How to Fight the Coronavirus

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How to fight the coronavirus, SARS-CoV-2 and its disease, COVID-19

Michael Lin, PhD-MD
Associate Professor of Neurobiology, of Bioengineering and, by courtesy, of Chemical and Systems Biology
Stanford University
Lin Lab Briefing 2020-03-13
Revised 2020-03-20

Regularly updated here by Michael Lin

Warning: Contains facts
Bonus: Hand sanitizer recipe

This is not a pretty powerpoint

  • This is an informational document.
  • This is not a TED talk. It is not meant to entertain or dazzle or push an idea with beautiful graphics.
  • So there will be a lot of text, because there is a lot of info that needs to be explained. Graphics will be used as data primarily. You will have to do some reading.

Some context for the numbers you will see

Total population

  • 330M USA
  • 40M California (CA)

Flu (influenza) deaths this season

  • 40,000 USA (range 20,000 to 60,000) (www.cdc.gov/flu/about/burden/pre liminary-in-season-estimates.htm)
  • 5,000 CA, estimated. From a population of 40M, if 25% infected with flu virus, this means an infection fatality rate (IFR) of 0.05%. If 12.5% infected, then IFR = 0.1%.

~60,000 flu + pneumonia deaths per year
1.2M heart disease and cancer deaths per year ➔
All-cause deaths: 2.8M per year

Some definitions

COVID-19 stands for “coronavirus disease 2019”

  • It refers to the disease, not the virus. In practice, “COVID-19 cases” is used to refer to having a positive 2019 coronavirus lab test regardless of symptoms
  • WHO introduced the disease name COVID-19 with great fanfare (after weeks of discussions) at a time when there was no virus name, so it got picked up by the press as the virus name, incorrectly.
  • An example of a mis-use is “COVID-19 can survive on surfaces” (https://abcnews.go.com/Health/covid19-days-surfaces-experiment– findings/story?id=69569397), which is nonsensical, technically speaking.
  • In addition, COVID-19 is a terrible name for a disease, because you can’t append the word “virus” to describe the pathogen, as ”COVID-19 virus” would mean “coronavirus disease 2019 virus”, which sounds silly and indeed reveals the disease name to lack any informational value whatsoever.
  • Previously we named diseases by some sort of description of signs/symptoms, e.g. severe acute respiratory syndrome = SARS. WHO could have named the disease simply “SARS2” and it would have been both accurate and descriptive.

2019-nCOV was the initial  name given by some infectious disease organization for the virus, where nCOV stands for novel coronavirus. But this name is hard to remember because it starts with a generic term (the year). It is also inconsistent with coronavirus naming conventions. It is also misleading, because it gives the misimpression that the virus is especially novel. It’s not. In fact it’s the least novel of the respiratory disease- causing viruses isolated in the molecular age. It’s defining feature is it’s NON-novelty…

SARS-CoV-2 is the Genbank name for the virus, because it is 96% identical in nucleotide sequence to SARS-CoV, the cause of SARS in 2003.

  • We will use this name because it is accurate and informative, revealing the high similarity between these two pathogens. This name thus reminds us that we can infer a lot about SARS-CoV-2 from existing data on SARS-CoV.
  • Ironically, the WHO decided not to name the virus SARS-CoV-2 for precisely this reason – to obscure the relationship between the two viruses (www.vox.com/2020/2/14/21135208/coronavirus-wuhan-china-covid-19-name– sars-cov-2). However we are scientists, we want clarity not obfuscation.

Coronaviruses (CoVs)

  • Positive-strand RNA viruses with large genomes (≥27,000 bases).
  • Alpha and beta types cause disease in humans.
  • Both types already known to cause the common cold, account for 10- 30% of cases (Pubmed 31971553).
  • Very stable – CoV OC43 isolates from 1960s and 2001 had only 2 amino acid differences (Pubmed 15280490)!
  • Many CoVs in bats.
  • Easily hops between species
    • MERS-CoV hopped from camels to humans
    • SARS-CoV hopped from bats to humans and civets
    • SARS-CoV-2 hopped from bats to humans
    • It looks like humans with colds gave mice hepatitis, or vice versa).

How might you kill SARS-CoV-2?

How might SARS-CoV-2 kill you?

Estimating infection (not disease) numbers

Deaths are mostly in older patients

This is true for both flu and COVID-19

We are still early in the process

Estimating new case rates in CA and Bay Area (updated 2020/3/18)

What should we do when 1 in 1000 in the Bay Area just got the virus?

How bad could this be?

