20200519T Day 140: Drive Shack Opens Up

Wind Surfing Beach near Davenport, CA – May 19, 2020

One stock that my brother recommended to me was Drive Shack. It is a Top Golf competitor that, as most other non-essential businesses, has been closed down due to the COVID-19 pandemic. This week, they opened back up and their stock opened up on Tues as well, closing at $1.43.

On Tues I visited a new beach where I saw some wind surfers. It reminded me of my kite surfing in Morocco.

I also worked a bit on my RV – mainly cleaning it up and testing the fridge which still refuses to operate.

 

20191219h Day -12: Influenza Immunity and Vaccines

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3D computer-generated rendering of an influenza virus. (Credit: Dan Higgins, courtesy of CDC/ Douglas Jordan)

20200520W Santa Cruz, CA: The first article to catch my eye today as I looked back to Dec 19, 2019, is Why your first battle with flu matters most, a article from the University of Arizona about a research paper published online on this same date: Childhood immune imprinting to influenza A shapes birth year-specific risk during seasonal H1N1 and H3N2 epidemics.

The researchers looked at Influenza virus subtypes H1N1 and H3N2 and found that “birth year-specific differences in childhood immune imprinting, not differences in evolutionary rate, explain differences in H1N1 and H3N2’s age-specific impacts.”

A result found by the researches was evidence to support the view that immune protection is stronger when acquired as a child rather than as an adult:

The fact that elderly cohorts show relatively weak immune protection against H3N2, even after living through decades of seasonal exposure to or vaccination against H3N2, suggests that antibody responses acquired in adulthood do not provide the same strength or durability of immune protection as responses primed in childhood.

Another possible conclusion not mentioned is that the H3N2 vaccinations, versus naturally acquired immunity, may partially explain the reduced immune protection in adults.

The University of Arizona article has some interesting quotes:

“Clearly, something compromises the immunity to strains that you see secondarily, even if they belong to the same group as your first exposure,” Worobey adds. “The second subtype you’re exposed to is not able to create an immune response that is as protective and durable as the first.”

In other words, our ability to fight off the flu virus is determined not only by the subtypes we have encountered over the course of our lives, but also by the sequence in which we have encountered them.

“Whichever subtype our immune system sees first lays down an imprint that protects us especially well against strains of the same subtype,” Worobey says, “but relatively poorly against strains from other subtypes, even though you’ve encountered those subsequently.”

The molecular causes of this effect are currently being studied, according to the researchers.

“Part of your immune system’s response to current infection is directed against the strain you first had as a kid, and that investment of fighting the last war appears to compromise your ability to form a fully effective immune response to the invader you encounter later,” Worobey says.

Regarding vaccines, Worobey, one of the researchers, has this to say:

“We need a vaccine that targets the deficits on an individualized level,” Worobey says. “Our work has clearly shown that the first virus we had can have a profound long-term effect. The bad side of that is that our immune system seems to be locked into fighting just one half of flu genetic diversity, and we need to find ways of breaking that.”

This research suggest to me that if we keep SARS-CoV-2 from infecting our children today, then they will be more susceptible to infection from SARS-CoV-2 even decades from now. It also makes sense to me that vaccines should not be the first solution thought of when deciding how to protect the population from a pathogen, and perhaps should be the last solution considered. Instead, the development of anti-virals that can assist the immune system in fighting off a viral pathogen make more sense. This would allow the body to naturally develop an immunity. Also, we need to develop treatments to improve recovery time and protect the body from the long-term effects of a particular viral infection.

20191220F Day -11: Human Coronaviruses and the Central Nervous System

20200520W Santa Cruz, CA: When I searched back 5 months to see what was going on related to the COVID-19 pandemic, I found a research paper published online on Dec. 20, 2019: Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?

Since the effect of COVID-19 on the CNS has also been discussed lately, I thought it would be interesting to go through this paper and see what quotes leap out at me. So here goes.

First from the Abstract, some key points so you know what you’re getting into. This is the entire Abstract from the paper in bullet form so that I can easily refer back to it later, if needed.

  1. Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia).
  2. Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes.
  3. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality.
  4. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases.
  5. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology).
  6. The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood.
  7. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.

