I am going to link to four studies in this post. I am going to use these to argue that there is in fact a rational strategy through which we can use vaccines to help end the pandemic AND that our current strategy does not resemble that strategy. Here is a plea to rethink our current approach.
Let’s Start With The Papers
Boosters Are Largely Ineffective At Preventing Omicron Infections
https://www.medrxiv.org/content/10.1101/2021.12.30.21268565v1?fbclid=IwAR3-W7C1PnXgJqGAbR3iXaPXcFY4Kfr-iYF8S1ES7T2jGWn4qwgjGpHA1JU
Despite aggressive pleas for people to get booster shots, this paper suggests pretty strongly that the reduction in the risk of infection is in fact less than 40%. Based on what we know about vaccine immunity, it is also likely that even this benefit is going to decline in relatively short order.
This is in stark contrast to Delta. What this paper shows us is that boosters acutely reduce Delta reinfections by over 90%. Omicron appears to escape the majority of this benefit. Thus, as Omicron takes over, we’d expect to see the impact of boosters on reducing infection continue to decline.
While I wrote before about how the booster benefit was closer to 70%, that paper was likely confounded by the presence of multiple variants at the same time. This is the first paper that specifically looked at cases that were sequenced, and thus we know how effective the boosters are against each variant. It also explains why we are still seeing exponential growth in places with high booster uptake. A reduction of less than 40% is insufficient to stop exponential growth, even if everyone were boosted.
Protection Against ICU Admission Appears Durable Even Without Boosters, And Johnson & Johnson May Offer The Best Long Term Reduction In Severe Disease
https://www.medrxiv.org/content/10.1101/2022.01.05.22268648v1
This paper suggests the opposite of what most people have been saying recently. All vaccines appear to maintain prolonged protection against ICU admission. There does appear to be a waning of effectiveness against severe disease. That waning however isn’t as pronounced with Johnson & Johnson, even after a single dose. Boosters do not appear necessary to maintain this protection.
The Johnson & Johnson Vaccine has gotten a bad rap lately due to some relatively rare side effects. We’ve ironically ignored much more common side effects in the mRNA vaccines while we criticize those impacts with Johnson & Johnson. If we are measuring the benefit of a vaccine by it’s acute ability to reduce infections, then this vaccine is less effective than its’ mRNA counterparts. On the other hand, it may be the most durable at preventing severe illness after infection.
The mRNA vaccines both appear to generate a very powerful up front immune response that then begins to wane relatively rapidly. The rapidity of that waning appears to be especially true for Pfizer. It is notable that the benefit of the two shot series of either of the above when looked at in the first paper against infection with Omicron is essentially zero.
What this paper coupled to the first suggest, is that no currently available vaccine effectively prevents Omicron infections, and that is true even with boosters. What they also suggest is that all vaccines appear to reduce severe disease, even without boosters. The benefits against severe disease in this paper aren’t weighed against Omicron specifically, which is a limitation. However, the next two papers are going to justify my argument that I believe it will still work.
T Cells Generated Against Other Variants Are Likely To Still Neutralize Omicron
https://www.technologynetworks.com/immunology/news/omicron-unlikely-to-escape-human-t-cell-response-357140
Alright, I posted an article with a reference to the paper instead of the highly technical paper, but you get the idea.
Cutting through the data in this paper brings us to an important conclusion. Those with either a prior vaccination OR a prior infection are very likely to have T cells that recognize Omicron. Even with a variant that has developed substantial evasion of antibodies, T cells still appear to be effective in the large majority of cases.
What this suggests is that those with prior immunity either from a natural infection or vaccination still maintain substantial immune defense against Omicron in most cases. It’s important to note that T cells don’t respond until Omicron has already infected a cell, and thus, this response is much more likely to be effective against severe disease than mild infections. We’d thus expect those with either a prior infection or vaccination to potentially remain resistant to severe disease, even in the setting of antibodies that wane or variants that escape them.
T Cell Responses Appear To Be Quite Durable
https://www.nature.com/articles/s41586-021-04280-x
This article is a bit older, but the point made here is critical. T cells generated against infection or vaccination are still present a year later. With this level of durability, we’d anticipate T cell memory to be quite durable, even perpetual. This is a critical point when looking at the prior paper. It may explain why even a year later, we are seeing very few severe reinfections. It may also explain why those who are vaccinated are less likely to have severe disease even if the vaccination was relatively remote.
When you are infected with any variant or vaccinated, the majority of people will develop robust and persistent T cells that are likely to help prevent severe disease down the road. At least with Omicron, the T cells appear to be effective even when antibodies are not.
Implications For Immunity
Before Omicron, I noted in prior posts that over 80% of Americans had circulating antibodies to Covid. These may be from prior infection or vaccination. This likely underestimated total immune memory. Basically, even before Omicron, there was a large amount of immune memory.
