020

  • Top takeaways 
    • At this point, we are past containment.  Containment is basically futile.  Our containment efforts won’t reduce the number who get infected in the US.  
    • Now we’re just trying to slow the spread, to help healthcare providers deal with the demand peak.  In other words, the goal of containment is to “flatten the curve”, to lower the peak of the surge of demand that will hit healthcare providers.  And to buy time, in hopes a drug can be developed. 
    • How many in the community already have the virus?  No one knows.
    • We are moving from containment to care.  
    • We in the US are currently where at where Italy was a week ago.  We see nothing to say we will be substantially different.
    • 40-70% of the US population will be infected over the next 12-18 months.  After that level you can start to get herd immunity.  Unlike flu this is entirely novel to humans, so there is no latent immunity in the global population.
    • [We used their numbers to work out a guesstimate of deaths— indicating about 1.5 million Americans may die.  The panelists did not disagree with our estimate.  This compares to seasonal flu’s average of 50K Americans per year.  Assume 50% of US population, that’s 160M people infected.  With 1% mortality rate that’s 1.6M Americans die over the next 12-18 months.]  
      • The fatality rate is in the range of 10X flu.
      • This assumes no drug is found effective and made available.
    • The death rate varies hugely by age.  Over age 80 the mortality rate could be 10-15%.  [See chart by age Signe found online, attached at bottom.]
    • Don’t know whether COVID-19 is seasonal but if is and subsides over the summer, it is likely to roar back in fall as the 1918 flu did
    • I can only tell you two things definitively.  Definitively it’s going to get worse before it gets better.  And we’ll be dealing with this for the next year at least.  Our lives are going to look different for the next year.

 

  • What should we do now?  What are you doing for your family?
    • Appears one can be infectious before being symptomatic.  We don’t know how infectious before symptomatic, but know that highest level of virus prevalence coincides with symptoms.  We currently think folks are infectious 2 days before through 14 days after onset of symptoms (T-2 to T+14 onset).
    • How long does the virus last?
      • On surfaces, best guess is 4-20 hours depending on surface type (maybe a few days) but still no consensus on this
      • The virus is very susceptible to common anti-bacterial cleaning agents:  bleach, hydrogen peroxide, alcohol-based.
    • Avoid concerts, movies, crowded places.
    • We have cancelled business travel.
    • Do the basic hygiene, eg hand washing and avoiding touching face.
    • Stockpile your critical prescription medications.  Many pharma supply chains run through China.  Pharma companies usually hold 2-3 months of raw materials, so may run out given the disruption in China’s manufacturing.
    • Pneumonia shot might be helpful.  Not preventative of COVID-19, but reduces your chance of being weakened, which makes COVID-19 more dangerous.
    • Get a flu shot next fall.  Not preventative of COVID-19, but reduces your chance of being weakened, which makes COVID-19 more dangerous.
    • We would say “Anyone over 60 stay at home unless it’s critical”.  CDC toyed with idea of saying anyone over 60 not travel on commercial airlines.
    • We at UCSF are moving our “at-risk” parents back from nursing homes, etc. to their own homes.  Then are not letting them out of the house.  The other members of the family are washing hands the moment they come in.
    • Three routes of infection
      • Hand to mouth / face
      • Aerosol transmission
      • Fecal oral route

 

 

  • What if someone is sick?
    • If someone gets sick, have them stay home and socially isolate.  There is very little you can do at a hospital that you couldn’t do at home.  Most cases are mild.  But if they are old or have lung or cardio-vascular problems, read on.
    • If someone gets quite sick who is old (70+) or with lung or cardio-vascular problems, take them to the ER.
    • There is no accepted treatment for COVID-19.  The hospital will give supportive care (eg IV fluids, oxygen) to help you stay alive while your body fights the disease.  ie to prevent sepsis.
    • If someone gets sick who is high risk (eg is both old and has lung/cardio-vascular problems), you can try to get them enrolled for “compassionate use” of Remdesivir, a drug that is in clinical trial at San Francisco General and UCSF, and in China.  Need to find a doc there in order to ask to enroll.  Remdesivir is an anti-viral from Gilead that showed effectiveness against MERS in primates and is being tried against COVID-19.  If the trials succeed it might be available for next winter as production scales up far faster for drugs than for vaccines.  [MoreI found online.]
    • Why is the fatality rate much higher for older adults?
      • Your immune system declines past age 50
      • Fatality rate tracks closely with “co-morbidity”, ie the presence of other conditions that compromise the patient’s health, especially respiratory or cardio-vascular illness.  These conditions are higher in older adults.
      • Risk of pneumonia is higher in older adults.

 

  • What about testing to know if someone has COVID-19? 
    • Bottom line, there is not enough testing capacity to be broadly useful.  Here’s why.
    • Currently, there is no way to determine what a person has other than a PCR test.  No other test can yet distinguish “COVID-19 from flu or from the other dozen respiratory bugs that are circulating”.
    • A Polymerase Chain Reaction (PCR) test can detect COVID-19’s RNA.  However they still don’t have confidence in the test’s specificity, ie they don’t know the rate of false negatives.
    • The PCR test requires kits with reagents and requires clinical labs to process the kits.
    • While the kits are becoming available, the lab capacity is not growing.
    • The leading clinical lab firms, Quest and Labcorp have capacity to process 1000 kits per day.  For the nation.
    • Expanding processing capacity takes “time, space, and equipment.”  And certification.   ie it won’t happen soon.
    • UCSF and UC Berkeley have donated their research labs to process kits.  But each has capacity to process only 20-40 kits per day.  And are not clinically certified.
    • Novel test methods are on the horizon, but not here now and won’t be at any scale to be useful for the present danger.

 

  • How well is society preparing for the impact?
    • Local hospitals are adding capacity as we speak.  UCSF’s Parnassus campus has erected “triage tents” in a parking lot.  They have converted a ward to “negative pressure” which is needed to contain the virus.  They are considering re-opening the shuttered Mt Zion facility.
    • If COVID-19 affected children then we would be seeing mass departures of families from cities.  But thankfully now we know that kids are not affected.
    • School closures are one the biggest societal impacts.  We need to be thoughtful before we close schools, especially elementary schools because of the knock-on effects.  If elementary kids are not in school then some hospital staff can’t come to work, which decreases hospital capacity at a time of surging demand for hospital services.
    • Public Health systems are prepared to deal with short-term outbreaks that last for weeks, like an outbreak of meningitis.  They do not have the capacity to sustain for outbreaks that last for months.  Other solutions will have to be found.
    • What will we do to handle behavior changes that can last for months?
      • Many employees will need to make accommodations for elderly parents and those with underlying conditions and immune-suppressed.
      • Kids home due to school closures
    • [Dr. DeRisi had to leave the meeting for a call with the governor’s office.  When he returned we asked what the call covered.]  The epidemiological models the state is using to track and trigger action.  The state is planning at what point they will take certain actions.  ie what will trigger an order to cease any gatherings of over 1000 people.

 

  • Where do you find reliable news?
    • The John Hopkins Center for Health Security site.   Which posts daily updates.  The site says you can sign up to receive a daily newsletter on COVID-19 by email.  [I tried and the page times out due to high demand.  After three more tries I was successful in registering for the newsletter.]
    • The New York Times is good on scientific accuracy.