  • If we did nothing and doubling rate remains 1 week, then in worst case, deaths and infections will grow exponentially until virus runs out of people to infect (using CA-only numbers now):
  • Compare to Spanish flu of 1917-1918: Cumulative infection rate 27%, IFR 2%. Spanish flu might have higher IFR than COVID-19, but medical care was much worse then (no ventilators, no drugs). In reality COVID-19 is likely the more severe disease. In any case, Spanish flu was devastating.

We need to ‘flatten the curve’ now

The next month is critical: March 16 to April 16. We must do whatever we can to reduce R0 or increase doubling time. It will take several weeks to know if it’s working.

If we are still doubling each week on April 16, we have only another month to get a second chance.

If that doesn’t work by May 16, there will be no third chance. We would have to immediately clamp down to avoid hospital overflow. This would require Wuhan-like measures such as central quarantine for sick and enforced home-isolation for everyone else.

What can flatten the curve?

  • Weather: Maybe 10 ºF increases the doubling time 2x (steady-state reduction in exterior virus levels by 50% per Pubmed 22312351, plus reducing time ×concentration of people indoors).
  • Goal is to reduce the reproductive number R0  (how many people infected by each patient).
    • Current R0  rate ~ 2 (one person infects 2 others. If they do this in 7 days, it explains doubling time of 1 week).
    • Drop R0  to 1.5: Doubling time would increase ~2-fold.
    • Drop R0  to 1.25: Doubling time would increase ~4-fold.
    • Drop R0  to 1.125: Doubling time would increase ~8-fold.
    • Drop R0  to 1.0: Doubling time would become infinite (constant rate of new cases).
  • Social distancing, wide testing and tracing, and strict hygiene (face masks, hand sanitizer): This is the approach in SK, Taiwan, Singapore, HK. This seems to have dropped R0  to 1.0 (constant rate of new cases).
  • Complete household isolation, immediate quarantining of symptomatic, strict hygiene: This was the approach in Wuhan. R0  dropped from 3.9 to 0.32.
  • Is presymptomatic or asymptomatic transmission a factor? Yes, but how much is unclear.

It’s not easy, but social distancing, fast testing, and immediate quarantining can be enough!

Thanks to early research, we already have drugs with activity against the virus

Camostat

Favipiravir/favilavir/Avigan/T-705 (Fujifilm Toyama)

Kaletra (lopinavir+ritonavir)

Chloroquine

Remdesivir (Gilead)

Drugs for reducing disease lethality

New treatments and vaccines

How CDC and FDA Failed

  • CDC being too slow to understand and discuss treatments and vaccines
    • Already approved drugs like chloroquine, favipiravir, and Kaletra can be used off-label without FDA re-approval, and doctors look to CDC for guidance.
    • CDC could have persuaded or contracted with drug manufacturers to produce more of these upon first indication of their efficacy, to be prepared.
    • It seems CDC did no such thing, as US manufacturers are only starting up chloroquine production now, after its mention in a White House press conference on 3/19 (newsroom.mylan.com/2020-03-19-Mylan-Ramps-Up-U-S-Manufacturing-of- Hydroxychloroquine-Sulfate-Ta blets-to-Meet-Potential-COVID-19-Patient-Needs).
    • This contrasts with Chinese companies who restarted production 1 month ago, 1 day after trial results (yicaiglobal.com/news/guangzhou-pharma-taps-old-antimalarial– drug-after-covid-19-use-is-proven).
  • Providing non-information in place of information. Example from CDC website (www.cdc.gov/coronavirus/2019-ncov/specific-groups/children-faq.html)
    • Q:  What is the risk of my child becoming sick with COVID-19?
    • A: “Based on available evidence, children do not appear to be at higher risk for COVID-19 than adults. While some children and infants have been sick with COVID-19, adults make up most of the known cases to date. You can learn more about who is most at risk for health problems if they have COVID-19 infection on CDC’s current Risk Assessment page.”
    • Better answer: “Children have milder disease courses than adults, although they may still transmit the disease at low efficiency to adults.” It’s clear that kids get less sick if at all. Why doesn’t the CDC say so? It won’t hurt to tell the truth! If you provide such lousy information, people will stop trusting you.

How White House failed

  • Not learning the facts well enough to make useful decisions such as ordering FDA to approve other tests and CDC to expand testing guidelines.
  • Not learning the facts well enough to become trustworthy to the public.
  • Not explaining to the public why social distancing is necessary to protect the elderly.
  • Not explaining to the public that social distancing does NOT mean disruption to food and supplies as long as people don’t hoard.
  • Not motivating people to do their part by (1) stepping up hygienic habits, (2) limiting non-essential activities that can spread the disease, and (3) not hoarding resources. Instead the press and local officials have taken the initiative to do this, but this creates the problem of too many information sources.
  • Hogging the spotlight instead of naming a trusted doctor or scientist to be the face of policy. Should have made sure Fauci was given the most attention by the press.

