COVID-19 vaccines

Since the roll-out of COVID-19 vaccines in late 2020 and throughout 2021, European governments have relied on mathematical modelling to inform policy decisions about COVID-19 vaccination.

We present a scenario-based modelling analysis in the Netherlands during summer 2021, to inform whether to extend vaccination to adolescents (12–17-year-olds) and children (5–11-year-olds).

We developed a deterministic, age-structured susceptible-exposed-infectious-recovered (SEIR) model and compared modelled incidences of infections, hospital and intensive care admissions, and deaths per 100,000 people across vaccination scenarios, before the emergence of the Omicron variant.

Our model projections showed that, on average, upon the release of all non-pharmaceutical control measures on 1 November 2021, a large COVID-19 wave may occur in winter 2021/22, followed by a smaller, second wave in spring 2022, regardless of the vaccination scenario. The model projected reductions in infections/severe disease outcomes when vaccination was extended to adolescents and further reductions when vaccination was extended to all people over 5 years-old. When examining projected disease outcomes by age group, individuals benefitting most from extending vaccination were adolescents and children themselves. We also observed reductions in disease outcomes in older age groups, particularly of parent age (30–49 years), when children and adolescents were vaccinated, suggesting some prevention of onward transmission from younger to older age groups.

While our scenarios could not anticipate the emergence/consequences of SARS-CoV-2 Omicron variant, we illustrate how our approach can assist decision making. This could be useful when considering to provide booster doses or intervening against future infection waves.

Data regarding the long-term protection afforded by vaccination for the SARS-CoV-2 infection are essential for allocation of scarce vaccination resources worldwide.

We conducted a retrospective cohort study aimed at studying the kinetics of IgG antibodies against SARS-CoV-2 in COVID-19-naïve patients fully vaccinated with two doses of Comirnaty mRNA COVID-19 vaccine. Geometric mean concentrations (GMCs) of antibody levels were reported. Linear models were used to assess antibody levels after full vaccination and their decline over time.

The study included 4,740 patients and 5,719 serological tests. Unadjusted GMCs peaked 28–41 days after the first dose at 10,174 AU/mL (95% CI: 9,211–11,237) and gradually decreased but remained well above the positivity cut-off. After adjusting for baseline characteristics and repeated measurements, the antibodies half-life time was 34.1 days (95% CI: 33.1–35.2), and females aged 16–39 years with no comorbidities had antibody levels of 20,613 AU/mL (95% CI: 18,526–22,934) on day 28 post-first-dose. Antibody levels were lower among males (0.736 of the level measured in females; 95% CI: 0.672–0.806), people aged 40–59 (0.729; 95% CI: 0.649–0.818) and ≥ 60 years (0.452; 95% CI: 0.398–0.513), and patients having haematological (0.241; 95% CI: 0.190–0.306) or solid malignancies (0.757; 95% CI: 0.650–0.881), chronic kidney disease with glomerular filtration rate (GFR) ≥ 30 (0.434; 95% CI: 0.354–0.532) or with GFR < 30 mL/min (0.176; 95% CI: 0.109–0.287), and immunosuppression (0.273; 95% CI: 0.235–0.317). Body mass index, cardiovascular disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes and inflammatory bowel diseases were not associated with antibody levels.

Vaccination with two doses resulted in persistently high levels of antibodies (≥ cut-off of 50 AU/mL) up to 137 days post-first-dose. Risk factors for lower antibody levels were identified.

Priority patients in England were offered COVID-19 vaccination by mid-April 2021. Codes in clinical record systems can denote the vaccine being declined.

We describe records of COVID-19 vaccines being declined, according to clinical and demographic factors.

With the approval of NHS England, we conducted a retrospective cohort study between 8 December 2020 and 25 May 2021 with primary care records for 57.9 million patients using OpenSAFELY, a secure health analytics platform. COVID-19 vaccination priority patients were those aged ≥ 50 years or ≥ 16 years clinically extremely vulnerable (CEV) or ’at risk’. We describe the proportion recorded as declining vaccination for each group and stratified by clinical and demographic subgroups, subsequent vaccination and distribution of clinical code usage across general practices.

Of 24.5 million priority patients, 663,033 (2.7%) had a decline recorded, while 2,155,076 (8.8%) had neither a vaccine nor decline recorded. Those recorded as declining, who were subsequently vaccinated (n = 125,587; 18.9%) were overrepresented in the South Asian population (32.3% vs 22.8% for other ethnicities aged ≥ 65 years). The proportion of declining unvaccinated patients was highest in CEV (3.3%), varied strongly with ethnicity (black 15.3%, South Asian 5.6%, white 1.5% for ≥ 80 years) and correlated positively with increasing deprivation.