 

 

  • Observations on China
    • Unlike during SARS, China’s scientists are publishing openly and accurately on COVID-19.
    • While China’s early reports on incidence were clearly low, that seems to trace to their data management systems being overwhelmed, not to any bad intent.
    • Wuhan has 4.3 beds per thousand while US has 2.8 beds per thousand.  Wuhan built 2 additional hospitals in 2 weeks.  Even so, most patients were sent to gymnasiums to sleep on cots.
    • Early on no one had info on COVID-19.  So China reacted in a way unique modern history, except in wartime.

 

  • Every few years there seems another:  SARS, Ebola, MERS, H1N1, COVID-19.  Growing strains of antibiotic resistant bacteria.  Are we in the twilight of a century of medicine’s great triumph over infectious disease?
    • “We’ve been in a back and forth battle against viruses for a million years.”
    • But it would sure help if every country would shut down their wet markets.
    • As with many things, the worst impact of COVID-19 will likely be in the countries with the least resources, eg Africa.  See article on Wired magazine on sequencing of virus from Cambodia.

So that is the synopsis provided by my friend’s colleague.

Unfortunately, the Trump administration has been dangerously incompetent in addressing-mitigating the public health and economic impact. Trump STILL HAS NOT DECLARED THIS A NATIONAL EMERGENCY!

Whitehouse spokespeople have stated Trump does not want to declare this an emergency because it would contradict his earlier statements that COVID19 is not a serious problem (he tweeted and stated it is less serious than the flu). If declared a NATIONAL EMERGENCY it would free up large amounts of money and resources for public health, FEMA, and economic assistance, yet it has not been done. INSTEAD, TRUMP is waiting for his son-in-law (who has no scientific training) to research COVID19 and make recommendations for national policy!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

SERIOUSLY???????????

This post and all posts are for informational, educational purposes and should not be taken as medical advice. Consult your health care practitioner for medical advise.

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

 

 

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Depression, Food, Sunshine, Gut Microbiome

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A family member was admitted to a psychiatric hospital this year with a major depressive episode. For the sake of anonymity lets call her Margie. I investigated the hospital and found that the medical director, chief nursing officer and CEO had excellent credentials. I asked Margie about her food choices, opportunity for exercise and time outdoors. All of these were deplorable. The only opportunity to spend time outdoors was to go outside with the smoking group for 20 minutes twice per day (cigarette breaks). There was no exercise program or exercise opportunity other than walking the halls and walking up and down the stairs with the smoking group going to/from a smoking session. The only green leafy vegetable available was iceberg lettuce (minimal nutritional value). Food options included high sugar and high starch content items, with very few vegetables and fresh fruits. Sugar and refined carbohydrates contribute to inflammation and gut dysbiosis, both of which contribute to psychiatric illness.

Margie had insomnia and depression. These two problems travel together and feed on each other. The lack of outdoor light in the morning and presence of artificial light in the evening all contribute to disruption of  circadian rhythm, worsening depression and insomnia. Lack of exercise also contributes to both.

Here is an excerpt of a letter I sent to her treating psychiatrist with copies to the CEO, medical director and chief nursing officer.

I do have concerns about the lack of availability at XXXXXXXXX Hospital of two essential components to mental health, specifically nutritional support and exercise.

So far the dietician has not yet consulted with XXXXX. I called the dietary department to discuss my concerns that she has been served primarily nutritionally deplete starch and sugar laden foods with a minimum of vegetables, fruit, healthy fat and protein. I was told that the only green leafy vegetable available is lettuce and when I inquired about other vegetables the response was very limited. Bob in the dietary department was great and very receptive to my concerns but seems somewhat limited in the availability of appropriate nutrient dense food at XXXXXXXX.

In addition, Maria tells me that XXXXXXX has no exercise program or exercise facility for patients. The importance of exercise and nutrition has been discussed extensively in the psychiatry literature.

Enclosed are a few review articles and abstracts relevant to nutrition and exercise for in-patient psychiatry. I hope you find these useful and would consider making efforts along the lines of the author’s recommendations in these studies and review articles.

I found the review by Dr LaChance and Dr. Ramsey “Antidepressant foods: An evidence-based nutrient profiling system for depression” to be most informative. You are probably aware that Dr. Ramsey has presented many lectures at the annual meeting of the American Psychiatric Association. The authors of the other studies enclosed have also been well represented at that meeting.

Despite requesting a response from the Medical Director, Chief Nursing Officer, and CEO, I never received any communication in response to my concerns.

The concept of “NUTRITIONAL PSYCHIATRY” has received much attention in the psychiatry literature. This article was published in the World Journal of Psychiatry. Antidepressant foods: An evidence-based nutrient profiling system for depression.

The article discusses nutrients that are “related to the prevention and treatment of depressive disorders”

Here is a summary:

Twelve Antidepressant Nutrients relate to the prevention and treatment of depressive disorders: Folate, iron, long-chain omega-3 fatty acids (EPA and DHA), magnesium, potassium, selenium, thiamine, vitamin A, vitamin B6, vitamin B12, vitamin C, and zinc.

The highest scoring foods were bivalves such as oysters and mussels, various seafoods, and organ meats for animal foods. The highest scoring plant foods were leafy greens, lettuces, peppers, and cruciferous vegetables.

This description aligns with the anti-inflammatory diet that I recommend to patients.

This dietary approach provides essential nutrients for brain health but also provides for healthy diversity in the gut microbiome,.

The relationship between psychiatric illness and the gut microbiome has been extensively reviewed in the medical literature.

Source of image:

Frontiers in Integrative Neuroscience, 11 September 2018 | https://doi.org/10.3389/fnint.2018.00033

This complicated picture depicts the interaction between food, gut microbiome, immune system, inflammation, endocrine system (stress response mediated by the hypothalamic pituitary adrenal axis), nervous system, neuro-transmitters including serotonin (the target of many ante-depressant medications). BBB is the blood brain barrier. ENS is the enteric nervous system. SCFAs are short chain fatty acids, very important for health, produced by “good” gut bacteria by using dietary fiber. SCFAs serve several useful purposes including nourishment for the cells that line the gut, protection of the tight junctions between those cells (prevent leaky gut), direct anti-inflammatory actions and more. Leaky gut leads to an increase in pro-inflammatory substances crossing the gut barrier and entering the body (instead of staying in the gut and leaving with stool) with a cascade of undesirable consequences. LPS (lipopolysaccharides) are bacterial wall toxins that stimulate the immune system and create inflammation. This inflammatory response is a major contributor to death in the setting of systemic infections (sepsis).

If you are interested in understanding this picture you can read the entire article here.

It is clear from this picture that the authors recommend beans and whole grains. I advise  against the consumption of grains and legumes in favor of colorful vegetables which provide for 5-7 times the amount of fiber per calorie compared to grains. Many reasons to avoid grains and legumes discussed on the website many times.

Fiber-rich diets are the main fermentable sources for SCFAs which contribute to the attenuation of systemic inflammation by inducing regulatory T cells. (Lucas et al., 2018) and through multiple other mechanisms.

SCFAs are one of many metabolites produced by gut bacteria that contribute to the prevention of depression

The mechanisms of action include direct communication to the brain through the vagus nerve, absorption of SCFAs into the blood where it can reach the brain and have beneficial effects, dampening of the inflammatory immune response, protecting the gut lining as mentioned above. These are depicted below.

