Present UK vaccination coverage is to supply future COVID-19 booster doses to people at excessive threat of great sickness from COVID-19, however it’s nonetheless unsure which teams of the inhabitants may gain advantage most. In response to an pressing request from the UK Joint Committee on Vaccination and Immunisation, we aimed to determine threat components for extreme COVID-19 outcomes (ie, COVID-19-related hospitalisation or dying) in people who had accomplished their major COVID-19 vaccination schedule and had obtained the primary booster vaccine.
We constructed potential cohorts throughout all 4 UK nations by way of linkages of major care, RT-PCR testing, vaccination, hospitalisation, and mortality information on 30 million individuals. We included people who obtained major vaccine doses of BNT162b2 (tozinameran; Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccines in our preliminary analyses. We then restricted analyses to these given a BNT162b2 or mRNA-1273 (elasomeran; Moderna) booster and had a extreme COVID-19 end result between Dec 20, 2021, and Feb 28, 2022 (when the omicron (B.1.1.529) variant was dominant). We fitted time-dependent Poisson regression fashions and calculated adjusted charge ratios (aRRs) and 95% CIs for the associations between threat components and COVID-19-related hospitalisation or dying. We adjusted for a variety of potential covariates, together with age, intercourse, comorbidities, and former SARS-CoV-2 an infection. Stratified analyses had been performed by vaccine kind. We then did pooled analyses throughout UK nations utilizing fixed-effect meta-analyses.
Between Dec 8, 2020, and Feb 28, 2022, 16 208 600 people accomplished their major vaccine schedule and 13 836 390 people obtained a booster dose. Between Dec 20, 2021, and Feb 28, 2022, 59 510 (0·4%) of the first vaccine group and 26 100 (0·2%) of those that obtained their booster had extreme COVID-19 outcomes. The chance of extreme COVID-19 outcomes lowered after receiving the booster (charge change: 8·8 occasions per 1000 person-years to 7·6 occasions per 1000 person-years). Older adults (≥80 years vs 18–49 years; aRR 3·60 [95% CI 3·45–3·75]), these with comorbidities (≥5 comorbidities vs none; 9·51 [9·07–9·97]), being male (male vs feminine; 1·23 [1·20–1·26]), and people with sure underlying well being circumstances—specifically, people receiving immunosuppressants (sure vs no; 5·80 [5·53–6·09])—and people with persistent kidney illness (stage 5 vs no; 3·71 [2·90–4·74]) remained at excessive threat regardless of the preliminary booster. People with a historical past of COVID-19 an infection had been at lowered threat (contaminated ≥9 months earlier than booster dose vs no earlier an infection; aRR 0·41 [95% CI 0·29–0·58]).
Older individuals, these with multimorbidity, and people with particular underlying well being circumstances stay at elevated threat of COVID-19 hospitalisation and dying after the preliminary vaccine booster and will, due to this fact, be prioritised for added boosters, together with novel optimised variations, and the rising array of COVID-19 therapeutics.
Nationwide Core Research–Immunity, UK Analysis and Innovation (Medical Analysis Council), Well being Information Analysis UK, the Scottish Authorities, and the College of Edinburgh.
Three vaccines have primarily been used within the UK—specifically, BNT162b2 (tozinameran; Pfizer–BioNTech), ChAdOx1 nCoV-19 (Oxford–AstraZeneca), and mRNA-1273 (elasomeran; Moderna).
Within the UK, the first vaccination schedule is 2 doses for almost all of the inhabitants or three doses for people who find themselves immunosuppressed. Booster doses have been supplied within the UK since September, 2021, initially for teams at excessive threat of great sickness from COVID-19. Nevertheless, the fast emergence of the extra transmissible omicron (B.1.1.529) variant of concern (relative to delta [B.1.617.2])—which was first seen within the UK in late November, 2021, and have become the dominant variant by mid-December—led to appreciable concern in public, skilled, and authorities circles, leading to a coverage initiative to fast-track the roll-out of the booster vaccine, together with to youthful individuals (all these aged 40 years and older), in an try to stop yet one more UK-wide lockdown over Christmas, 2021. From Nov 29, 2021, booster doses had been then prolonged to these aged 18 years and over, with a advisable hole of three months after major vaccination.
