COVID: Different Types of Immunity

 Much of the information , recommendations, observations opinions etc. regarding COVID is conflicting and confusing. One reason for this is that the certain subjects, such as immunity, are spoken of in vague and ambiguous terms. When someone speaks of immunity in one sense, such as herd immunity, it is countered by a counter-example which actually addresses a separate issue. To avoid this, it would perhaps be useful to define certain types of immunity. He are some suggestions:

1. Epidemic-limiting immunity. This type of immunity would limit and eventually end the epidemic. It is a population-level phenomenon, rather than an individual one. Vaccinations would be relevant to this type of immunity if the vaccines were highly effective in preventing both clinical disease and spread of coronavirus. Herd immunity would be the theoretical end point, although our understanding of herd immunity is likely an over-simplification. Our current experience with vaccines, re-infections, "breakthrough infections," "surges," and so forth suggest that the current batch of available vaccines have little effect on establishing this type of immunity.

2. Symptom-limiting immunity. This type of immunity is individual immunity that has the effect of decreasing the severity of disease in clinically apparent infections. The reason that it might be a useful distinction is because of the possibility that a person may have this type of immunity and still be able to transmit the infection. The current crop of vaccines do seem to provide temporary immunity of this type.

3. Mortality-limiting immunity. This is related to symptom-limiting immunity, but is potentially a meaningful distinction because different coronavirus variants may have different different mechanisms of causing death, or have disproportionate effects in different patient groups. For example, certain populations may be at increased risk of mortality if infected with COVID because of an increased risk of thrombotic complications. Others may be at greater risk of pulmonary or cardiovascular or renal complications. Furthermore, if the baseline mortality from COVID drops below a certain level, e.g. a case fatality rate of 0.5%, then this would affect the risk-benefit analysis of vaccination. It is difficult to tell if the current vaccines have significant effect on this type of mortality, although current data suggest that they do.

4. Infectivity-limiting immunity. This is similar to epidemic-limiting immunity, but is an individual phenomenon. It is worth considering separately because even if a vaccine were perfect at limiting symptoms and mortality, the individual immune response may be insufficient to limit viral replication and shedding. Thus, people could be asymptomatic spreaders, even if vaccinated, and vaccination would be an ineffective or relatively ineffective means of limiting the spread of disease. The current data seem to suggest that current vaccines, that target only the spike protein of the virus, do not provide this type of immunity. 

Using the above a a guide, and referring to the earlier post on interpreting COVID data, it would appear that:

1. Current COVID vaccines provide temporary symptom limiting and mortality limiting immunity in the  general population. It appears that these vaccines provide peak protection after approximately 5- 6 weeks, and that the immune protection is not durable; it begins to wane with a half-life of approximately 5 months, thus requiring booster vaccines, or ongoing exposure to live virus to maintain levels of immunity. The significance of this is that immunity of whatever type is time-dependent, and it is quite possible that people who had asymptomatic exposure to COVID have symptom, mortality and infectivity limiting immunity that is superior to someone who was vaccinated, but whose immunity has waned.

2. The current vaccines do not appear to be effective at limiting the spread of COVID, likely because they do not provide a sufficient immune response to suppress viral replication in infected individuals. The surge in cases in highly vaccinated populations such as the United Kingdom and Israel seem to be consistent with this hypothesis.

3. There is likely much more environmental influence on the behavior of the virus than the current mask and vaccinate strategies acknowledge. This would explain for example the different experiences between South Dakota and other states. It also makes fallacious the idea that case numbers are primarily influenced by policy interventions. Masking for example likely has very little influence on the number of hospitalizations due to COVID.

What to Make of COVID Information

 The current state of information regarding the COVID pandemic, vaccine efficacy, Delta variant, mask mandates, etc., is nothing if not confused. Reports of "surges," breakthrough infections, booster shots and so forth leave the answers to such basic questions as "do vaccines work?" and "does mask wearing do anything?" uncertain. There appears to be either no source of reliable information regarding these questions, or such sources are few and hard to come-by.