 

SCFAs and depression

Image Source : Microb Cell 2019 Oct 7,; 6(10): 451-481, PMID 31646148

Exercise protects against depression and is useful as therapy for depression.

In her discussion of depression as a brain inflammatory disorder Psychiatrist Emily Dean describes well some of these interactions.

This is not the first time I have observed  very limited access to nutritious foods, exercise and sunlight in the setting of a psychiatric hospital. Unfortunately, it will likely not be the last despite multiple studies and articles in the medical literature pointing to the importance of these three ingredients for general and psychiatric health.

To prevent and treat depression and other psychiatric illnesses, nutrition, exercise, sunshine are all important. Lack of these basic treatment modalities hampers recovery and health.

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.

Doctor Bob

 

 

 

 

COVID-19 UPDATE: Masks, social distancing much more important than cleaning surfaces.

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Today’s update from the Johns Hopkins Center for Health Security:

An editorial published in Nature discusses the need to shift focus away from surface decontamination as a mechanism to reduce SARS-CoV-2 transmission risk. Multiple studies have found that transmission of SARS-CoV-2 via contaminated surfaces, or fomites, is relatively rare compared to respiratory transmission via droplets or aerosols. Despite the evidence supporting respiratory exposure as the overwhelming driver of community transmission, numerous public health entities, including the WHO and US CDC, continue to emphasize the importance of surface decontamination, which can cause confusion among the public regarding transmission risk and appropriate protective measures. Notably, surface decontamination efforts, while highly visible and easy to recognize, are costly and likely not effective means of reducing transmission risk. The editorial calls for increased focus on improving ventilation and air filtration capacity to reduce respiratory exposure. Additionally, proper physical distancing and face mask use remain key tools in mitigating exposure and transmission risk for individuals.

The key to reducing the risk of symptomatic infection, especially moderate to severe illness and death appears to be vaccination.

While vaccination clearly reduces the risk of severe illness and death, we do not yet know whether or how much vaccination reduces the risk of carrying and transmitting the virus. So even after vaccination, an asymptomatic or minimally symptomatic person can still transmit the disease to others.

50-60% of viral transmission appears to be from asymptomatic individuals. So wearing a mask, social distancing, and avoiding unventilated crowded indoor spaces remains extremely important.

DOUBLE MASKING IS MORE EFFECTIVE THAN SINGLE MASKS.

A TRIPLE LAYER MASK OF TIGHTLY WOVEN FABRIC IS MORE EFFECTIVE THAN a SINGLE OR DOUBLE LAYER MASK.

N95 MASKS ARE MOST EFFECTIVE BUT THEY MUST FIT THE FACE WITH A TIGHT, SNUG FIT. 

TO IMRPOVE THE BARRIER FUNCTION OF MASKS WEAR A SNUG FABRIC MASK OVER A SURGICAL MASK OR OVER AN N-95. THIS WILL PROTECT BOTH THE WEARER AND THOSE AROUND THE WEARER. The fabric mask over a surgical or N-95 mask provides two mechanisms of protection. It adds an extra layer and it provides for a tighter fit of the underlying mask.

Doctors and nurses in hospitals and clinics often wear a surgical mask over an N-95. 

Face shields do not protect you or those around you from infection. Face shields and goggles (more so) likely decrease the risk of infection transmitted from aerosols that hit your eyes but do nothing for the most important mechanism of spread, breathing aerosols or droplets into your nose. Aerosols spread around a face shield into your nose. 

Think about smelling the pleasant odors of food cooking in a kitchen. Face shields will not block those aerosolized food vapors from entering your nose, but tightly fitting masks will do it to some degree.

SARS-CoV-2 virus is at least 10 times more lethal than an “average” case of influenza. Newer circulating variants have mutations that have probably increased the mortality rate.

SARS-CoV-2 is at least 10 times more easily transmitted compared to most respiratory viruses. Newer circulating variants have definitely increased ease of transmission by at least 30%. As a result, herd immunity will likely require 85-90% vaccination of a given population.

10 times 10 equals 100 TIMES MORE SERIOUS.

In addition, compared to other respiratory viruses, this virus will more frequently cause long lasting or even permanent damage and disability involving one or more organs (heart, lung, kidney, brain). Long-COVID can occur following minimally symptomatic illness and even after asymptomatic illness.

This virus is unique in that TRANSMISSION OCCURS MOST FREQUENTLY FROM ASSYMPTOMATIC INDIVIDUALS.

This occurs for two reasons.

1. Unlike most other respiratory viruses, there is a long time from the onset of when a person becomes infectious to when they become symptomatic. (an average of 5 days)

2. Some individuals never develop symptoms but are still highly infectious for up to 2 weeks.

Restaurants, bars, churches, meeting rooms, cafeterias, parties in closed spaces are situations for SUPERSPREADER EVENTS. An this includes SUPER BOWL PARTIES.

Studies in hospitals show that transmission to health care workers occurs most frequently in the cafeteria and in meeting rooms, not at the bedside where providers are wearing PPE.

In the context of the COVID 19 pandemic I will close with the usual summary.

  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. Supplement with Vitamin D3 to get your levels above 30 ng/ml. (read this Open Letter)
  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. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

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

Autoimmunity: Another reason why VACCINE is safer than INFECTION.

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There is growing evidence that self-attacking ‘autoantibodies’ could be the key to understanding some of the worst cases of COVID-19.

This might explain why lung damage and other organ damage sometimes continues to worsen AFTER the body seems to have cleared the SARS-CoV-2 virus. And it could explain why some individuals fail to mount an adequate immune response early in the disease.

With respect to the later, in September 2020 researchers at the Rockefeller University reported that > 10% of 987 patients with severe COVID-19 infection had antibodies that blocked type 1 interferon molecules, an essential part of the innate immune system.

Other researchers have screened patients with varying severity of COVID-19 and found higher prevalence of autoantibodies against the immune system in infected individuals compared to uninfected controls.

Yet another study found that some infected individuals had autoantibodies against proteins in their blood vessels, heart and brain.

Many patients with severe COVID suffer from life threatening blood clots. Phospholipids play a major role in controlling blood clotting. 52% of 172 people hospitalzied with COVID 19 were found to have anti-phospholipid antibodies.

Annexin A2 is a human protein that protects the integrity of small blood vessels in the lung. Researchers have found a significantly higher average level of anti-annexin A2 antibodies in people who died of COVID-19 compared to patients with less severe illness.

So far it is unclear whether the virus caused these antibodies or whether these unlucky individuals had higher than normal amounts of auto-antibodies prior to infection.

A paper published in the immunology literature just yesterday might shed some light on this issue as well as on the topic of LONG COVID.

We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause.

In other words, they tested antibodies against the SARS-CoV-2 virus to see whether they reacted against various kinds of human tissue. Here is what they found.

We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more.

This extensive immune cross-reactivity between SARS-CoV-2 antibodies and different antigen groups may play a role in the multi-system disease process of COVID-19, influence the severity of the disease, precipitate the onset of autoimmunity in susceptible subgroups, and potentially exacerbate autoimmunity in subjects that have pre-existing autoimmune diseases.

