Table 1.
Summary of findings based on each study
| First author (reference) | Type of study | Study population (N) | Male (%) | Mean age (SD) | Type | Time after vaccination | Changes in antibody level s | Vaccine efficacy against | Author’s opinion about booster dose | Summary of findings | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Infection | Disease severity | Mortality | ||||||||||
| A.Erice(19) Spain, 2021 |
Observational study | Adults | 62% | 46.0 years (SD 11.4 years) | mRNA vaccine | Serum samples were obtained a mean of 40.1 days (SD 2.8 days) and 88.8 days (SD 2.8 days) after the second dose of BNT162b2 | Median [IQR] anti-RBD titres 1.5 months after vaccination were 9,356 [5,844 - 16,876] AU/mL; three months after vaccination, median anti-RBD titres had declined to 3,952 [2,190 - 8,561] AU/mL (p <0.001) | Advanced severe COVID-19 has been reported in fully vaccinated individuals a median of 39.5 days after the second dose of BNT162b2 | A low anti-RBD antibody titer is one aspect related tothe advanced SARS-CoV-2 infection after complete vaccination with BNT162b2 | |||
| J.Favresse(20) Belgium, 2021 |
Ongoing multicenter, prospective, and interventional study | Healthcare professionals | 22.5 | 43 | mRNA COVID-19 vaccine | 3 months | The maximal antibody response was reached between days 28 and 42 (2204 versus 1,863; P = 0.20), with a 48.8–57.7-fold increase compared to day 14 (i.e. 38.2 U/mL) | As calculated by the one-compartmental model, the estimated half-life of antibodies observed from data collected until 90 days after vaccination for seronegative members was 55 days (95% CI: 37–107 days) | ||||
| W.Gou(21) China, 2021 |
Clinical trial | Healthy adults aged ≥18 | 41.1 and 59.5 in twoage groups | The mean (standard deviation) age was 43.1 (9.6) years in participants aged 18–59 years and 66.7 (4.3) in those aged ≥60 years (79.2% aged 60–69 years) | Inactivated | 90 days | Geometric mean titerof neutralizing antibody on day 90 after the third injection ranged from 87 to 129, respectively, among participants receiving three doses of vaccines | The initial results of the Phase 1/2 trial among adults, including those aged 60 years or older, showed that the inactivated vaccine against SARS-CoV-2 was safe and immunogenic. | ||||
| J.F. Hedges(24) USA, 2021 |
Cohort | 41.8 | mRNA | 6 months | The neutralization titers had declined 6 months after vaccination,similar to 6 months after natural infection. | The antibody responses induced by vaccination were significantly higher than those induced by natural infection. Therefore, the study suggests that vaccination is still vital, even for those naturally infected or diagnosed with COVID-19. | ||||||
| P.Naaber(16) Estonia, 2021 |
Longitudinal observational | Healthcare workers | 42 | 42.5 | mRNA | 6 months | In the first serum sample, the median anti-S-RBD IgG reached 540.0 AU/mL (IQR 64.5-1102.0). In the following tests, a progressive decay of antibodies was seen, up to the value of 55.7 AU/mL (IQR 26.2-84.7) at the 6-month follow-up | This study may allow to define a protective antibody threshold, below which the risk of break-through infections significantly increases and which could, hence, guide the time point when to offer a booster dose. | The study approves the persistence of anti-S-RBD neutralizing antibodies through 6 months after the vaccination. | |||
| M.Pouquet(26) France, 2021 |
Longitudinal survey | Health care workers | RNA-based vaccines | 6 months | ||||||||
| E. Terpos(18) | Prospective study | Health care workers | 32.9 | 48 | mRNA | 3 months | Three months after the second vaccination (i.e., on D111), the decline in NAb titers was even more prominent with a median inhibition of 92.7% (SD 11.8) | The longitudinal study is continuing in order to determine the time point of NAbs decrease below the positivity threshold, and the fading of protective immunity against COVID-19; when a booster vaccine dose might be necessary. | Both NAbs and anti-S-RBD antibodies, the maximum levels are seen at day 36. A statistically significant decrease in both types of antibodies was observed after day36 up to day111 | |||
| S. J. Thomas(9) 6 countries, USA, Turkey, Germany, South Africa, Brazil, Argentina; 2021 |
Clinical trial | Adolescents and adults | 50.9 | 51 | mRNA | 6 months | Vaccine efficacy of 91.1% | BNT162b2 effectively prevents COVID-19 for up to 6 months after the second dose across various populations, despite the emergence of SARS-CoV-2 variants, including the beta variant, and the vaccine continues to show a promising safety profile. | ||||
| M. Tré-Hardy(17) Belgium, 2021 |
Prospective study | Health care workers | 25.4 | 50.1 | mRNA | 5 months | Antibody values went from 400 [400-400] AU/mL at 3 months after first injection to 221.0 [202.3-241.2] AU/mL at 6 months after first injection, and from 400 [400-400] AU/mL at to 400 [365.0-400] AU/mL at | Introducing a booster dose, under certain circumstances, could have a significant impact in terms of public health | All applicants still had detectable SARS-CoV-2 IgG antibodies up to 5 months after complete vaccination. | |||
| I.Vicenti(27) Italy, 2021 |
Longitudinal study | Health care workers (HCWs) | 39.1 | mRNA | 3 months | Previously infected vaccinated HCWs (n=23): 546 Uninfected vaccinated HCWs (n=13): 20 |
In uninfected HCWs completing the two-dose vaccine program, a third mRNA vaccine dose is a sensible option to counteract the substantial NtAb decline occurring at a significantly higher rate compared with previously infected, vaccinated HCWs | Median NtAb at V2_90 (90±2 days after the second dose) was still significantly higher than median NtAb at V_0 (before receiving the first dose) both in HCWs with past mild disease (p=0.01) and in those experiencing asymptomatic infection (p=0.001). |
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| I.Waldhorn(22) Israel, 2021 |
Prospective follow-up report of the primary study | Cancer patients with solid tumors | 55 | 66 | mRNA | 166 ± 29 days | Both cohorts depicted a drastic decline in serology titer over time,but the titer remained above the threshold value | There was no notable difference in the median absolute serology titer between the seropositive individuals within the two cohorts (patients vs. controls). | ||||
| K. Zakaria(25) Kazakhstan, 2021 |
Clinical trial | Adults aged 18 years and older | 77.3 | 28 | Inactivated whole-virion | 6 months | An increase in the titers of neutralizing antibody was statistically significant, reaching Geometric Mean Titer of 5.1 (95% CI 3·5–7·6) on day 21 and Geometric Mean Titer of 100 (95% CI 77–129) on day 42. On day180 after the first immunization, the Geometric Mean Titer dropped to 7 (95% CI 5–7) | In both trials, specific antibodies were detected in MNA and ELISA on study day 180, but the titers dropped in comparison today 42. | ||||
SD: standard deviation; IQR: interquartile range; CI: confidence interval; S-RBD: spike protein receptor-binding domain; Ig: Immunoglobulin;NAb/NtAb: neutralizing antibody; MNA:microneutralization assay; ELISA:enzyme-linked immunosorbent assay.