It looks like much of the world is emerging from a summer of COVID and is now on the downward side of the epidemic curve. If we do not get another variant, it’s beginning to look like much, if not most of the world may be moving into post-COVID. Unfortunately, this does not mean the end of COVID, because between variants that are able to partially escape the vaccine, the 25 – 30% of adults that choose to take their chances against the virus, and the natural decrease in the first-level immunity provided by antibodies, it is likely that SARS-CoV2 will be present at some annoying level for the at least the intermediate future. Unless a new variant emerges into the environment, the combination of substantial immunity from vaccination, excellent immunity from natural infection, and continued development of anti-viral medications, it is reasonable to expect that COVID will take on a role in the world similar to influenza and because of the risk of serious disease or death is actually less with COVID than with influenza if you are immunized, it is reasonable to expect that 2022 will be a fairly normal year, at least from the standpoint of dealing with infectious diseases.
Case rates are down just about everywhere. Hospitalizations are trending down, and deaths are either down are appear to have reached their peak and are starting to go down. Major locations where this is not true include South Korea, which has a stubborn, but relatively low-level flat trend over the past 3 months. Singapore is seeing a fairly steep uptrend, although still at what would be considered low in absolute terms, and Eastern Europe is seeing another major wave. In South America, the epidemic is trailing off to nearly negligible levels compared to where it was just 6 – 8 weeks ago. Trends are hard to gauge in Africa, but even the hardest-hit county, South Africa, appears to be on a clear downward trajectory.
Clearly, the biggest COVID question for most people is in regards to boosters. If a government was to try to design an information and roll-out plan with the goal of creating the most confusion and undermining confidence in vaccines and the entities managing the program, then they could not have done a “better” job.
Perhaps the issue was summed up best in a paraphrased statement from one of the members of the Advisory Committee on Immunization Practices, yesterday: We’re not even being clear on what our goal is, here. Are we trying to minimize any degree of COVID-related disease or to minimize hospitalization and death? That’s exactly the right question, but governments around the world have not been clear on the answer. At the outset, the goal of lockdowns and rapid vaccination programs was the latter: minimizing the bad outcomes of hospitalizations and deaths. But what happened was that reporting systems and the media focused on the “big numbers” associated with case counts even after we developed good treatments that reduced the threat of death, and even after we immunized the most vulnerable in society, reducing the risk of death in immunized people to below the risk of death from influenza (in a typical year) for people vaccinated against that disease.
The existing vaccine regimens, even the less effective vaccines such as those of Chinese origin, have proven to be very effective in preventing bad outcomes, but with the Delta variant and somewhat decreasing antibody-based immunity over time, even immunized people are still vulnerable to infection and if infected, some degree of transmission. Preventing all infections was not the initial goal of the vaccination programs, the goal was preventing bad outcomes that would kill people and overwhelm the healthcare system. They have undoubtedly accomplished that goal.
Here is what you need to know about the background on why boosters may be needed in 4 bullets:
- The current vaccines all work. In almost all people, they create antibody immunity that effectively and significantly reduces the risk of infection by increasing the “dose” of the virus that would be required to infect someone.
- They also create other immunity, mainly cellular immunity (t-cells and b-cells) that are the calvary and respond more after the fact to a superficial or localized infection and prevent that infection from becoming widespread or deep-seated in the rest of the body. These other immunized appear to be much more durable and long-lasting than antibody-based immunity.
- The antibody-based immunity declines over time, and with that decline, the number of viral particles that your body can be exposed to without getting an initial localized infection also declines. If this happens, in most healthy people, cellular immunity comes to the rescue and prevents severe infection and bad outcomes.
- Immunocompromised people, which to a more limited extent, includes the extremes of age, will have lower thresholds for both localized infections and for overwhelming the secondary cellular immunity. For them, it is important to raise immunity as high as possible to prevent even initial infection.
So all of this is why the member of the Advisory Committee on Immunization Practices made the point about what the goal is. If what we want to accomplish is to significantly decrease the risk of severe disease, then we need to consider boosters only for those at risk and only in circumstances where the vaccine is demonstrated to not sustain adequate antibody response. If the goal is to drive down the case counts, eliminate all infections, then boosters need to be more widespread, even if this means reducing the vaccine available in other parts of the world and increasing risks of vaccine side effects.
All vaccines have a rate of side effects – that is unavoidable and the goal is to give a vaccine dose that creates enough immunity without overwhelming or overcharging the immune system. Generally, those side effects can just make people miserable for a couple of days, but sometimes, the side effects can be more serious such as the rare blood clots or heart inflammation issues we have seen with vaccines up to now. Simply saying that people did fine with the initial vaccine doses, so they’ll do fine with another one is not always true. If we have achieved our initial goal of preventing bad outcomes, it is even more important that another dose is proven not to unacceptably increase the risk of side effects before embarking on a widespread program. That is the issue that the FDA and CDC committees are wrestling with and that was glossed over by the President in his initial announcement last month. Simply put, when does the benefit outweigh the risk.
There is one additional issue. We know that vaccine producers are working on vaccines that more directly target the delta variant. It is very likely that such a vaccine would have a much better chance of overcoming the breakthrough issues we are seeing with the current vaccine, BUT, if it was administered as a Fourth dose, the side effects (or some other immunology issues) become more concerning. So there is some consideration that for those NOT at high risk, they would be better off waiting until that is available. Unfortunately, the vaccine companies and the government have gone silent on this as they worry that people may stop getting initial doses of the current vaccine if they think that a delta-tailored version is around the corner.
So putting that all together:
- If you got Pfizer, which was administered with a slightly lower dose of mRNA and on a more rapid schedule that promoted rapid protection and lower side effects, but not as much durability, AND you are in an at-risk group by age or disease, then a booster is likely in your best interest. The ACIP will be voting on the definition of at-risk groups, but we would tend to be fairly lenient on that definition. Others should hold off to see what happens with delta-modified boosters, at least for a few more months.
- If you got Moderna, the evidence is that you are still well-protected, except in more highly at-risk groups such as those with well-defined immunodeficiencies such as after transplants or those taking medications that decrease immunity. As with Pfizer, others should hold off to see what happens with delta-modified boosters, at least for a few more months. Additionally, Moderna has indicated that a lower dose will likely be required and this will be important for reducing side effects while still boosting immunity. So don’t rush out to get a booster.
- If you got Johnson & Johnson, there is not likely going to be any definitive guidance in the immediate future, but it is likely that you will need a booster before too long. Johnson & Johnson had very good reasons for a one-shot series and those indications will likely continue, but optimal immunity will likely require a second dose. There is not adequate data yet on the risk-benefit of that or whether it would be better to get a second dose with a different type of vaccine, as is being done in Europe. No one is authorized to immunize in this manner, and Johnson & Johnson does give good protection against bad outcomes. So, for Johnson & Johnson recipients, you need to be patient for a few more weeks to a couple of months but expect that a booster of some type is on the horizon.
- If you got Astra-Zeneca, because of the clotting issues noted, authorities are being a bit more careful on recommending boosters. It is very likely that an eventual recommendation will be made for boosting with an mRNA vaccine if you initially received Astra-Zeneca. Of course, the US authorities are not involved in this decision process, so it is a bit unclear who will take the lead on making recommendations along these lines, especially since the WHO has come out strongly against all boosters since current regimens are accomplishing initial goals and there are still large parts of the world waiting for the vaccine.