Do people with medical comorbidities require a booster dose of COVID-19 vaccine?

The following information resources have been selected by the National Health Library and Knowledge Service Evidence Virtual Team in response to a question from the National Immunisation Advisory Committee (NIAC). The resources are listed in our estimated order of relevance to practicing healthcare professionals confronted with this scenario in an Irish context.  In respect of the evolving global situation and rapidly changing evidence base, it is advised to use hyperlinked sources in this document to ensure that the information you are disseminating to the public or applying in clinical practice is the most current, valid and accurate. For further information on the methodology used in the compilation of this document ¾ including a complete list of sources consulted ¾ please see our National Health Library and Knowledge Service Summary of Evidence Protocol.

Download Full Summary of Evidence (PDF)

Irish and/or International Guidance

Joint Committee on Vaccination and Immunisation (Great Britain) (14 September 2021) JCVI statement regarding a COVID-19 booster vaccine programme for winter 2021 to 2022^[1]

The Joint Committee on Vaccination and Immunisation (JCVI) has been asked by the Secretary of State for Health and Social Care in the UK to consider the options for and timing of a booster programme to re-vaccinate adults in order to reduce mortality, morbidity and hospitalisations from COVID-19 over the 2021 to 2022 winter period as well as to minimise the COVID-19 case infection rate and the chance of new variants emerging.

JCVI advises that for the 2021 COVID-19 booster vaccine programme individuals who received vaccination in Phase 1 of the COVID-19 vaccination programme ¾ priority groups 1 to 9 ¾ should be offered a third dose COVID-19 booster vaccine. This includes:

• those living in residential care homes for older adults
• all adults aged 50 years or over
• frontline health and social care workers
• all those aged 16 to 49 years with underlying health conditions that put them at higher risk of severe COVID-19 ¾ eg those with chronic respiratory, cardiac, liver or neurological disorders, individuals with diabetes or severe mental illness, morbidly obese individuals, or younger adults in long-term care ¾ and their adult carers
• adult household contacts (aged ³16 years) of immunosuppressed individuals

Food and Drug Administration (FDA) (United States) (22 September 2021) [Press Release] FDA Authorizes Booster Dose of Pfizer-BioNTech COVID-19 Vaccine for Certain Populations^[2]

On 22 September, 2021, the US Food and Drug Administration amended the emergency use authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine to allow for use of a single booster dose to be administered at least 6 months after completion of the primary series in:

• individuals 65 years of age and older;
• individuals 18 through 64 years of age at high risk of severe COVID-19; and 
• individuals 18 through 64 years of age whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19.

“Today’s authorization applies only to the Pfizer-BioNTech COVID-19 Vaccine.”

To support the authorization for emergency use of a single booster dose, the FDA analyzed safety and immune response data from a subset of participants from the original clinical trial of the Pfizer-BioNTech COVID-19 vaccine. In addition, consideration was given to real-world data on the vaccine’s efficacy over a sustained period of time provided by both US and international sources. The immune responses of approximately 200 participants from 18 to 55 years of age who received a single booster dose approximately 6 months after their second dose were assessed. The antibody response against SARS-CoV-2 virus one month after a booster dose of the vaccine compared to the response one month after the two-dose primary series in the same individuals demonstrated a booster response. 

Additional analysis conducted by the manufacturer as requested by the FDA compared the rates of COVID-19 accrued during the current Delta variant surge among original clinical trial participants who completed the primary two-dose vaccination series early in the clinical trial to those who completed a two-dose series later in the study. The analysis submitted by the company showed that during the study period of July and August 2021, the incidence of COVID-19 was higher among the participants who completed their primary vaccine series earlier. The FDA determined that the rate of breakthrough COVID-19 reported during this time period translates to a modest decrease in the efficacy of the vaccine among those vaccinated earlier. Safety was evaluated in 306 participants from 18 to 55 years of age and 12 participants 65 years of age and older who were followed for an average of over two months. The most commonly reported side effects were pain, redness and swelling at the injection site, as well as fatigue, headache, muscle or joint pain and chills. Of note, swollen lymph nodes in the underarm were observed more frequently following the booster dose than after the primary two-dose series.