Here are some interesting facts quoted from the Introduction:

  1. Considering all types of viral infections, between 6000 and 20,000 cases of encephalitis that require hospitalization occur every year in the United States, representing about 6 cases per 100,000 infected persons every year.
  2. Viruses represent the most prevalent pathogens present in the respiratory tract. Indeed, it is estimated that about 200 different viruses (including influenza viruses, coronaviruses, rhinoviruses, adenoviruses, metapneumoviruses, such as human metapneumovirus A1, as well as orthopneumoviruses, such as the human respiratory syncytial virus) can infect the human airway.
  3. new respiratory viral agents emerge from time to time, causing viral epidemics or pandemics associated with more serious symptoms, such as neurologic disorders. These peculiar events usually take place when RNA viruses like influenza A, human coronaviruses, such as MERS-CoV and SARS-CoV, or henipaviruses, present in an animal reservoir, cross the species barrier as an opportunistic strategy to adapt to new environments and/or new hosts.

In the rest of the paper, I found these quotes of interest:

Respiratory viruses such as RSV, henipaviruses, influenza A and B, and enterovirus D68 are also sometimes found in the blood and, being neuroinvasive, they may therefore use the hematogenous route to reach the CNS.

 

Influenza viruses are classified in four types: A, B, C and D. All are endemic viruses with types A and B being the most prevalent and causing the flu syndrome, characterized by chills, fever, headache, sore throat and muscle pain. They are responsible for seasonal epidemics that affect 3 to 5 million humans, among which 500,000 to 1 million cases are lethal each year. Associated with all major pandemics since the beginning of the 20th century, circulating influenza A presents the greatest threat to human health.

 

Last but not least, human coronaviruses (HCoV) are another group of respiratory viruses that can naturally reach the CNS in humans and could potentially be associated with neurological symptoms. These ubiquitous human pathogens are molecularly related in structure and mode of replication with neuroinvasive animal coronaviruses.

Taken together, all these data bring us to consider a plausible involvement of HCoV in neurological diseases.

As I read the following, I’m struct by how it could be written about the current SARS-2 (COVID-19) pandemic. Even the CFR of 10% is not that far off if there is only limited testing. I’m curious now to know if serological testing of SARS-1 has been done in SARS-1 outbreak areas to determine the true infection spread in those areas.

The 2002–2003 SARS pandemic was caused by a coronavirus that emerged from bats (first reservoir) to infect palm civets (intermediary reservoir) and then humans . A total of 8096 probable cases were reported and almost 10% (774 cases in more than 30 countries) of these resulted in death. The clinical portrait was described as an initial flu-like syndrome, followed by a respiratory syndrome associated with cough and dyspnea, complicated with the “real” severe acute respiratory syndrome (SARS) in about 20% of the patients. In addition, multiple organ failure was observed in several SARS-CoV-infected patients .

And the following “inefficient human-to-human transmission” and “more efficient human-to-human transmission in S. Korea” mentioned below shows how both of these universes can exist.

Although possible, human-to-human MERS-CoV transmission appears inefficient as it requires extended close contact with an infected individual. Consequently, most transmission have occurred among patients’ families and healthcare workers (clusters of transmission). A more efficient human-to-human transmission was observed in South Korea, during the 2015 outbreak of MERS-CoV. Even though it has propagated to a few thousand people and possesses a high degree of virulence, MERS-CoV seems mostly restricted to the Arabic peninsula and is not currently considered an important pandemic threat. However, virus surveillance and better characterization are warranted, in order to be prompt to respond to any change in that matter.

As I read the following about SARS-1 and MERS, the same populations seem to be infected except that not much is reported about SARS-2/COVID-19 affecting infants.

As of October 8, 2019, the World Health Organization (WHO) reported that MERS-CoV had spread to at least 27 different countries, where 2468 laboratory-confirmed human cases have been identified with 851 being fatal (https://www.who.int/emergencies/mers-cov/en/). As observed for the four circulating strains of HCoV, both SARS-CoV and MERS-CoV usually induce more severe illnesses, and strike stronger in vulnerable populations such as the elderly, infants, immune-compromised individuals or patients with comorbidities.

A comparison between the endemic coronavirus, HCoV-OC43, and both SARS-CoV-1 and SARS-CoV-2 seems like it would be helpful in better understanding these coronaviruses.

After an intranasal infection, both HCoV-OC43 and SARS-CoV were shown to infect the respiratory tract in mice and to be neuroinvasive. Over the years, we and others have gathered data showing that HCoV-OC43 is naturally neuroinvasive in both mice and humans.

Here’s a mention of the viral glycoprotein (S):

Immune cell infiltration and cytokine production were observed in the mouse CNS after infection by HCoV-OC43. This immune response was significantly increased after infection by viral variants, which harbor mutations in the viral glycoprotein (S).

Virus–cell interactions are always important in the regulation of cell response to infection. For HCoV-OC43, we clearly showed that the viral S and E proteins are important factors of neurovirulence, neuropropagation and neurodegeneration of infected cells.