Omicron appears to be evading antibodies, but not T cells. It is important to note that this means that those who are infected are going to be much more likely to have mild disease. It also means they are likely to develop Omicron specific antibodies in addition to the antibodies they already have to a prior variant. For the small percentage that had neither form of immunity, this variant is likely to change that.
This means that we are likely to have a population with substantial hybrid immunity against multiple variants within the next couple of months. That is going to be true regardless of what vaccination decisions people make. Notably, natural immunity from Omicron will be important going forward. New variants are progressively more different than the wild type virus originally identified in Wuhan. Widespread immunity to Omicron means that we are likely to see at least some crossover immunity with future variants as well.
Does this mean we will have “herd immunity?” I don’t personally think so. I have come to believe that there really is no such thing with Covid. Like the other dozens of viruses that cause the common cold, this one is likely to be able to reinfect us again and again. I still believe this substantial underlying immunity is the key to normalcy. If most people have mild symptoms, this disease goes from crisis to nuisance.
What Is The Goal?
Throughout the pandemic, one of our biggest failures continues to be an inability to define an actual goal for our interventions. We have had no clearly defined goal, no clearly defined end point, and no clear metrics to help us decide whether we are succeeding. It isn’t a surprise that there has never really been a rational strategy to deal with the virus.
While we all agree that Covid is a bad thing, and we wish it didn’t exist, our agreements have seemed to end there. We have groups trying to live normally. We have groups trying to live fairly normally, with some precautions. We have some groups trying to live normally, but only in the setting of trying to vaccinate everyone. We still have groups pushing social mitigation. We still have groups lamenting the fact that we aren’t going back in to lockdown. It is clear that we can’t do all of these things at the same time. For those pushing more aggressive action, I’ve yet to hear a rational argument as to when we could stop.
It is however clear that most of the world is moving away from a containment strategy. In fact, I am aware of no one outside of China that is still pushing a “Covid Zero” approach. Our approaches need to change if our goal is to “live with the virus.”
I will say that a lot of the “live with the virus” strategies we are seeing still involve massive amounts of testing, mandates, mask triggers, and other interventions that in fact look very much like pretending to control the virus. If we move toward a goal of coexistence, then we need to ask what we want to live with forever. There are clearly parts of the nation that will be sufficiently opposed to the above, and we will continue to have no comprehensive strategy at all. What I will propose is unlikely to gain traction in and of itself, but I suspect we could all live with it.
Laying Out A Plan
I am going to break this idea out in to healthcare system measures, vaccination measures, treatment/prevention measures, and social measures. The goal of any sustainable plan is to be sufficiently palatable to the population that the large majority of people accept it. Implementing an overly aggressive plan that people won’t follow is not effective. If we’ve learned nothing from the last two years, I hope we’ve at least learned that.
We also need a plan that empowers individuals to protect themselves. Strategies that rely on trying to force everyone to protect others have led to a lot of divisiveness in the US, but not a whole lot of protection. System interventions should be at the group level, but individual treatments and recommendations should really be more targeted to individuals.
Healthcare System Measures
In a mass casualty incident, the first thing we usually do is surge and triage. That is, we bring all of our resources to bear and then figure out how to best utilize those limited resources. One of the biggest failures during the pandemic has been our unwillingness to triage resources. This has led to a persistent full court press in hopeless situations with associated shortages of both beds and staff. Aggressive treatment in futile cases is almost certainly one of the major sources of healthcare burnout. This leads to fewer staff and lower staff efficiency.
We need specific benchmarks of hospital strain, and those benchmarks don’t just need to apply to Covid. We then need objective measures of futility, and we can scale back resources from futile cases as those resources become more strained. I think it’s critical to make this objective, and if it is in fact related to Covid, Covid triage is paramount.
Our decision early on to shut down elective procedures at hospitals regardless of Covid strain led to furlough of staff and worsened staff shortages. This has subsequently put strain on the remaining staff and led to a cycle of stress that leads to more shortages. We have only now begun to normalize surge teams that assist in the most hard hit areas of the nation, but such a thing should be part of a more global strategy. Similarly, applying mandates to workers further reduces staffing, and we really ought to consider those impacts when trying to surge. There is no evidence that forcing staff to vaccinate reduces Covid transmission, but there is a lot of evidence it ultimately reduces staff.
Thus again, healthcare strategies should revolve around surge and triage. I believe that the perpetual forced wearing of masks by providers also leads to burnout and limits comraderie. On the other hand, many staff may perpetually want to wear masks. Rather than just telling everyone to wear a mask, I believe that we should do the following:
Provide N95 masks to all providers who want one. This should be a standard going forward.
