Both studies come from two different regions of the world and provide real-life evidence of the impact on clinical efficacy of vaccination in previously infected individuals who subsequently receive vaccination. The main message of both studies is that they demonstrate the real effectiveness of the concept of hybrid immunity in terms of protection against infection and severe infection, which had been well documented using immune response parameters (antibodies and cells). Both studies show results in large population groups and with a statistically correct approximation.

Therefore, the data are consistent with previous studies with smaller populations or based on meta-analyses combining previous evidence.

The study from Brazil clearly shows a greater effect of a vaccination schedule with two doses of vaccine (of any of the vaccines used in Spain to date) than with a single dose in those previously infected.

In contrast, the Swedish study compares only hybrid immunity with one or two doses of the same vaccines, but against natural infection alone. It does not have sufficient numbers of people to compare between the one- and two-dose groups. Interestingly, the Swedish study shows that the protective effect against reinfection and severe infection is not only stronger, but also longer lasting, reaching a follow-up of up to 20 months. On the other hand, the same study shows that the protective effect is reduced in people over 65 and, above all, over 80 years of age. This is a weakness of the Brazilian study, which does not relate the findings by age range and, in addition, 75% of the population analysed was under 45 years of age. The Brazilian study, on the other hand, has the limitation indicated by the authors themselves that there is no control of subject selection and they have not controlled access to diagnostic tests for reinfection in the included population, and it is possible that there is some bias.

The main implication of the study is the validation of the immunological findings of the concept of hybrid immunity advanced as early as June 2020 by Shane Crotty and Alessandro Sette. This effect lasts up to 20 months and highlights that the vaccination passport should include vaccination alongside natural infection when determining immunisation status and protection against covid-19.

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Both studies confirm what is already known: that vaccines boost acquired immunity after natural infection with SARS-CoV-2, increasing protection, especially against severe disease.

Both the Brazilian and Swedish studies have the statistical power of large numbers of individuals. In both cases, the results provide valuable information on the rate of reinfection, and the consequences of reinfection, in individuals with natural immunity and in many cases subsequently vaccinated.

The major limitation of the two studies is that the data predate omicron, which is the currently predominant variant, and which has changed the landscape of reinfection possibilities. As has been shown, omicron is much more able than previous variants to escape the immunity (in terms of antibodies) provided by both infections with other variants and vaccination. Omicron can therefore cause reinfection more easily than previous variants, and therefore the results of these studies in terms of efficacy in preventing reinfection cannot be directly extrapolated to the current situation.

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