Since 11 December 2020, the Pfizer-BioNTech COVID-19 vaccine has been available under Emergency Use Authorization (EUA) for individuals 16 years of age and older. The authorization was expanded on 10 May 2021 to include those from 12 to 15 years of age, and again on 12 August 2021 to include the use of a third dose of a three-dose primary series in certain immunocompromised individuals 12 years of age and older. EUAs can be used by the FDA during public health emergencies to provide access to medical products that may be effective in preventing, diagnosing or treating a disease, provided that the FDA determines that the known and potential benefits of a product, when used to prevent, diagnose or treat the disease, outweigh the known and potential risks of the product.

Centers of Disease Control and Prevention (United States) (24 September 2021) CDC Statement on ACIP Booster Recommendations^[3]

This updated interim guidance from the CDC allows for millions of Americans who are at highest risk for COVID-19 to receive a Pfizer-BioNTech COVID-19 booster shot to help increase their protection.

The CDC recommends that:

• people 65 years and older and residents in long-term care settings should receive a booster shot of Pfizer-BioNTech’s COVID-19 vaccine at least 6 months after their Pfizer-BioNTech primary series
• people aged 50–64 years with underlying medical conditions should receive a booster shot of Pfizer-BioNTech’s COVID-19 vaccine atleast 6 months after their Pfizer-BioNTech primary series
• people aged 18–49 years with underlying medical conditions may receive a booster shot of Pfizer-BioNTech’s COVID-19 vaccine at least 6 months after their Pfizer-BioNTech primary series, based on their individual benefits and risks
• people aged 18-64 years who are at increased risk for COVID-19 exposure and transmission because of occupational or institutional setting may receive a booster shot of the Pfizer-BioNTech COVID-19 vaccine at least 6 months after their Pfizer-BioNTech primary series, based on their individual benefits and risks

Many of the people who are now eligible to receive a booster shot received their initial vaccine early in the vaccination program and will benefit from additional protection. With the Delta variant’s dominance as the circulating strain and cases of COVID-19 increasing significantly across the United States, a booster shot will help strengthen protection against severe disease in those populations who are at high-risk for exposure to COVID-19 or the complications from severe disease.

European Centre for Disease Prevention and Control (ECDC) (1 September 2021) Interim public health considerations for the provision of additional COVID-19 vaccine doses^[4]

The ECDC states that it is important to distinguish between booster doses for people who responded adequately to primary vaccination and additional doses for those with weakened immune systems who did not respond adequately. Booster doses are given to vaccinated people ¾ ie those who have completed a primary series of COVID-19 vaccination ¾ to restore protection after it would have waned. On the other hand, additional doses as part of a primary vaccination series may be given to people with severely weakened immune systems, as they may not achieve an adequate level of protection from the standard primary vaccination.

When assessing the need for possible booster doses of COVID-19 vaccine from the public health perspective, it is important to keep in mind the main objective of the vaccination strategy: preventing severe cases of COVID-19. Vaccine effectiveness against severe disease should preferably be chosen as the primary outcome of interest for assessing whether there is a clear need for a booster dose in specific groups.

The available evidence at this time regarding real-world vaccine effectiveness and the duration of protection shows that all vaccines authorised in the EU/EEA are currently highly protective against COVID-19-related hospitalisation, severe disease and death, suggesting there is no urgent need for the administration of booster doses of vaccines to fully vaccinated individuals in the general population. The option of administering an additional vaccine dose to people who may experience a limited response to the primary series of COVID-19 vaccination such as some categories of immunocompromised individuals should already be considered now. This is to be seen as an extension of the primary vaccination series for these specific groups, and not as a booster. Consideration could also be given to providing an additional dose as a precautionary measure to older frail individuals, in particular those living in closed settings: eg residents of long-term care facilities.

Full vaccination against COVID-19 of all eligible family contacts and close contacts ¾ including professionals providing care ¾ of immunocompromised and vulnerable individuals should also be considered.

