Protection Due to Previous SARS-CoV-2 Infection

To the Editor

Although it is true that the effectiveness of previous SARS-CoV-2 infection in preventing reinfection varies across the spectrum that encompasses the B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), and B.1.1.529 (omicron) variants, it is also necessary to draw attention to the role of changeableness in the SARS-CoV-2 variant subtypes responsible for previous infection. Altarawneh et al. (March 31 issue)1 state that the consistency of their estimates of protective efficacy suggested that differences in protective efficacy that are based on variant status may not be considerable (see the Supplementary Appendix, available with the full text of their article at However, Reynolds et al.2 found that after the receipt of a single vaccine dose, participants who had previously been infected with the original strain had an S1 receptor-binding domain response that was 3.9 times as high as that observed in counterparts who had previously been infected with the alpha variant (P=0.004).

The implication is that the phenomenon of enhanced vaccine response would be less effective if the infection involved a heterologous spike protein from a variant of concern than if the infection involved a spike protein that was homologous with the spike protein expressed by the vaccine. Arguably, there might even be a hierarchy of immune responses, depending on the heterologous infection subtype. Insights to be gained from research about the relation between protective efficacy and variant subtype in a previous infection may also inform the formulation of future vaccines.

Oscar M.P. Jolobe, M.B., Ch.B.
Manchester, United Kingdom

No potential conflict of interest relevant to this letter was reported.

This letter was published on June 8, 2022, at

  1. 1. Altarawneh HN, Chemaitelly H, Hasan MR, et al. Protection against the omicron variant from previous SARS-CoV-2 infection. N Engl J Med 2022;386:1288-1290.

  2. 2. Reynolds CJ, Gibbons JM, Pade C, et al. Heterologous infection and vaccination shapes immunity against SARS-CoV-2 variants. Science 2022;375:183-192.