Nationwide Swedish study strengthens evidence for a third booster COVID vaccine dose

Vaccines are effective against coronavirus disease 2019 (COVID-19) and protect from the risk of infection and severe illness and death. However, breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have raised concerns about waning vaccine effectiveness.

Several studies indicate that vaccines protect against severe illness up to 6 months after vaccination. There are, however, few reports of vaccine effectiveness beyond six months.

A nationwide study from Sweden investigates the effectiveness of COVID-19 vaccination against the risk of symptomatic infection, hospitalization, and death up to 9 months post-vaccination. This study is published on the Preprints with The Lancet website while awaiting peer review.

Vaccine effectiveness data

Clinical studies have demonstrated high efficacy of the BNT162b2 (Pfizer-BioNTech), mRNA1273 (Moderna), and ChAdOx1 nCoV-19 (Oxford/AstraZeneca) COVID-19 vaccines. Further observational studies have evaluated high real-world effectiveness. However, there are reports of waning vaccine effectiveness against symptomatic infection.

Currently, there is some indication of waning vaccine effectiveness against infection up to 6 months post-vaccination. However, protection against severe illness appears to be maintained.

The evidence is limited and inconsistent because of evaluations of different vaccines that may have variable long-lasting effects, a low proportion of old participants in the studies, and varying and relatively short follow-up times.

A retrospective study

This new retrospective cohort study was conducted using Swedish nationwide registries. The 3,640,421 individuals included in the study were vaccinated with at least one dose of any COVID-19 vaccine (ChAdOx1 nCoV-19, BNT162b2, or mRNA-1273) in Sweden until 26 May 2021 and 1,331,989 had a confirmed infection until 24 May 2021.

Statistics Sweden, the national agency for statistics, randomly sampled one individual from the total population of Sweden and matched them according to the birth year, sex and municipality. These matched individuals had neither been vaccinated nor infected with COVID-19 on the date of first vaccination dose or infection of the matched vaccinated individual. This total population of 5,833,003 individuals was updated concerning vaccination status and SARS-CoV-2 infections until 4 October 2021.

From this total cohort, each fully vaccinated individual was matched to one randomly sampled unvaccinated individual with respect to birth year and sex. This cohort comprised 1,684,958 individuals forming 842,974 matched pairs.

Description of selection of the cohort.

Description of selection of the cohort.

Another cohort formed using less strict matching criteria resulted in 3,966,630 individuals forming 1,983,315 pairs.

Data on individuals were collected from the Swedish Vaccination Register and SmiNet register managed by the Public Health Agency of Sweden. These registries have a 100% coverage of the total population.

Data on cases of symptomatic infection and severe COVID-19, i.e., hospitalization or 30-day mortality after confirmed infection, were collected from 12 January to 4 October 2021.

Vaccine effectiveness data from Sweden

Within the study group, it was observed that the vaccinated individuals more often had homemaker service, were more often born in Sweden, had more medical diagnoses, and had a higher level of education when compared to unvaccinated individuals. The term homemaker refers to domestic services provided to individuals (primarily elderly individuals) who live at home but need help with shopping, cleaning, meal preparation, and similar tasks.

Vaccine effectiveness of BNT162b2 against infection waned progressively from 92% at day 15-30 to 47% at day 121-180 to no effectiveness from day 211 onwards. This waning was slightly slower for mRNA-1273.

The effectiveness of mRNA-1273 was 59% from day 181 onwards. The effectiveness of ChAdOx1 nCoV-19 was lower and waned faster, with no effectiveness detected from day 121 onwards, showing a negative value of effectiveness, -19%. This means that the unvaccinated individuals were more protected than the ChAdOx1 nCoV-19 vaccinated individuals. However, effectiveness from heterologous ChAdOx1 nCoV19 / mRNA-1273 was 66% and was maintained from 121 days onwards.

In this study, vaccine effectiveness was lower and waned faster among men and older individuals. Vaccine effectiveness against severe COVID-19 waned from 89% at day 15-30 to 42% from day 181 onwards.

This waning effectiveness was notable among men, older frail individuals, individuals with comorbidities, and ChAdOx1 nCoV-19 vaccine.

Limitations of the study

It is possible that the study included individuals with previous asymptomatic infections. This would confound the results of the investigation. If these individuals happened to be in the unvaccinated cohort, their natural immunity due to a previous infection might have attenuated the estimated vaccine effectiveness. In addition, the infection pressure during the study period was low. This would also attenuate the estimated vaccine effectiveness.

Implications of the study

The findings of this study strengthen the evidence-based rationale for the administration of a booster dose, prioritizing the individuals at high risk of severe illness and death. Thus, these findings may have implications for vaccination strategies and public health policies.

*Important notice

Preprints are early-stage research papers that have not been peer-reviewed. Therefore, the findings should not be used for clinical or public health decision-making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed.