Immune protection against SARS-CoV-2 re-reinfection and immune imprinting

Author:

Chemaitelly HiamORCID,Ayoub Houssein H.ORCID,Tang PatrickORCID,Hasan Mohammad R.,Coyle PeterORCID,Yassine Hadi M.ORCID,Al-Khatib Hebah A.ORCID,Smatti Maria K,Al-Kanaani ZainaORCID,Al-Kuwari EinasORCID,Jeremijenko AndrewORCID,Kaleeckal Anvar HassanORCID,Latif Ali Nizar,Shaik Riyazuddin MohammadORCID,Abdul-Rahim Hanan F.ORCID,Nasrallah Gheyath K.ORCID,Al-Kuwari Mohamed GhaithORCID,Butt Adeel A.,Al-Romaihi Hamad EidORCID,Al-Thani Mohamed H.ORCID,Al-Khal Abdullatif,Bertollini RobertoORCID,Abu-Raddad Laith J.ORCID

Abstract

AbstractWe investigated epidemiological evidence for immune imprinting by comparing incidence of re-reinfection in the national cohort of individuals with a documented Omicron (BA.1/BA.2) reinfection after a pre-Omicron primary infection (designated as the reinfection cohort), to incidence of reinfection in the national cohort of individuals with a documented Omicron (BA.1/BA.2) primary infection (designated as the primary-infection cohort). This was done using a matched, retrospective cohort study that emulated a randomized “target trial”. Vaccinated individuals were excluded. Associations were estimated using Cox proportional-hazard regression models. Cumulative incidence of infection was 1.1% (95% CI: 0.8-1.4%) for the reinfection cohort and 2.1% (95% CI: 1.8-2.3%) for the primary-infection cohort, 135 days after the start of follow-up. The adjusted hazard ratio (aHR) for infection was 0.52 (95% CI: 0.40-0.68), comparing incidence in the reinfection cohort to that in the primary-infection cohort. The aHR was 0.59 (95% CI: 0.40-0.85) in a subgroup analysis in which primary infection in the reinfection cohort was restricted to only the index virus or Alpha variant. In the first 70 days of follow-up, when incidence was dominated by BA.2, the aHR was 0.92 (95% CI: 0.51-1.65). However, cumulative incidence curves diverged when BA.4/BA.5 subvariants dominated incidence (aHR, 0.46 (95% CI: 0.34-0.62)). There was no evidence that immune imprinting compromises protection against Omicron subvariants. However, there was evidence that having two infections, one with a pre-Omicron variant followed by one with an Omicron subvariant, elicits stronger protection against future Omicron-subvariant reinfection than having had only one infection with an Omicron subvariant.

Publisher

Cold Spring Harbor Laboratory

Reference46 articles.

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