Close monitoring of vaccine effectiveness data and breakthrough infections, particularly among vulnerable groups at risk of severe COVID-19 and among those living in closed settings, should be continued and decisions adapted accordingly should a substantial decrease in effectiveness be noted in one or more population groups.

When in contact with individuals at risk of severe disease, physical distancing, the wearing of face masks, and hand and respiratory hygiene remain pivotal measures for reducing the risk of SARS-CoV-2 transmission. These non-pharmaceutical interventions should always complement vaccination, in particular in high-risk settings such as long-term care facilities or hospital wards with patients at risk of severe COVID-19.

The benefits and risks of possible booster doses need to be clearly outlined and compared. Benefits may include increased protection against severe disease, mild-to-moderate disease, post COVID-19 condition (“long COVID”), SARS-CoV-2 infection, and virus transmission. Risks include possible safety concerns and public health implications such as impact on vaccine confidence and global availability of vaccines. Communication about possible additional vaccine doses should be carefully considered and delivered in a transparent, proactive and clear manner to avoid affecting vaccine confidence. The distinction between strengthening the response to primary vaccination series, for example in immunocompromised individuals and boosters for waning immune response or vaccine escape should be clearly articulated.

In the context of many countries outside of the EU/EEA still struggling to receive and administer enough vaccine doses to their populations, special consideration should be given to the current global shortage of COVID-19 vaccines, which could be further worsened by the administration of booster COVID-19 vaccine doses for the general population in EU/EEA countries.

European Centre for Disease Prevention and Control (ECDC) (23 September 2021) Overview of the implementation of COVID-19 vaccination strategies and deployment plans in the EU/EEA^[5]

This report provides an updated overview of the progress of national COVID-19 vaccination strategies in European Union/European Economic Area (EU/EEA) countries, including updates on overall vaccine uptake and uptake by target group; vaccination strategies and policies; challenges and good practices with the rollout, including vaccine acceptance and hesitancy; and strategies to increase vaccination uptake.

As of 12 September 2021, 13 countries recommend an additional dose as an extension of the primary series ¾ ie to immunocompromised individuals ¾ and 9 countries recommend both an additional dose as an extension of primary series and as a booster dose for waning immunity. 7 countries are currently discussing additional and booster dose recommendations, and one country does not currently have recommendations.

Extracted from Table 8: Summary of recommendations for additional dose and/or booster dose (n=30)

Point-of-Care Tools

BMJ Best Practice (2021) Coronavirus Disease 2019 (COVID-19): Prevention^[6]

See Section: Booster Doses

Observational data to support the safety and efficacy of booster doses are emerging, but their follow-up periods are too short to assess long-term effectiveness, and the number of trial participants is small. The studies also focus on plasma neutralising antibodies and don’t take into account the protection provided by cellular immunity.

In the US, the Food and Drug Administration has authorised an additional (third) dose of the Pfizer-BioNTech and Moderna mRNA vaccines in moderately to severely immunocompromised people at least 28 days after the completion of the initial vaccine series. It has also authorised a single booster dose of the Pfizer-BioNTech vaccine to be administered at least 6 months after the completion of the primary series in certain people. The US Centers for Disease Control and Prevention recommends that the following groups should receive a booster dose: people aged ≥65 years and residents in long-term care settings; and people aged 50 to 64 years with certain underlying medical conditions. It recommends that the following groups may receive a booster dose: people aged 18 to 49 years with certain underlying medical conditions based on their individual benefits and risks; and people aged 18 to 64 years who are at increased risk for exposure and transmission because of occupational or institutional setting based on their individual benefits and risks.

In the UK, the JCVI advises that a third primary dose be offered to people aged ≥12 years with severe immunosuppression. The third primary dose should ideally be given at least 8 weeks after the second dose, with special attention paid to current or planned immunosuppressive therapies. Choice of vaccine depends on age and the previous vaccine used. The JCVI has also advised that people who were vaccinated during phase 1 of the vaccination programme in priority groups [adults ≥50 years of age, frontline health and social care workers, people living in residential care homes, people aged 16 to 49 years with underlying conditions that put them at higher risk and their adult carers, adult household contacts of immunosuppressed people] should be offered a booster dose no earlier than 6 months after completion of their primary course. Influenza and COVID-19 vaccines may be administered together where operationally practical.

