Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections

Abstract

Background: Reports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear. Methods: We conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naive individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel. Results: SARS-CoV-2-naive vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) 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 naive vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naive 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.

Anti- SARS-CoV-2 Receptor Binding Domain Antibody Evolution after mRNA Vaccination

“…Taken together with the overall decay in neutralizing activity there can be 1-2 orders of magnitude decrease in serum neutralizing activity after or months against variants when compared to the peak of neutralizing activity against Wuhan Hu-1. Thus, antibody mediated protection against variants is expected to wane significantly over a period of months, consistent with reports of reinfection in convalescent individuals and breakthrough infection by variants in fully vaccinated individuals [39][40][41][42] .…”

“…However, vaccine-elicited memory monoclonal antibodies show more modest neutralizing potency and breadth than those that developed after natural infection 1,7 . Notably, the difference between the memory compartment that develops in response to natural infection vs mRNA vaccination reported above is consistent with the higher level of protection from variants conferred by natural infection 42 .…”

A Systematic Review of the Protective Effect of Prior SARS-CoV-2 Infection on Repeat Infection

“…However a recent pre-print from a study conducted in the United Kingdom found among persons infected during a period of nearly exclusive Delta SARS-CoV-2 transmission, those fully vaccinated with BNT162b2 and ChAd0x1 (had similar levels of protection (82% and 67%, respectively) as those with previous infection (73%) (Pouwels;. Additionally, in a recent retrospective cohort study that was conducted in Israel which compared rates of SARS-CoV-2 infection or reinfection with the Delta variant among SARS-CoV-2-naïve individuals who received the BNT162b2 vaccine to people who had recovered from COVID-19, found that vaccinated, but SARS-CoV-2-naïve people, had an increased risk of infection with the Delta variant when compared to people who had recovered from COVID-19 (Gazit et al, 2021). This association was statistically significant in two models that either matched to the time of the first event (13.1-fold increased risk) or did not match to time of first event (6.0-fold increased risk).…”

The Evolving Faces of the SARS-CoV-2 Genome

“…(ii) Insufficient and/or waning protection due to immune evasion of SARS-CoV-2 delta. A recent 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 (Biontech-Pfizer) two-dose vaccine-induced immunity [53]. The waning protection is possible due to the too short interval between first and second dose (3-6 weeks) [40].…”