This newsletter was split into two parts so as not to get cut off in email browsers. Expect part two to come out tomorrow where I explain why we should be more concerned about the virus mutating and provide novel tips on how to thrive during the pandemic, both physically and mentally.

It’s April 1st, 2020. If only the headlines were a joke. Our nation’s leaders will soon be faced with a difficult choice. Hunker down for another four months and wreck the economy or let people out in two months and kill an additional hundred thousand people.

Professor Samir Bhatt, Senior Lecturer at the Imperial College of London, and his colleagues calculate that, globally, up to 43 million people have been infected with SARS-CoV-2. They predict that if we’d gone about our normal lives, COVID-19 would have caused 7 billion infections and 40 million deaths this year. Shielding only the elderly may have halved the number of deaths, a strategy the UK initially entertained, but health systems would have been overwhelmed, so that tactic was largely abandoned.

Based on the advice of professional epidemiologists, most nations have adopted a stretch-it-out and hope it doesn’t return strategy. It seems to be working so far. Rates of new cases are declining in Europe and the US. If the current suppression strategies are sustained, then 38.7 million lives globally will be saved this year, the epidemiologists at the Imperial College calculate. 

But epidemiologists aren’t economists. We can not stay home for the rest of the year - the economic impact would be too high. We are three weeks into the shutdown and already factories are ceasing production, brick-and-mortar retail stores and restaurants are closed, unemployment spikes are unprecedented, commodity prices have plunged, and a wave of loan defaults is expected.

A colleague on a global pandemic response panel tells me the panel’s best estimate is that the US economy will rebound rapidly, but only if the nation returns to work in 60 days. After that, it’s anyone’s guess. No one, not even the experts, are willing to estimate the full economic impact of COVID-19. It will depend on how long it takes to get back to work and how many times we will be sent back home. 

When can we go back to work and school? Will the infections spike again? Will normal life ever return?

Two weeks ago, I predicted that we probably won’t be allowed out of our homes until late-June, and possibly July. This went against mainstream predictions and shocked a lot of people who were expecting this all to be over mid-April. Yesterday, the state of Virginia announced a stay-at-home order until June 10th. Other states will follow the lead. That means kids won’t be going back to school this semester and it puts us over the 60-day economic cliff.

When epidemiologists extend their models beyond summer, the predictions are bleak. No matter what we do, the total number of COVID-19 cases and deaths don’t change appreciably over the next 18 months because the virus will come back, as it may be in China. In fact, delaying the spread could make it worse if the peak is pushed off until next winter when the virus can spread more easily (see the figure below). Modeling of the UK outbreak suggests that social distancing measures might be needed for large parts of the next two years including school and university closures. Let’s hope not.

Unless drugs are found to lower fatality rates, more than 200,000 people will die in the US, even with the current strategy of stay-at-home for 4 to 5 months. If we can hold the rate of infection at levels that our hospitals can manage for the next 18 months, by keeping our distance from each other and staying at home if there’s a resurgence, we should be able to buy time until a vaccine can abruptly put an end to the pandemic. 

It’s not all bad news:

• There are 57 drug and 39 vaccine trials underway.

• In the past two days, the number of new COVID-19 cases in US states have finally started to slow. 

• The number of people moving around is down ~80% according to wrist biotracker and vehicle GPS data. 

• The number of people with fevers has declined below seasonal levels, according to Bluetooth thermometer company Kinsa. 

• The FDA approved the use of both hydroxy-chloroquine and plasma from recovered patients. 

• Incredibly, the overall death rate has also dropped below normal, for reasons we can only speculate.

• Stress tests on the banks show much greater health than in 2008. 

• Scientists, journalists, programmers, and governments have created a valuable (but sometimes overwhelming) body of work to inform us where we currently stand.

