Evidence before this study

We searched PubMed, medRxiv, and SSRN on May 27, 2021, for studies using free text and related MeSH terms for hospital admission following COVID-19 vaccination, using the terms “COVID-19 breakthrough infections”, “COVID-19 vaccines (MeSH)”, and “COVID-19 (MeSH)”. We only considered studies published in English. A study in Israel on 596 618 individuals who received the BNT162b2 (Pfizer–BioNTech) vaccine reported that 110 vaccinated individuals were admitted to hospital and there were nine deaths due to COVID-19 up to 42 days after vaccination. However, nearly all individuals (96%) in the study received a second dose of vaccination (95% of participants received the second dose before day 24). Public Health England reported that 9% of people aged 80 years or older who tested positive for COVID-19 after a first dose of BNT162b2 vaccine and 7% of people who received a first dose of the ChAdOx1 (Oxford–AstraZeneca) vaccine were subsequently admitted to hospital for COVID-19. A preprint study in northwest London followed up 389 587 people for an average of 29 days after the first dose of vaccine, with 288 patients admitted to hospital (155 in the first 14 days after vaccination). A separate report of the ISARIC/CO-CIN study in the UK reported that, since the start of the vaccination programme, one in 25 people admitted to hospital for COVID-19 had received at least one vaccine dose. Of the 42 788 people recruited to this study since Dec 8, 2020, 4·2% had been vaccinated (1685 with one dose and 27 with two doses), with a median time from vaccination to admission to hospital of 10 days.

Added value of this study

This national-level analysis found that at 14 days or longer since the first vaccine dose, there were 883 COVID-19 admissions to hospital and 541 deaths in almost 2·57 million individuals in Scotland. Older age, increasing number of underlying comorbidities, recent admission to hospital, being in a high-risk occupation, being a care home resident, being male, being socioeconomically deprived, and being an ex-smoker were all associated with an increased risk of severe post-vaccine COVID-19 events. By contrast, previous COVID-19 infection had a protective effect.

Implications of all the available evidence

The rollout of the COVID-19 vaccination programme was associated with low numbers of post-vaccination serious COVID-19 outcomes at 14 days or longer since vaccination. Whether the same degree of protection is maintained beyond the analysed period of follow-up and once lockdown measures are lifted remains to be seen. As the rollout of vaccination programmes continues worldwide, there is a need to identify those at increased risk of breakthrough infections and identify mechanisms to reduce those risks. The benefits of an expedited second dose compared with a longer gap between vaccinations are unclear, as there is potential longer-term gain from an enhanced immune response with a longer interval between the doses.