Many people have developed preferred positions on the coronavirus and will stick to those positions regardless of evidence. I accept that I will probably alienate those people. However, we don’t need to hurt ourselves with crazy views on the coronavirus. We don’t have to become overly obsessed with partisan politics, worshipping science as a religion, or trying to look smart by saying that we oppose fear porn. It’s important that we talk about the coronavirus and start getting to the truth.
- Surgical masks have very little or no effect on becoming infected. A lot of people will not want to hear it but that is what the evidence is saying.
- Health authorities know very little about what works because very little research is being performed (unless that research involves vaccines or therapeutics).
- mRNA vaccines will not end the pandemic.
- We have effective tools against the coronavirus. However, for political reasons, many countries will not adopt all of those tools.
- We are probably going to have to live with the coronavirus.
I think that the future will be… different… rather than bleak. Vaccines and advances in early treatment might allow society to operate with fewer (or even zero) social restrictions. However, the virus will be a part of our lives and change how we behave. Work-from-home, online shopping instead of in-person shopping, not travelling internationally, etc. will likely stick around at lower levels.
We need to rethink masks
Currently, it looks highly likely that the coronavirus is spread mainly through aerosols. (Imagine somebody smoking. The more smoke that we inhale, the greater our chances of developing an infection.) However, we haven’t been able to translate that knowledge into an effective public health intervention. There has only been one randomized controlled trial on masks. The DANMASK-19 study mailed surgical masks to the intervention group and instructed them on their use. The study did not find a statistically significant benefit to the mask intervention. That tells us that mask interventions will not have a significant impact on the pandemic.
The study did suggest that surgical masks have a small effect on reducing infections. 1.8% of the mask group developed a confirmed case of SARS-CoV-2 infection while 2.1% of the control group did. However, the study was too small to reliably detect a difference. A sufficiently large study would be able to detect a small benefit or harm from surgical masks (assuming that a benefit or harm exists).
In a logical world, we would rethink our mask strategy.
- Masking harder could be a potential solution. We know that surgical masks allow aerosols to pass through. When the fit is imperfect, unfiltered air moves around the sides of the mask and into the wearer’s lungs. When the fit is perfect, the mask’s filtering still allows aerosols to pass through because the filtering efficiency is low. Elastomeric masks, commonly used by political demonstrators who don’t like tear gas, are fairly cheap (<$50) and are far more effective at filtering aerosols than surgical masks and N95s. Research shows that elastomeric masks retain their fit better than N95s. The flaws of surgical masks and N95s would neatly explain why hospitals constantly fail at preventing COVID-19 outbreaks in that workplace. However, nobody has performed an intervention study on elastomeric masks so we don’t know how effective they are at preventing COVID.
- Building more hospitals could be another solution.
- Figuring out how to move more activities outdoors could be a solution. One study based on contact tracing data found that an infected person transmitted the virus indoors at 18.7X the rate compared to outdoor transmission. A randomized controlled trial on some type of intervention (e.g. telling people to be outdoors instead of indoors, allowing outdoor activities during a lockdown, etc.) could confirm those results.
The current situation is not good because there is a lot that we don’t know and we aren’t doing the research to find out. The DANMASK-19 study was not well received by the scientific community. Many scientists defended the existing masking narrative and ignored the evidence challenging their dogma.
I am guilty of contributing to the hype over masking. I told you about masking in March 2020 before most health authorities did so. Unfortunately, it turns out that this promising intervention did not translate into real world results. We should research why our understanding of aerosol transmission failed. It will be hard to succeed if we don’t understand our mistakes.
*Full disclosure: I started wearing a 3M elastomeric mask even though I don’t know how well it works. This Youtube video goes over everything that you’d want to know about elastomeric masks if you want to buy one for yourself.
Health authorities know very little about what works… unless it involves vaccines or expensive drugs
Despite our best efforts, hospitals and nursing homes continue to have outbreaks despite mass vaccination (e.g. both shots of a mRNA vaccine) and frequent testing. There hasn’t been much research as to how the coronavirus spreads in these workplaces and why our protection measures don’t work as well as we’d like. One study at the Cambridge University hospital compared FFP3 respirators to surgical masks. (FFP3 masks filter more aerosols than N95s.) The authors argue that switching to FFP3 masks greatly reduced the level of hospital-acquired infection among healthcare workers. A randomized controlled trial would provide more definitive evidence as to whether or not better masking will help.
When it comes to vaccines, there are multiple well-funded research labs researching why vaccines lose effectiveness against variants. I’ve covered that topic in my previous post on evolutionary theory. A lot of research is being done on making vaccines better but very little research is being done on making hospital practices better.