And this on Hemagglutinin-esterase (HE protein) seems of interest:

We have also demonstrated that the HE protein is important for the production of infectious HCoV-OC43 and for efficient spreading between neuronal cells, suggesting an attenuation of the eventual spread into the CNS of viruses made deficient in fully active HE protein, potentially associated with a reduced neurovirulence.

This final paragraph sums up the risk of chronic human neurological diseases tied to coronavirus infections.

Like for several other respiratory viruses, accumulating evidence now indicate that HCoV are neuroinvasive in humans and we hypothesize that these recognized respiratory pathogens are potentially neurovirulent as well, as they could participate in short- and long-term neurological disorders either as a result of inadequate host immune responses and/or viral propagation in the CNS, which directly induces damage to resident cells. With that in mind, one can envisage that, under the right circumstances, HCoV may successfully reach and colonize the CNS, an issue largely deserted and possibly underestimated by the scientific community that has impacted or will impact the life of several unknowing individuals. In acute encephalitis, viral replication occurs in the brain tissue itself, possibly causing destructive lesions of the nervous tissue with different outcomes depending on the infected regions. As previously mentioned, HCoV may persist in the human CNS as it does in mice and potentially be associated with different types of long-term sequelae and chronic human neurological diseases.

The conclusions specifically calls out human coronaviruses. It also states the belief that Koch’s postulates should be modified to account for cases where diseases result rarely from a prior infection. It also refers to Multiple Schlerosis.

Several human respiratory viruses are neuroinvasive and neurotropic, with potential neuropathological consequences in vulnerable populations. Understanding the underpinning mechanisms of neuroinvasion and interaction of respiratory viruses (including HCoV) with the nervous system is essential to evaluate potentially pathological short- and long-term consequences. However, viral infections related to diseases that are rare manifestations of an infection (like long term chronic neurological diseases), represent situations where Koch’s postulates [] need to be modified. A series of new criteria, adapted from Sir Austin Bradford Hill, for causation [,] was elaborated by Giovannoni and collaborators concerning the plausible viral hypothesis in MS [].

The feeling I’m having now is to understand the fear that anti-vaccine folks have when presented with the idea of giving everyone in the world a “limited” viral infection in order to provide everyone with protective antibodies.

 

20200518M Day 139: Trump Takes Hydroxychloroquine+Zinc Prophylactically

20200518M Santa Cruz, CA: While I was writing 20200517u Day 138: Some US States have 6x Higher CFR – Hydroxychloroquine?, it was reported that Trump takes Hydroxychloroquine and Zinc prophylactically. So, I thought I’d make this post short and just add a couple updates on hydroxychloroquine.

  1. May 18, 2020: StatNews.com reporter Andrew Joseph writes a health article: Utah went all-in on an unproven Covid-19 treatment, then scrambled to course-correct, which discusses the history of Utah and hydroxychloroquine.
  2. May 18, 2020: From NPR report Despite FDA Caution, Trump Says He Is Taking Hydroxychloroquine As A Preventative “President Trump on Monday revealed to reporters that he has been taking hydroxychloroquine and zinc to protect against the coronavirus” for about 10 days.

20200517u Day 138: Some US States have 6x Higher CFR – Hydroxychloroquine?

20200517u Santa Cruz, CA: I’m curious about the almost 5-9x difference in case fatality rate (CFR) between the US states with the lowest CFR and the US states with the highest CFR. As of today, the CFR for the United States is 5.96% (275 deathsPerM divided by 4615 casesPerM).

The four best states have a CFR near 1%:

  1. Wyoming: 1.07% (14 deathsPerM / 1303 casesPerM)
  2. Utah: 1.11% (25 deathsPerM / 2258 casesPerM)
  3. South Dakota: 1.11% (50 deathsPerM / 4507 casesPerM)
  4. Nebraska: 1.20% (64 deathsPerM / 5349 casesPerM)

The seven worst states have a CFR over 6%:

  1. Michigan: 9.57% (490 deathsPerM / 5121 casesPerM)
  2. Connecticut: 9.11% (956 deathsPerM / 10495 casesPerM)
  3. New York: 7.85% (1456 deathsPerM / 18498 casesPerM)
  4. Louisiana: 7.24% (536 deathsPerM / 7407 casesPerM)
  5. New Jersey: 6.99% (1167 deathsPerM / 16685 casesPerM)
  6. Pennsylvania: 6.85% (352 deathsPerM / 5141 casesPerM)
  7. Massachusetts: 6.74% (841 deathsPerM / 12479 casesPerM)

Timeline of Hydroxychloroquine related actions in the US States above. In reviewing these, I thought I might notice that some states were treating with hydroxychloroquine and others were not. If this is going on, I think doctors and pharmacists are keeping this information to themselves due to the politics surrounding hydroxychloroquine.