In Europe, the European Medicines Agency recommends that a booster dose of an mRNA vaccine may be given to people with severely weakened immune systems at least 28 days after their second dose. Although there is no direct evidence that the ability to produce antibodies in these patients offered protection, it is expected that the extra dose would increase protection at least in some patients. The risk of side effects after a booster is not known and is being carefully monitored.

UpToDate (2021) COVID-19: Vaccines to prevent SARS-CoV-2 infection^[7]

See Section: ROLE OF BOOSTER VACCINATIONS

Because of the possibility of waning immunity and decreased efficacy against variants that might escape the immune response directed against Spike proteins targeted by the original vaccines, several countries have initiated or announced plans to administer a booster vaccine for individuals who have been fully vaccinated. In the United States, the Food and Drug Administration (FDA) has authorized and the CDC recommends a booster doses in specific populations for all available vaccines.

Among individuals who received a primary mRNA vaccine series (BNT162b2 [Pfizer COVID-19 vaccine] or mRNA-1273 [Moderna COVID-19 vaccine]), the CDC recommends a booster dose 6 months after the primary series for certain high-risk adults:

• Adults 65 years or older should receive a booster dose.
• Adults 50 years or older at risk for severe COVID-19 because of comorbidities [eg cancer, cerebrovascular disease, chronic kidney disease, COPD, diabetes mellitus, heart conditions such as heart failure or cardiomyopathies, HIV, neurologic conditions, obesity, solid organ or blood stem cell transplantation, use of corticosteroids or other immunosuppressive medications] should receive a booster dose.
• Adults aged 18 to 50 years and at risk for severe COVID-19 because of comorbidities may receive a booster dose after weighing the individual risks and benefits.
• Adults aged 18 to 64 years who have occupational or institutional risk of exposure to SARS-CoV-2 such as health care workers or those living in congregate settings may receive a booster dose after weighing the individual risks and benefits.

Among individuals who received a primary vaccine series with Ad26.COV2.S (Janssen COVID-19 vaccine), the CDC recommends a booster dose at least two months after the primary series.

Booster doses following a primary vaccine series are a distinct issue from administering a third dose of an mRNA vaccine for the primary series in certain immunocompromised patients.

Data from observational studies have suggested that vaccine protection against SARS-CoV-2 infection wanes over time. However, protection against hospitalization and severe COVID-19 appears to be preserved. As an example, a review of data on nursing home residents reported to a national database in the United States suggested that vaccine effectiveness against laboratory-confirmed SARS-CoV-2 infection among this population declined from 75% in March to May 2021 to 53% during June to July 2021. Similarly, in a study of state-wide data in New York that included approximately 10 million vaccinated adults, age-adjusted vaccine effectiveness against SARS-CoV-2 infection declined from 92% to 75% from May to July 2021; however, effectiveness against hospitalization remained stable over that time at 90% to 95%. Another study of 3000 hospitalized patients estimated vaccine effectiveness against COVID-19-related hospitalization as 86% 2 to 14 weeks after vaccination and 84% 13 to 24 weeks after vaccination.

Although overall vaccine effectiveness against severe disease and hospitalization appears largely preserved, the same observational studies suggest that it is lower among older adults, among whom there may be some decline in effectiveness over time.

Evidence that a booster vaccine may improve vaccine effectiveness is limited to observational data and data on immunogenicity. As an example, in an observational study from Israel of over one million individuals 60 years or older who had received two doses of BNT162b2 (Pfizer-BioNTech COVID-19 vaccine) at least five months previously, receipt of a booster dose was associated with an 11-times lower rate of infection compared with those who did not receive a booster (absolute difference 87 infections per 100,000 days) and a 20-times lower rate of severe illness (absolute difference 7.5 cases per 100,000 days). Given the observational design, it is uncertain whether some of these differences could have been related to other variables such as exposure risk or testing differences; there was also limited follow-up time following receipt of the booster.