Addressing misinformation

I want to commend scientists who have played an important role in disseminating truthful and science-based information. Notables include Drs. Anthony Fauci, Peter Attia, Peter Hotez, Rhonda Patrick, and Trevor Bradford. Startup entrepreneur Tomas Pueyo collated an enormous amount of information in this article, which received high praise by academics and I was impressed by the clarity of the article by Ed Yong at The Atlantic about how the pandemic might play out. AP Fact Checker, Snopes, STAT News, The Wall Street Journal, and The New York Times are working overtime to check claims.  

For every one of these exemplars of accuracy, there are many others spreading misinformation. Perhaps the worst was the Internet meme that spread across the globe in multiple languages this week, which began, “Great news!! A coronavirus vaccine is ready. Able to heal the patient within 3 hours." These memes, produced by idle or nefarious hands, would be amusing if not for the vast number of people who believe them. (Note: Vaccines don’t cure diseases, period).

This coronavirus almost certainly came from a bat, probably horseshoe bat. Not from a scuffle with a CIA agent at a Wuhan bioweapon lab. Not from a snake. Not from some exotic animal soup, the temperature of which would have killed the virus. And I’m not going to waste time explaining why 5G networks were not involved. 

In the scientific community, the website Pubmed.org is the go-to search engine for peer-reviewed papers. Pre-print websites like bioRxiv.org and medRxiv.org that publish work before peer-review are godsends. Journals like Nature, Cell, Science, The Journal of Virology, and the New England Journal of Medicine remain the standard for scientific rigor. Many journals are making their COVID-19 papers open access, so anyone can read them.

What should leaders do now?

Besides the seemingly obvious things, like establishing national warehouses of pandemic supplies and practising the gold standard 3T responses, test, track, and treat, here’s what we should do as a nation: 

1. Make it illegal for non-essential workers to congregate or travel for the next 45 days. By then we should see if hospitals are coping and some medicines are helping.

2. Recommend that people cover their faces in public with a cloth or mask, even if it only stops them touching their faces and keeps nasal humidity high. 

3. Set up a global repository of clinical data that collates bloodwork, autopsy data, e.g. utilizing Georgetown University’s COVID-19 AI open dataset (CORD).

4. Determine the genomes of patients (alive and dead) to know if there is a genetic component that predicts severity. There are 12 known variants in the ACE2 gene alone (I explain this more in part two).

5. Encourage citizens to improve their health. Move, eat less often, avoid processed carbs, and quit smoking. Immediately.

And going forward: 

6. Establish a US Bioforce, alongside the Airforce, Army, Navy, Spaceforce and National Guard. The virus has killed more people than the Afghanistan war and will do more economic damage.

7. Set up a global and centralized system to track viruses in wild animals, viruses in people, and body temperatures. One of the companies I founded seven years ago, called Arc-Bio, is developing such a system and is already manufacturing viral detection kits.

I look forward to hearing your suggestions for what we should do. You can email them to me at info@lifespanbook.com

Thank you to everyone who already emailed or messaged my team with questions and ideas. We couldn’t respond to everyone, but we did read them all and have put together some answers. After reading hundreds of scientific papers and listening to a network of experts, first, let me dispel some more rumors.

The true origin story

It is debated whether the virus passed through a population of scaly, ant-eating pangolins on its way to humans, which were also traded until China banned the exotic animal trade in February. One of the genes looks like a pangolin coronavirus, but the similarity could just be coincidental.

Knowing how the virus came to infect humans is important if we are to prevent the next pandemic. As Francis Collins, Director of the NIH noted in his recent article in Nature, it was certainly a single human infection that led to the pandemic. If the virus leaped into more than one human, the researchers would expect a greater number of mutations. 

The fact that it came from Asian bats is no surprise to scientists, least of all to Peter Daszak from the EcoHealth Alliance, who has collected and studied coronaviruses for more than a decade. In 2010, I was in the audience watching his riveting TEDMED talk. Pointing to a picture of a horseshoe bat he said, “We showed they are the main reservoir of SARS. And people eat bats all over Asia.” 