  1. March 4, 2020: From Nebraska UNMC, Clinical trial begins for COVID-19 medication, a video of Andre Kalil, MD, leading a COVID-19 Clinical Trial
  2. March 7, 2020: New York Executive Order restricts dispensing hydroxychloroquined
  3. March 17, 2020: Nebraska Medicine post recommendations for Hydroxychloroquine treatment: COVID-19 Antiviral and Pharmacotherapy Recommendations
  4. March 21, 2020: President Trump Tweet that ““HYDROXYCHLOROQUINE & AZITHROMYCIN, taken together, have a real chance to be one of the biggest game changers in the history of medicine.”
  5. March 23, 2020: No. 202.10: Continuing Temporary Suspension and Modification of Laws Relating to the Disaster Emergency, an executive order from Andrew Cuomo, Governor of the State of New York, which included the following: “No pharmacist shall dispense hydroxychloroquine or chloroquine except when written as prescribed for an FDA-approved indication; or as part of a state approved clinical trial related to COVID-19 for a patient who has tested positive for COVID-19, with such test result documented as part of the prescription. No other experimental or prophylactic use shall be permitted, and any permitted prescription is limited to one fourteen day prescription with no refills.”
  6. March 25, 2020: Notice of Designation of Scarce Materials or Threatened Materials Subject to COVID-19 Hoarding Prevention Measures Under Executive Order 13910 and Section 102 of the Defense Production Act of 1950, which specifically identifies “Drug product with active ingredient chloroquine phosphate or hydroxychloroquine HCl”
  7. March 27, 2020: Utah Medical Association Email, which included the statement ”

    recommending that providers use a long-standing medication to treat COVID-19. This medication, Hydroxychloroquine, Hydroxychloroquine/zinc compound or Chloroquine/zinc is showing some promising data for affecting the course of COVID-19.” This was followed by an email the next day that said “The UDOH has withdrawn its guidance on hydroxychloroquine from March 27. They are instead endorsing the launching of the clinical studies and urging patients to participate in the trial to get access to the investigative drugs in a controlled environment with gathering of data.”

  8. March 28, 2020: FDA Emergency Authorization for use of Hydroxychloroquine
  9. March 29, 2020: Limitations on Prescribing and Dispensing of Medications for Treatment of COVID-19, New Jersey order for limiting hydroxychloroquine prescriptions
  10. April 6, 2020: Penn researchers assess hydroxychloroquine for Covid-19
  11. April 13, 2020: South Dakota launched the nation’s first statewide clinical research study to investigate hydroxychloroquine: Sanford Health to lead clinical trial for COVID-19 treatment
  12. April 13, 2020 (last updated):  COVID-19: Hydroxychloroquine, Chloroquine, and Azithromycin has different state policies on hydroxychloroquine
  13. April 16, 2020: Federal, state authorities step up efforts to prevent hoarding of chloroquine, hydroxychloroquine
  14. April 24, 2020: FDA Safety Warning on use of Hydroxychloroquine
  15. April 27, 2020: Boards of pharmacy and other actions relating to COVID-19 prescribing:

    “The A.M.A. is calling for a stop to any inappropriate prescribing and ordering of medications, including

    chloroquine or hydroxychloroquine, and appealing to physicians and all health care professionals to follow the highest standards of professionalism and ethics,” said AMA President Patrice A. Harris, MD.

  16. May 12, 2020 (last updated): NIH Treatment Guidelines “There are insufficient clinical data to recommend either for or against using chloroquine or hydroxychloroquine for the treatment of COVID-19″

 

20200516S Day 137: Fine-Structure Constant

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Sunset walk – Santa Cruz, CA – May 16, 2020

20200516S Santa Cruz, CA: In the search for absolute truth about reality and the universe, I find it enlightening to take note of dimensionless values. These are also important from a universe surfing point-of-view because they will be the same in all universes (or at least all universes obeying the same fundamental physics as our universe). Dimensionless constants do not depend on arbitrary measurement standards, such as grams, meters, or seconds.

