#17,061
Later today I'm scheduled to get the COVID bivalent booster, and I expect it will provide me with some substantial (albeit, temporary) protection over this fall and winter. Combined with my recent flu vaccination - and my decision to continue to wear face masks in public venues - I'm about as protected as I can reasonably hope to be.
But it is no guarantee that I'll come away unscathed.
People of my age (> 65) are simply at greater risk (from flu & COVID) than most younger adults. We mount a less robust immune response to vaccines in general, and have more comorbidities. While we are fairly easy to identify and target for boosters, there are other - often less well defined groups - at greater risk from COVID as well.
All of which brings us to a Lancet report, released today, which utilizes the massive nationwide health-care datasets maintained by Trusted Research Environments (TREs) in England, Northern Ireland, Scotland, and Wales, to better define who benefits most from COVID booster vaccines.
They describe their study cohort as:
Our cohorts consisted of individuals aged 18 years and older who had completed their primary vaccine schedule (first and second doses) with BNT162b2 (Pfizer) or ChAdOx1 (Moderna) nCoV-19 vaccines only or had subsequent booster doses of BNT162b2 or mRNA-1273 vaccines between Dec 8, 2020, and Feb 28, 2022.
And their primary focus:
Using data on more than 16 million UK residents > 18 who had received at least the two primary mRNA vaccinations - and more than 13 million who received a booster - researchers kept track of outcomes (hospitalisations and/or deaths) until the end of the study period on Feb 28, 2022.We sought to describe the clinical and demographic characteristics and estimate risk factors for individuals who had severe COVID-19 outcomes after completing the primary vaccination schedule or subsequent booster dose during the period when the omicron variant was dominant.
We found an increased risk of severe COVID-19 outcomes beginning 10 weeks after completing the primary vaccination schedule, with this risk reducing after the first booster dose.This UK-wide analysis, in addition to confirming some of the previously identified risk factors for severe COVID-19 outcomes such as older age and use of immunosuppressants, has also highlighted additional risk factors, such as chronic kidney disease, neurological disorders, heart failure, and chronic obstructive pulmonary disease. Most importantly, we demonstrate a substantive increased risk associated with high multimorbidity.
This is a lengthy, detailed, and at times technical report and those interested in the fine points will want to follow the link to read it in its entirety. I've reproduced the summary below, and will have a brief postscript after the break.
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
Utkarsh Agrawal, PhD † Stuart Bedston, PhD † Prof Colin McCowan, PhD † Jason Oke, PhD † Lynsey Patterson, PhD † Prof Chris Robertson, PhD † et al.
Open Access Published:October 15, 2022 DOI:https://doi.org/10.1016/S0140-6736(22)01656-7
Summary
BackgroundCurrent UK vaccination policy is to offer future COVID-19 booster doses to individuals at high risk of serious illness from COVID-19, but it is still uncertain which groups of the population could benefit most. In response to an urgent request from the UK Joint Committee on Vaccination and Immunisation, we aimed to identify risk factors for severe COVID-19 outcomes (ie, COVID-19-related hospitalisation or death) in individuals who had completed their primary COVID-19 vaccination schedule and had received the first booster vaccine.