You can read the full study here: https://www.frontiersin.org/articles/10.3389/fimmu.2020.617089/full

Cross reactivity between antibodies against COVID-19 virus and human tissue was found for every major organ system in the human body.

The concept of “molecular mimicry” has been well described in auto-immunity for many years. This occurs when a portion of a foreign protein (on for example a virus or bacterium) is identical to a portion of a protein found in human tissue. When the immune system responds to invasion by a virus or bacteria it creates antibodies to various proteins on the invader. But in so doing the anti-bodies can react against human tissue that shares a small common string of amino acids (referred to as an epitope).

A famous example of molecular mimicry occurs with Rheumatic Heart Disease in which antibodies against the bacteria responsible for Strep Throat cross react with heart tissue causing destruction of heart valve tissue and a resultant leaky heart valve. In this situation cross reaction can also occur with tissue in joints resulting in arthritis, another hallmark of rheumatic fever. These were serious complications of Strep Throat before Penicillin became widely available.

So far we know that sicker COVID-19 patients demonstrate antibodies against multiple types of human tissue.

We also know that antibodies that react against various portions of the virus can also react against human tissue.

Finally we know that multi-organ failure is an inflammatory response wherein the immune system, rather than the virus, causes organ failure.

It would be a reasonable conclusion that auto-immunity can acutely contribute to cytokine and bradykinin storm.

It would also be a reasonable conclusion that auto-immunity contributes to LONG COVID.

So why would that make an mRNA vaccine safer?

The mRNA vaccine results in antibodies against one part of the virus (one epitope, the spike protein).

But infection results in antibodies against MULTIPLE PARTS OF THE VIRUS (multiple epitopes). Because multiple antigens or epitopes are involved in the immune response to infection, it increases the probability that cross reaction with multiple human tissues can result.

From an autoimmune perspective, the mRNA vaccine is much safer.

Obviously, given the fact that over 400,000 deaths have resulted in the US from this infection and no deaths have been attributed to the vaccine, the vaccine appears to be much safer than infection. Both the Pfizer and Moderna vaccine have decreased the risk of symptomatic infection by 95%. Severe symptomatic infection can lead to death. Even asymptomatic infection can cause LONG COVID. The risk-benefit analysis overwhelmingly favors the vaccine.

For a deeper dive into auto-immunity and COVID-19 here are a few more references:

High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms

Autoantibodies against type I IFNs in patients with life-threatening COVID-

Diverse functional autoantibodies in patients with COVID-19

Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19

 Association between anti-interferon-alpha autoantibodies and COVID-19 in systemic lupus erythematosus

Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19

 IgM autoantibodies recognizing ACE2 are associated with severe COVID-19

Is the association between IgG anti‐cardiolipin autoantibodies and COVID‐19 severity related to the lung injury or to the SARS‐CoV‐2 infection?

Do cross-reactive antibodies cause neuropathology in COVID-19?

Immunoserologic detection and diagnostic relevance of cross-reactive autoantibodies in coronavirus disease 2019 patients

Anticardiolipin IgG Autoantibody Level Is an Independent Risk Factor for COVID‐19 Severity

Rheumatic manifestations of COVID-19: a systematic review and meta-analysis

The immunology of multisystem inflammatory syndrome in children with COVID-19

Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated 

In the context of the COVID 19 pandemic I will close with the usual summary.

  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. Supplement with Vitamin D3 to get your levels above 30 ng/ml. (read this Open Letter)
  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. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

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

Vitamin D for All, the time is right

2 Replies

On Dec 7, 2020 a group of more than 100 scientists signed a letter recommending that governmental agencies and major medical organizations endorse their recommendation for universal Vitamin D supplementation at adequate doses in order to decrease the risk of COVID-19 infection and death.

https://vitamindforall.org/letter.html

The letter cites multiple converging sources of data from several studies that should no longer be ignored.

“To all governments, public health officials, doctors, and healthcare workers,
[Residents of the USA: Text “VitaminDforAll” to 50409 to send this to your state’s governor.]
Research shows low vitamin D levels almost certainly promote COVID-19 infections, hospitalizations, and deaths. Given its safety, we call for immediate widespread increased vitamin D intakes .
Vitamin D modulates thousands of genes and many aspects of immune function, both innate and adaptive. The scientific evidence shows that:
● Higher vitamin D blood levels are associated with lower rates of SARS-CoV-2 infection.
● Higher D levels are associated with lower risk of a severe case (hospitalization, ICU, or death).
● Intervention studies (including RCTs) indicate that vitamin D can be a very effective treatment.
● Many papers reveal several biological mechanisms by which vitamin D influences COVID-19.
● Causal inference modelling, Hill’s criteria, the intervention studies & the biological mechanisms indicate that vitamin D’s influence on COVID-19 is very likely causal , not just correlation.“

I have previously discussed the relationship between low Vitamin D levels and COVID-19 infection.

https://practical-evolutionary-health.com/2020/05/02/covid-19-link-to-vitamin-d-status-should-doctors-prescribe-sunshine/

Since that post several more studies have been published strengthening the evidence that low levels of Vitamin D are not only ASSOCIATED with increased risk of infection, severe illness and death from COVID-19, but that this relationship is CAUSATIVE.

80% of patients requiring ICU care for COVID-19 infection have low vitamin D levels (25-OH Vitamin D levels less than 30 ng/ml)

“The data strongly suggests that vitamin D is the safest, easiest, and most important anti-pandemic measure the world is failing to prioritize,” says Karl Pfleger, Ph.D., biotech investor, former Google data scientist, and one of the organizers of VitaminDforAll.org.

More than 80 percent of COVID-19 patients are deficient in Vitamin D, studies show.

But how much vitamin D should an adult take and in what form?

As discussed in the letter, 3875 IU (97 micrograms) of Vitamin D3 daily is required for 97.5% of adults to reach a level of 20 ng/ml. 6200 IU (155 mcg) are required for 97.5% of adults to reach a level of 30 ng/ml. These doses far exceed the RDA (minimum daily requirement) necessary to prevent rickets.

On a sunny day, not too far from the equator, adult humans are capable of generating 10,000 units of vitamin D per day from the interaction of sunlight with skin. Human studies have demonstrated NO TOXICITY with daily supplementation of 10,000 units Vitamin D3 per day. Because of the risks of skin cancer, common use of sun block, distance from the equator, and a decrease in the ability of humans to make vitamin D from sunlight as we age, too many people have chronically low levels.

Vitamin D is a fat soluble vitamin. On a given daily dose it takes about 3 months to reach a steady state (stable tissue levels).

The point of that open letter and similar letters which have been published in major medical journals is the following. There exists today enough data to support universal supplementation with safe doses of Vitamin D3, well above the RDA, in order to decrease the risk of COVID-19 infection, risk of severe illness, and risk of death with the infection. Any further delay, waiting for more data is senseless. The risk benefit calculation based on present data is a “no-brainer”.

My wife and I have been supplementing with 4000 IU per day. Fauci is reported to be taking 6000 IU per day. We take it with food in order to maximize absorption. Our levels have been measured. Our levels are >30 ng/ml, <40 ng/ml on this dose. These are protective levels.

The amount of supplementation necessary to achieve these levels varies from person to person, season to season, and varies with distance from the equator. Some individuals will require less, some more to achieve levels above 30 ng/ml. But adults can safely take the daily amount recommended in VitaminDforall, http://HTML version.

