Tracy Marie

4 yrs

COMPARING SARS-COV-2 NATURAL IMMUNITY TO VACCINE-INDUCED IMMUNITY: REINFECTIONS VERSUS BREAKTHROUGH INFECTIONS
RESULTS:
SARS-CoV-2-naïve vaccinees had a 13.06-fold increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naïve vaccinees had a 5.96-fold increased risk for breakthrough infection and a 7.13-fold increased risk for symptomatic disease. SARS-CoV-2-naïve vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected.
CONCLUSIONS:
This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.
RESULTS:
Model 1 – previously infected vs. vaccinated individuals, with matching for time of first event
After adjusting for comorbidities, we found a statistically significant 13.06-fold increased risk for breakthrough infection as opposed to reinfection.
As for symptomatic SARS-COV-2 infections during the follow-up period, 199 cases were recorded, 191 of which were in the vaccinated group and 8 in the previously infected group.
After adjusting for comorbidities, we found a 27.02-fold risk for symptomatic breakthrough infection as opposed to symptomatic reinfection.
Nine cases of COVID-19-related hospitalizations were recorded, 8 of which were in the vaccinated group and 1 in the previously infected group.

Model 2 –previously infected vs. vaccinated individuals, without matching for time of first event
When comparing the vaccinated individuals to those previously infected at any time (including during 202, we found that throughout the follow-up period, 748 cases of SARS-CoV-2 infection were recorded, 640 of which were in the vaccinated group (breakthrough infections) and 108 in the previously infected group (reinfections).
After adjusting for comorbidities, a 5.96-fold increased risk for breakthrough infection as opposed to reinfection could be observed.
Overall, 552 symptomatic cases of SARS-CoV-2 were recorded, 484 in the vaccinated group and 68 in the previously infected group. There was a 7.13-fold increased risk for symptomatic breakthrough infection than symptomatic reinfection. COVID-19 related hospitalizations occurred in 4 and 21 of the reinfection and breakthrough infection groups, respectively. Vaccinated individuals had a 6.7-fold increased to be admitted compared to recovered individuals. Being 60 years of age or older significantly increased the risk of COVID-19-related hospitalizations.

DISCUSSION:
This is the largest real-world observational study comparing natural immunity, gained through previous SARS-CoV-2 infection, to vaccine-induced immunity, afforded by the BNT162b2 mRNA vaccine. Our large cohort, enabled by Israel’s rapid rollout of the mass-vaccination campaign, allowed us to investigate the risk for additional infection – either a breakthrough infection in vaccinated individuals or reinfection in previously infected ones – over a longer period than thus far described. Our analysis demonstrates that SARS-CoV-2-naïve vaccinees had a 13.06-fold increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for a symptomatic disease as well.
Broadening the research question to examine the extent of the phenomenon, we allowed the infection to occur at any time between March 2020 to February 2021 (when different variants were dominant in Israel), compared to vaccination only in January and February 2021. Although the results could suggest waning natural immunity against the Delta variant, those vaccinated are still at a 5.96-fold increased risk for breakthrough infection and at a 7.13-fold increased risk for symptomatic disease compared to those previously infected. SARS-CoV-2-naïve vaccinees were also at a greater risk for COVID-19-related-hospitalization compared to those who were previously infected.
This analysis demonstrated that natural immunity affords longer lasting and stronger protection against infection, symptomatic disease and hospitalization due to the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity.

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