Some articles that caught my interest for future study are:

  1. Ask Ethan: What Is The Fine Structure Constant And Why Does It Matter?
  2. Four direct measurements of the fine-structure constant 13 billion years ago
  3. Most Accurate Determination of the Fine Structure Constant
  4. Why the number 137 is one of the greatest mysteries in physics
  5. Fine-Structure Constant from Sommerfeld to Feynman
  6. Twin Concept of Fine Structure Constant as the ‘Self Number-Archetype’
  7. 11. Book 3 – Calculation of the exact value of the fine structure constant, alpha
  8. Highly charged ions could measure changes in fine-structure constant
  9. An exact formula for the Electro Magnetic coupling constant

 

20191222u Day -9: Cough Trending Highest in 5 Years

Screen Shot 2020-05-17 at 4.15.35 PM
REF: Google Search Terms Cough Pneumonia Fever Infection Shortness of Breath over last 5 years
Screen Shot 2020-05-17 at 4.21.11 PM
Zoom into last 20 months
Screen Shot 2020-05-17 at 4.22.11 PM
Google search terms since first COVID-19 confirmed case on Nov 17, 2019

20200517u Santa Cruz, CA: Looking back to Dec. 22, 2019, I read a research paper today that said “shortness of breath” began increasing in WeChat searches beginning Dec. 22, 2019. So, I was curious how searches on Google have been. Of the Topics I searched, “Infection” seems to be the Google Topic that most represents the COVID-19 pandemic. I did notice that the Topic “Cough” hit a 5 year high on Dec. 22, 2019. The Topics “Pneumonia” and “Infection” jumped a month later on Jan. 20, 2020. While most of the Topics I looked into have now gone back down close to pre-pandemic levels, “Infection” is still a hot Topic.

In other events, on this Dec. 22, 2019, a rally was held in Hong Kong to show support for the Uighur minority in China. How related these masks are to the masks that are coming will only be understood in the future.

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Protesters attend a rally in Hong Kong Dec. 22, 2019, to show support for the Uighur minority in China. (Photo: Dale de la Rey/AFP/Getty Images)

 

20200515F Day 136: Mountain Biking Down Aptos Fire Road

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Looking South to Rio Del Mar Beach, Aptos, CA – May 15, 2020 (Credit: SurfingTheUniverse.com)

20200515F Santa Cruz, CA – Today was a good exercise in feeling into the different universes around me in order to get to the one that I wanted. It was difficult to find the beginning of the biking trail where my brother was waiting. My brother had given me directions that led me and my beloved down a dirt road. Multiple times I felt like I was on the wrong road and wanted to back down the road or turn around whenever there was room. Each time, my beloved said “No, keep going so we can find your brother”, and I would continue. In the moment I continued, I believed I was on the right road but then shortly after I would lose faith again. I also had not really been excited about going mountain biking whereas my beloved was much more excited to go. It’s interesting to look back now and see how our different interest levels allowed us to be surrounded by a different number of universes.

It’s obvious to me now that my beloved was surrounded by more universes in which we did go mountain biking. This allowed her to more accurately feel whether or now we were on the correct road and should continue. She knew also if we turned around, we would be closer to the universe where we didn’t go mountain biking.

I’m glad that we eventually found my brother and family and friends. It was a fun ride down to the beach!

20191223M Day -8: Lady Bird Lake Reflections from Austin, Texas

Lady Bird Lake – Austin, TX – Dec 23, 2019 (Credit: SurfingTheUniverse.com)

20200515F Santa Cruz, CA: Back in December, I was in Austin. My beloved flew in for the holidays. We walked along Lady Bird Lake during the day. It was a beautiful sunny day.

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Lady Bird Lake – Austin, TX – Dec 23, 2019 (Credit: SurfingTheUniverse.com)

Meanwhile, the press was reporting on how this flu season was turning out different than past flu seasons. I’m not sure who decided that the unusual flu season would be the focus of the news and medical press on this day. Here is an article that caught my eye:

Rare B Flu Strain Causing Early Surge This Season from passporthealthusa.com

Here are some quotes of interest:

Dave Osthus is a statistician and flu forecaster at Los Alamos National Laboratory. Osthus explained that the current “2019/20 season is already worse than three of the past 20 flu seasons ever were, and the worst part of the flu season—historically late December through early March—hasn’t happened yet.”

especially this one ending with “worst than imagined”:

Looking at the influenza trends, the CDC was able to publicize that the flu season has “about a 40% chance of a peak in late December, a 30% chance of a peak in January, and a 25% chance of a peak in February.” These numbers may change as the season continues, but the outcome will remain the same or even become worse than imagined.

Looking back in time, it was reported in May that the 2018-2019 flu season was also “unusual”:

The just-ended 2018-2019 flu season was relatively mild compared to the last season, during which nearly 80,000 people in the U.S. died of flu-related illness.

The 2018-2019 season has been unusual, though, because the flu came in two waves: one that peaked at the end of December, and a second that peaked in early March.

It seems that “unusual” flu seasons will be the usual for the foreseeable future.