Immunogenicity and real-world effectiveness of COVID-19 vaccines in Lebanon: Insights from primary and booster schemes, variants, infections, and hospitalization

Abstract

In this study, we conducted a case-control investigation to assess the immunogenicity and effectiveness of primary and first booster homologous and heterologous COVID-19 vaccination regimens against infection and hospitalization, targeting variants circulating in Lebanon during 2021-2022. The study population comprised active Lebanese military personnel between February 2021 and September 2022. Vaccine effectiveness (VE) against laboratory-confirmed SARS-CoV-2 infection and associated hospitalization was retrospectively determined during different variant-predominant periods using a case-control study design. Vaccines developed by Sinopharm, Pfizer, and AstraZeneca as well as Sputnik V were analyzed. Prospective assessment of humoral immune response, which was measured based on the SARS-CoV-2 antispike receptor binding domain IgG titer, was performed post vaccination at various time points, focusing on Sinopharm and Pfizer vaccines. Statistical analyses were performed using IBM SPSS and GraphPad Prism. COVID-19 VE remained consistently high before the emergence of the Omicron variant, with lower estimates during the Delta wave than those during the Alpha wave for primary vaccination schemes. However, vaccines continued to offer significant protection against infection. VE estimates consistently decreased for the Omicron variant across post-vaccination timeframes and schemes. VE against hospitalization declined over time and was influenced by the variant. No breakthrough infections progressed to critical or fatal COVID-19. Immunogenicity analysis revealed that the homologous Pfizer regimen elicited a stronger humoral response than Sinopharm, while a heterologous Sinopharm/Pfizer regimen yielded comparable results to the Pfizer regimen. Over time, both Sinopharm's and Pfizer's primary vaccination schemes exhibited decreased humoral immunity titers, with Pfizer being a more effective booster than Sinopharm. This study, focusing on healthy young adults, provides insights into VE during different pandemic waves. Continuous research and monitoring are essential for understanding vaccine-mediated immune responses under evolving circumstances.

Fig 1. COVID-19 in Lebanon: The daily number of COVID-19 cases throughout the waves of the pandemic in Lebanon and associated SARS-CoV-2 variants between January 2021 and September 2022.

Reference: Edouard Mathieu, Hannah Ritchie, Lucas Rodés-Guirao, Cameron Appel, Charlie Giattino, Joe Hasell, Bobbie Macdonald, Saloni Dattani, Diana Beltekian, Esteban Ortiz-Ospina and Max Roser (2020)—"Coronavirus Pandemic (COVID-19)". Published online at OurWorldInData.org. Retrieved from: ’https://ourworldindata.org/coronavirus’ [Online Resource]. N.B.: X-axis: month-year; Y-axis left: number of confirmed daily cases. In this study, we examined vaccine effectiveness during five periods of high or peak circulation of SARS-CoV-2 variants [–24]: 1. SARS-CoV-2 Alpha cases: Personnel were categorized as such if they initially tested positive between February 21st, 2021, and May 31st, 2021, as the majority of cases in Lebanon were primarily attributable to the circulating Alpha variant during that period. 2. SARS-CoV-2 Delta cases: Personnel were classified as such if they first tested positive between July 21st, 2021, and November 7th, 2021, as the majority of cases in Lebanon were predominantly attributable to the circulating Delta variant during that time. 3. SARS-CoV-2 Mixed (Delta and Omicron (B.1.1.529)) cases: Personnel fell into this category if they first tested positive between November 8th, 2021, and December 31st, 2021. This period represented an overlap between two variants, with residual Delta infection incidence in the community alongside the gradual increase in Omicron infections. 4. SARS-CoV-2 Omicron (B.1.1.529, sublineages BA.1, BA.1.1, or BA.2) cases: Personnel were designated as such if they first tested positive between January 1st, 2022, and March 7th, 2022, as these sub-lineages predominantly circulated during that time frame. 5. SARS-CoV-2 Omicron (B.1.1.529, sublineages BA.4 or BA.5) cases: Personnel were identified as such if they first tested positive between June 21st, 2022, and September 7th, 2022, as these sub-lineages predominantly circulated during that period.

Fig 2. Study profile.

Abbreviations: VE = vaccine effectiveness, SPh = Sinopharm (BBIBP-CorV), AZ = AstraZeneca (ChAdOx1 nCoV-19), PFZ = Pfizer-BioNTech (BNT162b2), SPTV = Sputnik V (Gam-COVID-Vac).

Fig 3

Effectiveness of the available COVID-19 vaccination schemes against laboratory-confirmed infections during the (A) Alpha variant wave, (B) Delta variant wave, (C) Mixed Delta and Omicron BA.1 variant wave,(D) BA.1/BA.2 Omicron variant wave, and (E) BA.4/BA.5 Omicron variant wave. Abbreviations: AZ = AstraZeneca (ChAdOx1 nCoV-19), mo = months, PFZ = Pfizer-BioNTech (BNT162b2), SPh = Sinopharm (BBIBP-CorV), SPTV = Gamaleya’s Sputnik V (Gam-COVID-Vac), VE = vaccine effectiveness. N.B. Data are presented as effectiveness point estimates, with error bars indicating the corresponding 95% confidence intervals.

Fig 4

Effectiveness of the available COVID-19 vaccination schemes against acute-care hospitalization attributed to laboratory-confirmed infections during the (A) Alpha variant wave, (B) Delta variant wave, (C) Mixed Delta and Omicron BA.1 variant wave, and (D) BA.1/BA.2 Omicron variant wave. Abbreviations: AZ = AstraZeneca (ChAdOx1 nCoV-19), mo = months, PFZ = Pfizer-BioNTech (BNT162b2), SPh = Sinopharm (BBIBP-CorV), SPTV = Gamaleya’s Sputnik V (Gam-COVID-Vac), VE = vaccine effectiveness. N.B. Data are presented as effectiveness point estimates, with error bars indicating the corresponding 95% confidence intervals.

Fig 5. Humoral immune responses to SARS-CoV-2 spike protein following various primary vaccination schemes and booster doses with Sinopharm or Pfizer vaccines among COVID-19-naïve participants at different time points.

Abbreviations: IgG = immunoglobulin G, BAU = Binding Antibody Unit, mo = months, PFZ = Pfizer-BioNTech (BNT162b2), SPh = Sinopharm (BBIBP-CorV). N.B: The initial measurement for anti-S-IgG was deemed negative if the index was < 1.00 (seronegative) and positive if the index was ≥ 1.00 (seropositive). All readings were standardized to BAU/mL using the WHO international standard for the VIDAS®3 SARS-CoV-2 IgG (VIDAS®3 SARS-CoV-2 IgG index = 1 (cutoff) = 20.33 BAU/mL). Antibody titers were reported as geometric mean titers (GMT) with corresponding 95% confidence intervals (CIs). One-sample Kolmogorov–Smirnov test was used to assess data distribution normality. Kruskal–Wallis test, followed by Dunn’s multiple comparison post-hoc test, was used to compare unpaired nonparametric data among the groups (antibody levels). ns (not significant), P > 0.05, *: P ≤ 0.05, ***: P ≤ 0.001, ****: P ≤ 0.0001.