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Vaccinated yet vulnerable

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As a transplant nephrologist, my patients along with a lot of other immunocompromised patients wonder about the vaccines available for Covid-19. Fortunately, most, if not all, of my patients have been vaccinated, yet numerous questions and issues remain.

For many, the regular two-dose Covid-19 vaccine regimen — and in some cases, even a third dose — didn’t provide sufficient immune protection. As a result, hundreds if not thousands of immunocompromised Filipinos have been struggling with how they will achieve vaccine-induced immunity.

When the vaccines came out, no one knew how immunocompromised people would respond to them. They were excluded from the big clinical randomized trials. Very early on, we started to measure antibody levels in people who are immunocompromised after one dose, after two doses — and it was very clear that the more immunocompromised you were, the lower your immune response to the vaccine. Two shots for appeared to be inadequate. There appeared to be a good response to a third shot or booster shot.

I take care of transplant patients who take immunosuppressive agents to prevent their transplanted organs from rejecting, but that suppresses their immune system response to vaccines as well. In transplant patients, even with three shots in the currently recommended regimen, about half of transplant patients might not reach an antibody level that correlates with clinical protection.

It is absolutely critical for anyone who is immunocompromised to get vaccinated. Even if they don’t have a lot of detectable antibodies, they likely have some amount of protection. They’re still at risk of acquiring the disease at a higher rate with more severe infection than people who are immunocompetent, although maybe not as severe as if they had not been vaccinated at all.

PHOTOGRAPH COURTESY OF
pexels/nataliya vaitkevich
It is absolutely critical for anyone who is immunocompromised to get vaccinated.

It is also likely that there is some protection by reducing the severity of disease. The fact that people with no antibodies after two shots do sometimes have a lot of antibodies after a third, showing that each dose primes the immune system. While we can measure antibodies and neutralizing antibodies, there are other factors such as memory B-cell and T-cell activity and we don’t really have good ways of quantifying this or correlating it with protection.

One of the big issues right now is that there is still no formal recommendation for antibody testing. We know from large studies that at least in people who are immunocompetent, higher antibody levels directly correlate with clinical protection. In those with normal immune systems, T-cell responses, B-cell responses, and antibody responses all work in synchrony. That synchrony might be broken, for example, in the transplant patient who is on T-cell inhibitors.

However, antibody testing does provide some information. For example, if an immunocompromised person has had three doses, and their antibody levels are low, in all likelihood they are not protected and need to be incredibly careful. If their antibody levels are very high, there still might be less protection than in someone with a normal immune system, because their T-cell response might be suboptimal. But at least they have a sense of this when they make risk-benefit decisions about their lives. If they have to go to work, if they have to interact with people, at least they have a sense of where their protection might be.

PHOTOGRAPH COURTESY OF CDC.GOV

Unfortunately our vaccine guidelines don’t provide much help for the immunocompromised patient. They aren’t individualized and they don’t give doctors the ability to individualize care. Some of my patients have already been boosted but show relatively low levels of antibodies. Even if I wanted to get them a fourth dose, I actually can’t because doses are limited. Outside of clinical trials, basically every medical provider who cares for immunocompromised people is limited.

The truth is, we are building the plane as we fly it. Fortunately, trials are underway looking at people who so far have failed to reach a reasonable antibody level with whatever vaccine regimen they’ve received. These studies will hopefully answer what dosing regimen is appropriate for immunocompromised patients, and whether vaccines have to be partnered with a particular reduction in immunosuppression.

Some transplant patients desperate for protection have essentially resorted to experimenting on themselves finding ways to get the doses that they “think” they need, which is problematic. This would be done better in a data-driven manner, where we know where they stand in terms of their antibody responses, we know what immunosuppressive drugs they take, we know what their immune system looks like, and we can make personalized decisions for them.

We need to give medical providers, the ones who know these patients some wiggle room to help them make these decisions. After all that’s what doctors do. We individualize care for our patients. For any other medication I give my patients, I have the permission to individualize care. For vaccines, we aren’t actually able to do this just yet.

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