COVID-19 Vaccination Effectiveness in the Population of Friuli Venezia Giulia, North-East Italy. Control of Bias Associated with Divergent Compliance to Policies in a Test-negative Case-control Study

Overview

Journal BMC Public Health

Publisher Biomed Central

Specialty Public Health

Date 2023 Dec 11

PMID 38082276

Authors

Valentina Rosolen

Federico Turoldo

Gianna Zamaro

Flavio Del Bianco

Patrizio Pezzotti

Luigi Castriotta

Fabio Barbone

Affiliations

Soon will be listed here.

Abstract

Background: Vaccine effectiveness (VE) studies consolidate knowledge of real-world effectiveness in different contexts. However, methodological issues may undermine their conclusions: to assess the VE against COVID-19 within the Italian population, a specific threat to validity is related to the consequences of divergent compliance to the Green Pass policy.

Methods: To address this challenge we conducted a test negative case-control (TNCC) study and multiple sensitivity analysis among residents aged ≥ 12 in Friuli Venezia Giulia Region (FVG), North-east Italy, from February 1, 2021 to March 31, 2022. Information regarding 211,437 cases of COVID-19 infection and 845,748 matched controls was obtained from the regional computerized health database. The investigation considered: COVID-19 infection, hospitalization, and death. Multiple conditional logistic regressions adjusted for covariates were performed and VE was estimated as (1-OR COVID-19)x100. Mediation analyses were carried out to offset potential collider variables, particularly, the number of swabs performed after the introduction of pandemic restrictions.

Results: Full-cycle VE against infection decreased from 96% (95% CI: 96, 97) in the Alpha period to 43% (95% CI: 42, 45) in the Omicron period. Booster dose raised the protection in Omicron period to 67% (95% CI: 66, 67). Against the evasive Omicron variant, the protection of the booster dose was 87% (95% CI: 83, 90) for hospitalization and 90% (95% CI: 82, 95) for death. The number of swabs performed was included as a covariate in the adjustments, and the mediation analysis confirmed that it was a strong mediator between vaccination and COVID-19-related outcomes.

Conclusions: The study suggests that, under similar TNCC settings, mediation analysis and adjustment for number of diagnostic tests should be included, as an effective approach to the challenge of differential testing behavior that may determine substantial selection bias. This correction allowed us to align with results from other studies that show how full-cycle VE against infection was initially high but decreased over time by variant circulation, counterbalanced by booster dose that raised protection across variants and outcome severity.

References

Sheikh A, McMenamin J, Taylor B, Robertson C . SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet. 2021; 397(10293):2461-2462. PMC: 8201647. DOI: 10.1016/S0140-6736(21)01358-1. View

Sullivan S, Tchetgen Tchetgen E, Cowling B . Theoretical Basis of the Test-Negative Study Design for Assessment of Influenza Vaccine Effectiveness. Am J Epidemiol. 2016; 184(5):345-53. PMC: 5013887. DOI: 10.1093/aje/kww064. View

Patel M, Bergeri I, Bresee J, Cowling B, Crowcroft N, Fahmy K . Evaluation of post-introduction COVID-19 vaccine effectiveness: Summary of interim guidance of the World Health Organization. Vaccine. 2021; 39(30):4013-4024. PMC: 8166525. DOI: 10.1016/j.vaccine.2021.05.099. View

Suarez Castillo M, Khaoua H, Courtejoie N . Vaccine-induced and naturally-acquired protection against Omicron and Delta symptomatic infection and severe COVID-19 outcomes, France, December 2021 to January 2022. Euro Surveill. 2022; 27(16). PMC: 9027152. DOI: 10.2807/1560-7917.ES.2022.27.16.2200250. View

Acuti Martellucci C, Flacco M, Soldato G, Di Martino G, Carota R, Caponetti A . Effectiveness of COVID-19 Vaccines in the General Population of an Italian Region before and during the Omicron Wave. Vaccines (Basel). 2022; 10(5). PMC: 9146679. DOI: 10.3390/vaccines10050662. View

Montanari Vergallo G, Rio A, Negro F, Zaami S . COVID-19 vaccine mandates: what are the current European public perspectives?. Eur Rev Med Pharmacol Sci. 2022; 26(2):643-652. DOI: 10.26355/eurrev_202201_27891. View

