From the Dean: On vaccine ‘Breakthroughs’

Over the past year and a half, I’ve written a variety of columns about the impact of the pandemic on the School and how our faculty, staff, and students have risen to the attendant challenges. Today I’d like to address some health aspects of the pandemic itself and focus on so-called breakthrough infections, since there are some important misconceptions floating around. I’ll try not to get too wonky in my discussion – I promise!

First, let’s start with some definitions so that we are on the same page. Breakthrough infections in this context refer to documented occurrences of COVID-19 – regardless of the severity of the symptoms – that are diagnosed in fully vaccinated individuals. Fully vaccinated individuals are defined in turn as people who are at least two weeks following the completion of whatever vaccination schedule they were on – one shot for the Johnson & Johnson product, and two shots for both the Pfizer and Moderna products.

Many recent news reports have highlighted the increasing frequency over time of breakthrough cases and have raised concerns that this indicates that vaccine efficacy is decreasing as time goes on. While that concern is legitimate and clearly is something that is being monitored closely by our public health enterprise, there is a much less worrisome explanation that is the major factor involved in the increasing number of breakthrough cases. In fact, it is a “good news” explanation! It turns out – maybe somewhat counterintuitively – that the percentage of cases that are due to breakthrough infections goes up as more people get vaccinated! What? You get a higher percentage of breakthrough cases as more people get vaccinated? How can that be? Well, consider these two extremes: first, consider the situation where no one in a community is vaccinated. The percentage of breakthrough cases obviously will be zero, since one can’t have a breakthrough case where there is nothing (no vaccine protection) to break through. But second, consider the hypothetical case where now everyone in that community has been vaccinated. In that situation, the frequency of breakthrough cases is 100 percent since any case – by definition – has to be a breakthrough infection. So in this example, we would see a dramatic increase in portion of cases that are breakthrough simply as a consequence of more people getting vaccinated, regardless of vaccine efficacy.

Notice that even in this scenario the number of breakthrough cases in a community with 100% vaccine uptake will still be lower than the COVID-19 case count in a community with no vaccination program. Thus, there is not one but two possible explanations for an increasing proportion of breakthrough cases over time – the worrisome one that vaccine efficacy is decreasing, and the reassuring one that more people are getting vaccinated. So how should we distinguish between the two contrary causes? Don’t focus on the fraction of total cases that are due to breakthrough infections; instead, assess the frequency of cases seen in the not fully vaccinated group compared with the frequency of cases (breakthrough) in the vaccinated group. The technical term for this analysis is “incidence rate ratio” or IRR.

Using this preferred method, the incidence rate found in the not fully vaccinated group is compared with the incidence rate found in the fully vaccinated group and used to calculate an IRR. This comparison yields some impressive findings. Since the delta variant became the dominant form of SARS-CoV-2 in the United States at the start of the summer, comparison IRRs reveal that fully vaccinated people have a five-fold reduced risk of infection, and a greater than 10-fold reduction in the likelihood of hospitalization or death when compared with the un- or partially vaccinated population. This was true even though the absolute number of breakthrough infections increased somewhat as more people got vaccinated. Further details are available in a report from the Centers for Disease Control and Prevention (CDC) released last week.The bottom line is clear – breakthrough infections are not a major concern with the delta variant (at least so far) and vaccination results in impressive protection against the more worrisome complications of COVID-19 (severe infections resulting in hospitalization or death). There really are not a lot of medical interventions where we can lower the risk of hospitalization or death by more than 10-fold, that’s for sure!

I hope this explanation helps clarify the issue of breakthrough infections and how to put the numbers in the proper perspective. Stay safe!

Joshua Wynne, MD, MBA, MPH
Vice President for Health Affairs, UND
Dean, UND School of Medicine & Health Sciences