In this episode, infectious disease and pandemic preparedness expert, Amesh Adalja, M.D., puts the current pandemic into context against previous coronaviruses as well as past influenza pandemics. Amesh also provides his interpretation of the evolving metrics which have contributed to big variations in modeling predictions, whether this will be a seasonally recurring virus, and perhaps most importantly—how we can be better prepared for the inevitable future novel virus. Finally, Amesh explains where he sees positive trends which give him reasons for optimism.

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We discuss:

Amesh’s background in infectious disease [2:40];

When did the virus actually reach the US? And when did Amesh realize it would pose a real threat to the US? [4:00];

Comparing and contrasting COVID-19 to previous pandemics like the Asian flu of 1958 and the Spanish flu of 1918 [8:00];

Will COVID-19 be a recurring seasonal virus every year? [14:00];

Will a future vaccine be specific to this COVID-19 or will it also cover previous coronaviruses as well? [15:15];

What does Amesh think might be the true case fatality rate of SARS-CoV-2? [16:15];

Why did early models over predict infections and deaths by order of millions? [18:30];

Role of government—How does Amesh view the role of local versus central government in dealing with a future pandemic? [21:50];

What went wrong with testing and how could we have utilized it more effectively? [25:15];

Future pandemic preparedness—why Amesh is cautiously optimistic [27:30];

Should there be different policies and restrictions for places like New York City compared to less populated and less affected places across the US? [30:15];

Why mass gatherings might be disproportionately driving the spread of the virus [32:30];

Learning from HKU1, a lesser-known novel coronavirus from 2005 [34:00];

Thoughts on Sweden’s herd immunity approach [36:10];

The efficacy of masks being worn in public and what role they will play as restrictions are slowly lifted [37:20];

What are some positive trends and signs of optimism? [39:15]; and

More.

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Show Notes

Amesh’s background in infectious disease [2:40]

Amesh is an infectious disease emergency medicine and critical care physician

His entire career is focused on the issue of pandemic preparedness, pandemic prediction, infectious disease and national security, and emerging infectious disease

He’s worked on H1N1, Ebola, and agents of bio-terrorism

“This is an outbreak that had been on my radar before it hit headlines.”

When did the virus actually reach the US? And when did Amesh realize it would pose a real threat to the US? [4:00]

Back in December…

He was trying to take what the Chinese were saying at face value

However, the Chinese were originally reporting this to only be animal to human (and not human to human)

Amesh was skeptical

Eventually a Lancet paper came out which showed someone who got ill had no contact with a wet market suggesting human to human transmission was possible

This false reporting by the Chinese gave the virus a “very big headstart” in spreading across the planet

Do you think it’s possible that this virus was in the United States? Potentially even within an individual prior to December 31st?

Won’t rule out the possibility

May have been sporadic cases

But the data don’t show that there were widespread cases prior to January

At what point was Amesh becoming convinced that this was going to enter the US in a manner that was going to pose real difficulty for the country?

“I knew it was going to enter the United States almost from the onset.”

Once it was clearly possible to transmit human to human (Just like H1N1), it wasn’t going to be containable, says Amesh

–What Amesh did NOT realize was…

How difficult it would be to contain in the US

And that was because our testing capability wasn’t as good as Amesh assumed

Secondly, many people had mild to no symptoms so it was hard to know who has it much less do contact tracing

“That became completely unmanageable because we basically were allowing this virus to have about two months of unabated spread in the United States, and that’s something that most of us did not think would happen because we thought that we were much more resilient to these types of infections than we really were.”

Comparing and contrasting COVID-19 to previous pandemics like the Asian flu of 1958 and the Spanish flu of 1918 [8:00]

In 1958, a novel flu virus spread in the US killing about 100,000 people

The worst flu season since then was 2017-2018 which killed ~80,000 people

Flu has a lot of similarities with coronavirus:

They both are transmitted through the respiratory route

They both have symptoms that include coughing and sneezing and sore throat and muscle aches and pains and fever.

However… This is in ADDITION to the flu In the 50s, people were used to the flu so they sort of took it in stride In 2009 with H1N1, it spread like crazy to 61 million people and started to stress the healthcare system but it has a case fatality rate of less than seasonal flu



An influenza pandemic still remains the biggest pandemic threat that we face…

Some avian influenza has a CFR of 65%

For example, if H7N9 even figured out how to efficiently go human to human we’d be in a MUCH more dire situation

With COVID-19…

We are fortunate that COVID-19 CFR is less than 1% (maybe as low at .3%)

“But we didn’t do that great of a job within, in terms of diagnostic testing and hospital capacity and personal protective equipment. So that’s magnified this and that’s the human factor that’s magnified what the virus could do.”

“I’m a little more worried about our pandemic resiliency based on how badly we’ve handled a 1% case fatality rate, pandemic virus, where you’ve got cascading decisions by governors in States and countries all around the world that really have magnified the damage that the virus has done.”

It’s better to think about different cities separately than to just look at the US as a whole…

Depending on density of population

When they began social distancing, etc.

Will COVID-19 be a recurring seasonal virus every year? [14:00]

There are currently 4 types of coronaviruses that recur seasonally

They cause about 25% of the colds we get

They are quite mild

Amesh thinks that SARS-CoV-2/COVID-19 will be a fifth strain of seasonal coronavirus with “intermediate” severity

Why are SARS and MERS not seen seasonally?

They are mostly animal to human

Summarizing why this will likely be recurring seasonally:

“When you look at their outbreaks, they’re very specialized. They’re happening in healthcare facilities have poor infection control and it doesn’t really sustain itself in the human population. Whereas if you look at the other four coronaviruses, the ones that cause common colds, they are ubiquitous. They transmit very easy. They have a mild spectrum of illness which allows people to go about their daily life and spread, and this new novel coronavirus does appear to be more like them in terms of their transmissibility. So that’s why I think that this will be the fifth seasonal coronavirus until there’s a vaccine.”

Will a future vaccine be specific to this COVID-19 or will it also cover previous coronaviruses as well? [15:15]

Probably not the first vaccine we get

But it’s possible that one down the road will cross protect against other types of coronaviruses

What does Amesh think might be the true case fatality rate of SARS-CoV-2? [16:15]

It’s been hard to calculate because we have a “severity bias”

South Korea and Germany has done more testing so Amesh looks at their data

Germany just showed it to be 0.37%, for example

Amesh estimates the true CFR to be between 0.3% to 0.66% range

But this is an AVERAGE

Things like age and underlying conditions make the CFR different

“Some people will have much, much higher risks and some people have lower risks, and I think that’s sometimes lost in nuance when you try to come up with one number.”

Why did early models over predict infections and deaths by order of millions? [18:30]

Some of the earliest predictions from models suggested 200+ million people would get infected and 2-4 million Americans would die

Those seems to now look like wild over predictions

What contributed to this?

The models have many assumptions

Each small adjustment in the assumptions can make a huge impact on the end number

⇒ One example, hospitalization rate

Hospitalization rate was probably overstated

There clearly is a severity bias in who gets tested… which leads to a number like 15 to 20% getting admitted to the hospital

Amesh says the real hospitalization rate is probably closer to 5%

“[They were] using the wrong denominator, I think, to come up with what their case fatality ratios are, what their ICU bed needs would be, and what their mechanical ventilation needs would be.”

Role of government—How does Amesh view the role of local versus central government in dealing with a future pandemic? [21:50]

US government is unique in healthcare where power is vested at the local and state level and the federal government is more of a coordinator

Amesh is generally supportive of this set up given that local health departments are the ones running it because they actually know their community, they know their capacities, they know where their gaps are, and they’re able to really be on the ground with the people and able to do great things when it comes to stopping an outbreak

However, often they are under resourced during a pandemic

“What you need to really do is have those local health departments actually operating the way that they should be and thought of as part of the whole pandemic response apparatus. Whereas many people think of just the CDC, the NIH and parts of the health and human services department as the main pandemic apparatus.”

Amesh says that confusing part for the public is that there were some conflicting recommendation from federal to state to local areas

“I do think that when the process works well with local, state and federal government all in step, all doing the appropriate roles, I do think it works pretty well. You have a locally managed federally coordinated response, which I think is the best way to think about how it would be ideally done.”

What went wrong with testing and how could we have utilized it more effectively? [25:15]

-The CDC put out guidance that was too restrictive as to who could get tested

Originally that was… Only people that had traveled to China in the last 14 days Had to have lower respiratory tract symptoms or pneumonia We weren’t testing mild cases and we weren’t testing people that hadn’t come from China



-A better way to do this would have been…

This is a respiratory virus and as many overlapping symptoms with common colds and flus

you should think about this in your patients and we are going to allow testing to be done if you have certain risk factors for this

And they shouldn’t just be restricted to you having severe disease or having traveled to China

“ That would have changed the way that the general public and clinicians would have thought about this .”

-We also had a scarcity of testing and reagents and nasal swabs

-AND it was all compounded by bureaucratic hiccups such as the CDC test having to go through FDA emergency use authorization before it could be distributed to the US

Future pandemic preparedness—why Amesh is cautiously optimistic [27:30]

Amesh thinks that since this pandemic has impacted so many people from a health perspective but perhaps even more so an economic perspective…

…that this one will not be forgotten

In the past, we’ve sort of “reacted” to things like anthrax in 2001, bird flu in 2005, H1N1 in 2009, Ebola in 2013, and then Zika after that

But once those were gone it sort of faded

Amesh is optimistic that the people will now prioritize pandemic preparedness and demand that their politicians take the proper steps

Should there be different policies and restrictions for places like New York City compared to less populated and less affected places across the US? [30:15]

Amesh definitely thinks we should be implementing different strategies across the country

There are places that can start to think about lessening restrictions Less social distancing Opening up more businesses Opening up schools



Definitely need to start considering opening up medical centers for non-COVID patients: “In places where they’re not inundated because you’re going to get other health consequences that are not captured by the models which are really measurable and will pay for down the road.”