Proof earlier than this research
We searched PubMed, medRxiv, and SSRN on June 27, 2022, for English research investigating extreme COVID-19 outcomes after vaccination utilizing the search phrases “COVID-19 breakthrough infections (MeSH)”, “COVID-19 vaccines (MeSH)”, and “COVID-19 (MeSH)”. Our searches recognized 133 research. Earlier proof has constantly proven that vaccination with the primary booster dose reduces the chance of SARS-CoV-2 an infection, and COVID-19-related hospitalisation and dying. An evaluation of nationwide information from Israel estimated first booster dose of BNT162b2 mRNA vaccine effectiveness of 92% (95% CI 82–97) towards extreme COVID-19. One other nationwide research from Qatar within the omicron period estimated vaccine effectiveness of BNT162b2 towards extreme COVID-19 as 77% (95% CI 56–88). We’ve got beforehand reported on threat components for extreme COVID-19 outcomes after first and second vaccine doses of the first schedule, however there’s little population-based proof concerning the components related to COVID-19-related hospitalisation and dying after the primary booster dose within the omicron period.
Added worth of this research
We discovered an elevated threat of extreme COVID-19 outcomes starting 10 weeks after finishing the first vaccination schedule, with this threat lowering after the primary booster dose. This UK-wide evaluation, along with confirming among the beforehand recognized threat components for extreme COVID-19 outcomes corresponding to older age and use of immunosuppressants, has additionally highlighted further threat components, corresponding to persistent kidney illness, neurological issues, coronary heart failure, and persistent obstructive pulmonary illness. Most significantly, we display a substantive elevated threat related to excessive multimorbidity.
Implications of all of the out there proof
Because the pandemic continues to evolve, vaccination programmes and mitigation methods have to evolve to prioritise these at highest threat of extreme COVID-19 outcomes. This UK-wide population-based investigation has discovered that, after the primary vaccine booster, older individuals, these with excessive multimorbidity, and people with sure underlying well being circumstances stay at highest threat of COVID-19-related hospitalisation and dying. The UK’s Joint Fee on Vaccination and Immunisation ought to think about prioritising these people for the forthcoming autumn booster dose programme, ideally with novel optimised vaccines, and COVID-19 therapeutics.
Work in Israel confirmed that, though a booster lowered the chance of extreme COVID-19 outcomes (ie, COVID-19-related hospitalisation or dying), these occasions continued at a charge of 1·68 occasions per 1000 person-years.
In one other research finished in Israel,
vaccine effectiveness of the primary booster dose towards extreme COVID-19 sickness was estimated to be 92%. In a research by Arbel and colleagues,
in contrast with people who weren’t boosted, COVID-19 mortality was lowered by 90% in people who obtained a booster dose. Though these research recommend that the primary booster dose has been useful, there’s little proof about components related to extreme COVID-19 outcomes within the boosted inhabitants.
reported that older age, multimorbidity, hospitalisation within the 4 weeks earlier than vaccination, working in a high-risk occupation, being a care dwelling resident, socioeconomic deprivation, being male, and being an ex-smoker elevated the chance of extreme COVID-19 outcomes after the primary dose of the first vaccination schedule. Nevertheless, this evaluation was finished when the alpha (B.1.1.7) variant was dominant. It’s essential to characterise components related to elevated threat for people after the primary booster dose in order that they are often prioritised for future boosters and doubtlessly even be supplied COVID-19 therapeutics.
Present UK vaccination coverage is to supply future booster doses to people at excessive threat, however it’s nonetheless unsure which teams of the inhabitants may gain advantage most.
In response to an pressing request from the UK’s Joint Fee on Vaccination and Immunisation (JCVI), we sought to explain the medical and demographic traits of people related to elevated threat of COVID-19-related hospitalisation and mortality at 14 days or extra after receiving the booster dose of the BNT162b2 or mRNA-1273 vaccine. Working with population-based information from throughout the UK’s 4 nations supplied us the chance to populate information gaps in particular person nation datasets (eg, for HIV) and generate exact estimates for uncommon threat teams.
Examine design and inhabitants
We used 4 close to real-time nationwide health-care datasets saved in separate safe Trusted Analysis Environments (TREs) in England, Northern Eire, Scotland, and Wales. Every of those datasets included info on medical and demographic traits of every particular person, their vaccination standing and kind of vaccine used, and data on constructive SARS-CoV-2 an infection from RT-PCR and subsequent COVID-19-related hospitalisation or dying. We had been unable to report on an infection locally setting based mostly on home-antigen testing that was not confirmed with RT-PCR.
