Coronavirus & Resilience Part II

A medical perspective 11 things we learned

As we predicted, we were not able to get through all of the material on the community meeting. In particular, Dr. Adrian Rawlinson’s perspective. Adrian is a fellow guru and has a pragmatic and balanced perspective on what we are all going through. We will have a follow-up Zoom in two weeks, but rather than wait, Dr. Rawlinson volunteered to summarize his “11 things we’ve learned” below.

We hope this is helpful and please feel free to ping the community back if you have additional questions or advice. We are all learning how to communicate better in the new normal. If you have thoughts or best practices on how we can improve getting information out in a timely and effective manner we also appreciate the feedback!

Our next Zoom will be Friday, March 27th at noon.

As the good doctor recommends at the end of his 11 point “things we’ve learned” Please stay safe and follow the guidelines. Get out into nature, read a book, binge watch Netflix and enjoy the rest of the weekend.

Luis, Merrill, Chris, & Nick

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Fellow founders & Gurus,

I want to thank Chris, Merrill and the BGF team for a great call yesterday. I was hoping to chime in from a medical perspective but we ran out of time.

I think it’s very important that we all continue to educate ourselves about COVID-19 and disseminate good, science-based information to those around us — whether that be family members, co-workers, employees, etc.

As a physician, I have been trying to digest all the data and multiple conversations on this topic. While there is a tremendous amount of good information out there we have to be careful about disseminating false claims, misleading data, etc. I don’t profess to be an expert in Infectious Diseases but I did spend 6 months in an ID hospital in the UK many years ago :)

Chris did send out a few links which I urge you to watch. He also highlighted the prevention strategies which are well delineated — hand washing, disinfectants, social distancing, etc — so I won’t go over all those. It’s worth signing up for the CDC email alerts.

As most of you are probably staying home this weekend I think it’s good to think about a household plan of action. Here are the main items to start thinking about recommended by the CDC;

• Talk with the people who need to be included in your plan.
• Plan ways to care for those who might be at greater risk for serious complications.
• Get to know your neighbors.
• Identify aid organizations in your community.
• Create an emergency contact list.
• Choose a room in your home that can be used to separate sick household members from those who are healthy.

The CDC also has some information here about the implications for Businesses and Employees. If you should start to exhibit any symptoms please refer to this factsheet.

I am following several ID (Infectious Disease) experts and have attempted to keep a list of the current facts as they are presented. I am connected with a lot of these folks on LinkedIn. Feel free to search the hashtags #coronavirus #covid19 #sarscov2 etc. I have put together a list of the main points as I understand them. Here goes…..

1. Nomenclature:

I think it’s important to understand the definitions…

• 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

2. 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

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

3. World diffusion (ongoing) of SARS-CoV-2 pandemic of 2020 originating in Wuhan.

SARS-CoV-2 — or COVID-19 — is not the most lethal or transmissible of viruses but it is high in both categories. 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 the 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)
• Obesity seems to be a risk factor
• 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

3.Disease Transmission:

• 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
• 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)

4. 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

5. 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

6. What about treatment or vaccines?

You may have heard of Convalescent plasma coronavirus therapy :

• 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

• The 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

But 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

People are asking about a possible vaccine:

• 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

• The 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

Peter Hotez MD 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
• If you are interested — for funding support please email Peter directly: hotez@bcm.edu

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

• Some identified modes: Microdroplets on the surface, directly on someone, airborne, fecal
• A recent paper reported fomite survival on different surfaces:
• ~72hr on plastic
• 48hr on cardboard
• 24hr on steel
• 8–24hr on copper
• So it can live on multiple surfaces for at least 8hr to 72hr
• Mode of transmission is significant because the virus can survive and transfer in a number of different ways.

8. COVID-19 has 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 others become very ill and will a high mortality rate
• Mortality rate: 0.6–3.4 %
• 4–20% 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 the transmission of disease and nursing homes
• Peter Hotez MD testified in front of Congress, calling the virus an “angel of death for older people”
• Poses a lot of questions — eg can we visit granny? etc. Social isolation — not good.

9. Concerning geographic regions in the US

• 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 the infection rate and numbers

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

10. Risk Reduction.

We still have some say in our response to this at the federal, local, state and personal levels. Self-isolating and quarantining when necessary (any signs or symptoms). The plea is 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 weigh risk vs socialization important
• Want to protect and isolate individuals
• Socialization and seeing others is very (psychologically important)

11.In the coming weeks…

• Our ID and epidemiology experts will need to 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

I honestly think we are only about 5% in this situation. Let’s all work together and support each other through these difficult times.

Please stay safe and follow the guidelines. Get out into nature, read a book, binge watch Netflix and enjoy the rest of the weekend.

Best,

Dr. Adrian Rawlinson