First, there is no COVID information that should not be scrutinized for ulterior motives, insular agendas, and shaky foundation. The course of the pandemic has seen news media awash with anecdotes, dubious associations, unfounded claims, contradictory recommendations, inaccurate modeling and "unexpected" events. It is certainly possible that information regarding COVID is slanted to encourage compliance with "best-we-can-do" but still not very good interventions. It is also at least possible that political motives, such as interest of teachers unions in delaying return to in-person teaching affect the content and presentation of COVID information. Controversial topics such as vaccine passports, and the "right" of strangers to know an individuals vaccination status may be surrogates for other political or even cultural interests. What seems certain is that the simplistic models that are used to support things like six-foot social distancing, double masking, and lockdowns do not appear to be validated by actual experience.

There are several items of information that add confusion to the state of popular COVID knowledge, but which nonetheless may be used to understand the current state of the COVID pandemic and efforts to control it. Among these are reports of a significant number of "breakthrough" infections in vaccinated people, and exponential increases in the number of cases in places with relatively high vaccination rates such as the United Kingdom, Israel and the Seychelles. Other observations, such as a divergence in the case numbers and mortality rates, marked regional variation in case numbers that seem to be independent of vaccination rates, and the rapid rise and fall of infection numbers in India suggest that we are relying on incomplete understanding of the virus, immunological response and the influence of environmental factors. There are also intriguing observations regarding the quantification of virus found in vaccinated and unvaccinated people that may explain much of the confusing experience.

With specific regard to vaccinations, the rise in breakthrough cases and surges in relatively highly vaccinated populations suggests several possibilities. If we consider the state of vaccine information over the past year, we observe that vaccines were reported to have >90% efficacy in preventing COVID, that these vaccines were perhaps associated with blood clots, myocarditis, and hearing loss, that they were at least somewhat efficacious against the Delta variant, that boosters would be needed, etc. Much of these data seem to be unconfirmed extrapolations from limited observations, perhaps mixed in with wishful thinking and pubic relations spin. Again, the key to understanding this and resolving some of the apparent contradictions in this information is the observation that viral counts in vaccinated and unvaccinated people appear to be similar.

There are some straightforward but perhaps overly simplistic explanations for the COVID experience to date. One is that the vaccines do not work, which is likely at least somewhat true for the Russian and Chinese vaccines; that they work but the protection against infection decays exponentially, with a half-life of about 4 to 8 months (thus the need for "boosters;" or perhaps that the rational approach taken to develop COVID vaccines was based on an incomplete understanding of immunity against COVID.

We may take as true the following: vaccines are intended to stimulate the immune system to produce antibodies against the coronavirus spike protein; the vaccines do in fact produce measurable antibody responses; these antibodies are not reliable in protecting against subsequent infection and viral replication, even if they mitigate the severity of a particular infection and perhaps reduce morbidity and mortality. Here is a hypothesis that may explain these phenomena: the important immunological response to COVID is not the production of antibodies directed against the spike protein. These antibodies may decrease the effective inoculation viral dose, but do not stimulate an immune response that prevents or hinders viral replication. This is why viral counts in vaccinated and unvaccinated people are similar, and if the hypothesis is true, explains why vaccinated people can infect others.

Our understanding of the immune response is that antigens are taken up by immune cells, which then present antigens that direct the immune system to stimulate a protective, and likely complicated response that combats the infection. It may be the case that the spike protein is not the most efficient, or competent antigen to stimulate an effective response. It may be reasonable to target the spike protein because that supposedly provides specificity with regard to the pathogen, but the assumption that one antigen is the same as another in terms of immune response is possibly fallacious. Therefore when we use a surrogate for vaccine effectiveness, such as antibody count, we miss what we are actually interested in: effectiveness at preventing the spread of infection. 

Since coronaviruses describe a large class of pathogens, it is possible that the human immune system is more efficient if it does develop lasting immunity to every coronavirus encountered during the course of a lifetime. In other words, there may be a sound evolutionary basis for why the immune response to coronaviruses is not durable. Whatever the case, breakthrough infections, "surges" in vaccinated populations and considerations of booster shots all suggest that vaccination does not provide durable immunity against COVID. This does not mean that vaccination is futile, or does not provide a benefit. It rather suggests that expectations for vaccine efficacy should be prudently tempered, and that widespread vaccination even if effective eventually hits a point of diminishing returns.

The upshot of all of this is that the apparently confused state of COVID Information likely has many causes, from spun and slanted reporting, to inappropriate extrapolations from limited data, to incompletely understood pathophysiology of disease and immune response.