Observe-up was from 14 days after finishing the first vaccination schedule till COVID-19-related hospitalisation, COVID-19-related dying, or the top of the research interval (ie, Feb 28, 2022). We excluded occasions that occurred inside the first 14 days after completion of the first vaccination schedule to permit time for a full immune response to be mounted.
For a similar purpose, the 14-day interval after a booster dose was counted because the publicity interval after the first vaccine dose.
In England, moral approval was granted by the Well being Analysis Authority London Central Analysis Ethics Committee (reference quantity REC reference 21/HRA/2786; built-in analysis utility system quantity 30174). In Northern Eire, research approval was granted by the Trustworthy Dealer Service (HBS) Governance Board (undertaking quantity 064; the HBS course of doesn’t require separate Nationwide Analysis Ethics Service governance approval). In Scotland, moral approval was granted by the Nationwide Analysis Ethics Service Committee (Southeast Scotland 02; reference quantity 12/SS/0201), and the approval for information linkage was granted by the Public Profit and Privateness Panel for Well being and Social Care (reference quantity 1920–0279). In Wales, analysis performed inside the Safe Anonymised Info Linkage Databank was finished with the permission and approval of the impartial Info Governance Assessment Panel (undertaking quantity 0911). Particular person written affected person consent was not required for this research.
used the Neighborhood Well being Index quantity, which is a novel identifier utilized in all health-care contacts throughout Scotland, to deterministically hyperlink major care information on 5·4 million individuals (round 99% of the inhabitants) from 940 common practices, secondary care information from Scottish Morbidity Report 01 and Speedy Preliminary Inpatient Information, laboratory information from Digital Communication of Surveillance in Scotland, vaccination standing information from the Turas Vaccination Administration Software, and mortality information from Nationwide Information of Scotland.
used Anonymised Info Linkage Discipline, masking 3·2 million people (total inhabitants), which is a pseudonymised distinctive identifier utilized in all health-care contacts throughout Wales, to hyperlink population-level major care data of 329 (84%) of 391 Common Practitioner practices throughout Wales, all hospital admissions, and RT-PCR testing outcomes for all the inhabitants from a cohort designed for finding out COVID-19-related outcomes.
Inhabitants traits and covariates
BMI, SARS-CoV-2 an infection earlier than the first dose of the vaccine (labeled as 10 assessments), the interval between first and second vaccine doses (labeled as 3–6 weeks, 7–8 weeks, 9–10 weeks, 11–12 weeks, and >13 weeks), health-care administrative areas (NHS areas in England, native councils in Northern Eire, and well being boards in Scotland and in Wales; outcomes for administrative areas should not proven on this Article), socioeconomic deprivation standing (based mostly on quintiles of Index of A number of Deprivation in England, Northern Eire A number of Deprivation Measure in Northern Eire, Scottish Index of A number of Deprivation in Scotland, and Welsh Index of A number of Deprivation in Wales
), and the variety of pre-existing comorbidities beforehand identified to be related to extreme COVID-19 end result (the variations in measurement between nations are detailed within the Strategies part within the appendix [p 10]).
The entire record of comorbidities included within the variety of pre-existing comorbidities and included as a part of the second evaluation is listed within the appendix (pp 8–9). We examined time since vaccination in durations of three–9 weeks, 10–19 weeks, and ≥20 weeks from completion of the first vaccination schedule, and three–5 weeks, 6–8 weeks, and 9 weeks or extra for the booster doses individually. To permit for variation in background ranges of group an infection, we cut up the info by calendar week. We examined RT-PCR check outcomes to find out what quantity of SARS-CoV-2-positive assessments every day had been because of the omicron variant. Information steered that omicron was dominant after Dec 14, 2021 (appendix p 2). We then included all of the occasions (extreme COVID-19 outcomes) after Dec 20, 2021, to permit for the identified lag between an infection and extreme outcomes.
circumstances beforehand recognized by QCOVID as excessive threat,
and the supply of knowledge inside every nationwide dataset. To calculate the RRs for 36 particular person comorbidities (in England, Scotland, and Wales), separate fashions had been fitted. These fashions adjusted for all of the aforementioned variables aside from the variety of pre-existing comorbidities.