Data on immunogenicity are consistent with the observational data. In a small trial of 23 individuals who had received two doses of BNT162b2 (Pfizer-BioNTech COVID-19 vaccine), neutralizing antibody titers against wild-type virus, the Beta variant and the Delta variant following receipt of a third dose eight to nine months later were higher than those detected following the initial two vaccine series. The rate and severity of adverse reactions following the booster dose were similar to those following the second dose in prior trials. Similar findings from a larger trial were included in a report to the FDA. Data presented to that FDA indicate that booster doses of mRNA-1273 and AD26.COV2.S also result in increases in binding and neutralizing antibody titers compared with pre-boost with similar reactogenicity profiles to those with the primary series. Efficacy data from trials evaluating two doses of AD26.COV2.S also support use of a booster for this vaccine.

Irish and/or International Literature

Pouwels et al (2021) [Preprint] Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK^[8]

The effectiveness of the Pfizer-BioNTech, AstraZeneca and Moderna vaccines against new SARS-CoV-2 infections requires continuous re-evaluation, given the increasingly dominant Delta variant. The authors investigated the effectiveness of the vaccines in a large community-based survey of randomly selected households across the United Kingdom. Among the survey findings, the authors found that there was no evidence that the effect of vaccination on new PCR-positives differed between those reporting vs. not reporting long-term health conditions.

Figure: Protection against all new PCR-positive episodes over time from second dose by long-term health conditions

Whitaker et al (2021) [Preprint] Pfizer-BioNTech and Oxford AstraZeneca COVID-19 vaccine effectiveness and immune response among individuals in clinical risk groups^[9]

COVID-19 vaccines have been found to be highly effective in general population cohorts; however, data on effectiveness among individuals with clinical conditions that place them at increased risk of severe disease is limited.

Methods: The authors used GP electronic health record data, sentinel virology swabbing and sentinel antibody testing within a cohort of over 700 practices across England (representing 10% of the population) to estimate antibody response to vaccination and vaccine effectiveness against medically attended COVID-19 among individuals in clinical risk groups. Adjusted prevalence ratios of S-antibody positivity and titres after vaccination were estimated by clinical risk group. Adjusted vaccine effectiveness was estimated using a cohort analysis and a nested test negative case-control analysis.

Findings: There was no notable reduction in S-antibody positivity or titres in most clinical risk groups. The only clinical risk group with significantly reduced S-antibody response after one and two doses was the immunocompromised group who had a 68% (95%CI: 43% to 82%) reduction in the geometric mean titre after two doses. Reduced vaccine effectiveness against clinical disease was also noted in the immunosuppressed group after one dose; however, after a second dose of either vaccine, high levels of effectiveness were seen (Pfizer: 73.0%, 95%CI 33.9 to 89.0%; AstraZeneca 74.6%, 95%CI 18.7 to 92.1%).

Interpretation: These findings would support maximising coverage with two doses in immunosuppressed individuals.

Israel et al (2021) Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection _^[10]

Immune protection following either vaccination or infection with SARS-CoV-2 decreases over time.

Objective: To determine the kinetics of SARS-CoV-2 IgG antibodies following administration of two doses of BNT162b2 vaccine or SARS-CoV-2 infection in unvaccinated individuals.

Methods: Antibody titers were measured between January 31, 2021 and July 31, 2021 in two mutually exclusive groups: 1. vaccinated individuals who received two doses of BNT162b2 vaccine and had no history of previous infection with COVID-19; and 2. SARS-CoV-2 convalescents who had not received the vaccine.