At the same time, we haven’t done much research as to how mRNA vaccines will work against a pandemic. Brazil did one such study for non-mRNA vaccines. Researchers extensively vaccinated the town of Serrana between February and April. Unfortunately, the town’s epidemiology data shows that the pandemic and coronavirus deaths have continued despite vaccination. You may find news stories about Project S touting the success of vaccines- however, the epidemiology data says something else. While a similar study for mRNA vaccines would be very useful, I’m not aware of such a study. This means that many societies went all-in on vaccines without knowing whether or not their plan would work.
The current situation is insane. Health authorities are not performing enough research to figure out what is and isn’t working despite spending billions of dollars on vaccine and therapeutics research (which are essentially pharma subsidies). In the case of surgical masks and ivermectin, health authorities simply ignore evidence that they find inconvenient. They are bumbling their way through a pandemic and hoping that their preferred solution (vaccines) will magically save the day. Because the mRNA vaccines are surprisingly good against the current dominant variants, there is a chance that their bumbling may sort of work. At the same time, we don’t know if vaccine effectiveness will hold because it is likely that more vaccine resistance will emerge with future variants.
mRNA vaccines will not end the pandemic
We don’t know that much about how well vaccines prevent transmission because it is hard to measure. Many people believe that vaccines are less effective at preventing transmission than they are at preventing a detectable infection. Observational studies have some problems but they are all we have at the moment.
An observational analysis from the United Kingdom estimates that vaccines reduce transmission by 40-50%. That data is somewhat stale at this point and is from a semi-vaccinated population where 93% of population was partially vaccinated instead of fully vaccinated. While the reduction of transmission is significant, it is not enough to end the pandemic by itself. I haven’t seen these same UK researchers from Public Health England (PHE) publish an updated analysis based on newer data.
Another data point is the the country of Israel, which leads the world in mRNA vaccinations. Currently, about 57% of the Israeli population is fully vaccinated with a mRNA vaccine. Despite a medium level of vaccination, Israel is currently dealing with a rapidly growing outbreak. The chart below shows the effective reproduction rate of the coronavirus in Israel; numbers above 1 indicate growth (rather than decline) and higher numbers indicate more rapid growth. The current R number happens to be higher than pre-vaccination time periods and is almost as high as when the coronavirus first appeared in Israel.
Unfortunately, what we’re seeing is that the virus spreads really fast and vaccines don’t do enough to slow down the spread.
The public messaging around vaccines
When health authorities overpromise on what vaccines will do, they will lose credibility when vaccines underdeliver. This may cause some people to avoid vaccines even though they have some value. While vaccines have lower effectiveness against the current variants, they still have a protective effect. While they will likely lose effectiveness against future variants, their protection is unlikely to erode completely. And while we may someday encounter a new variant that is highly vaccine resistant, some protection should still be better than none.
As far as vaccine safety goes, health authorities are in a predicament. Regulation for COVID vaccines has been lax compared to drugs that didn’t go through emergency use authorization. If we want to know whether or not vaccines are safe in pregnant women, we should run randomized controlled trials on pregnant women. One trial (NCT04754594) is currently running for the Pfizer/Biontech vaccine. I find it interesting that some people will make claims about vaccine safety in pregnant women before all of the data is in.
I really have no idea how safe/unsafe the COVID vaccines are. Please do not listen to this blog for vaccine safety information.
The potential to do better
Based on the current evidence, we know that we have powerful tools that work against the coronavirus:
- mRNA vaccines.
- Contact tracing.
There are other tools that show some promise and require more research:
- Cheap, rapid testing.
- Measures to fight aerosol transmission (e.g. better ventilation, HEPA filters, upper room UV, elastomeric masks, telling citizens to go outside and avoid sharing indoor air with non-household members, etc.).
The problem right now is that most health authorities are biased towards vaccines and expensive therapeutics. They aren’t particularly interested in fighting the pandemic if it doesn’t fully align with their political interests.
The political situation may change in the future because political positions can quickly change. We’ve seen it happen for masks, border control policy, asymptomatic transmission, and aerosol transmission. However, I am not very good at predicting the timing of that.
Living with the coronavirus
It now looks like the coronavirus will eventually infect most of humanity. Most countries are pursuing a strategy of reopening (which will lead to the virus growing exponentially like in Israel) and going all-in on vaccines. If hospital capacity is the limiting factor, then it is likely that cases will go up and hospitalizations will fall (or stay roughly the same). It won’t take that long before most people get infected one or more times.
