March 14, 2020

COVID-19

#97 – Peter Hotez, M.D., Ph.D.: COVID-19: transmissibility, vaccines, risk reduction, and treatment

“The next two weeks will be the critical period where we may start to see this reach a peak.”  —Peter Hotez, M.D., Ph.D.

Read Time 8 minutes

In this episode, Dr. Peter Hotez M.D., Ph.D., Dean for the National School of Tropical Medicine Baylor College of Medicine, shares his expertise on viral disease and how it applies specifically to the coronavirus disease (COVID-19) and the virus that causes it (SARS-CoV-2). Dr. Hotez informs us about the current state of disease progression, which has many unknowns, but has thus far been greatly determined by the delayed response time and lack of testing. Moreover, we discuss what we can do on a country, state, community, and individual level in order to collectively slow transmission of the disease. He shares with us a potential hope in convalescent plasma therapy and underscores the need for US federal involvement – particularly in the creation of a specialty task force to address areas of concern and unknowns. 

Disclaimer: This is information accurate as of March 13, 2020, when it was recorded.

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We discuss:

  • The disease and the virus: transmissibility and lethality [04:30];
  • Disease transmission: US playing catch-up [12:00];
  • Convalescent plasma coronavirus therapy [16:00];
  • Remdesivir drug treatment and vaccination challenges [19:45];
  • Disease mechanism and reported pathology [27:45];
  • Most concerning geographic regions in the US [39:00];
  • Risk reduction [46:30]; and
  • More.

Show Notes

The disease and the Virus: transmissibility and lethality [04:30]

Virus Nomenclature 

  • SARS-CoV2 is the virus; COVID-19 is the disease which that virus spreads
  • MERS-CoV, SARS-CoV, SARS-CoV-2 (i.e., COVID-19) are three examples of coronaviruses
  • This virus is not SARS-CoV-1, it’s not MERS-CoV, and it’s not influenza. It is a unique virus with unique characteristics but has particular similarities to SARS-CoV-1
  • Based on the historical and current global health threats caused by Coronavirus pathogen,  this vaccine type should be prioritized

The world has seen three pandemics caused by coronavirus in the 21st century 

1 | Severe acute respiratory syndrome coronavirus (SARS-CoV-1) was identified in 2003 following a 2002 outbreak, originating in Asia

Figure 1. World diffusion of SARS-CoV-1 pandemic in 2003 seeing transmission from Asia to rapid growth in Canada. Image credit: (Banos and Lacasa., 2007)

2 | Middle East respiratory syndrome coronavirus (MERS) appeared in 2012 from Saudi Arabia

Figure 2. World diffusion of MERS-CoV pandemic in 2012 originating from the Middle East. Confirmed cases from 2012-2013. Image credit: Vox.com

3 | The novel COVID-19 (SARS-CoV-2)

Figure 3. World diffusion (ongoing) of SARS-CoV-2 pandemic of 2020 originating in Wuhan, of Central Hubei province, China. Image credit: (The New York Times

The novel COVID-19 coronavirus is comparatively a higher concern …

  • SARS-CoV-2 – or COVID-19 – is not the most lethal or transmissible of viruses but it is high in both categories

Figure 4: How the new coronavirus (SARS-CoV-2) compares with other infectious diseases. Image credit: (New York Times)

COVID-19 is particularly lethal for certain sub-population groups while others are less affected

  • Children and adolescents don’t seem to get sick but are viral carriers, increasing transmission rate 
  • The most vulnerable people are those that are/have one or more of the following: 
    • Over the age of 70 years old
    • An underlying condition (metabolic disease – heart disease, diabetes, hypertension)
    • On immunosuppressive therapy
    • Healthcare worker/first responders

There are two primary mysteries about groups afflicted:

  1. Adolescents and young children don’t get sick 
  2. Healthcare workers contract a severe version of the virus, despite their age group

A perfect storm whereby the populations becoming ill makes the virus particularly destabilizing and dangerous…

  • In afflicting healthcare workers, the virus takes out caretakers of those who are or become sick
  • Those that provide care are severely impacted
    • In Wuhan, China – reports suggested that at least 1,000 healthcare workers became infected and about 15% of those became seriously ill 
  • First responders have to self-quarantine if they come in contact with the virus, so that is another pillar of aid that gets hit

Disease transmission: US playing catch-up [12:00]

  • The U.S. was very behind in diagnostic testing and allowing the virus to circulate for a long period of time 
  • Ruoran Li and Marc Lipsitch have reported from studies out of China that when there is a longer time-to-response, healthcare infrastructure takes the load of impact 

