Chin et al. (Nov. 10 issue)1 report the effectiveness of messenger RNA vaccination and previous SARS-CoV-2 infection against infection with the B.1.1.529 (omicron) variant of SARS-CoV-2 among residents and staff in the California state prison system. Their findings support the hypothesis proposed by Altarawneh et al.2 — that hybrid immunity may be estimated by calculating 1 minus ([1 minus vaccine effectiveness] multiplied by [1 minus the effectiveness of previous infection]).

We used this formula to estimate hybrid immunity based on the vaccine effectiveness and protection conferred by natural infection reported by Chin et al. Both forms of protection were used as separate inputs. We then compared our estimate of hybrid immunity with that observed by Chin et al., and the two estimates agreed well. In the complex current landscape of mixed vaccine-derived and natural population-level immunity, and with limited data regarding the degree of hybrid protection against emerging variants, this method of estimating hybrid immunity is useful for understanding total population immunity and providing variables for Covid-19 simulation models in particular.

Jessie Zeng, M.P.H.
Joshua Szanyi, M.D.
Tony Blakely, Ph.D.
University of Melbourne, Melbourne, VIC, Australia
[email protected]

The authors report that the Population Interventions Unit of the University of Melbourne is currently conducting separate vaccine effectiveness research, which is funded by Moderna, in Victoria, Australia. Moderna had no involvement in this letter. The authors report no further potential conflict of interest.

This letter was published on December 28, 2022, at NEJM.org.

1. Chin ET, Leidner D, Lamson L, et al. Protection against omicron from vaccination and previous infection in a prison system. N Engl J Med 2022;387:1770-1782.

2. Altarawneh HN, Chemaitelly H, Ayoub HH, et al. Effects of previous infection and vaccination on symptomatic omicron infections. N Engl J Med 2022;387:21-34.

The authors reply: Zeng et al. suggest that the findings of our study on confirmed infections support the hypothesis proposed by Altarawneh et al.1 in their article on symptomatic infections — that is, hybrid effectiveness can be estimated by assuming that the effects of vaccination and the effects of previous infection are independent. We chose to use interacted vaccination history and history of previous infection because the analyses for each population had at least one significant interaction term with the use of Bonferroni correction. This approach may explain some of the differences between the (interacted) estimates in our study and those of Zeng et al. Their simulations sampled from separate probability distributions of vaccine effectiveness and effectiveness of previous infection (i.e., they were not interacted). Notably, in our secondary analysis, in which we estimated the incremental effectiveness of a third dose of vaccine, we observed similar effectiveness across various infection histories among the staff but not among the population of residents.

Taken together, we do not find clear evidence that our study supports the hypothesis that hybrid immunity can be estimated with the use of independent effects of vaccination and previous infection. However, we agree with Zeng et al. that this is an important area for further study, particularly given new variants and waning of immunity.

Elizabeth T. Chin, Ph.D.
Jeremy D. Goldhaber-Fiebert, Ph.D.
Stanford University School of Medicine, Stanford, CA
[email protected]

Since publication of their article, the authors report no further potential conflict of interest.

This letter was published on December 28, 2022, at NEJM.org.

1. Altarawneh HN, Chemaitelly H, Ayoub HH, et al. Effects of previous infection and vaccination on symptomatic omicron infections. N Engl J Med 2022;387:21-34.