The suggested protocol for those not already receiving the recommended intake is 10,000 IU (250mcg) daily for 2-3 weeks (or until achieving 30ng/ml if undergoing testing), followed by taking 2000-4000 IU daily thereafter.

In the context of the COVID 19 pandemic I will close with the usual summary.

  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. Supplement with Vitamin D3 to get your levels above 30 ng/ml. (read this Open Letter)
  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. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

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

UK variant, Ro and herd immunity

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The new SARS-CoV-2 variant first appearing in southern England has a transmission advantage of 0.4 to 0.7 points higher in reproduction number, also known as R0, compared to the initial strain, British researchers found.

From the study itself:

There is a consensus among all analyses that the VOC has a substantial
transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8.

The researchers published their findings on the school’s website. VOC means “variant of concern”.

In other words, this new variant has an Ro which is 1.4 to 1.8 times higher than the previously circulating predominant strain.

CDC has concluded that based on genetic studies (discussed in a previous post) and reactivity to antibodies found in the blood of vaccinated individuals it appears unlikely to impact COVID-19 vaccine effectiveness. This conclusion has been reached by multiple immunologists who did those studies. (See https://practical-evolutionary-health.com/2020/12/31/new-uk-sars-cov-2-variant-we-see-no-evidence-that-the-reported-mutations-would-substantially-increase-reinfection-risk-or-decrease-vaccine-efficacy/)

So what is the reproduction number? Ro is the average number of individuals infected by one person. A Ro of 2 means that every infected person on average infects 2 other people.

When a critical proportion of a population becomes immune, called the herd immunity threshold (HIT), the disease no longer spreads exponentially in the population. The disease reaches an endemic steady state. It neither grows nor declines exponentially.

From Wikipedia:

This threshold can be calculated from the effective reproduction number Re, which is obtained by taking the product of the basic reproduction numberR0, the average number of new infections caused by each case in an entirely susceptible population that is homogeneous, or well-mixed, meaning each individual can come into contact with every other susceptible individual in the population,[and S, the proportion of the population who are susceptible to infection, and setting this product to be equal to 1:

Ro X S = 1

S can be rewritten as (1 − p), where p is the proportion of the population that is immune so that p + S equals one. Then, the equation can be rearranged to place p by itself as follows:

Ro x (1-p) = 1, 1-p = 1/Ro, so {\displaystyle p_{c}=1-{\frac {1}{R_{0}}}.}

When the effective reproduction number Re of a contagious disease is reduced to and sustained below 1 new individual per infection, the number of cases occurring in the population gradually decreases until the disease has been eliminated.

An assumption in these calculations is that populations are homogeneous, or well-mixed, meaning that every individual comes into contact with every other individual, when in reality populations are better described as social networks as individuals tend to cluster together, remaining in relatively close contact with a limited number of other individuals. In these networks, transmission only occurs between those who are geographically or physically close to one another. The shape and size of a network is likely to alter a disease’s HIT, making incidence either more or less common

But transmission is not just affected by the characteristics of the virus, it is also affected by the behavior of the population in which the virus is observed. So it is complicated. As stated by the authors of the transmission study.

We note that these estimates of transmission advantage apply to a period
where high levels of social distancing were in place in England; extrapolation to other
transmission contexts therefore requires caution.

So if social distancing is relaxed, fewer people wear masks, more people congregate, then this variant could have a much higher Ro.

Ro for measles is 12-18 rendering HIT at 92-95%

Ro for SARS CoV-1 (2002-2004 pandemic) was estimated at 2-5 rendering HIT 50-80%

Ro for SARS CoV-2 (COVID-19) has been estimated at 2.5-4 giving and HIT of 60-75%.

This is not the first variant to demonstrate increased transmission. A new variant emerged in February of 2020 called D614G which had a higher Ro compared to the previously circulating predominant strain. Such strains with higher transmission rates eventually become the predominant strain circulating in a population.

So just as more people suffer from pandemic fatigue and drop their guard we have a more easily transmitted virus. Now is not the time to loosen up on precautions.

In the context of the COVID 19 pandemic I will close with the usual summary.

  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. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

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

New UK SARS CoV-2 variant: “we see no evidence that the reported mutations would substantially increase reinfection risk or decrease vaccine efficacy.”

1 Reply

We must all be thankful for the immunologists who continue to stay on top of the pandemic. They have our backs.

Recent tweets posted by reliable experts who have evaluated the mutations in the B.1.1.7 strain.

We used our database of 579 COVID patient samples to evaluate immune evasion the UK variant (B.1.1.7). Overall takeaway is reassuring: we see no evidence that the reported mutations would substantially increase reinfection risk or decrease vaccine efficacy. (1/n)

Here is some data from the lab of Winn Haynes. @hayneswa

I would prefer this in a manuscript, but given the time of year and that I’m tired, I’ll just tweet the data regarding the UK #COVID19 variant: PRNT50 values from COVID patients for SARS2 WT WA1 vs a mutant that contains N501Y (among other spike mutations).

What does this mean?

In the words of Prof Akiko Iwasaki

As RT above, @TheMenacheryLab has shown functionally that the N501Y mutation in the RBD does not evade existing antibodies’ ability to block replication. (8/n)

Eric Topol:

The good news is that it is not anticipated the current vaccines, which rely on inducing neutralizing antibodies to the spike protein, will be affected by B.1.1.7 or N501Y

If you want to keep up on these issues I suggest you follow Akiko Iwasaki on twitter.

Prof. Akiko Iwasaki

@VirusesImmunity

Bottom line:

The vaccines should work for this new variant despite the mutations.

There is no evidence that the new strain is more lethal (time will tell).

It is probable that the new strain is more easily transmitted (greater affinity for the ACE2 receptor and recent epidemiologic data)

Masks, social distancing, hand washing will continue to work.

Improved ventilation (in-door settings) remains important.

If you want to visit and celebrate, DO IT OUTDOORS with masks and distancing.

Humans need social interaction, this can be done safely without ignoring hygiene recommendations. Socialize and exercise safely outside.

Super-spreader events (such as Whitehouse holiday parties) should be avoided.

Religious services should be held outdoors with precautions. Tents with distancing and masks work!

If you are sick isolate.

Remember, individuals are most infectious before symptoms develop and for the first 5 days after symptom onset. So even though you feel well, you could be a spreader.

Everyone is vulnerable.

Young previously healthy teens and adults are dying and suffering Long-Covid with significant chronic illness.

If you are obese, overweight, pre-diabetic, or have diabetes, now would be a good time to go low-carb with an anti-inflammatory diet. The benefits occur immediately even before or without weight loss.

In the context of the COVID 19 pandemic I will close with the usual summary.

  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. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

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.

Happy New Year

Doctor Bob

COVID 19 Immune Response, How does it fail?

1 Reply

Dr. Akiko Iwasaki, an immunologist at Yale, has led an amazing research team from the start of this pandemic, analyzing the immune response of patients sick with COVID 19. She has co-authored a review of the immune response to be published in the January edition of Scientific American.

Iwasaki A, Wong P.  The immune havoc of COVID-19.  Scientific American, January 2021, 35-41.