Figure 5. Comparison of Guangzhou and Wuhan intervention impact. Image credit: (Marc Lipsitch)

  • Guangzhou intervened much earlier in epidemic and had a much smaller peak in bed demand
    • Early intervention spares the health system from intense stress (e.g., Philadelphia vs. St. Louis)
  • Early intervention means action is taken prior to the number ramp (e.g., citing Guangzhou that intervened when they had 7 cases and 0 deaths vs. Wuhan that had 495 confirmed cases, 23 dead)

In the US, there is concern about hospital inundation 

  • US will not intervene as did Guangzhou 
  • Already too late in response time
  • The U.S. first case was likely at the beginning of February and the spread of virus went unaddressed for more than a month

In order to slow the disease spread, social distancing is important

  • The U.S. will now start to test and we will see in the next 1-2 weeks which communities have significant levels of transmission
  • We could potentially intervene in those places and shift the growth curve 

“We have lost the opportunity to avoid an epidemic” —Peter Hotez M.D., Ph.D.

Convalescent plasma coronavirus therapy [16:00]

In an interview with Alisyn Camerota on CNN … Peter referenced how he emphasized that this is not the time to assign fault 

Quote TK “Now is not the time to assign fault … we can do that later. Right now we have to focus on the task at hand” – Peter Hotez M.D., Ph.D.

  • One of the first order of action is to find an intervention while vaccine and antiviral drug intervention are pursued 
  • Colleague Arturo Casadevall is pushing the idea for a low-cost antibody therapy intervention 
  • The strategy takes antibodies from individuals that have been infected and have since recovered
  • Casadevall and his colleagues have already started testing this therapy for use
  • One report summarizes the effectiveness of convalescent plasma as a potential therapy for COVID-19, citing historical situation learnings (e.g., SARS-CoV-1, The 1918 Spanish Flu)

The logistics of this solution are not as straightforward…Government intervention is necessary

  • Method requires apheresis, blood banks, centrifuge
  • Would require Center for Biologics Evaluation and Research (CBER FDA) guidance
  • Arturo thinks putting together a federal task force would be necessary

The solution is scalable …

  • 300mL for someone seriously ill (so 1 donor to 1 recipient) 
  • As a prophylaxis treatment, 5mL for someone equates to ~ one donor for dozens of individuals 

Remdesivir drug treatment and vaccination challenges [19:45]

  • Remdesivir has been recently recognized as a promising antiviral drug against a wide array of RNA viruses
  • Gilead’s antiviral drug Remdesivir stands out for potential to treat coronavirus. The drug has rapidly moved to phase 3 studies, with data expected by April
  • Antiviral medication development and application will move a lot faster than vaccines

Technical challenges associated with vaccine developments

  • Vaccines are the highest bar there is in terms of testing because it involves immunizing healthy individuals 
  • Makes it difficult to compress timelines 
  • Development and trial process can last 2-3 years 
  1. Phase 1 for safety 
  2. Phase 2 expanded to demonstrate safety and some efficacy 
  3. Phase 3 for safety and efficacy in natural disease conditions 
  • Process should not be rushed
  • With respect to Coronavirus vaccines – there is a risk of immune enhancement –  where vaccine could actually make things worse (seen in lab animals)
  • Similar to 1960’s Respiratory syncytial virus (RSV) vaccine – inactivated vaccine in which vaccine recipients did worse, with more hospitalizations 

Vaccination promise with spike protein receptors

  • One study identified  a target for vaccine and therapeutic development
  • From which an NIH grant was submitted based on the identification of a highly promising lead candidate vaccine antigen, the receptor-binding domain (RBD) of the SARS-CoV spike (S) protein

Figure 6. SARS-CoV-2 spike proteins are similar to SARS-CoV proteins (pictured).  Image credit (Du and Jiang, 2009)

  • SARS-CoV-1 and SARS-CoV-2 have about 80% similarity in terms of genetic code bound to the same receptor such that vaccine development approval for SARS-CoV-1 could also apply to SARS-CoV-2 

Hotez and his colleagues have NIH funding but no investment… 

  • The vaccine could be repurposed but the team require prospective donors in order to move it to clinical trials 
  • Funding is often a problem when creating vaccines for neglected diseases 
  • For funding support please email Peter directly: [email protected] 

Disease mechanism and reported pathology [27:45] 