Flacco M, Soldato G, Acuti Martellucci C, Carota R, Di Luzio R, Caponetti A . Interim Estimates of COVID-19 Vaccine Effectiveness in a Mass Vaccination Setting: Data from an Italian Province. Vaccines (Basel). 2021; 9(6). PMC: 8227269. DOI: 10.3390/vaccines9060628. View

Fabiani M, Puopolo M, Morciano C, Spuri M, Spila Alegiani S, Filia A . Effectiveness of mRNA vaccines and waning of protection against SARS-CoV-2 infection and severe covid-19 during predominant circulation of the delta variant in Italy: retrospective cohort study. BMJ. 2022; 376:e069052. PMC: 8829820. DOI: 10.1136/bmj-2021-069052. View

Chang S, Liu H, Wu J, Xiao W, Chen S, Qiu S . Effectiveness of BNT162b2 and mRNA-1273 Vaccines against COVID-19 Infection: A Meta-Analysis of Test-Negative Design Studies. Vaccines (Basel). 2022; 10(3). PMC: 8954872. DOI: 10.3390/vaccines10030469. View

10.

Grgic Vitek M, Klavs I, Ucakar V, Serdt M, Mrzel M, Vrh M . Vaccine effectiveness against severe acute respiratory infections (SARI) COVID-19 hospitalisations estimated from real-world surveillance data, Slovenia, October 2021. Euro Surveill. 2022; 27(1). PMC: 8739341. DOI: 10.2807/1560-7917.ES.2022.27.1.2101110. View

11.

Pearce N . Analysis of matched case-control studies. BMJ. 2016; 352:i969. PMC: 4770817. DOI: 10.1136/bmj.i969. View

12.

Shao W, Chen X, Zheng C, Liu H, Wang G, Zhang B . Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern in real-world: a literature review and meta-analysis. Emerg Microbes Infect. 2022; 11(1):2383-2392. PMC: 9542696. DOI: 10.1080/22221751.2022.2122582. View

13.

Tseng H, Ackerson B, Luo Y, Sy L, Talarico C, Tian Y . Effectiveness of mRNA-1273 against SARS-CoV-2 Omicron and Delta variants. Nat Med. 2022; 28(5):1063-1071. PMC: 9117141. DOI: 10.1038/s41591-022-01753-y. View

14.

VanderWeele T, Tchetgen Tchetgen E . Mediation Analysis With Matched Case-Control Study Designs. Am J Epidemiol. 2016; 183(9):869-70. PMC: 4851996. DOI: 10.1093/aje/kww038. View

15.

Corrao G, Rea F, Di Martino M, De Palma R, Scondotto S, Fusco D . Developing and validating a novel multisource comorbidity score from administrative data: a large population-based cohort study from Italy. BMJ Open. 2017; 7(12):e019503. PMC: 5770918. DOI: 10.1136/bmjopen-2017-019503. View

16.

Riccardo F, Ajelli M, Andrianou X, Bella A, Del Manso M, Fabiani M . Epidemiological characteristics of COVID-19 cases and estimates of the reproductive numbers 1 month into the epidemic, Italy, 28 January to 31 March 2020. Euro Surveill. 2020; 25(49). PMC: 7730489. DOI: 10.2807/1560-7917.ES.2020.25.49.2000790. View

17.

Lipsitch M, Jha A, Simonsen L . Observational studies and the difficult quest for causality: lessons from vaccine effectiveness and impact studies. Int J Epidemiol. 2016; 45(6):2060-2074. PMC: 5841615. DOI: 10.1093/ije/dyw124. View

18.

Griffith G, Morris T, Tudball M, Herbert A, Mancano G, Pike L . Collider bias undermines our understanding of COVID-19 disease risk and severity. Nat Commun. 2020; 11(1):5749. PMC: 7665028. DOI: 10.1038/s41467-020-19478-2. View

19.

Rijnhart J, Lamp S, Valente M, MacKinnon D, Twisk J, Heymans M . Mediation analysis methods used in observational research: a scoping review and recommendations. BMC Med Res Methodol. 2021; 21(1):226. PMC: 8543973. DOI: 10.1186/s12874-021-01426-3. View