Should we worry about COVID-19 mutating?

There have been stories claiming that the coronavirus isn’t changing rapidly. It is. Only about 1,000 genomes have been sequenced worldwide, so there is a lot we are missing. Even so, according to Nextstrain.org, a site that tracks viral genomes across the planet, the virus is mutating like an influenza virus, faster than dengue and measles (see graphs below)* and even faster than other coronaviruses. The published rate of change has gone up by 20% in the past two weeks.

Very few people, with the exception of people like Trevor Bradford, an associate member at the Fred Hutchinson Cancer Research Center, few people are honestly discussing why, how, where, and what this means for the future.

This could be good news or bad news, depending on how humanity’s luck breaks over the next 12 months. We are witnessing, in real-time, a global game of roulette.

The genome of the coronavirus is extraordinarily long for a virus. It has over a dozen genes encoded by over 30,000 bases. For comparison, the common cold viruses and HIV are only ~9,200 bases long. Most mutations will make the virus less dangerous. Some will put a stop signal in the middle of a protein and render the virus impotent. Others will just make the virus less efficient because the viral proteins need to work together with the human proteins in a complex dance. If they change, they probably won’t work as well. 

The type of mutation that is most dangerous is called a “missense” mutation because it changes which amino acids make up viral proteins. A few amino acid changes in a protein can make a huge difference in how that protein behaves, like how slight tweaks to computer software can change how that software works. 

Amino acid changes in one of over a dozen current coronavirus genetic variants around the globe could lead to an even more infectious or lethal strain or render detection kits less accurate. The genetic changes that caused the 1957 influenza pandemic changed only 5 amino acids in that virus’s surface protein. On March 15th, the most mutated viral sample had 10 mutations, including the one in the spike protein gene that we definitely don’t want to mutate. Two weeks later, there was one with 16 mutations, 14 of which were missense, fortunately not all in the spike protein. But if these strains continue to mutate over the next 18 months, they could make vaccines less effective or trigger a doomsday scenario where our immune system is unable to prevent reinfection.

Fortunately, most viral experts say such possibilities are highly unlikely. Not zero, mind you. We’ve never had a truly global pandemic caused by a coronavirus in billions of people, changing and evolving, which is why I continue to monitor the situation.

New information on slowing the spread

The humidity of our homes and workplaces can play a major factor that determines our susceptibility to viral infections. Dry air destroys the mucus lining of our airways so viruses can gain access. 

Animal and human studies show that 50% relative humidity (known as RH) is optimal to maintain our airways and protect from viruses. Low humidity (20–35%) greatly increases rates of infection. In winter, homes and workplaces sampled in NY and Midwest were ~24% RH. If you don’t have a humidifier in very cold winters or other dry climates, get one.

What about masks? At the beginning of this pandemic, in an effort to prevent panic purchases, the US government downplayed the effectiveness that masks have in slowing the spread of transmission of viral infections. This simply wasn’t true.

In a Cochrane Review on the subject, six out of seven studies showed that face masks (surgical and N95) offered significant protection against SARS. Another one found that consistently wearing a mask in public was associated with a 70% reduction in the risk of catching SARS. Even a tea towel provides some protection and limits how often you touch your face. Vacuum cleaner bags were quite effective, but use a clean one.

NAD, resveratrol, fasting, and how to prepare

Many people have asked me, “does NAD boosting or resveratrol work?” The answer is we don’t know. Lives are at stake here. In cell culture, resveratrol does counteract numerous viruses, including MERS, SARS-1, and HIV. Whether or not it works in the human body to slow viruses hasn’t been tested, but it’s relatively safe and I continue to take it while I’m safe at home. As for NAD, it’s plausible, but again we have no human data. NAD may increase the prevalence of the ACE2 that the virus uses to enter cells. But again, we just don’t know.

My advice to a friend was to get in the best physical and mental shape these next couple of months: 
 

1. Maintain cardio fitness, which will increase capillary and red blood cell counts. Lift weights if possible. Move.

2. Don’t be low in iron but also don’t overdose.

3. Keep taking your medicines unless an MD says to stop.

4. Eat less often during the day. I skip at least one meal, usually breakfast, and eat sensibly at other meals.

5. Avoid super intense exercise or long-term fasting.

6. Take 2500 - 5000 IU of vitamin D3 a day, which doctors say keeps your immune system in good shape.

7. Keep blood sugar levels in check by avoiding sugar and processed grains.

8. Focus on plants. Meats should include fish, preferably on the low end of the food chain to avoid heavy metals.

9. Eat colored plants, either fresh or snap-frozen, and don’t overcook them. They contain xenohormetic molecules that activate cell defenses.

10. Include nuts, avocado, and olive oil in your diet. Oleic acid from these foods will activate SIRT1, the defense enzyme, the same way resveratrol does (fasting also liberates oleic acid from fat stores). 

11. Keep humidity up in the home to maintain airway health and mucus. If your house isn’t humidified, get a humidifier for the bedroom.

12. Turn off breaking news channels. Read a book. Listen to a podcast. Make something.

13. Get sufficient sleep. Consider L-theanine. Avoid screens at night. Avoid big meals and alcohol near bedtime. Download f.lux software to dim the screens. If you use your phone in bed, wear blue-light blocking glasses.

Don't get down

As for daily life, make sure you, your parents, and grandparents don’t get lonely or depressed. Make video calls. We just bought Portals, little video screens, for the kitchens of all our close relatives so it’s easy to stay in touch every day.

My wife Sandra and our three kids are holed-up on Cape Cod, Massachusetts. My 20-person lab at Harvard has stopped all its medical research, except for a few critical experiments being maintained by three lab volunteers, who we deeply appreciate. 

Sandra has planted indoor vegetables and our family is eating healthily, avoiding sugar, and exercising most days, either by running and taking walks away from others, or lifting weights. We’ve even started video sessions with our trainer, an example of new industries emerging.

If you are at home with more time than before, think of something you’ve always wanted to learn: a new instrument, juggling, a foreign language. You may never have an opportunity like this.

I am inspired by Decameron, a book containing 100 tales told by a group of young people sheltering in a villa outside of Florence to escape the plague. They spent their time telling tales, performing practical jokes, and sharing life lessons. We are at such a time. We need to stick together and tell tales and jokes. This won’t be over soon but it will be over.

What does the future look like? If you’ve read my book Lifespan, you’ll know I’ve thought a lot about this topic and I don’t shy away from making predictions; they help us deal with the present and prepare for what may come. And prepare for what may come. We will be sheltering in place for at least another two months and may have to return again later this year if social distancing doesn't work.

That's the truth. But recall that after 1918 and 1945, the world recovered from far worse. I predict we are in for a bad couple of years, but by 2022, we will all be heading into what future historians will call the Roaring 20’s.

Please stay safe out there. Even better, if you can, don’t be out there. A special thanks to all the essential workers, farm-hands, researchers and drug makers, caregivers, veterinarians, nurses and doctors who continue to work and save lives, while the rest of us shelter.

And remember, this too shall pass.

David


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

*A previous version of this newsletter said that mutation rate units used for flu, etc were SITE/year but Cov-2 was inadvertently TOTAL SITES/year. Since CoV-2 has a 30kb genome, its rate = 24-30/30kb or ~1 x 10^-3, still faster than regular CoVs, dengue & measles but similar to flu. Things are going fast but, as a scientist, I will always correct any errors and admit mistakes. The implications and biology I discussed are still completely valid.