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Social media and even the news are awash with conflicting information surrounding the relative immunological benefits of COVID-19 vaccination versus those of vaccination with one of the approved vaccines against SARS -CoV2 (the virus that causes COVID-19). This is because the various studies have been conducted around the world using a variety of methods and standards, with many of the studies not being peer reviewed, but simply pre-print papers, or even simply opinion. Based on the highest quality science, however, the following picture has emerged. First, as expected, those who have had neither a previous SARS-CoV2 infection nor COVID-19 vaccination are the least protected of all. Second, people with a previous SARS-CoV2 infection (symptomatic or not) who are subsequently vaccinated are the best protected of all. And finally, those who are fully vaccinated with no history of infection by the virus are better protected than survivors of previous SARS-CoV2 infection who have not been vaccinated.
In other words COVID-19 vaccination is better than natural immunity, which raises the question of how this can be. Intuitively, people often assume that natural infection should prime the immune system better than any vaccine, as has been the case with many diseases, but this phenomenon does not occur universally. With some infectious diseases, getting infected actually does not incur immunity. In a few cases, dengue fever for instance, which is caused by dengue virus, previous infection makes one more susceptible to the virus. This involves a phenomenon called antibody enhancement, making it likely that a second exposure to the virus will produce worse disease than the first. In the case of COVID-19, the data do not seem to indicate that a first infection will make a second infection worse. There will be a good amount of protection. But that protection will not be as good as the protection that you will acquire from vaccination. The reason may be related to the design of the vaccines, the ones that are approved and demonstrating good efficacy, resulting in an immune response different from the immune response to natural infection with SARS-CoV2.
Early in the pandemic, we began discussing how the SARS-CoV2 virus makes you sick. Recall from our early discussions that the viral coat, the outer part of the virus, contains spike protein projecting outward, and that these spike proteins enable the virus to attach to, and invade, body cells. This is especially true deep in the respiratory tract, where the surfaces of cells are abundant with the particular protein to which SARS-CoV2 attaches by way of the spike proteins, namely a cell surface protein called ACE-2, or the ACE-2 receptor.
Scientists and doctors are finding that, while symptomatic COVID-19 is fairly common in fully vaccinated people with no major health issues, such people rarely develop severe COVID-19 disease. It seems as if immunity against the virus affecting cells deep in respiratory tract and otherwise deep in the body persists, even as immunity against upper respiratory symptoms, such as cold symptoms wanes. So, while the virus may thrive to some extent in the upper respiratory tract, it seems not to be attaching well to ACE-2 in vaccinated people.
This makes total sense, because the vaccines are designed to produce an immune response, not merely against the spike protein, which has many epitopes (regions that can generate an immune response, each characterized by particular antibodies that attach to that region), but particularly against the part of the spike protein that attaches to ACE-2. In contrast, immune response to a natural infection, an infection with SARS-CoV2 is much more broad, not specific to the attachment region on the spike protein, but to the entire spike protein and also other molecules on the surface of the virus. Natural immunity is a more comprehensive response to the virus, but immunity from vaccination seems to be more focussed on the part of the viral spike protein that enables the virus to cause disease.
This is plausible mechanism as to why vaccination seems to work better than previous infection with the virus in terms of protecting you against the virus. Adding to this perspective, please remember getting a SARS-CoV2 infection to produce natural immunity in the first place is a very dangerous way to acquire natural immunity. This is particularly true for pregnant women, who, as we have discussed in past, are at elevated risk for developing severe disease, and requiring invasive ventilation and other aggressive treatments if they do become infected. Furthermore, COVID-19 in a pregnant women puts the fetus at risk, particularly for pre-term delivery, with all of its negative consequences.
