key: cord-0796227-4t8sa7be authors: Quattrocchi, Annalisa; Tsioutis, Constantinos; Demetriou, Anna; Kyprianou, Theopisti; Athanasiadou, Maria; Silvestros, Valentinos; Mamais, Ioannis; Demetriou, Christiana A.; Theophanous, Fani; Soteriou, Soteroulla; Gregoriadou, Chryso; Anastasiou, Eleni; Kolios, Panayiotis; Ηaralambous, Christos; Gregoriou, Ioanna; Kalakouta, Olga; Nikolopoulos, Georgios title: Effect of vaccination on SARS-CoV-2 reinfection risk: a case-control study in the Republic of Cyprus date: 2022-01-20 journal: Public Health DOI: 10.1016/j.puhe.2022.01.008 sha: 0c5b982e448f0f55cd775ff10951b2e251e9dd2a doc_id: 796227 cord_uid: 4t8sa7be Objectives We explored the effectiveness of COVID-19 vaccines in preventing reinfection in the Republic of Cyprus. Study design Matched case-control study (1:2). Methods Cases were adults with a first episode of SARS-CoV-2 infection in 2020 and a second episode (i.e., reinfection) between June-August 2021. Controls were adults with only one infection episode in 2020 (i.e., not reinfected). Matching was performed by age, gender, and week of diagnosis for first episode. The reinfection date of a case was applied to the matched controls for estimating full or partial vaccination status. Cases and controls were classified as unvaccinated, partially vaccinated (i.e., vaccination series not completed or final dose received ≤14 days before the reinfection date) or fully vaccinated (i.e., final dose received >14 days before the reinfection date). Conditional logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (CI) for full or partial vaccination, against no vaccination, between controls and cases. Results This study showed that controls were more likely to be vaccinated (OR for full vaccination: 5.51, 95% CI: 2.43-12.49) than cases. Conclusions This finding answers a pressing question of the public and supports the offer of vaccination to people with previous SARS-CoV-2 infection. Reinfection rates following initial acquisition of SARS-CoV-2, the virus that causes COVID-19, seem to be low 1 . This could be explained, at least partly, by the establishment of immunological memory after SARS-CoV-2 infection 2 , although questions are still lingering regarding the long-lasting protection from clinical disease. Vaccines have further shielded human populations due to their high effectiveness against COVID-19 infection, hospitalization and death 3 . The emergence of variants, the predominance of the more infectious Delta SARS-CoV-2 variant of concern (1.617.2), and waning humoral immunity pose significant challenges on the level of vaccination coverage that is needed to impede viral spread. Nevertheless, vaccines continue to offer, at the moment, high-level protection from hospitalization and death 4 . As the pandemic progresses and transmission continues to occur, the likelihood of reinfection increases. We have previously reported a reinfection rate of 0.08% among COVID-19 cases diagnosed in Cyprus until February 2021, within a median period of 7 months after first infection 5 . Public Health England reported a cumulative 1.2% reinfection rate between April and June 2021, with higher risk of reinfection >6 months after the first episode due to the Delta variant 6 . More recently, a reinfection rate around 1%, due to Delta variant, has been confirmed in the UK by the Scientific Advisory Group for Emergencies (https://www.gov.uk/government/publications/sage-99-minutes-coronavirus-covid-19response-16-december-2021). Given the above, we sought to explore the effectiveness of vaccines in preventing reinfection in the Republic of Cyprus. During the COVID-19 pandemic, the Unit for Surveillance and Control of Conditional logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (CI) for full vaccination or partial vaccination (against no vaccination) in controls vs. cases. Furthermore, stratified analysis was performed by vaccine brands (Pfizer-BioNTech, which was delivered to the majority of the population, and all other brands combined). For all analyses, Stata v.16 was used. During the study period (Table 1) . Among cases, 7.5% and 8.6% were partially vaccinated and fully vaccinated, respectively, compared with 12.9% and 32.8% of controls. A total of 9 individuals were admitted to hospitals during the study period; 8 patients were from control group and 1 from the cases group (4.3% vs. 1.1%, p=0.151). Considering all vaccine brands, the odds of full vaccination were 4.5 times greater in controls than in cases (n = 233; OR = 5.51; 95% CI = 2.43-12.49). Similarly, partial vaccination was almost twice as likely in controls than in cases (n = 193, OR = 2.60; 95% CI = 1.05-6.47) ( Table 1) . Vaccination decreases the likelihood of infection and offers high-level protection from severe disease; thus, increasing vaccination coverage has allowed societies to resume activity. The spread of the Delta variant has altered the course of the pandemic, leading to a significant surge in many settings in the summer of 2021, including Cyprus, and increasing the necessary level of population immunity to limit viral spread. The dynamics of long-term protection through natural immunity remain largely unknown; despite evidence for establishment of immune memory 2 , waning of neutralizing antibody levels raise the potential for reinfection. the Pfizer-BioNTech vaccine, which was primarily used in Cyprus, and for the other vaccines combined, though statistical significance was not reached in the latter case probably due to the smaller sample size. Of interest, in our analysis, the estimated reinfection risk for the unvaccinated was higher. A recent study from the basic sciences field also showed that the neutralization capacity of antibodies of vaccinated individuals with previous SARS-CoV-2 infection was better than that of people who got the vaccine without previous exposure to the virus 8 . The Delta variant is considered an immune evasive variant with an increased risk of reinfection. Hence, our findings are even more timely given the fact that the reinfections in this study were observed during the surge of the Delta wave in Cyprus. It is likely that the synergy of natural and vaccine-generated immunity provides stronger and broader immune responses than what is expected including against multiple variants 9 . The interpretation of our results is subject to certain limitations. Possible bias could be due to inconsistencies in the matching variables between the different registries of vaccination and surveillance. Lack of genomic sequencing data did not allow the confirmation of suspected reinfections. In addition, small numbers precluded risk analysis for hospitalization. Furthermore, although Cyprus has a high testing rate per population, as of 10 May 2021, testing became thereafter a requirement for unvaccinated persons to resume certain activities 10 ; this may have led to sampling bias, thus overestimating the ORs in our analyses. In conclusion, our findings support the benefit of vaccination for persons previously infected with SARS-CoV-2. While access to vaccination has increased, public health actions should be directed towards maximizing protection among vaccine-eligible individuals. The study was approved by the Cyprus Bioethics Committee (approval number ΕΕΒΚ ΕΠ 2021.01.197, October 7 th , 2021). This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. None declared J o u r n a l P r e -p r o o f and their 95% confidence intervals (CI), from conditional regression, refer to odds of full or partial vaccination (against no vaccination) in controls (without reinfection from SARS-CoV-2) vs. cases (with reinfection). °Cases were considered fully vaccinated if a complete COVID-19 vaccine series was received >14 days before the cases' reinfection date. Cases were considered partially vaccinated if ≥1 dose of vaccine was received, but the vaccination series was either not completed or the final dose was received ≤14 days before their reinfection date. For control participants, the same criteria were applied, using the matched case's reinfection date. SARS-CoV-2 re-infection risk in Austria SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months. The New England journal of medicine Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study SARS-CoV-2 reinfection in patients recovered from COVID-19 in the Republic of Cyprus SARS-CoV-2 Variants of Concern and Variants of Interest -Technical briefing 19 Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination -Kentucky Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity High genetic barrier to SARS-CoV-2 polyclonal neutralizing antibody escape SafePassˮ Decision as of 10 May