If we give up on avoiding infections, then our new goals should be:
- Reducing mortality and health problems caused by COVID.
- Avoiding a situation where hospitals run out of capacity.
One way that we can try to reduce the severity of disease is to reduce the viral dose that people receive. It is likely that severity of COVID-19 is highly correlated to the amount of virus that somebody is exposed to (see this experiment on hamsters and references 12-27 in this paper).
A high dose happens if somebody spends hours indoors in a poorly-ventilated room. Certain activities like singing, talking, and eating cause infected people to emit more aerosols than breathing, leading to a higher viral dose. We may be able to fight this by:
- Replacing indoor activities with outdoor activities, where possible.
- Encouraging work from home
- ???Elastomeric respirators/masks???
- Increasing ventilation for indoor spaces.
- Not singing indoors.
Research is needed to figure out what actually works and whether these interventions translate into less severe disease. Airplanes already implement good ventilation and HEPA filters to scrub recirculated air. Unfortunately, outbreaks of SARS-CoV-2 and other respiratory infections do occur on aircraft. Research is needed to verify if disease would be much worse without ventilation and HEPA filters. I’m open to the idea that aerosol transmission may be very difficult to fight. However, we should certainly research whether or not improved ventilation and filtering can help us return to normal (e.g. because wearing elastomeric masks and being outdoors all the time is not normal) or to get the mortality rate down. Unfortunately, it may take a while for this research to happen.
Advances in early treatment will reduce hospitalizations and deaths.
The leading theory at the moment is that COVID-19 consists of 2 stages.
- The viral replication phase. In this phase, the virus is multiplying and the body is working on killing off all of the virus particles. The disease is mild at this stage so patients may not realize the danger they could face.
- The inflammatory phase. The immune system overreacting is what causes people to die from COVID-19. The body has already killed off all of the virus so antiviral drugs will not work at this point.
The treatments that work during the viral replication phase must be given early while there is still an opportunity to reduce the viral load. The scientific community will likely embrace the concept of early treatment because it would justify greater usage of expensive treatments like monoclonal antibodies. Pharma companies will make the most money if every infection should be treated early with an expensive drug. Hopefully those drugs will have more benefit than harm. To be fair to the pharma industry, some early treatments do look promising. As well, some have randomized controlled trials supporting their use in early treatment.
There is a good chance that early treatment turns into a massive industry. For example, if there are 100 million patients at $3000 each, that is a $300 billion market every year (!!!). Because the top 15 most infected countries in the world (the US is one of them) have had more than 10.4% of their population infected by COVID, the market may be much larger. We may see a world where several percent (or more) of the population experiences a confirmed infection every year. Many people who get infected do not realize that they are asymptomatic and don’t turn into a confirmed case, so I would caution against estimating too high. This might create problems for society eventually because there will be political pressure to keep the early treatment market going instead of pursuing an eradication strategy that would eliminate that massive market. Perhaps the ideology will be that social restrictions should be avoided to create an ‘equitable’ world.
Better contact tracing and other ways of enabling very early detection would make early treatments more effective and increase the total addressable market. However, health officials haven’t thought that far ahead into the future. Currently, the supply of early treatments (e.g. antivirals like remdesivir, monoclonal antibodies) is the limiting factor so demand generation is not an issue yet.
One piece of good news is that we have many existing drugs that are good at suppressing the immune system (e.g. methylprednisolone) and stopping an overactive immune system from killing the patient. Randomized controlled trials have proven that some of those drugs are effective at reducing mortality.
The evidence does show that mRNA vaccines are highly effective at reducing hospitalizations and death. I’m open to the idea that some countries will get hospitalizations low enough (or build hospital capacity high enough) that they can return to normal life without the problem of overflowing hospitals. However, there is a lot of uncertainty as to whether or not that will happen.
History suggests that new coronavirus variants will emerge and that the dominant variants will regain some of the transmissibility and lethality lost to vaccines. In the short term, we may see a honeymoon phase where vaccines seem like they work well enough. Then some new variant emerges, spreads everywhere within 3 months, and causes society to implement social restrictions because they are risk-adverse when it comes to healthcare capacity running out. The chicken industry has seen problematic variants emerge even though the IBV coronavirus vaccine is excellent against non-variants.
Even if turns out that life can return to normal, it would take some time for consumer behaviour to change. I think that there will be a segment of society that will be risk adverse, holding onto COVID-avoiding behaviours such as:
- Avoiding business travel for conferences, face-to-face meetings, etc.