  • SARS-CoV virus use Angiotensin‐converting enzyme 2 (ACE2) as a functional receptor 
  • The ACE2 receptor binds the SARS‐CoV S protein with high affinity, explained in a 2005 paper
  • These type II alveolar cells (AT2) cells are particularly prone to viral infection due to high ACE2 expression

ACE2 receptor for entry may explain diverse symptoms in infected individuals 

  • ACE2, a cell-surface protein on cells in the kidney, blood vessels, heart, and, importantly, lung AT2 alveolar epithelial cells
  • The GI manifestations are consistent with the distribution of ACE2 receptors
  • The receptors are most abundant in the cell membranes of lung AT2 cells, as well as in enterocytes in the ileum and colon
  • At least 10% of reported hospitalized patients presented presented with GI symptoms 

The major route of transmission is not clear… there may be multiple 

  • Some identified modes: Microdroplets on surface, directly on someone, airborne, fecal
  • Recent paper reported fomite survival on different surfaces:
    • aerosols, up to 3 hours post aerosolization
    • up to 4 hours on copper
    • up to 24 hours on cardboard
    • up to 2-3 days on plastic and stainless steel (13hr median half-life on steel; 16hr median half-life on plastic)

Ro and transmissibility

  • The collective picture explains why virus is so transmissible: 
    • Can live on multiple surfaces for at least 8hr to 72hr
    • Mode of transmission is significant because virus can survive and transfer in a number of different ways 
  • This means there is a high reproductive number (Ro)  
    • Refers to the number of people that will get infected if a single person has this virus 
    • 2.24-3.58 get infected for a single individual
    • Compared to that of the seasonal flu: 1.2-1.3
    • And compared to measles: 12-18
  • There are a lot of individuals who do not get sick but spread the virus 
  • And some other become very ill and will a high mortality rate
    • Mortality rate: 0.6-3.4 /4% 
    • 4-20x higher than influenza 
    • Among older populations, mortality is 10-20% 

Transmission is an issue in nursing homes

  • First community transmission in Kirkland, Washington 
  • Killed 13 people; ~13% mortality 
  • There was not a lot of guidance around transmission of disease and nursing homes 
  • Peter testified in front of Congress, calling the virus an “angel of death for older people” 

“Over the years I have always had an interesting career that balancing being a working scientist – an M.D., Ph.D. vaccine scientist for neglected disease interventions with that advocacy in places where I have seen gaps […] and help raise awareness.”  —Peter Hotez M.D., Ph.D.

Most concerning geographic regions in the US [39:00] 

  • Any urban area of the US is vulnerable 
  • We have seen it take off in Seattle, New Rochelle, some uptick in NYC 
  • Where there are congregations of big, urban populations 
  • Have to believe that any large urban centers are vulnerable 
  • Large urban centers generally have better public health infrastructures so that could be another reason those areas are more vulnerable 

An increase in testing will give a better picture of infection rate and numbers

  • There is and will be a big demand on the healthcare system 
  • There is risk of hospital bed shortage 

“The next two weeks will be the critical period where we may start to see this reach a peak.”  —Peter Hotez M.D., Ph.D.

  • Antibody therapy offers people hope and helps to avoid the spread of panic
  • There is not a lot of margin for hospitals to operate so the coping in response to demand remains to be a big unknown 
  • Ezekiel Emanuel has written about U.S. healthcare and cost structure

Model estimates of disease spread

“All models are wrong, some are useful” —George Box

  • Mac Lipsitch has estimated that over 70% of the world’s population may become infected
  • Estimates are based on models

“One thing that always impresses me working with modelers is that a modest change in assumptions of what goes into the model can often have huge differences. The only comfort I take in that is if current models for infection rate are anything like the models I have worked with: a small change in assumption can result in 2-3 logarithmic reduction in deaths…” —Peter Hotez M.D., Ph.D.

Risk Reduction [46:30]

  • We still have some say in our response to this:
    • at the federal, local, state and personal level 
    • Self isolating and quarantining when necessary (any signs or symptoms) 

The plea for federal guidance and specialty task forces 

  • We need specialists to come together as a task force on a given issue (e.g., antibody-based technology, nursing home care structures, mental health experts, metabolic disease teams) – all to try and understand what is going on
  • Older individuals in clusters are high risk but the challenge is to weight risk vs socialization important 
    • Want to protect and isolate individuals 
    • Socialization and seeing other is very (psychologically important) 

“This is where I say I am a vaccine scientist but pretty good at understanding infectious disease epidemiology. But there is a point where decisions become so tricky that I start to exceed where I feel comfortable.” —Peter Hotez M.D., Ph.D.

