Vaccine Effectiveness, Burden and Impact Studies (VEBIS) - Vaccine effectiveness hospital admission with Severe Acute Respiratory Infection

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)
• Data collection methods:
  Primary data collection

Non-interventional study

• Non-interventional study design:
  Case-control

Study drug and medical condition

• Name of medicine:
  COMIRNATY

  JCOVDEN

  NUVAXOVID

  SPIKEVAX

  VAXZEVRIA
• Study drug International non-proprietary name (INN) or common name:
  COVID-19 MRNA VACCINE (NUCLEOSIDE-MODIFIED)

  COVID-19 VACCINE (RECOMBINANT, ADJUVANTED)

  DAVESOMERAN

  ELASOMERAN

  IMELASOMERAN

  RAXTOZINAMERAN

  TOZINAMERAN
• Anatomical Therapeutic Chemical (ATC) code:
  (J07BN01) covid-19, RNA-based vaccine

  covid-19, RNA-based vaccine

  (J07BN02) covid-19, viral vector, non-replicating

  covid-19, viral vector, non-replicating

  (J07BN04) covid-19, protein subunit

  covid-19, protein subunit
• Medical condition to be studied:
  COVID-19

  Influenza
• Additional medical condition(s):
  Severe Acute Respiratory Infection (SARI)

Population studied

• Short description of the study population:
  This hospital-based vaccine effectiveness study was conducted primarily in countries with pre-existing SARI surveillance systems, to facilitate the recruitment of patients. Therefore, the study population comprised individuals of all ages who belonged to the target group for vaccination, were hospitalised with SARI symptoms in participating hospitals/services and had no contraindication for COVID-19 vaccination.
• Age groups:
  • Paediatric Population (< 18 years)

    • Neonate

      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
    • Children (2 to < 12 years)
    • Adolescents (12 to < 18 years)
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  5500

Study design details

• Study design:
  This is a multi-centre, hospital-based, test-negative, case–control study, using pooled data from several countries.
• Main study objective:
  The primary objective of this vaccine effectiveness study is:; • To measure, within each European participating country and in a pooled, multi-country analysis, the direct effect (effectiveness) of overall and product-specific COVID-19 vaccines against SARI due to laboratory confirmed SARS-CoV-2 in hospitalised patients, in order to provide up-to-date information on the ability of COVID-19 vaccines to prevent severe disease under real conditions of use.
• Setting:
  All SARI patients who consented to participate (where this is a requirement) and were not part of the exclusion; criteria were included in the study. Patients were not enrolled in the study if they:; • were unwilling to participate or unable to communicate and give consent (the consent could also have been provided by their legal representative or by specific consent procedures that are acceptable according to the; local ethical review process);; • had a contraindication for the COVID-19 vaccine;; • could not be swabbed due to severe septum deviation, obstruction or other conditions that contraindicate;; or; • had a history of hospitalisation within the 14 days immediately prior to this admission (including transfers from other hospitals).; Patients were not included in this analysis if they:; • were living in a long-term care facility;; • had errors in vaccination dates (e.g. first dose date was later than second dose date) or a non-recommended delay between the doses for two-dose regimens (<21 days for Comirnaty, <28 days for Vaxzevria or; Spikevax);; • had onset of SARI symptoms >3 days after their swab;; • were swabbed >10 days after symptom onset; or; • received the first or second vaccine dose within 14 days of symptom onset.
• Comparators:
  An individual was considered vaccinated against COVID-19 with a product-specific vaccine under the following; categories:; • Fully vaccinated with the primary series (two-dose vaccine): patients were considered fully vaccinated if they received both doses at least 14 days* before symptom onset (whether homologous or heterologous vaccine products were received).; • Fully vaccinated with the primary series (single-dose vaccine): patients were considered fully vaccinated if they received one dose at least 14 days* before symptom onset.; • Fully vaccinated with the primary series plus booster: patients were considered fully vaccinated with the primary series plus booster if they were fully vaccinated (according to the definitions above), followed by a booster dose at least 14 days* before symptom onset.; • Partially vaccinated (two-dose vaccine): patients were considered partially vaccinated if they received only one of the two primary series doses at least 14 days* before symptom onset or received the second dose on the same day as or after symptom onset.; • Unvaccinated: patients were considered unvaccinated if they did not receive a COVID-19 vaccine or if they were vaccinated on the same day as or after symptom onset.; The period between December 2021 and September 2022 was used as a proxy for the Omicron-dominant period, using GISAID data to define week numbers for each participating country when ≥80% or <80% sequenced samples belonged to the Omicron variant.
• Outcomes:
  The outcome of interest for the primary analysis was SARS-CoV-2 infection that was laboratory confirmed by RT-PCR (documented either on admission to hospital or within 14 days before admission) in patients of all ages who were hospitalised with SARI symptoms
• Data analysis plan:
  The vaccine effectiveness estimated in this analysis was among hospitalised SARI patients aged 20 years and older, who were swabbed between 20 December 2021 and 30 September 2022. Vaccine effectiveness for fully vaccinated with the primary series plus booster was calculated relative to unvaccinated patients. Relative vaccine effectiveness for fully vaccinated with the primary series plus booster was calculated relative to patients who were fully vaccinated with the primary series (single or two-dose vaccination).; Vaccine effectiveness is calculated as 1 minus the odds ratio (OR), where the OR is estimated from logistic regression (OR is the ratio of the odds of being vaccinated among cases over the odds of being vaccinated among controls). Study site (country) was included in the logistic regression as a fixed effect, with date of swab modelled as swab month (as a categorical variable) or as a restricted cubic spline of swab date. Additional adjustments included sex, age group (as a categorical variable), and at least one of four commonly collected chronic conditions (diabetes, heart disease, lung disease and asthma). For the age-specific vaccine effectiveness estimates, SARI patients were stratified into three age groups: 20–59 years, 60–79 years and ≥80 years. For time-since vaccination-specific vaccine effectiveness estimates, vaccinated SARI patients were stratified into 14-59 days, 60-119 days, 120-179 days, 180-239 days and 240-299 days since booster dose vaccination. ; To avoid sparse data bias, vaccine effectiveness estimates were not calculated where the total number of vaccinated cases and controls was fewer than 20.