- Working from home
- Online shopping
- Take-out instead of sit-down restaurants
- Not going to movie theatres, cruises, etc.
There are real uncertainties as to what the future holds. Many new variants will emerge and we probably won’t be able to predict how problematic they will be. We still aren’t sure if the Delta (Indian) variant is deadlier; Scotland and UK data suggests that the hospitalization rate is almost double compared to the Alpha (UK) variant. For the UK data, search for the word Cox in the latest version of their technical briefing. The latest estimate is that Delta variant cases have 1.8X the rate of hospitalization.
Some people will act out of fear because they don’t trust health authorities. The credibility of health officials has been taking a hit for various reasons:
- The culture wars. There are incentives for the anti-woke side of the culture wars to discredit Anthony Fauci and to point out areas where health authorities have flip flopped on a position (e.g. masks, closing borders to China early in the pandemic, etc.).
- Politics influencing the World Health Organization. The World Health Organization does not recognize Taiwan as an independent country because it panders to the CCP’s political agenda.
- The lab leak theory. There is evidence that health authorities, Dr. Anthony Fauci, and top scientific journals participated in a cover-up of the lab leak theory. One lab leak narrative- that the US is partly responsible for the leak because it funded the Wuhan Institute of Virology via EcoHealth Alliance- reflects very poorly on Fauci because Fauci oversaw the funding of the WIV. Fauci is now supporting the narrative that a lab leak is possible and that the US is not to blame for it. Fauci has recently called on China to release the medical records associated with a 2012 incident with Mojiang miners; he supports the possibility of a lab leak. (Personally I don’t think that the US is to blame. But we don’t need to get into that.)
- The war against ivermectin.
We don’t need to get into whether or not cautious behaviour is justified. What matters is how some people will behave in the real world. A risk-adverse segment of the population means that some areas of the economy won’t return to normal right away.
It could very well be the case that the fears turn out to be somewhat justified. SARS-CoV-2 has already evolved a high level of resistance against the AstraZeneca vaccine- it was only 21.9% effective in South Africa. That level of vaccine resistance naturally emerged during the AstraZeneca clinical trials without evolutionary pressure from vaccines. It’s reasonable to expect evolution to erode the protection created by other vaccines.
Strip clubs are back ¯\_(ツ)_/¯
While strip clubs are probably not the safest activity during a pandemic, they have recovered financially. Some industries may recover even though their safety is questionable. The chart below shows that revenues and operating income have mostly recovered for RCI Hospitality, a publicly-traded strip club chain.
The safety of an activity may have little impact on the economic recovery of that activity.
The giant science experiment ahead
The current hope is that vaccines will turn the coronavirus into a mild flu (*for those who vaccinate) and the vaccine resistance situation doesn’t get worse.
If this experiment doesn’t work out, we may see on-again off-again social restrictions as variants spread through the population before burning out. Among the countries with the highest case rates per capita, several of them -USA, Andorra, Czechia, Sweden- have seen cases decline significantly in the past few months. It is likely the case that natural infection and vaccination helps build up protection in the population. I wouldn’t be surprised if some areas of the world go a few months without social restrictions (or very low social restrictions) and continue to have low case counts.
Advances in early treatment (and late treatment) will allow society to reopen with the population catching the coronavirus, although it may take a while before we implement effective treatments due to political reasons.
One could make the argument that this giant science experiment should have been tested on a smaller scale first. But that doesn’t matter now- many countries will go down this path and demonstrate how well it works in the world.
The safe prediction is to bet on the world using a lot more mRNA vaccines and expensive treatments. Many of the treatments have scientific evidence backing them and (more importantly) have political influence on their side. I’m far less certain about the coronavirus recovery plays. Many of them trade at very high valuations so they may be worth betting against for that reason.
There are crazy and insane things happening with the coronavirus situation. We know how to do science but we are doing shockingly very little unless it involves vaccines or therapeutics. It is what it is.
At the end of the day, we should accept the world as it is and make the best out of our situation. While the cynic in me would point out the profitable future ahead for mRNA vaccines, there are other things to be optimistic about. Most of the greatness in the world still remains. Humanity continues to make incredible advances in technology. The first computer games I played looked like this:
Our quality of life keeps going up. We aren’t worrying about war, genocide, famine, or other terrible things that have happened to people. Things are pretty good right now when our biggest issue is the coronavirus.
*Disclosure: Long MRNA, GILD calls, and REGN calls. No position in RICK. Short DAL (airline) and LYV (music concerts) via put options.