All statistical analyses had been finished utilizing the statistical software program R: in England, R model 4.2.0 was used; in Northern Eire, R model 4.1.0 was used; in Scotland, R model 3.6.3 was used; and in Wales, R model 4.1.2 was used. Statistical analyses had been carried out in England by JO (and independently checked by SB and UA), in Northern Eire by LP (and independently checked by DTB), in Scotland by UA (and independently checked by CR), and in Wales by SB (and independently checked by FT).
Function of the funding supply
The funders of the research had no function in research design, information assortment, information evaluation, information interpretation, or writing of the report.
Desk 1Mixed pattern traits and charges of extreme COVID-19 outcomes for people who obtained major vaccine doses throughout England (N=11·4 million), Northern Eire (N=40 000), Scotland (N=3·1 million), and Wales (N=1·6 million)
Charges are per 1000 person-years.
Desk 2Mixed pattern traits and charges of extreme COVID-19 outcomes for people who obtained a booster dose, throughout England (N=9·7 million), Northern Eire (N=24 000), Scotland (N=2·7 million), and Wales (N=1·4 million)
Charges are per 1000 person-years.
Threat components related to extreme COVID-19 outcomes after receiving a booster dose had been just like these related to worse outcomes after completion of the first vaccination schedule. There was an elevated threat of extreme COVID-19 outcomes 9 weeks or extra after receiving a booster dose of BNT162b2 or mRNA-1273 vaccine (≥9 weeks vs 3–5 weeks; aRR 1·20 [95% CI 1·07–1·35]). People with a larger variety of comorbidities (≥5 comorbidities vs none; 9·51 [9·07–9·97]), who had been older (aged ≥80 years vs 18–49 years; 3·60 [3·45–3·75]), or who had been male (male vs feminine; 1·23 [1·20–1·26]) had been additionally related to elevated threat of extreme COVID-19 outcomes.
Desk 3Pooled analyses of Poisson-adjusted charge ratios for demographic and medical traits related to COVID-19-related hospitalisation or dying amongst people who obtained booster doses
Total estimates are proven in addition to these stratified by kind of vaccine at second dose.
This UK-wide evaluation has recognized those that stay liable to extreme COVID-19 outcomes after the primary vaccine booster dose. Our findings recognized threat components which were beforehand reported (eg, age and being immunosuppressed), however we additionally recognized a variety of further threat teams and highlighted the substantial elevated threat posed by multimorbidity. These threat components translated into each analyses in a dose-dependent method. Our outcomes confirmed that there have been advantages of the primary vaccine booster dose, indicated by the lowered charge of extreme COVID-19 outcomes after booster doses, altering from 8·8 occasions per 1000 person-years (59 510 complete occasions) to 7·6 occasions per 1000 person-years (26 100 complete occasions). Though decrease, this threat remains to be considerable in public well being phrases, necessitating consideration of additional booster doses, starting with these at highest threat. These insights now should be factored into plans for the roll-out of the autumn COVID-19 booster programme and people who needs to be prioritised for COVID-19 therapeutics.
Our choice to analyse population-based cohorts throughout totally different UK nations supplied the chance to fill information gaps current in particular person nations (eg, HIV exceptionalism within the devolved administrations). Extra strengths included our capacity to regulate for a variety of covariates, and the pooling of knowledge from throughout the UK, thereby permitting for precision of estimates for teams of sufferers with uncommon circumstances. Confining our evaluation to the interval throughout which omicron was dominant was an extra power.
Furthermore, a number of of the sooner hospital admissions within the research might need not been brought on by omicron, contemplating that no variant has ever been 100% dominant.
Our findings additionally recommend that every one teams aged 65 years and over had been at elevated threat of great outcomes relative to the reference group (aged 18–49 years), indicating the necessity to think about the second dose of booster in these older adults. Our evaluation is in settlement with findings from different work,
which has proven discount in extreme COVID-19 outcomes after booster. Our findings recommend that there have been round 8 extreme COVID-19 occasions per 1000 person-years, which is larger than the determine reported in a research in Israel.
