Protection and Waning of Natural and Hybrid Immunity to SARS-CoV-2

Abstract

Background Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides natural immunity against reinfection. Recent studies have shown waning of the immunity provided by the BNT162b2 vaccine. The time course of natural and hybrid immunity is unknown. Methods Using the Israeli Ministry of Health database, we extracted data for August and September 2021, when the B.1.617.2 (delta) variant was predominant, on all persons who had been previously infected with SARS-CoV-2 or who had received coronavirus 2019 vaccine. We used Poisson regression with adjustment for confounding factors to compare the rates of infection as a function of time since the last immunity-conferring event. Results The number of cases of SARS-CoV-2 infection per 100,000 person-days at risk (adjusted rate) increased with the time that had elapsed since vaccination with BNT162b2 or since previous infection. Among unvaccinated persons who had recovered from infection, this rate increased from 10.5 among those who had been infected 4 to less than 6 months previously to 30.2 among those who had been infected 1 year or more previously. Among persons who had received a single dose of vaccine after previous infection, the adjusted rate was low (3.7) among those who had been vaccinated less than 2 months previously but increased to 11.6 among those who had been vaccinated at least 6 months previously. Among previously uninfected persons who had received two doses of vaccine, the adjusted rate increased from 21.1 among those who had been vaccinated less than 2 months previously to 88.9 among those who had been vaccinated at least 6 months previously. Conclusions Among persons who had been previously infected with SARS-CoV-2 (regardless of whether they had received any dose of vaccine or whether they had received one dose before or after infection), protection against reinfection decreased as the time increased since the last immunity-conferring event; however, this protection was higher than that conferred after the same time had elapsed since receipt of a second dose of vaccine among previously uninfected persons. A single dose of vaccine after infection reinforced protection against reinfection.

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone

“…This held true in individuals with efficient neutralizing responses and contained disease manifestations ( Figure 4 D and Supplementary Figure S2B ). This feature may either reflect a more targeted humoral response induced by vaccination over natural infection, or the superiority of hybrid immunity over immunity elicited by infection alone [ 36 , 93 , 100 , 101 , 102 ]. The observation that BTI patients with higher anti-N antibody levels had the highest neutralizing activity argues in favor of the second hypothesis.…”

“…Conversely, breakthrough infection after vaccination confers some cross-protection, while Omicron BA.1 infection alone offers limited protection against pre-Omicron and against Omicron BA.2 and BA.2-related sublineages [ 92 , 95 , 96 ]. Hybrid immunity appears to cross-protect more efficiently than infection or vaccination individually and seems to be more durable [ 36 , 49 , 100 , 101 , 102 , 120 , 121 ], likely as a result of antibody affinity maturation [ 67 , 99 , 122 , 123 ]. In our case, BTI patients were not followed longitudinally and the time elapsed since infection was not known.…”

Depression, aging, and immunity: implications for COVID-19 vaccine immunogenicity

“…On the other hand, some studies have reported discrepant results. For instance, an Israeli study performed during the B.1.617.2 (delta) variant wave of the pandemic, examined the waning of natural immunity in a recovered, unvaccinated cohort [ 96 ]. After controlling for ethnicity and exposure risk, the number of confirmed infections per 100,000 person-days at risk ranged from 14.2 in 16–39 year-old persons infected 4–6 months previously to 34.9 in individuals infected more than 1 year previously.…”

“…After controlling for ethnicity and exposure risk, the number of confirmed infections per 100,000 person-days at risk ranged from 14.2 in 16–39 year-old persons infected 4–6 months previously to 34.9 in individuals infected more than 1 year previously. In the ≥60 year category, the equivalent number of confirmed infections per 100,000 person-days at risk ranged from 4.2 to 12.4 [ 96 ].…”

Dawn of the hybrid immunity era in long-term care facilities

“…Similar to vaccine-induced and infection-induced immunity, hybrid immunity also wanes over time. 4 , 5 , 6 , 7 Unsurprisingly, omicron can evade hybrid immunity acquired in the pre-omicron era. 5 , 6 Nevertheless, hybrid immunity seems to protect well against severe COVID-19 caused by omicron, at least in young populations.…”