Clinical codes indicative of COVID-19 vaccinations being declined are commonly used in England, but substantially more common among black and South Asian people, and in more deprived areas. Qualitative research is needed to determine typical reasons for recorded declines, including to what extent they reflect patients actively declining.

In July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe.

Using a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection.

Individuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination.

Overall VE was 74% (95% CI: 69–79), 76% (95% CI: 71–80), 63% (95% CI: 48–75) and 63% (95% CI: 16–83) among those aged 30–44, 45–59, 60–74 and ≥ 75 years, respectively. VE among those aged 30–59 years was 78% (95% CI: 75–81), 66% (95% CI: 58–73), 91% (95% CI: 87–94) and 52% (95% CI: 40–61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52–77), 65% (95% CI: 48–76) and 83% (95% CI: 64–92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30–59 years was 87% (95% CI: 83–89) at 14–29 days and 65% (95% CI: 56–71%) at ≥ 90 days between vaccination and onset of symptoms.

VE against symptomatic infection with the SARS-CoV-2 Delta variant varied among brands, ranging from 52% to 91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% at 90 days or more between vaccination and onset.

Omicron subvariant BA.2 circulation is rapidly increasing globally.

We evaluated the neutralising antibody response from vaccination or prior SARS-CoV-2 infection against symptomatic infection by BA.2 or other variants.

Using 50% plaque reduction neutralisation tests (PRNT50), we assessed neutralising antibody titres to BA.2, wild type (WT) SARS-CoV-2 and other variants in Comirnaty or CoronaVac vaccinees, with or without prior WT-SARS-CoV-2 infection. Titres were also measured for non-vaccinees convalescing from a WT-SARS-CoV-2 infection. Neutralising antibodies in BA.2 and BA.1 breakthrough infections and in BA.2 infections affecting non-vaccinees were additionally studied.

In vaccinees or prior WT-SARS-CoV-2-infected people, BA.2 and BA.1 PRNT50 titres were comparable but significantly (p < 10 ^− 5) lower than WT. In each group of 20 vaccinees with (i) three-doses of Comirnaty, (ii) two CoronaVac followed by one Comirnaty dose, or (iii) one dose of either vaccine after a WT-SARS-CoV-2 infection, ≥ 19 individuals developed detectable (PRNT50 titre ≥ 10) antibodies to BA.2, while only 15 of 20 vaccinated with three doses of CoronaVac did. Comirnaty vaccination elicited higher titres to BA.2 than CoronaVac. In people convalescing from a WT-SARS-CoV-2 infection, a single vaccine dose induced higher BA.2 titres than three Comirnaty (p = 0.02) or CoronaVac (p = 0.00001) doses in infection-naïve individuals. BA.2 infections in previously uninfected and unvaccinated individuals elicited low (PRNT50 titre ≤ 80) responses with little cross-neutralisation of other variants. However, vaccinees with BA.1 or BA.2 breakthrough infections had broad cross-neutralising antibodies to WT viruses, and BA.1, BA.2, Beta and Delta variants.

Existing vaccines can be of help against the BA.2 subvariant.

The start of the COVID-19 vaccination campaign among French healthcare and welfare sector workers in January 2021 offered an opportunity to study psychological antecedents of vaccination in this group.

We explored whether knowledge and attitude items related to social conformism and confidence in systems contributed to explaining intention for COVID-19 vaccination.

We developed a knowledge and attitude questionnaire with 30 items related to five established and two hypothetical psychological antecedents of vaccination (KA-7C). The online questionnaire was distributed from 18 December 2020 to 1 February 2021 through chain-referral via professional networks, yielding a convenience sample. We used multivariable logistic regression to explore the associations of individual and grouped KA-7C items with COVID-19 vaccine intention.

Among 5,234 participants, the vaccine intention model fit (pseudo R-squared values) increased slightly but significantly from 0.62 to 0.65 when adding social conformism and confidence in systems items. Intention to vaccinate was associated with the majority opinion among family and friends (OR: 11.57; 95% confidence interval (CI): 4.51–29.67) and a positive perception of employer’s encouragement to get vaccinated (vs negative; OR: 6.41; 95% CI: 3.36–12.22). The strongest association of a knowledge item was identifying the statement ‘Some stages of vaccine development (testing) have been skipped because of the epidemic emergency.’ as false (OR: 2.36; 95% CI: 1.73–3.22).

The results suggest that social conformism and confidence in systems are distinct antecedents of vaccination among healthcare and welfare workers, which should be taken into account in vaccine promotion.