Nevertheless, the timeframe of this research and that of Bar-On and colleagues
was totally different. The elevated threat of an infection and extreme COVID-19 outcomes seen as time elapsed since completion of the first vaccination schedule was corrected by the booster, and this waning of vaccine effectiveness displays present reported work.
discovered that earlier SARS-CoV-2 an infection was related to a lowered threat of extreme COVID-19, there’s a caveat that an infection with totally different variants may not confer the identical diploma of safety, and the population-scale roll-out of booster vaccines has precluded evaluation of earlier immunity owing to logistical challenges, which means that boosting stays applicable amongst people with earlier SARS-CoV-2 an infection in the intervening time. Nevertheless, as additional proof accumulates, the chance of extreme COVID-19 outcomes amongst people who had been beforehand contaminated with SARS-CoV-2 virus needs to be reassessed.
which confirmed that peak antibody responses had been seen within the first month after vaccination however then declined nearly four-fold over the next 10 weeks. Equally, post-booster antibody responses have been proven to peak, however immune waning then happens quickly, with one research
reporting a 5·5-fold lower in peak antibody titre inside 16 weeks. As a result of we didn’t have entry to serological information inside this research, we couldn’t decide if people with particular medical threat components mounted a full immune response after a booster, however a earlier research
has reported suboptimal immunological responses throughout lots of the teams recognized in our evaluation as being at elevated threat of extreme COVID-19 outcomes. Thus, there’s a want for follow-on work to research dangers of extreme COVID-19 outcomes after booster in those that have been proven to mount a full immunological response.
Our findings point out a variety of demographic and medical components related to elevated medical threat of extreme COVID-19 outcomes regardless of booster vaccination and lift questions relating to future approaches to reinforce safety. Elevated medical threat inside older individuals is just not surprising and is prone to replicate underlying frailty, comorbidity, and immune senescence. Certainly, this sample is seen with different respiratory viruses, regardless of the introduction of novel adjuvanted vaccine formulations. Immune senescence is a characteristic frequent to a number of threat teams and signifies that, regardless of sturdy immunogenicity, present COVID-19 vaccines can’t ship equal safety to all people. Future approaches ought to purpose to enhance vaccine immunogenicity and contain a variety of novel methods, together with variant-specific immunogenic brokers, introduction of viral proteins along with spike, and the incorporation of immunodominant mobile epitopes. Nevertheless, these approaches are unlikely to beat immune suppression in probably the most weak teams and for that purpose further approaches, corresponding to administration of anti-spike monoclonal antibodies and antivirals, also needs to be thought-about.
These findings have been shared with JCVI and the Chief Medical Officers and Chief Scientific Advisers of the UK nations and are actually being thought-about because the UK plans its autumn COVID-19 booster vaccine programme. This evaluation has helped to generate well timed insights that are actually getting used to assist determine and prioritise people most certainly to profit from second vaccine boosters and COVID-19 therapeutics. Coverage makers is not going to solely want to think about this proof (and every other proof) on threat teams, but in addition the logistical facets of administering booster doses to a considerable proportion of the UK’s inhabitants.
There’s a want to research immunological responses to vaccination in those that have been recognized as being at excessive threat after a primary booster dose. Our plan is to proceed to analyse information on uptake and influence of second dose boosters because the vaccine programme proceeds.
In abstract, this UK-wide, population-based evaluation has discovered that people who obtained their first booster vaccination had been at lowered threat of COVID-19-related hospitalisation or dying in contrast with those that had solely accomplished their major vaccination schedule. Older age, these with the next variety of comorbid circumstances, and people with a variety of particular underlying circumstances had been, nonetheless, discovered to be at elevated threat of extreme COVID-19 outcomes and would possibly notably profit from further, preferentially novel, COVID-19 boosters, pre-exposure prophylaxis, and COVID-19 therapeutics.
AS, CRS, CR, and LR conceived the unique EAVE II research. AS conceived this research. UA and CMC led the writing of the paper and edited the ultimate manuscript with assist from AS, SB, ZG, and AA-L. SdL and MJ conceived how Analysis and Surveillance Centre information may help this research and are the guarantors of those information; JO performed these analyses, JO; and SdL, MJ, and RSMT added the evaluation on information from England to the paper. LP and DTB had been chargeable for information cleansing, and LP contributed to the evaluation in Northern Eire. UA accessed and verified the underlying information and is chargeable for information cleansing and evaluation in Scotland. SB accessed and verified the underlying information and is chargeable for information cleansing and evaluation in Wales. CR oversaw all of the analyses. All authors contributed to the research design and all authors contributed to drafting the paper and revised the manuscript for necessary mental content material. All authors have seen and authorised the ultimate textual content and gave last approval of the model to be printed.
