Primary COVID-19 Infection Plus Vaccination Significantly Protects Against Reinfection

Hybrid immunity from primary COVID-19 infection and subsequent BNT162b2 vaccination was found to elicit strong cross-protection against reinfection caused by Omicron and Delta variants. These study results were published in International Journal of Infectious Diseases.

Between August 2021 and March 2022, researchers interviewed a randomly selected, age-stratified cohort of individuals who had recovered from COVID-19 infection and had donated convalescent plasma in 2020. Study participants were interviewed during the Delta (August 2021-December 2021) and Omicron (December 2021-March 2022) waves. Information captured in the interviews included vaccination history, SARS-CoV-2 testing frequency, and the occurrence laboratory-confirmed reinfection between primary infection onset and the date of the interview. Outcomes assessed included reinfection occurrence, immunoglobulin (Ig)G anti-spike antibody levels, and neutralizing antibody titers against wild-type, Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. Exposure variables included patient age and sex, fever, and hospitalization at the time of primary infection.

Among 1004 participants included in the final analysis, the median age was 31.1 years, 78.6% were men, 15.3% were hospitalized and 60.8% had fever during primary infection, and 13.7% were unvaccinated. Of note, 45.2%, 33.5%, and 7.6% of participants received 1, 2, or at least 3 vaccine doses, respectively, following primary infection.

The overall incident rate of COVID-19 reinfection during the pre-Omicron wave (until December 15, 2021) was 2.8% (95% CI, 1.8-3.8). Reinfections during this period occurred between 4.6 and 18.0 (median, 11.4) months following primary infection. In addition, reinfection risk in this period was reduced by 71% among participants who experienced fever during primary infection. Multivariable analysis showed that the occurrence of fever during primary infection (adjusted risk ratio [aRR], 0.23; 95% CI, 0.07-0.80; P =.021) and subsequent vaccination receipt (aRR, 0.07; 95% CI, 0.02-0.21; P <.001) were significantly associated with decreased risk for reinfection.

In the Omicron period, the overall incidence of reinfection was 21.6% (95% CI, 18.0-25.4), with reinfections occurring between 12.7 and 22.2 (median, 16.8) months following primary infection. Significant predictors for decreased reinfection risk during this period included older age (≥35 years) and high neutralizing antibody levels measured after primary infection. Multivariable analysis showed that high neutralizing antibody levels measured at the time of primary infection (aRR, 0.59; 95% CI, 0.36-0.95; P =.031) and subsequent vaccination receipt (aRR, 0.47; 95% CI, 0.27-0.82; P =.007) were significantly associated with decreased reinfection risk.

Limitations of this study include that contact was reestablished for only 48.4% of the study population, the low percentage of participants who provided sera during the follow-up period (22%), and the use of self-reported data for vaccination history and reinfection occurrence.

According to the researchers, “It follows that hybrid immunity reaching a critical pre-existing level of anti-S IgG binding and neutralizing antibodies could be sufficient to prevent reinfections with new SARS-CoV-2 variants even with substantial genetic changes.”