MethodsWe constructed prospective cohorts across all four UK nations through linkages of primary care, RT-PCR testing, vaccination, hospitalisation, 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). We fitted time-dependent Poisson regression models and calculated adjusted rate ratios (aRRs) and 95% CIs for the associations between risk factors and COVID-19-related hospitalisation or death. We adjusted for a range of potential covariates, including age, sex, comorbidities, and previous SARS-CoV-2 infection. Stratified analyses were conducted by vaccine type. We then did pooled analyses across UK nations using fixed-effect meta-analyses.FindingsBetween Dec 8, 2020, and Feb 28, 2022, 16 208 600 individuals completed their primary vaccine schedule and 13 836 390 individuals received a booster dose. Between Dec 20, 2021, and Feb 28, 2022, 59 510 (0·4%) of the primary vaccine group and 26 100 (0·2%) of those who received their booster had severe COVID-19 outcomes. The risk of severe COVID-19 outcomes reduced after receiving the booster (rate change: 8·8 events per 1000 person-years to 7·6 events per 1000 person-years). Older adults (≥80 years vs 18–49 years; aRR 3·60 [95% CI 3·45–3·75]), those with comorbidities (≥5 comorbidities vs none; 9·51 [9·07–9·97]), being male (male vs female; 1·23 [1·20–1·26]), and those with certain underlying health conditions—in particular, individuals receiving immunosuppressants (yes vs no; 5·80 [5·53–6·09])—and those with chronic kidney disease (stage 5 vs no; 3·71 [2·90–4·74]) remained at high risk despite the initial booster. Individuals with a history of COVID-19 infection were at reduced risk (infected ≥9 months before booster dose vs no previous infection; aRR 0·41 [95% CI 0·29–0·58]).InterpretationOlder people, those with multimorbidity, and those with specific underlying health conditions remain at increased risk of COVID-19 hospitalisation and death after the initial vaccine booster and should, therefore, be prioritised for additional boosters, including novel optimised versions, and the increasing array of COVID-19 therapeutics.
(SNIP)
Discussion (Excerpt)
Our findings indicate a range of demographic and clinical factors associated with increased clinical risk of severe COVID-19 outcomes despite booster vaccination and raise questions regarding future approaches to enhance protection. Increased clinical risk within older people is not unexpected and is likely to reflect underlying frailty, comorbidity, and immune senescence. Indeed, this pattern is seen with other respiratory viruses, despite the introduction of novel adjuvanted vaccine formulations. Immune senescence is a feature common to several risk groups and indicates that, despite strong immunogenicity, current COVID-19 vaccines cannot deliver equivalent protection to all individuals. Future approaches should aim to improve vaccine immunogenicity and involve a range of novel strategies, including variant-specific immunogenic agents, introduction of viral proteins in addition to spike, and the incorporation of immunodominant cellular epitopes. However, these approaches are unlikely to overcome immune suppression in the most vulnerable groups and for that reason additional approaches, such as administration of anti-spike monoclonal antibodies and antivirals, should also be considered.These findings have been shared with JCVI and the Chief Medical Officers and Chief Scientific Advisers of the UK nations and are now being considered as the UK plans its autumn COVID-19 booster vaccine programme. This analysis has helped to generate timely insights that are now being used to help identify and prioritise individuals most likely to benefit from second vaccine boosters and COVID-19 therapeutics. Policy makers will not only need to consider this evidence (and any other evidence) on risk groups, but also the logistical aspects of administering booster doses to a substantial proportion of the UK's population.There is a need to investigate immunological responses to vaccination in those who have been identified as being at high risk after a first booster dose. Our plan is to continue to analyse data on uptake and impact of second dose boosters as the vaccine programme proceeds.In summary, this UK-wide, population-based analysis has found that individuals who received their first booster vaccination were at reduced risk of COVID-19-related hospitalisation or death compared with those who had only completed their primary vaccination schedule. Older age, those with a higher number of comorbid conditions, and those with a range of specific underlying conditions were, however, found to be at increased risk of severe COVID-19 outcomes and might particularly benefit from additional, preferentially novel, COVID-19 boosters, pre-exposure prophylaxis, and COVID-19 therapeutics.
Just counting those over 64 years of age, there are nearly 55 million Americans who automatically fall into the `high risk' category from COVID (and flu). Yet uptake (thus far) of the bivalent COVID booster at this writing is just shy of 15 million (27.7%), and more than half of adults recently polled indicated little interest in getting the seasonal flu vaccine this year.
Add in the continued reduced effectiveness of many COVID therapeutics due to the emergence of newer Omicron variants, and you could have the recipe for a difficult winter ahead.
Stay tuned. It could be a bumpy ride.