Declaration of pursuits
AS and CR are members of the Scottish Authorities Chief Medical Officer’s COVID-19 Advisory Group. AS is a member of the Scottish Authorities’s Standing Committee on Pandemic Preparedness, the UK Authorities’s New and Rising Respiratory Virus Threats Advisory Group (referred to as NERVTAG) Threat Stratification Subgroup, the Division of Well being and Social Care’s COVID-19 Therapeutics Modelling Group, and was a member of AstraZeneca’s COVID-19 Strategic Thrombocytopenia Taskforce. All AS’s roles are unfunded. CMC experiences analysis funding from the Medical Analysis Council, Well being Information Analysis UK, the Nationwide Institute for Well being and Care Analysis, and the Scottish Chief Scientist Workplace. SVK was Co-Chair of the Scottish Authorities’s Skilled Reference Group on COVID-19 and ethnicity and is a member of the SAGE subgroup on ethnicity. SVK acknowledges funding from an NRS Senior Medical Fellowship (SCAF/15/02), the Medical Analysis Council (MC_UU_00022/2), and the Scottish Authorities Chief Scientist Workplace (SPHSU17). CR is a member of the Scientific Pandemic Influenza Group on Modelling, Medicines and Healthcare merchandise Regulatory Company Vaccine Profit and Threat Working Group. SdL obtained funding by way of his college for vaccine-related analysis from AstraZeneca, GSK, Sanofi, Seqirus, and Takeda. He has been a member of advisory boards for AstraZeneca, Sanofi, and Seqirus, and is Director of the Analysis and Surveillance Centre. All different authors declare no competing pursuits.
This work was funded by the Nationwide Core Research–Immunity group. This analysis is a part of the Information and Connectivity Nationwide Core Examine, led by Well being Information Analysis UK in partnership with the Workplace for Nationwide Statistics and funded by UK Analysis and Innovation (grant ref MC_PC_20060), with help from the DaC-VaP-2 research additionally funded by UK Analysis and Innovation (grant ref MC_PC_20058). The research entitled “Use of nationwide linked well being care, serological information, and viral genomic information to determine and characterise post-third and -booster dose vaccine breakthroughs at a inhabitants stage” is a partnership between the College of Edinburgh, Swansea College, Oxford College, Queen’s College of Belfast, College of St Andrews, and The Workplace for Nationwide Statistics. The authors want to acknowledge all different undertaking collaborators not concerned in these analyses however who’re contributing to wider discussions and previous outputs. EAVE II is funded by the Medical Analysis Council (MR/R008345/1) with the help of BREATHE–The Well being Information Analysis Hub for Respiratory Well being (MC_PC_19004), which is funded by way of the UK Analysis and Innovation Industrial Technique Problem Fund and is delivered by way of Well being Information Analysis UK. Extra help has been offered by way of Public Well being Scotland and Scottish Authorities Director-Common Well being and Social Care. We thank Dave Kelly from Albasoft for his help with making major care information out there, and James Pickett, Wendy Inglis-Humphrey, Vicky Hammersley, Maria Georgiou, Laura Gonzalez Rienda, Pam McVeigh, Amanda Burridge, Sumedha Asnani-Chetal, and Afshin Dastafshan for his or her help with undertaking administration and administration. We acknowledge the help of the EAVE II Affected person Advisory Group. We thank the sufferers and follow of the Analysis and Surveillance Centre who permit information sharing, and EMIS, TPP, Cegedim, and Wellbeing for assist with pseudonymised information extraction. Rachel Byford and the ORCHID information group extracted these information, and Sneha N Anand undertaking managed. We additionally acknowledge the assistance from Paul Moss and Samantha Lycett for in answering the opinions. The authors want to acknowledge the assistance offered by the employees of the Trustworthy Dealer Service inside the Enterprise Providers Organisation Northern Eire (BSO). The Trustworthy Dealer Service is funded by the BSO and the Division of Well being for Northern Eire. The authors alone are chargeable for the interpretation of the info and any views or opinions offered are solely these of the authors and don’t essentially symbolize these of the BSO.
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