Overall a complete lack of analysis/judgment/foresight by leadership at FDA/CDC/WH

Recommendations – health

  • At the first sign of CoVID19 symptoms (right), stay away from others and get tested. Put on a mask and keep your hands clean in the presence of others until you know your test results.
  • Recall the worry is about transmitting virus to older people, even if you have mild symptoms you do not want to transmit the virus to others.

Recommendations – hygiene

  • Don’t shake hands and stay 6 ft away from people outside your household – these are easy.
  • But ”wash your hands often” and “don’t touch your face” are confusing without context –  how often is often? Why can’t I touch my face? Should I ask someone to scratch my itchy nose for me? Shouldn’t I also worry about what I’m touching, not just my hands? If so, what cleaning solutions should I use?
  • I’ll provide some details. I treat hands and objects similarly, and I am pretty strict:
    • To protect yourself, sanitize your hands right before eating and right after touching things touched by others.
    • To protect others, use clean hands to touch others’ things or when handling things to others.
    • Sanitize objects you get, and only give out sanitized objects. For example, I have hand sanitizer open and ready to clean my credit card right after I get them back from cashiers, before I put it back in my wallet.
    • Outside your house, sanitize smooth surfaces you will touch directly with your hands (e.g. tables and chair edges, wherever you put your phone and computer).
    • I keep track of whether hands/objects are clean. As long as they have not encounted unknown/dirty things after their last cleaning, they don’t need to be recleaned. This is why I suggest immediate sanitation of hands after touching  unknown/dirty things, so you can resume using your clean things without worry.
    • You can open doors with your body or foot, and use paper towels to handle faucets or knobs.
    • Create clean zones – your house, your office (if you’re allowed to work), your car.
    • Sanitization can be done by soap and water (hands) or hand sanitizer (hands or objects) or Windex (objects).
    • “Disinfectants” like bleach or quarternary amines are for large areas for which soap (due to the need to rinse) or alcohol (due to fumes, expense) are not practical. If you can use soap or alcohol, you don’t need them.
    • Finally, if your hands are clean, you can touch your face! But remember to sanitize them before you touch other people’s stuff.

Recommendations – face masks

Face masks: yes or no?

  • My recommendations for mask usage are based on relative risks
    • At current infection rates and in normal activities, most people would be wasting masks.
    • But masks would be useful in proximity with strangers (airplane, train, Uber/Lyft, and especially hospital or clinic).
    • They are warranted for at-risk people, i.e. the immunocompromised or elderly, in public.
    • If the infection rates climb then they would be useful for everybody out in public.
    • They are absolutely recommended for people who are sick for avoid transmitting viruses.
  • Mask use is controversial because of limited supply
    • To assure those who need masks most get them, try to conserve them, and buy a small supply.
    • It is better to do social distancing without masks than social crowding with masks. In Asia, where most people take public transport, masks are considered a necessity and are handed out by authorities.
    • Given that some people are more at-risk, there should be no stigma/shaming for wearing masks.
    • 3/19 update: my views have now been validated by a former FDA commissioner: https://twitter.com/ScottGottliebMD/status/1240243298725486592. You can only deny facts for so long.
  • What if you don’t have masks, and the stranger next to you is coughing?
  • How to use masks
    • Make sure to clean your hands well before putting on or taking off masks.
    • For the soft surgical masks, bend the hard edge to fit your nose (colored side out), put on your nose and pull the straps over your ears, then stretch the mask down to cover your chin.
  • How to conserve face masks
    • Disposable masks are meant to be worn “once” then throw away, but once is not defined. To conserve, it’s reasonable to use one mask one day if you’re not seeing patients. (Quarantine officials forced Grand Princess passengers to use one mask for 9 days: reut.rs/39RVWuy. I would not recommend that at all.)
    • When alone, use clean hands to lower the mask to your chin. This gives a chance for the mask to dry out, which makes it more effective. You can also do the same when you need to drink.
    • When eating, you don’t want stuff dropping from the mask onto your food, so remove the mask completely and set in a clean place outside-up.
    • As the outside of a used mask is potentially dirty, you should clean your hands after touching it, or you can have your hands wet with hand sanitizer the whole time you handle it.
    • To clean and reuse masks, place in oven at 70ºC = 160ºF for 30-60min, or expose both sides in a UV sterilizer. Alcohol is not recommended (mp.weixin.qq.com/s/3QYVWO4kj5qwuSHnhcM9uQ). 3/20 update: Before rule-lovers complain, I’ll point out that UV sterilization and reuse of masks is now being done by hospitals (www.nytimes.com/2020/03/20/health/coronavirus-masks-reuse.html). Funny how single-use rules promoted by manufacturers are taken as inviolable truth, until they are revealed as not.