Set benchmarks for high and low risk periods, allowing healthcare workers relief from this rule during periods when cases are very low
We should focus the use of masks on N95 in patient care areas when cases are high for those who are wearing masks. I suspect that proper wearing of N95 masks in high risk areas during periods of high transmission would be far more effective than having staff perpetually wear less effective surgical masks at all times.
While individual systems may attempt to limit transmission between staff, I’m not sure that ever really happens long term. A focus on tracing and quarantine of staff may not truly be terribly effective. We tend to suspend these systems due to a lack of staff right at the time where they would matter anyway. Instead, a system that provides backup in the case of illness and allows sick people to be sick would be more effective. The current system tends to quarantine some low risk exposures while marginally ill people feel compelled to go to work to prevent the system from collapsing. The first creates strain with limited benefit. The second is where a lot of your transmission likely occurs, and isn’t stopped by the aggressive action. If we do trace, we should instead have the high risk worker engage in protective behaviors at work. I personally don’t believe that this will ultimately provide much benefit in the future either way.
We should similarly define strain not by “cases,” but rather by metrics that look at hospital utilization. This should take in to account normal hospital use, excess burden beyond that normal use, and what percentage of that burden is due to patients specifically admitted for respiratory illness. This seems infinitely achievable.
The goal here is to build a system that humanizes healthcare workers and creates a reasonable work environment, while acknowledging that some measures may be necessary to keep things running during discrete periods of strain. Over time, perpetual intervention equals no intervention as compliance dwindles.
Vaccination Measures
It is no secret that I morally oppose vaccine mandates and passports. In this case however, all of the evidence that I presented earlier suggests that these measures really only provide marginal benefit in terms of transmission at best. We are completely misusing vaccines, as though the goal is to make the disease disappear. It is abundantly clear that we are never going to make it disappear with vaccines, and thus that should no longer be the goal.
While I would avoid compulsion, a laudable public health goal would be to have every American in a high risk group have some degree of underlying immunity. I believe the attempts at compulsion and ignoring prior infection are hurting our ability to do this over time. Similarly, an effective vaccine in lower risk groups is great, but I am concerned that failure to acknowledge real side effects in low risk groups has in fact led to greater hesitancy in high risk groups.
I similarly would want to continue trials on alternative vaccines. Let’s be clear that even if data suggesting that severe side effects are rare holds up for our current mRNA vaccines, the overall side effect profile is incredibly unpleasant. There are three advances that I would love to see in vaccination:
The availability of Novavax. This protein subunit vaccine remains the only vaccine to engage phase III trials in a manner compatible with US approval that uses a technology that was in widespread use before Covid. I know people who were holding out for Novavax
We need to stop vilifying the one dose Johnson and Johnson Vaccine. Most criticisms of this vaccine are based on either side effects that occur at 1 in 100,000 doses or less OR efficacy against infection. As I pointed out, every vaccine is now not terribly effective against infection. We additionally need to study this on younger people. This is not an emergency, but this is the vaccine with low rates of the side effect that is most common in young men (myocarditis), and the highest risk group is too young to use it. Similarly, pushing to make this a two dose regimen isn’t clearly necessary to achieve what should be the primary goal of severe disease reduction.
There should be a renewed focus on whole virus and inhaled vaccines. These would potentially avoid original antigenic sin and reduced IgA production concerns.
Now to be perfectly clear, it’s not obvious that vaccination will be beneficial at all in the future (too early to tell). I will say that giving repeated boosters of the original strain Spike protein as the virus evolves really makes no sense as a long term strategy. Similarly, it isn’t clear that it may not make sense to target future vaccines to high risk groups. This is evolving science, but we shouldn’t just pretend we have the answers. In the interim, a vaccine strategy that focuses on high risk people with no immunity is likely going to be the highest yield. For those with a documented prior infection, especially if they’ve developed antibodies as a marker of a true immune response, the data surrounding Omicron suggests again that this group shouldn’t be treated differently than those who were vaccinated. I will note the antibody titer isn’t what is likely important. Rather, the presence of antibodies suggests that a broad immune response occurred.
I will also say that as a worldwide public health measure, vaccination of high risk groups everywhere would be much higher yield in relieving strain than perpetually giving boosters to low risk people in rich nations. Similarly, progressively updated “passport” systems become political. They are paradoxically reducing vaccination in parts of the country. There is no evidence that you are safer next to a vaccinated versus an unvaccinated person with Omicron.
As a final note, we need better monitoring systems in the US. We need better active monitoring. We miss the overwhelming majority of even serious side effects, and we often show rates of these side effects far below nations with better monitoring systems. Any cost benefit decision is impossible if you don’t actually understand the costs. I’m tired of pulling my vaccine data from the UK or Israel or Korea because we aren’t doing a good enough job of compiling it.