Here is the link.

http://The Immune Havoc of COVID-19 – Scientific American

Before reading that article, a good place for a lay person to start would be her 8 minute youtube video, Immunology 101.

After watching that video and reading the Scientific American article, if you want a deeper dive into some of her team’s research, watch this video (28 minutes).

The Scientific American article discusses many of the unique characteristics of SARS CoV-2 compared to two previous corona viruses SARS CoV-1 and MERS. SARS CoV-2 which causes the illness called COVID-19, evades the human immune system in many ways. Those who become seriously ill, requiring ICU care, seem to suffer a time lag in their immune response compared to those who suffer less severe illness. In addition, the T-cell response in sicker patients is subdued and inadequate to clear the virus. Finally, a hyper-inflammatory response is present in most who succumb to the illness. Dr. Iwasaki discusses how the Cytokine storm of COVID-19 differs significantly from that seen with other viral infections and likely includes a new phenomenon referred to as a Bradykinin Storm which involves another major component of the immune system. There may even be an auto-immune component to this disease in some or many patients.

“Early in the pandemic, physicians did detect elevated cytokines in patients, but the amount of these proteins and the subsequent inflammatory state they evoked differed from that of a classic cytokine storm.“

“We observed high levels of IL-5 and IL-17,cytokines not classically associated with antiviral immune activity. Instead these cytokines initiate a seemingly misguided
response—one better suited for infections by parasites and fungi.
We have yet to understand whether this response causes damage
to tissue or just diverts resources the body needs to fight the virus.“

In the second video linked above Dr. Iwasaki describes how men and women demonstrate different immune responses with a higher fatality rate observed among men.

Much has been learned but much remains to be discovered as this pandemic continues to unfold.

There are a few clear facts emerging from multiple studies and observations.

Masks and social distancing work. Masks protect both the wearer and those around the wearer.

Most transmission occurs by droplets and aerosol (emitted from the nose and mouth).

Six feet of distancing is helpful but does not guarantee protection. Cases of transmission in restaurants via air flow from HVAC units have been described in which the infected person transmitting disease is far removed from the people becoming infected. (aerosol spread). Droplets and aerosol studies have demonstrated that coughing and sneezing can project infectious particles up to 26 feet.

The most dangerous circumstances for transmission include indoor confined spaces, with multiple people interacting for long periods of time (restaurants, bars, meeting rooms, parties, social gatherings).

Ventilation and air turnover are important factors.

This virus is unique in that higher viral loads and transmissibility occur BEFORE ONSET OF SYMPTOMS, rendering this virus more dangerous than previous pandemics. This can occur in patients who later develop symptoms or in people who carry the virus without ever developing any symptoms.

Some estimate that as much as 50% of transmission occurs from people exhibiting no symptoms.

Finally, “herd immunity” for infectious disease has never been achieved by reaching a critical number of infected people. “Herd immunity” has only been achieved in the past with vaccination programs. Herd immunity does not mean that disease transmission ceases, it means that transmission rates are very low.

What is herd immunity?

When most of a population is immune to an infectious disease, this provides indirect protection—or herd immunity (also called herd protection)—to those who are not immune to the disease.

For example, if 80% of a population is immune to a virus, four out of every five people who encounter someone with the disease won’t get sick (and won’t spread the disease any further). In this way, the spread of infectious diseases is kept under control. Depending how contagious an infection is, usually 50% to 90% of a population needs immunity to achieve herd immunity.

Most experts estimate that vaccination of at least 70% of the population will be required to reach some degree of herd immunity for COVID-19.

Here is a 2 minute discussion of herd immunity from Johns Hopkins before the Pfizer-BioNtech and Moderna vaccines were given Emergency Use Authorization by the FDA.

In the context of the COVID 19 pandemic I will close with the usual summary.

  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. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

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

New COVID strain in UK: Is it more dangerous?

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A new strain of the SARS-CoV-2 virus has been identified in an area of the UK. The media are reporting on this as a new, more easily transmitted or more virulent strain.

Hold on!

There are theoretical concerns that some of the many mutations identified in this virus might make it more contagious and/or cause more severe illness. But this has not been confirmed by clinical data. The case rate in this part of UK is accelerating, leading to more restrictive social measures, but it is not clear whether this is related to human behavior, virus mutations, or a combination of both.

Caution would be prudent.

Here is the link to the posted report.

Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations

This report appears on the website:

SARS-CoV-2 coronavirusnCoV-2019 Genomic Epidemiology

This strain is of concern for several reasons.

It presents an unusually high number of mutations.

One of these mutations increases the virus’s affinity to the human ACE2 receptor.

Another mutation has been linked to evasion from the human immune system.

This strain accounts for an increasing proportion of cases in parts of England.

The number of cases of this strain is growing, and the number of regions reporting this strain are growing.

This combination of facts should be a red flag and the authors of the post state:

The rapid growth of this lineage indicates the need for enhanced genomic and epidemiological surveillance worldwide and laboratory investigations of antigenicity and infectivity.

In other words, it needs to be studied and tracked to see if it is significantly more contagious and what impact it has on the pandemic (spread of spread, intensity of illness, morbidity-mortality).

The authors speculate on the possible causes for this large a number of mutations in a single strain. They suggest that the administration of antibody therapy to immune deficient-depressed chronically infected patients could create conditions of evolutionary pressure for rapid and diverse mutation. If that theory is correct, given that there is no data demonstrating reduced mortality rates with this form of treatment, we may be creating a problem with an unproven therapeutic intervention (iatrogenesis).

Convalescent plasma is often given when patient viral loads are high, and Kemp et al. (2020) report that intra-patient virus genetic diversity increased after plasma treatment was given.

Hmmmmmmmmmmmmmm!

Stay tuned for updates.

Also, please read my post from 12/18/20 on the Pfizer-BionTech vaccine. I have made a few minor corrections and clarifications since the original post.

Covid 19 Vaccine: Statistics, Safety, Efficacy, What is a Confidence Interval? | Practical Evolutionary Health (practical-evolutionary-health.com)

In the context of the COVID 19 pandemic I will close with the usual summary.

  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. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

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

Who was the greatest scientist of the 20th century?

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Many would say Albert Einstein, some might suggest Stephen Hawking. But arguably, the greatest might have been a little known, modest but ill-tempered and often vulgar-mouthed virologist named Maurice Hilleman.

Hilleman’s twin sister died at birth, his mother died 2 days later. His father gave him over to his aunt and uncle and he worked their farm in Montana. For want of funds he deferred college until his brother returned from divinity school and convinced him to attend Montana State. He was raised in a deeply religious family and was observed to read Darwin’s Origin of the Species while in church as a teenager.

He went on to graduate school for microbiology and discovered that Chlamydia, previously thought to be a virus, was an intra-cellular bacteria.

Shortly after graduate school and at the request of the US military he developed a vaccine for Japanese Encephalitis which was wreaking havoc with US soldiers in the Pacific during WW2.

He made a list of serious childhood illnesses and decided to devote his life to developing vaccines for all of them.

During his career he developed over 40 vaccines.

From Wikipedia:

Of the 14 vaccines routinely recommended in current American vaccine schedules, he developed eight: those for measles, mumps, hepatitis A, hepatitis B, chickenpox, Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae bacteria.[2][4] He also played a role in the discovery of the cold-producing adenoviruses, the hepatitis viruses, and the potentially cancer-causing[5] virus SV40.

