BREAKING Agrawal et al.: “Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals

Agrawal et al.: Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales

Key summary finding:

This UK-wide analysis has identified those who remain at risk of severe COVID-19 outcomes after the first vaccine booster dose. Our findings identified risk factors that have been previously reported (eg, age and being immunosuppressed), but we also identified a range of additional risk groups and highlighted the substantial increased risk posed by multimorbidity. These risk factors translated into both analyses in a dose-dependent manner.
General methods:
Constructed prospective cohorts across all four UK nations through linkages of primary care, RT-PCR testing, vaccination, hospitalization, and mortality data on 30 million people. We included individuals who received primary vaccine doses of BNT162b2 (tozinameran; Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccines in our initial analyses. We then restricted analyses to those given a BNT162b2 or mRNA-1273 (elasomeran; Moderna) booster and had a severe COVID-19 outcome between Dec 20, 2021, and Feb 28, 2022 (when the omicron (B.1.1.529) variant was dominant).’
Key statements and results that were and are worrisome as the push remains for boosters:
i)“16 208 600 (over 16 million) individuals aged 18 years and older had received primary doses of COVID-19 vaccines in England, Northern Ireland, Scotland, or Wales between Dec 8, 2020, and Feb 28, 2022, and were followed up until hospitalisation, death, or the end of the study period.”
ii)“There was an increased risk of severe COVID-19 outcomes 10 weeks after completing the primary doses of BNT162b2 or ChAdOx1 nCoV-19 (≥20 weeks vs 3–9 weeks; aRR 4·55 [95% CI 4·16–4·99]). Individuals with a greater number of comorbidities (≥5 comorbidities vs none; 7·98 [7·73–8·24], who were older (aged ≥80 years vs 18–49 years; 8·12 [7·89–8·35]), who had a higher BMI (≥40 vs 18·5–24·9; 1·75 [1·69–1·82]), or who were male (male vs female; 1·19 [1·17–1·21]) were also associated with increased risk of severe COVID-19 outcomes.”
iii)“Individuals with a history of SARS-CoV-2 infection (infected ≥9 months before the booster dose vs no previous infection) were found to be at reduced risk of severe COVID-19 outcomes (0·38 [0·29–0·49].”
Pay attention to the above statement iii)
iv)“13 836 390 individuals received a booster vaccine of BNT162b2 or mRNA-1273 and were followed up until hospitalization, death, or the end of the study period on Feb 28, 2022. In the period after booster vaccination, 26 100 (0·2%; 7·6 events per 1000 person-years) individuals had severe COVID-19 outcomes. 10 439 820 individuals received the booster dose of Pfizer (BNT162b2) and 3 396 570 individuals received the booster dose of Moderna (mRNA-1273), leading to 2360 and 23 740 severe COVID-19 outcomes, respectively.”
v)“Risk factors associated with severe COVID-19 outcomes after receiving a booster dose were similar to those associated with worse outcomes after completion of the primary vaccination schedule.”
vi)“There was an increased risk of severe COVID-19 outcomes 9 weeks or more after receiving a booster dose of Pfizer (BNT162b2) or Moderna (mRNA-1273) vaccine (≥9 weeks vs 3–5 weeks; aRR 1·20 [95% CI 1·07–1·35]). Individuals with a greater number of comorbidities (≥5 comorbidities vs none; 9·51 [9·07–9·97]), who were older (aged ≥80 years vs 18–49 years; 3·60 [3·45–3·75]), or who were male (male vs female; 1·23 [1·20–1·26]) were also associated with increased risk of severe COVID-19 outcomes.”
Critical statement vi)
vii) “There was a protective effect among individuals with a history of SARS-CoV-2 infection (infected ≥9 months before booster dose vs no previous infection; aRR 0·41 [95% CI 0·29–0·58]). Individuals with increasing multimorbidity were associated with increased risk of severe COVID-19 outcomes (two vs none, aRR 3·35 [95% CI 3·21–3·50]; three vs none, 4·78 [4·56–5·00]; four vs none, 6·34 [6·03–6·66]).”
viii) “The presence of any of the underlying conditions of interest was associated with an increased risk of severe COVID-19 outcomes. This risk was particularly high among those receiving immunosuppressants (yes vs no; aRR 5·80 [95% CI 5·53–6·09]), individuals with a history of a rare neurological condition (yes vs no; 5·30 [4·90–5·74]), and individuals with chronic kidney disease (chronic kidney disease stage 5 vs no; 3·71 [2·90–4·74].” Figure 3 below.
Figure 3: Pooled analyses of Poisson-adjusted rate ratios for specific clinical risk factors associated with COVID-19-related hospitalisation or death among individuals who received booster doses of mRNA-1273 or BNT162b2