Treatment Measures
As treatments improve in concern with immunity, we could theoretically improve to the point where healthcare system measures are no longer necessary at all. We may get the disease down to a level where the strain it causes is relatively controllable and predictable. I do believe that we’ve vilified potential treatments in this nation. While I have not bought in to the idea that outpatient therapy is as effective as its’ proponents, we ought to stop preventing physicians from using their clinical judgment when using medications off label.
Similarly, developing new therapeutics should be a high priority. I do think we need to have a more controlled rollout of these interventions. New drugs may have consequences.
We really also need a public health emphasis on overall health. This is not specific to the pandemic, but it has been highlighted by it. We could largely alleviate hospital strain under our current system with a sufficiently healthy diet and consistent exercise. In a separate post at some point, I intend to get in to how obesity and lack of exercise can potentially triple hospital admissions.
Social Measures
Widespread closures and shutdowns have substantial consequences that we are only beginning to understand. School closures similarly have had profound consequences. Whatever one’s individual opinion on particular interventions, it is very clear every forced social measure is controversial. Every single one. Long term, forced measures are likely to lead to no measures or paradoxical measures like we have today.
We need a significant focus on ventilation. This will actually slow nearly all respiratory viruses, and it is thus a win-win that is largely uncontroversial. Buildings with certain capacities or population density should be evaluated for air purifiers or upgraded ventilation systems. Special consideration ought to be given to schools and hospitals. Unlike masks, no one opposes improved air quality.
Forced testing and contact tracing remains a darling of the public health establishment and the enemy of half of the public. I would suggest that making testing available is largely uncontroversial if you don’t tie testing to shutdowns or quarantine. Right now, opposition to testing is largely opposition to quarantine or isolation. Long term contact tracing of a widespread airborne virus that you are not trying to eliminate is not going to work.
If the goal is not to contain the virus, then schools shouldn’t be quarantining students. Sick students should still stay home. Students with mild or marginal illness may still benefit from wearing a high quality mask (like an N95) while symptomatic. The focus should be keeping every child in school and making school largely normal. I am concerned that “test to stay” programs and other tools that have the intention of achieving that goal will in fact simply identify some strings of asymptomatic transmission and actually lead to more missed days of school for students. The topic of school measures frankly could be an entire post in and of itself.
We really need to drop blanket low quality mask mandates. They don’t help very much and lead to a lot of controversy. We ought to develop a metric of system strain like we do with hospitals, and masks can be used as follows when that strain is high (Note that I mean illness leading to hospital strain, not widespread cold symptoms):
N95 or KN95 masks in congregate living facilities of high risk people like nursing homes or group homes
N95 or KN95 masks made available to high risk people if they choose when going out in public. I don’t think it works to force this, but it empowers people to protect themselves
N95 or KN95 available in places where high risk people are likely to be, such as hospitals, doctor’s offices, treatment centers, and perhaps places like prisons.
Similarly, we need to separate the entities evaluating data from those engaged in rulemaking. We also need to separate the financial interests of those evaluating data from those making rules. Right now, the CDC, NIH, white house, and multiple large pharmaceutical companies are so egregiously intertwined, that no one trusts anyone. That’s not good.
We need to educate the public on safer ways to meet with high risk people when transmission is high and then let the public determine its risk tolerance. One can wear a mask, meet outside, etc… Lots of choices to reduce transmission for concerned people.
Putting It Together
This is not meant to be comprehensive. It is a start. If we ever want to have a sustainable system in place, it needs to take everyone’s concerns in to account. It similarly needs to allow people to operate within their respective risk tolerances when possible. It also needs to stop making decisions that lead to minority harm in the name of the greater good. Even if we think that's a good thing (and I don’t) it leads the minority to rebel.
One day, we will face a bigger threat than Covid. We can continue to botch our response to this, and the biggest risk is still largely what we’ve done to ourselves. We need to get our house in order however, as one day, a larger threat is likely.
I also want to be clear that in general, I am very pro-vaccine. Before Covid, it was never really a question that myself and my family would have all of our vaccines. I maintain skepticism about our Covid vaccine approaches, because we’ve already seen substantial shifts around new data. In fact, by the time we are done rolling out a strategy, the current data rarely supports it. We don’t even know what the right regimen looks like and for whom. I also believe in medical autonomy, and I only believe force should be used in the most extreme circumstances. In this case, it’s still not clear that there’s any potential benefit to vaccination beyond oneself in the long term.
Moderate and sustainable strategies are unlikely to happen at this point. It’s just too late, and hopefully, we are coming toward the end of the pandemic phase of this illness. I say hopefully, because we won’t know it’s over until it’s been over. I hope that by putting out ideas that might work a reasonable compromise, we might avoid the Covid debacle when the next crisis comes along.