The story of the mumps vaccine is fascinating. His daughter developed mumps. He swabbed her throat, took the sample to his lab and cultured the virus in chicken embryo cells. Over 2 years he developed a series of virus mutations in successive dishes of embryo cells. Each virus culture became less virulent for humans. This had never been done before. Eventually, he had a “live-attenuated” virus that could be used for human vaccination.

His work was performed under what would now be considered primitive scientific conditions but it was state of the art for his time.

It has been estimated that his work saves over 8 million lives every year.

Paul Offit MD, Director of Vaccine Development at Children’s Hospital in Philadelphia (U Penn.) a present day preeminent vaccinologist, spent 72 hours interviewing Maurice Hilleman when he was dying from cancer, to record his amazing history.

The folks who worked for Maurice Hilleman were intensely loyal. He was totally devoted to science and vaccine development. Yet on the day he died, Paul Offit walked into a room filled with pediatricians where he was giving a lecture and not one pediatrician knew who he was or what he had accomplished.

From Wikipedia:

Robert Gallo, co-discoverer of HIV, the virus that causes AIDS, once said “If I had to name a person who has done more for the benefit of human health, with less recognition than anyone else, it would be Maurice Hilleman. Maurice should be recognized as the most successful vaccinologist in history.”[14]

After Hilleman’s death Ralph Nader wrote, “Yet almost no one knew about him, saw him on television, or read about him in newspapers or magazines. His anonymity, in comparison with Madonna, Michael Jackson, Jose Canseco, or an assortment of grade B actors, tells something about our society’s and media’s concepts of celebrity; much less of the heroic.”[15]

A documentary film titled Hilleman: A Perilous Quest to Save the World’s Children, chronicling Hilleman’s life and career, was released in 2016 by Medical History Pictures, Inc

In 2007, Paul Offit published a biography of Hilleman, entitled Vaccinated: One Man’s Quest to Defeat the World’s Deadliest Diseases

Maurice Hilleman – NCBI – NIH

Maurice Hilleman | Nature Medicine

Maurice Hilleman – Wikipedia

In the context of the COVID 19 pandemic I will close with the usual summary.

  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. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

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 Vaccine: Statistics, Safety, Efficacy, What is a Confidence Interval?

2 Replies

This week began the saga of vaccine implementation for the mRNA vaccine developed by the Pfizer-BioNtech partnership. The New England Journal of Medicine published a peer-reviewed article reporting the data from the RCT (Randomized Controlled Trial) and an Editorial appeared on the same day in the NEJM. You can view both here:

http://Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

http://SARS-COV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention

If you go to the first link you can click on a link to a 3 minute video that summarizes the results. The video is informative and succinct.

https://www.nejm.org/do/10.1056/NEJMdo005933/full/?requestType=popUp&relatedArticle=10.1056%2FNEJMoa2034577

Here is the most important table in the peer-reviewed article:

Age > 55 includes >=65 and >=75, Age >= 65 includes age >=75. If age>= 75 were not listed separately, all age groups would have statistical significance. This is why overall number of infections in the vaccine group is 8 but the total of the four age groups is 9. One of the 3 infections in age >55 was 65 or older. Got it?

Look at the third column labeled “Surveillance Time”. The first number in this column is described under the caption as “total time in 1000 person-years for the given endpoint..” So multiply by 1000 and you get a number that represents “person years” of observation. This is an odd number but a reasonable way to present information. The trial data covers a period of 6 months starting from when the first patient was vaccinated. The median duration of observation was 2 months after vaccination with the second dose. (50% of patients had been vaccinated for more than 2 months and 50% of patients less than 2 months)

The number in parentheses gives the number of people in each category of age, sex, race/ethnic group, country.

Notice that as we descend through the age groups from youngest to oldest, the number of participants decreases significantly in >= 65 and >=75 years old.

Now go to the last column labeled “Vaccine Efficacy, %”. The first number is the overall efficacy for that age group. But how confident are we about that efficacy % for each age group? The numbers in the parentheses represents a range or “confidence interval” which is determined statistically. This range is determined by the number of people in each (age) group and by the difference between the placebo and drug treatment outcome in that age group.

Note that the confidence interval widens as you go down from younger to older age groups. That is primarily because the number of people represented by the groups age >=65 and >= 75 are much smaller than the first two age groups.

For the age group > 65, the efficacy is reported at 94.7%. But that is an average number that shows that compared to the placebo group, the symptomatic infection rate in the vaccinated group was 94.7% lower. For the age group between >=65, there were 19 cases of symptomatic infection in the placebo group and only 1 in the vaccine group. 1/19 equals 0.0526. 1 minus 0.0526 equals 0.947 or 94.7% (rounding).

What is a 95% confidence interval?

The 95% confidence interval is the the range over which we are 95% confident the “true” value falls within. In other words, for age >=65 there is a 95% probability that the true vaccine efficacy falls somewhere between 66.7% and 99.9%. As more people age >=65 are entered into the trial, the confidence interval will get narrower for that age group provided the difference between the placebo and vaccine group remains the same. If the difference between placebo and vaccine groups increases AND the number of people in this age group increases, the confidence interval will shrink further.

This is a fantastic result!

But now look at the confidence interval for age >=75. It is -13.1-100. A minus number is in the range. That means we do not have enough people in the study age 75 or older to reach a “statistically significant” conclusion. There were only 774 folks who received the vaccine and 785 people who received the placebo in this age group. 5 in the placebo group got sick, 1 in the vaccine group got sick. This difference shows a “trend” but does not reach “statistical significance”. We need more data for this group.

But again, do not lose heart. Based on this data, which includes efficacy and safety overall, I recommend that my 92 year old mother-in-law receive the vaccine as soon as it is available.

What is “statistical significance”?

Simply stated, a result is “statistically significant” in a drug trial if the probability that the difference between the placebo group and the drug group occurred by accident (or by chance) is less than or equal to 5%. Or to put it another way, the probability that the difference between placebo and drug did not occur by chance but rather represents a true difference in outcome is 95% or greater. 5% is the standard cutoff point in medical trials. This is usually reported as a “p value”. If a p value is less than or equal to 0.05 the difference is considered statistically significant.

“Clinical significance” is another issue. For example, a drug might only decrease relative risk of an event by 5%, but the result could be “statistically significant”.

In the case of this vaccine, the clinical significance is outstanding.

Here is another important chart.

Protection begins at day 14 after first dose

This chart demonstrates that 14 days after the first dose of vaccine protection from symptomatic infection begins. The blue line shows infections in the placebo group, the red line is the vaccine group. They diverge at day 14. Thereafter the divergence increases. This makes sense. It is consistent with our understanding of how the immune system works. This time course is very reassuring.

Now let us look at side effects.

These are the usual side effects expected with any vaccine. Symptoms such as fever, malaise, local reaction at the injection site, muscle aches are all to be expected. This profile is a little worse than the flu vaccine, but less compared to the shingles vaccine.

So far 2 episodes of anaphylaxis have occurred in the US and in UK with the vaccine rollout. (millions of doses already given) This can happen with any vaccine, that is why 15 minutes of observation following vaccination is part of the protocol and the vaccine should only be administered in a location that has epinephrine available to treat a severe allergic reaction.