In the coming weeks…

  • Peter will be focusing on incidence and prevalence data in the weeks to come
  • As we increase testing, we will be able to observe which new communities become infected 
  • Vaccine trials have begun in Washington which is a positive but we will also see immune enhancement, if there is any, in volunteer population 
  • Make sure to take a retrospective look to what was learned the previous week 
  • We have to continually reevaluate 

“This is where we are right now and this virus is racing so quickly […] new pathogens in general set you [an infrastrucutre] to look stupid […] but this one especially because it is so fast moving and transmissible” —Peter Hotez M.D., Ph.D.

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35 Comments

  1. Hey Peter, have you heard or Chloroquine? Apparently it has some mechanism for facilitating Zinc uptake by cells, aiding in the disruption of the viral replication…some doc that makes videos to help study for med school tests posted a YouTube video on it in his channel.

  2. Kudos to you Dr.Attia.
    Educating the general public and our patients is of the utmost importance to assure positive results of their treatment.It should be the obligatory first goal of the medical profession. This transforms the equation of our interaction with Patients. “Doing something to someone”(no control on the part of the patient),to “doing something WITH someone”(implies a partnership with our patients where they have a beneficial sense of control over their health)
    What you do fulfills that goal.Thank you.Luisa Fijman M.D.

  3. My bet is SARS are a result of the collapse of the 2018 flu pandemic. descriptions are identical. Given it happened before virology it most likely was a corona virus. If you consider the youngest individual to have been exposed and survive turned 80 in 2000. SARS I appears in 2002. The timeline is clear.

  4. Thanks Peter. A true labor of love amid the current crisis. And especially meaningful to this nurse in a now more challenged (and anxious) ICU.

  5. Any reason to believe ACE inhibitors might drive increased susceptibility to infection or severe itchiness?

  6. Peter, I disagree with your guest’s assertion that it isn’t time to assign blame.

    It seems to me appropriate that the common name for this virus should be ‘Wuhan Virus’ given the account by Dr. Gwynne Dyer in his March 11 commentary that makes it clear “…everybody knows that China made a mess of this.”

  7. Thank you so much for getting this available- I feel like everyone is longing for direction and facts- which are sparse especially from our elected officials. This is invaluable!

  8. There are conflicting opinions on using ARB’s such as losartan with respect to the effects of increased ACE2 expression on the SARS-COV-2 virus and COVID-19 disease severity. Until studies are done, I wonder if there are any opinions or advice on this topic. Below are links to different articles on the topic. Neil Zlatniski MD
    https://onlinelibrary.wiley.com/doi/full/10.1002/ddr.21656
    https://link.springer.com/article/10.1007%2Fs00134-020-05985-9
    https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30116-8/fulltext#coronavirus-linkback-header

  9. I haven’t yet listened to this episode, but wanted to thank you for the excellent YouTube four-parter on COVID-19. It had the key, tried-and-true public health message, plus somewhat higher-level scientific content than what one usually gets in the higher-quality health journalism. Especially valuable was your firm denunciations of vitamin D, colloidal silver, and “vitamin C on your testicles” as putative cures or prophylactics against SARS-CoV2: of course, FTC and FDA are saying the same thing, but I’m sure that a lot of your listeners are somewhat skeptical to those authoritative but very conservative sources, and will listen much more from a person like you, who is scientifically careful but willing to go out further on the limb than what is firmly nailed-down. I salute you, sir: all told the series was valuable to me, to your diverse listenership, and to public health.

    • You know why? Because “vitamin D, colloidal silver, and Vitamin C” can’t be patented and used to price gauge the average consumer by corrupt pharma company’s MDs are brain washed by.

      They’re not a cure for COVID, but there is a plethora of evidence showing these over the counter supplements and help prevent and protect against viruses.

      • For example… Take a look at the remarkable research done on colostrum as a potent way to protect against viruses.

        Prevention of influenza episodes with colostrum compared with vaccination in healthy and high-risk cardiovascular subjects: the epidemiologic study in San Valentino.

