Is vaccination better than prior infection?

In my job, ‘I told you so’ is a very unsatisfying experience. We’ve all experienced the spark of schadenfreude when, after a bitter disagreement with another, we are proven right in unassailable terms. It’s a wicked joy, no doubt fueled by some deep-seated insecurity, but it is a joy nonetheless. You would think the opportunities for the elation of ‘I told you so’ abound in medicine. After all, we tell people to do things all the time for their own good and they resist us more often than you would think. Unfortunately, this is not the case.

While suiting up to see my first critically ill COVID patient in several months I felt the schadenfreude brimming when the resident told me he was unvaccinated. I, along with just about every other doctor in the world, have been preaching the merits of vaccination to anyone who will listen. I wrote about it when I got my first dose back in December 2020. I think I made a strong case and that was long before we had several months of data and experience showing better than expected efficacy and safety. So when I went into room 504 there was a small part in the back of my head giddy with the prospects of the ‘I told you so’. Don’t get me wrong. I am not a monster. I wasn’t going to lay it on him right out of the gate. I had a plan for a more subtle drop of sarcasm to get the point across without being too harsh. Not as pleasurable as a pointed finger and playground sing-song but effective nonetheless. Well, that was my plan – until I saw him.

He was lying perfectly still in the bed (any movement made him severely short of breath and dropped his oxygen). He had the BIPAP ventilator mask keeping his oxygen levels at a safe range. There was sweat glistening on his forehead and a look of fear in his eyes. What instantly ended my schadenfreude, however, was a small tear emerging from the corner of his right eye. He didn’t need a self-righteous and pompous doctor telling him he had made a mistake, the regret was oozing from his febrile body.

That night I got another call. This time for a young woman who was 12 weeks pregnant. She had delayed getting the vaccine because she was worried about what effects it would have on her fertility. She was being sent to the ICU because her oxygen levels had dropped rapidly. The virus was seriously threatening the life and development of her baby more than the vaccine could. There was no room for ‘I told you so’ here either.

Unfortunately, this is how it usually happens in medicine. Many times healthcare workers are left with an emptiness inside. When we think of the harm that will come when people don’t take our advice it creates a great tension inside of us. It’s a mixture of frustration and anxiety (and a bit of bruised ego as well). There is a release of the tension when we’re proven right, but it is overwhelmed by the sadness caused by the terrible outcome we predicted becoming a reality.

The Pfizer vaccine is now FDA approved and the others will soon follow. The approval was a formality. No new data has been presented, nor was needed, to show the great success of the vaccines. The first subject got their shot over a year ago and the results have been borderline miraculous. In spite of that, there are those that are hesitant (or even downright militant).

If someone has had a prior infection is there a benefit to getting vaccinated ?

One reason many have given for not getting vaccinated is that they believe they are protected from a prior COVID infection. They think that the immune response they generated to their first infection is just as good as the vaccine, but is this really true? If someone has had a prior infection is there a benefit to getting vaccinated or is their natural immunity just as good?

There was a study that was not yet peer-reviewed or published that was picked up by some internet media outlets and has given many the impression that prior infection was better than the vaccines. One headline read “Israeli Study: Natural Immunity Provides 13 Times More Protection Against Delta Than Pfizer’s Vaccine”. When you read that headline it gives the impression that previously infected individuals get no benefit from the vaccine. This conclusion would be incorrect.

The study had three groups: 1) Individuals who had been previously infected 2) Individuals who were vaccinated and not previously infected and 3) Individuals who were previously infected and had one dose of the Pfizer vaccine. Their results (as noted in the headline) were that prior infection was better than the vaccine (i.e. group 1 had fewer COVID cases than group 2). This conclusion is dubious and not generalizable. There were a couple serious problems with the conclusions drawn by the headline of that news article. First, this was a young cohort (average age was 36) with only 4% being over 60. The most vulnerable are over age 60 so it is reasonable to think that these findings would have been much different if there were older subjects. Second, this was not a study of broad population-based testing but only of people who came in to get tested. The population of those who get tested might not represent a broad enough sample of the population of those who were vaccinated skewing the results in some way.
Those who had prior infection plus one dose of vaccine had a lower rate of reinfection than those with prior infection alone – and that was only after one dose.

  

Those who had prior infection plus one dose of vaccine had a lower rate of a reinfection than those with prior infection alone – and that was only after one dose.

Even with those major issues, the most important conclusion of this study (which was completely ignored by the news article) was the fact that those who had prior infection plus one dose of vaccine had a lower rate of reinfection than those with prior infection alone – and that was only after one dose of the Pfizer vaccine. Two may have been even better. So, in fact, this study shows that it is very beneficial for those with prior infection to get vaccinated. There is more data to corroborate this result.

An analysis of antibody testing done before and after extensive vaccinations collected >8,000 samples with 26% being from unvaccinated individuals. The analysis also showed that mRNA vaccination rapidly induces a much stronger and broader antibody response than prior infection alone. A study of previously infected individuals published in the Journal of the American Medical Association showed that antibody levels increased sixfold after vaccination. A study published in the journal Science compared the sera of people who had prior COVID from the original strain to those who did not both before and after vaccination. In the blood of previously infected patients who were not vaccinated, neutralization of the alpha and beta variants was variable and weak whereas neutralizing capacity increased approximately 1000-fold after vaccination.

An evaluation of the association between vaccination and COVID in previously infected individuals was done in Kentucky. They found that residents who previously had COVD and were not vaccinated had 2.34 times the odds of reinfection compared with those who were fully vaccinated. The findings from this study suggest that among previously infected persons, full vaccination is associated with a reduced likelihood of reinfection, and being unvaccinated is associated with a higher likelihood of being reinfected.

All of this is now even more important with the delta variant. This variant is more contagious and may cause more severe illness in unvaccinated individuals than earlier strains. Further, it would not be reasonable to assume that prior infection with a different strain would provide adequate protection without evidence.

Then there’s the common-sense argument which can be best summed up in the two pictures below. The picture on the right shows the percentage of hospital beds that are filled with COVID patients and the picture on the left shows vaccination rates. By using hospital utilization as opposed to cases you show the true burden of disease. It is clear that the current hotspots are in areas with lower rates of vaccination.

What’s interesting is that many of these places had high rates of COVID in earlier waves from earlier variants. If a prior infection was truly protective there should be no impact of vaccination on hospitalization rates. This is clearly not the case.

Finally, there’s my personal experience. I live and work in Maryland which has very high vaccination rates. When the cases peaked last winter, our ICU was filled with COVID patients and we were overflowing to other units. Last winter, the gentleman I referenced at the beginning would not have been admitted to the ICU because, even though he was critically ill, we were only taking people on death’s door to the ICU because of a lack of beds.

Lets sum this all up:

1. The vaccines induce a much stronger antibody response than previous infection.
2. People with prior infection who are not vaccinated are significantly more likely to get reinfected.
3. The vaccines work against the variants, including Delta.
4. The current rise in cases is happening in areas with low vaccination rates.

That’s the evidence. I think it’s clear that to assume that prior infection obviates the need for vaccination is not supported by the current evidence. Please get your vaccination, prior infection or not. I don’t want to have to say ‘I told you so’.