All this will depend on what’s happening locally:

How much transmission do you have?

What is the antibody status of your population?

What’s your hospital capacity?

What is your ability to do diagnostic testing?

Do you have the new rapid tests available in many different places?

“ All of that can help condition how we get back to normal. ”

Until we have vaccine… the one place where we need to be the most careful is mass gatherings

“We can start taking steps and I hope that we start doing it because this cost is something that is measurable and it increases every day and I do think that they’re going to be [other] consequences that are not captured by our models, which are really only focused on coronavirus.”

Why mass gatherings might be disproportionately driving the spread of the virus [32:30]

German data recently suggested that mass gatherings that are disproportionately driving the spread

A mass gathering brings people from wide geographic areas

At an NFL game, for example, people are close to each other and they are screaming and yelling which results in particles coming from their mouths

We saw what happened at a choir practice recently

Mass gatherings are going to be a challenge until a vaccine comes out because…

The density

The fact that people come from different geographic regions and then just disperse

Mass gatherings are a particular problem when it comes to communicable infectious diseases

Learning from HKU1, a lesser-known novel coronavirus from 2005 [34:00]

Hong Kong University found a novel coronavirus (HKU1) in 2005

Coronavirus was on their radar because of the 2003 SARS situation

They found HKU1 in some people who had pneumonia that tested negative for SARS

They then looked in other countries and found it in Cleveland in the proportion of patients that were hospitalized for Coronavirus—HKU1 is disproportionately in patients who died or were on ventilators

“ And it was basically everywhere you looked. ”

It flew under the radar because we do a poor job of testing for respiratory viruses

While Amesh doesn’t think SARS-CoV-2 was widespread prior to January in the US, he would not be surprised if there were undiagnosed cases that were “hidden” in our cold and flu season as early as December

“I do think that’s an important lesson to think about with a virus that can spread surreptitiously and you don’t know about it because our diagnostic curiosity is so bad for many infectious disease syndromes.”

Thoughts on Sweden’s herd immunity approach [36:10]

Sweden has sort of elected to not shut down to the extent that other European and Scandinavian countries have.

Peter asks, Have you paid attention to the transmissibility in Sweden or do you have any comments on it?

They’re trying to pursue a herd immunity strategy

You’re going to see more cases there, which is what they’re aiming for.

Amesh is a bit worried because their per capita ICU bed numbers are not very high and that’s what we’re really worried about is… Do you put an ICU into crisis? Do you have problems with ventilators?

Amesh says it will be instructive to learn how they do but thinks it will be a challenge to sort of cocoon the high-risk people

“It’s all going to depend upon who is getting sick and how well they can sequester their high risk groups, which I think is very daunting and challenging.”

The efficacy of masks being worn in public and what role they will play as restrictions are slowly lifted [37:20]

This is a controversial topic, says Amesh, but he does NOT believe masks are very helpful to the public

“I tend to be someone who’s not supportive of masks being worn by the public and especially not n95 masks, which I think are in short supply, unclear whether the public can actually bear wearing them for a long period of time because they’re not comfortable to wear.”

For those with clear symptoms (e.g., coughing/sneezing)…

They should definitely wear a mask in public

The question is…For people who are asymptomatic (having no symptoms), how transmissible are they if they don’t wear a mask?

This is an open question, says Amesh

The CDC made a recommendation to wear homemade masks

However, Amesh is not sure not sure how well those homemade masks prevent you from spreading it even if you ARE someone with symptoms because they don’t even stop the coughs and sneezes very well based on some studies that have been published.

Summary of Amesh’s take on the public wearing masks:

“I’m someone who doesn’t necessarily think that these masks are going to be very beneficial and they could be paradoxically negative because people may then refrain from washing their hands as much. They may not social distance as much, they may contaminate other people with their mask if they don’t store it properly or wash it…

…So I have a lot of concerns about mass, but I think that this is a, a decision that’s going to be made on a political basis and there is enough scientific controversy that I think politicians may use it as a way to move forward in a way that allows us to open schools, open businesses up if they have people wearing masks. But I’m not sure if we’ll get much benefit from them.”

What are some positive trends and signs of optimism? [39:15]

Most optimistic about…

Plateauing numbers in New York, Seattle, California.

California, for example, is taking ventilators and giving them to other states

Washington State is dismantling their field hospital that did not see any patients and returning ventilators

–We hear a lot about the bad places like New York, New Orleans, Chicago, Detroit…

But there are places that were preparing for a surge are now downsizing their nursing staff

Many field hospitals are closing down

Many ventilators are going back to the national stockpile

It’s important to know that it’s not going to be doom and gloom and every place

“All of that makes me very optimistic that we will be able to meet the challenge of this virus without putting any of our hospitals into crisis, that this is going to be a severe challenge for this country, but it’s not something that that is going to break the country.”

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