How effective is immunity after Covid recovery relative to vaccination? An Israeli study by Gazit et al. found that the vaccinated have a 27 times higher risk of symptomatic infection than the Covid recovered. At the same time, the vaccinated were nine times more likely to be hospitalized for Covid. In contrast, a CDC study by Bozio et al. claims that the Covid recovered are five times more likely to be hospitalized for Covid than the vaccinated. Both studies cannot be right.

I have worked on vaccine epidemiology since I joined the Harvard faculty almost two decades ago as a biostatistician. I have never before seen such a large discrepancy between studies that are supposed to answer the same question. In this article, I carefully dissect both studies, describe how the analyses differ, and explain why the Israeli study is more reliable. //

The CDC study did not create a cohort of people to follow over time. Instead, they identified people hospitalized with Covid-like symptoms, and then they evaluated how many of them tested positive versus negative for Covid. Among the vaccinated, 5% tested positive, while it was 9% among the Covid recovered. What does this mean?

Though the authors do not mention it, they adopt a de facto case-control design. While not as strong as a cohort study, this is a well-established epidemiological design. //

In the CDC study on Covid immunity, the cases are those patients hospitalized for Covid disease, having both Covid-like symptoms and a positive test. That is appropriate. The controls should constitute a representative sample from the population from which the Covid patients came. Unfortunately, that is not the case since Covid-negative people with Covid-like symptoms, such as pneumonia, tend to be older and frailer with comorbidities. They are also more likely to be vaccinated. //

The problem is that the CDC study answers neither the direct question of whether vaccination or Covid recovery is better at decreasing the risk of subsequent Covid disease, nor whether the vaccine rollout successfully reached the frail. Instead, it asks which of these two has the greater effect size. It answers whether vaccination or Covid recovery is more related to Covid hospitalization or if it is more related to other respiratory type hospitalizations. //

Covariate adjustments will typically change the point estimates somewhat, but it is unusual to see a change as large as the one from 1.77 to 5.49 that was observed in the CDC study. How can this be explained? It must be because some covariates are very different between the cases and controls. There are at least two of them. While 78% of the vaccinated are older than 65, 55% of the Covid recovered are younger than 65. Even more concerning is the fact that 96% of the vaccinated were hospitalized during the summer months of June to August, while 69% of the Covid recovered were hospitalized in the winter and spring months from January to May. Such unbalanced covariates are usually best adjusted for using matching as in the Israeli study. //

Concerning the Covid recovered, there are two key public health issues. 1. Would the Covid recovered benefit from also being vaccinated? 2. Should there be vaccine passports and mandates that require them to be vaccinated in order to work and participate in society?

The CDC study did not address the first question, while the Israeli study showed a small but not statistically significant benefit in reducing symptomatic Covid disease. Future studies will hopefully shed more light on this issue.

Based on the solid evidence from the Israeli study, the Covid recovered have stronger and longer-lasting immunity against Covid disease than the vaccinated. Hence, there is no reason to prevent them from activities that are permitted to the vaccinated. In fact, it is discriminatory.

Many of the Covid recovered were exposed to the virus as essential workers during the height of the pandemic before vaccines were available. They kept the rest of society afloat, processing food, delivering goods, unloading ships, picking up garbage, policing the streets, maintaining the electricity network, putting out fires, and caring for the old and sick, to name a few.

They are now being fired and excluded despite having stronger immunity than the vaccinated work-from-home administrators that are firing them.