        “After 3 months of follow-up, the number of days with flu was 3 times higher in the non-colostrum subjects. The incidence of complications and hospital admission was higher in the group that received only a vaccination compared with the colostrum groups. Colostrum, both in healthy subjects and high-risk cardiovascular patients, is at least 3 times more effective than vaccination to prevent flu and is very cost-effective.”

        https://www.ncbi.nlm…pubmed/17456621
        https://journals.sag…076029606295957

        Prevention and Treatment of Influenza with Hyperimmune Bovine Colostrum Antibody

        “Passive transfer of specific antibody (Ab) may provide a useful means of preventing or treating disease in unvaccinated individuals or those failing to adequately seroconvert, especially now that resistance to antiviral drugs is on the rise. These data suggest that a novel and commercially-scalable technique for preparing Ab from hyperimmune bovine colostrum could allow production of a valuable substitute for antiviral drugs to control influenza with the advantage of eliminating the need for daily administration. When the Ab preparations were given 3 days before infection (Fig. 7A and C), anti-PR8 IgG or F(ab’)2-treated mice not only survived (Lethal dose) but maintained their bodyweights”
        https://www.ncbi.nlm…les/PMC2964324/

        Effects of bovine colostrum on recurrent respiratory tract infections and diarrhea in children

        One hundred sixty children (aged 1–6 years) having recurrent episodes of URTI or diarrhea received BC for 4 weeks. The mean (± SD) total number of URTI (P < 0.0001), number of episodes of diarrhea (P < 0.001), and number of hospital admissions (P < 0.001) were significantly decreased after BC therapy
        https://journals.lww…ecurrent.9.aspx

        Prevention of flu episodes with colostrum and Bifivir compared with vaccination: an epidemiological, registry study.

        "The number of episodes registered with the immunnomodulators was significantly lower than those observed in patients using vaccination or no prevention (P<0.05). The number of days of disease was higher in untreated controls compared to the groups treated with immunomodulators (P<0.05) and 2 times higher in the vaccination group compared to the same groups (P<0.05). The average relative costs were significantly lower (2.3 times) in the immunomodulators groups in comparison with the other groups (P<0.05). No problems concerning tolerability or side effects were observed during the study."
        https://www.ncbi.nlm…pubmed/21183886

    • I saw the video you speak of (#4 in the series), and I don’t think he “firmly denounced” vitamins D and C. He stated that he recommends his patients continue with their normal supplementation. (I am about 99% sure Dr. Attia takes one supplement or another. Many physicians take nutraceuticals themselves, even in the absence of randomized triple-blind placebo-controlled human trials. They just work in a system that doesn’t necessarily permit them to recommend them to patients.) Dr. Attia was talking about far-fetched recommendations such as “do these 12 things and you’ll be fine”or “sit in a sauna all day long and you’ll be cured”. I personally haven’t seen any magical claims like this, but I am certain that his audience (on the whole well-educated) would not fall for anything outlandish. The only crazy thing I’ve seen is MMS, which is essentially bleach (definitely dangerous to take internally). Again, Dr. Attia’s audience would likely steer clear of such nonsense.

    • Of course no one can say C or D will make you bulletproof against SARS-2-CoV or any disease. No drug will either. But there is a large volume of evidence that both of these essential micronutrients have pleiotropic functions that enhance overall immunity.
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707683/
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166406/
      Although hyper-dosing on C is less dangerous, as the body flushes out the excess, over-doing D is not recommended, as it is a fat-soluble vitamin that is not as easily excreted. One systematic review and meta-analysis of individual participant data from randomised controlled trials showed that low to moderate dose (up to 1,000IU), not high dose D, lowers risk of acute respiratory infection: https://www.bmj.com/content/356/bmj.i6583
      Not individual medical advice, but just showing a couple of the many published scientific papers.

  10. I just coincidentally read a book “1491” about the Indians of the Americas and tho it’s hard to prove from so long ago but there is a good chance that the first visitors to America from the old world killed up to 95% of all the Indian populations before any of the slightly later comers even knew what had happened.

  11. Thank you Peter (and for all your podcasts)

    “Are we going the Italian or Singapore path?”

    The boat for the Singapore path sailed long ago (3 weeks). Even your swimming ability couldn’t catch that boat.

    Vitamin D: there are peer reviewed clinical trials that support the efficacy of Vitamin D (and zinc including Cochrane review).

  12. Thanks for getting this out. I’m an executive officer for a large metropolitan law enforcement agency; I’d like to use your show note’s statements about first responders being of higher risk when I brief our leadership. My goal is to encourage our agency to make procedural changes that heavily encourage social distancing between our officers when feasible. Could you please give me a reference for this so I can be better prepared for push back? Apologies, my limited googling abilities produced little of value concerning this.

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