Peter then showed a world map he had colored to show the viral hotspots his team identified, based on the prevalence of environmental disturbances and human-animal contact. 

“This is a predictive map of where the next HIV or SARS will emerge,” he said. The map showed a large, red hotspot over Hubei province, China.

“My colleagues say you can’t predict where the next outbreak will occur,” he said. But Peter was spot on.

Bats have hundreds of different viruses in them including hantavirus, Ebola, and SARS. Seven out of the fifteen known viral species have only been found in bats, which seem to tolerate infections because the bat immune system doesn’t overreact (see graphs below).

Knowing the customs of the region and the biology of coronaviruses, it is possible to reconstruct how the first human became infected. Deep in the wilderness of China's Yunnan province, a horseshoe bat coronavirus replicated and made a copying error. It was passed on to a relative, where it made another error, and another. 

Then early in November 2019, one of these animals either bit a person, breathed, or bled on them. It could have been a butcher at a wet market in Wuhan. It could even have been someone from the Wuhan Institute of Virology, who have been studying wild bats carrying hundreds of SARS-related viruses, including one almost identical to the SARS-CoV-2 only an hour’s drive south-west of Wuhan.

In one sense, coronaviruses are formidable foes. They have some of the largest and most complex genomes of all viruses, having perfected themselves, by some estimates, over the past 290 million years. 

On the other hand, they have an Achilles’ heel: a fragile membrane that is easily destroyed by soap, alcohol, heat, and antimicrobials on our skin. Visualize coronaviruses not like tiny cannonballs but more like fragile balloons that can easily pop (see schematic below). 

Coronaviruses need to get inside cells before their membrane disintegrates, and they use two cunning methods. One way, called endocytosis, is to trick the cell into making a concave pocket in its membrane that takes the virus inside, similar to a Trojan horse. This is also how flu viruses get in.

The other way is to use a lock and key, a process called membrane fusion. The virus binds tightly with a specific cell surface protein, like a key in a lock, which allows it to blend its own membrane with the victim’s cell’s membrane, like two bubbles merging. This is also how HIV and herpes get in.

Coronaviruses use both these methods, making viral entry particularly difficult to block, but there are ways. The key to their entry is the spike protein that decorates the surface of the virus, like a clove pushed in an orange (see diagram below). The spike protein will bounce off all other proteins in the body, except for the angiotensin-converting enzyme (ACE2). ACE2 is the lock that the spike fits into. It is made by cells in the kidney, spleen, heart and blood vessels, but it is by far the most abundant in intestines and the lung.

There’s a lot of discussion about the risk of taking common drugs that control blood pressure by modulating ACE enzymes. We have two ACE enzymes, ACE1 and ACE2, with opposing functions. Blood pressure medicines, such as enalapril and ramipril, block ACE1, but this can raise the levels of ACE2, potentially making COVID-19 worse. For now, The American College of Cardiology suggests patients keep taking their ACE inhibitors but be extra careful not to come in contact with potentially infectious people.

Coronaviruses are highly unstable, genetically speaking. One of the main reasons is their genome is not made of DNA but of RNA, a very ancient, primitive genetic material. RNA is typically a single-stranded molecule, whereas DNA is made of two separate strands, like a zipper, with one side heading in the opposite direction in a helix shape. The fingers that can lock the zipper together are called “bases,” and their sequence is the genetic code that tells a cell how to make proteins or more RNA. If a mistake is made while copying our genetic material, DNA, it can be corrected because there is another strand that can be used as a template to correct errors. But if an RNA virus makes a copying error, it is locked in forever. And those changes accumulate over time.

There have been stories claiming coronavirus isn't changing rapidly. It is. 

In part two I will continue to explain why we should be more concerned about the virus mutating and provide novel tips on how to thrive during the pandemic, both physically and mentally. Expect an email update tomorrow.

If you missed our March 18th COVID-19 update, you may find it here. Sign up for Lifespan Insiders here