This vaccine time sequence is historically unprecedented. This was made possible by a combination of advances in science and incredible action on the part of the public and private sectors in response to a global crisis. Prior to this, the shortest time to develop an effective vaccine was 4.5 years (measles mumps, and that was done by Maurice Hilleman with the help of a few lab assistants, more about Maurice in my next post).

I received my first dose of the vaccine today (as a member of hospital medical staff). I was directed to a CDC website to register as a vaccine recipient. The CDC will send me periodic questions on side effects which I will answer. If everyone participates in this program more data will become available on safety and efficacy. So please participate when you get the vaccine (vsafe.cdc.gov).

Many questions remain. Here is a quote from the NEJM editorial:

  1. Will unexpected safety issues arise when the number grows to millions and possibly billions of people?
  2. Will side effects emerge with longer follow-up?
  3. Implementing a vaccine that requires two doses is challenging. What happens to the inevitable large number of recipients who miss their second dose?
  4. How long will the vaccine remain effective?
  5. Does the vaccine prevent asymptomatic disease and limit transmission?
  6. And what about the groups of people who were not represented in this trial, such as children, pregnant women, and immunocompromised patients of various sorts?

The logistic challenges of manufacturing and delivering a vaccine remain daunting. This vaccine, in particular, requires storage at −70°C, a factor that may limit its deployment in some areas. Nevertheless, the remarkable level of safety and efficacy the vaccine has demonstrated thus far make this a problem that we should welcome solving. What appears to be a dramatic success for vaccination holds the promise of saving uncounted lives and giving us a pathway out of what has been a global disaster.

In the context of the COVID 19 pandemic I will close with the usual summary.

  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. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

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

LONG COVID, WHAT IS IT?

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I recently read an outstanding review of the topic “LONG COVID”. This has been defined in various ways. It can include persistent symptoms and/or organ damage following apparent “recovery” from the illness. There is no agreed upon definition. Our understanding is evolving. Time will tell how long symptoms can persist. It is clear that persistent symptoms and/or organ damage can occur even after minor illness or subsequent to asymptomatic positive PCR.

Full report can be found HERE

The following are EXCERPTS from the full report. References provided in the full report:

It has become clear in more recent months that an increasing number of individuals have been afflicted with persisting symptoms following a SARS-CoV-2 infection. Of these individuals, who have been referred to as “long-haulers” or as having “long COVID,” many did not initially experience a severe case of COVID-19, but rather had mild symptoms or were asymptomatic (Marshall, 2020)

According to Harvard Health, COVID-19 “long-haulers” include two groups of people affected by the virus (Komaroff, 2020):

· Those who experience some permanent damage to their lungs, heart, kidneys, or brain that may affect their ability to function.

· Those who continue to experience debilitating symptoms despite no detectable damage to these organs.

A team from the United Kingdom estimated that roughly 10% of individuals who have had COVID-19 experience prolonged symptoms (Greenhalgh et al., 2020). A guidance published on September 7, 2020 by Public Health England indicated that roughly 10% of “mild” COVID-19 cases who were not admitted to the hospital reported symptoms lasting more than four weeks (Public Health England, 2020).

Examples of some of the symptoms reported include:

· Prolonged low-grade fevers that do not respond to standard fever-reducing medications

· Neurological manifestations, such as memory loss and changes in the ability to recall words in a primary or secondary language

· Exercise-induced fatigue from walking around the block that led to a relapse of symptoms

· Symptoms in the central and peripheral nervous systems, gastrointestinal symptoms, skin problems, cardiovascular system occurrences

Some of the more commonly reported symptoms of long-COVID include: fatigue, cough, dyspnea, loss of taste and smell, muscle weakness, muscle and joint pain, headache, confusion, conjunctivitis, chest pain, decreased mobility and falls (Marshall, 2020; Paice et al., 2020).

On November 10th, 2020, the CDC updated its report entitled, “LongTerm Effects of COVID-19” (Centers for Disease Control and Prevention, 2020) to include the following information on long COVID: The most commonly reported long-term symptoms include:

· Fatigue

· Shortness of breath

· Cough

· Joint pain

· Chest pain

Other reported long-term symptoms include:

· Difficulty with thinking and concentration (sometimes referred to as “brain fog”)

· Depression

· Muscle pain

· Headache

· Intermittent fever

· Fast-beating or pounding heart (also known as heart palpitations)

More serious long-term complications appear to be less common but have been reported. These have been noted to affect different organ systems in the body. These include:

· Cardiovascular: inflammation of the heart muscle (in a German study 70% of patients had evidence of this, 80% of those patients had not been hospitalized)

· Respiratory: lung function abnormalities

· Renal: acute kidney injury

· Dermatologic: rash, hair loss

· Neurological: smell and taste problems, sleep issues, difficulty with concentration, memory problems

· Psychiatric: depression, anxiety, changes in mood

An organized study from Italy assessed the prevalence and types of persistent symptoms observed in 143 individuals after they were discharged from the hospital (Carfì et al., 2020)

The mean age of participants was 56.5 years old, with a range from 19 to 84 years of age, and 37% were female. The mean length of hospital stay was 13.5 days, and while in the hospital, 15% had received non-invasive ventilation, and 5% of the participants had received mechanical ventilation. The assessment described in the report occurred a mean 60.3 days after the onset of the first COVID-19 symptoms, and 12.6% were completely free of any virus related symptoms. The researchers reported that at a mean evaluation time of 60.3 days following COVID-19 symptom onset, 32% of the participants still had one to two symptoms, while 55% were still experiencing three or more symptoms.

The concept of chronic fatigue syndrome has been observed in individuals following infection with both viral and non-viral micro-organisms (Hickie et al., 2006). A study describing survivors of a SARS outbreak in Hong Kong stated that 40% had chronic-fatigue problems after three years and 27% met the criteria for chronic fatigue syndrome. The fatigue, also called postexertional malaise, results from a severe multi-organ crash following even light activities like a short walk. Similar effects have been reported after other large disease outbreaks (Hickie et al., 2006)

In summary, because the COVID-19 pandemic commenced only months ago, rather than years ago, the relatively long-term sequelae of COVID-19 are unknown; however, it seems that not unlike prior coronavirus outbreaks, COVID-19 has yielded reduced pulmonary and physical function, compromised quality of life and emotional distress. Unfortunately, prior outbreaks – including the SARS-CoV-1 epidemic — suggest that these associated effects can last for years (Marshall, 2020).

Challenges for people experiencing longer term effects from COVID19 can include:

· Widespread perception that people either die, get admitted to hospital, or recover after two weeks; however, it is clear that some individuals experience ongoing, or long COVID.

· Long COVID is a multisystem disease; thus, the symptoms vary significantly among the individuals with persisting effects from COVID19.

· It is unknown why some experience a prolonged recovery while others do not.

· Many individuals with mild or asymptomatic COVID-19 cases experience long-term COVID-19, but oftentimes, they were never initially tested for a SARS-CoV-2 infection, and therefore have not been flagged for a positive test result.

· There is a lack of consensus on diagnostic criteria for long COVID.

· Lack of guidance for reaching a working diagnosis and code for clinical datasets.

In the context of the COVID 19 pandemic I will close with the usual summary.

  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. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

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