Recommendations – activities

  • It’s okay to go out to buy essentials, get takeout, but assume anything can be carrying virus, so practice good hygiene as above, i.e. maintain 6ft separation, sanitize hands in between touching others’ things and your own things, pass only clean objects, and treat objects you acquire as dirty. Visiting the workplace should be fine if you work mostly alone and can take the same hygiene steps above. (3/19 update: CA citizens cannot go to workplaces except for some essential jobs.)
  • It’s okay to see relatives who are not sick to provide help, but again only if you can practice good hygiene. Limit duration and closeness of visits to elderly or immunocompromised relatives.
  • I have reversed my allowance for social visits to friends, given that many feel it’s uncool to practice good hygiene such as wearing face masks, not touching common objects. (3/19 update: Also not allowed in CA anymore.)
  • Buy groceries online. Ironically stay-in orders increase transmission risk at grocery stores, which are now packed. My estimate is 1 in 1000 might carry infections by early April. That number can pass through one store daily. If you must go, stay 6ft from others and sanitize hands and  purchases!
  • I suggest avoiding prepared salads or sandwiches, and retoasting/microwaving that pastry.
  • Don’t share food, obviously.
  • Go outside – sunlight is the best disinfectant.
  • Do safer activities – this is not the time you want to break a leg and have to go to the hospital.

Recommendations – travel

  • Large meetings that bring people from around the country are were obviously a big risk:
    • Large numbers of people who might breath the same air and touch the same things (e.g. at Biogen meeting, attendants used the same serving utensils at a buffet, and 70 got infected).
    • These people tend to travel many times so they can spread viruses further.
    • Viruses can be collected from many locations and transmitted to many others (e.g. Biogen).
    • Thus non-urgent meetings should be cancelled.
    • 3/16 update: Obviously no more conferences/festivals for a while.
  • Travel if you must, e.g. to help care for family (3/17 update: removed nonessential travel in compliance with most health officials’ directives). Students also need to go home! But due to the many points when exposure from strangers can occur, travel requires high vigilance. For example, sanitizing items that others give to you now includes your ID at the TSA checkpoint and the can of soda from the flight attendant. Sanitizing surfaces you touch now include tray tables, seat belts, armrests. Keeping your hands clean when touching your own things now means washing hands after closing the airplane bathroom door (because you don’t want germs on your zippers) and, after washing hands after finishing, opening the same door with your elbow (or a napkin). Make sure the ventilation nozzle is on full blast (it puts out HEPA-filtered air) – sanitize it or your hands after touching it, of course.
  • Similar hygienic tips apply to trains and buses and cars that are not your own.
  • A face mask would be useful in cars with others, trains, planes, crowded waiting areas.

No need to worry about supplies

  • 50% of people with virus have no symptoms but will become immune, just like most symptomatic people
  • 95% don’t need to go to the hospital
  • The workforce is not threatened
  • Farmers and truck drivers and store workers will be available for work
  • You don’t need to buy everything in sight
  • This is not the zombie apocalypse

Hand sanitizer recipe

  • Hand sanitizer is just 60-70% ethanol with moisturizers.
  • The ethanol you want to use is 95% non-denatured ethanol
    • 95% denatured ethanol has toxic additives to prevent drinking (will have a health hazard logo).
    • 100%/dehydrated/absolute/anhydrous ethanol has benzene, also toxic, from the purification process.
  • Isopropanol can be substituted for ethanol, but just takes longer to evaporate
    • 60-70% isopropanol is just as effective as 60-70% ethanol as a disinfectant.
    • 99-100% isopropanol (rubbing alcohol) can be purchased by the consumer as a cleaning and disinfecting agent.
  • The moisturizer can be aloe vera gel (available in drugstores) or glycerol (a common lab reagent, and an ingredient in moisturizers and makeup).

Lin Lab recipe: Mix two parts 95% non-denatured ethanol or 99-100% isopropanol with 1 part aloe vera gel or 90-100% glycerol. That’s it!

(Thanks to Yichi Su for testing, and Michael Westberg for the safety tips)

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