Results: A total of 2,653 individuals fully vaccinated by two doses of vaccine during the study period and 4,361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8-5644.6]) after the second vaccination, than in convalescent individuals (median 355.3 AU/mL IQR [141.2-998.7]; p<0.001). In vaccinated subjects, antibody titers decreased by up to 40% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of <50 AU/mL, while only 10.8% of convalescent patients were below <50 AU/mL threshold after 9 months from SARS-CoV-2 infection. Antibody levels in the vaccinated cohort decreased with age >60 (factor 0.7 CI 0.64-0.969); CKD (0.2 CI 0.143-0.281); COPD (0.63 CI 0.494-0.834); BMI <18.5 (0.359 CI 0.479-0.863); solid malignancy (0.642 CI 0.494-0.834); DM (0.72 CI 0.579-0.894); HTN (0.786 CI 0.639-0.966).

Conclusions: This study demonstrates individuals who received the Pfizer-BioNTech mRNA vaccine have different kinetics of antibody levels compared to patients who had been infected with the SARS-CoV-2 virus, with higher initial levels but a much faster exponential decrease in the first group.

Other Sources of Evidence

Public Health England (2021) Duration of protection of COVID-19 vaccines against clinical disease^[11]

In a negative case-control study to estimate vaccine effectiveness (VE) against symptomatic disease, hospitalisation and death, Public Health England found that overall protection against hospitalisation remained high throughout the follow-up period of 20+ weeks, even within clinical risk groups. Waning against hospitalisation appeared to be much more limited, with VE of approximately 95% with the Pfizer-BioNTech COVID-19 vaccine from 20+ weeks after vaccination. With the AstraZeneca COVID-19 vaccine, there appeared to be some waning to just under 80% VE against hospitalisation from 20+ weeks. Stratifying by age gave similar results to the overall analysis with some suggestion of increased waning with increased age; however, confidence intervals were wide.

Further stratifying the 40-64 year age group according to whether study participants were in a risk group indicated that the waning seen with AstraZeneca was restricted to those in clinical risk groups. In those aged over 65 years, waning appeared to be greater with both AstraZeneca and Pfizer among those in the clinically extremely vulnerable group, although data beyond 20 weeks was limited.

Centers for Disease Control and Prevention (United States) (2021) Underlying medical conditions associated with higher risk for severe COVID-19: Information for healthcare providers^[12]

The CDC lists the following conditions associated with a higher risk for severe COVID-19, as supported by at least one meta-analysis or systematic review: cancer; cerebrovascular disease; chronic kidney disease; chronic lung diseases limited to interstitial lung disease, pulmonary embolism, pulmonary hypertension, bronchopulmonary dysplasia, bronchiectasis, chronic obstructive pulmonary disease; chronic liver diseases limited to cirrhosis, non-alcoholic fatty liver disease, alcoholic liver disease, autoimmune hepatitis; diabetes mellitus; heart conditions such as heart failure, coronary artery disease or cardiomyopathies; mental health disorders limited to mood disorders including depression, schizophrenia spectrum disorders; obesity; pregnancy or recent pregnancy; smoking; tuberculosis.

Comorbidities associated with a higher risk for severe COVID-19 that are supported by at least one observational study: children with certain underlying conditions; Down syndrome; human immunodeficiency virus; neurologic conditions including dementia; overweight; sickle cell disease; solid organ or blood stem cell transplantation; substance use disorders; use of corticosteroids or other immunosuppressive medications.

Comorbidities that are supported by mostly case series or case reports: cystic fibrosis; thalassemia.

Comorbidities that are supported by mixed evidence: asthma; hypertension; immune deficiencies.

References

[1] Joint Committee on Vaccination and Immunisation (Great Britain) (14 September 2021) JCVI statement regarding a COVID-19 booster vaccine programme for winter 2021 to 2022. Accessed 27/10/2021.

[2] Food and Drug Administration (FDA) (United States) (22 September 2021) [Press Release] FDA Authorizes Booster Dose of Pfizer-BioNTech COVID-19 Vaccine for Certain Populations. Accessed 27/10/2021.

[3] Centers of Disease Control and Prevention (United States) (24 September 2021) CDC Statement on ACIP Booster Recommendations. Accessed 27/10/2021.

[4] European Centre for Disease Prevention and Control (ECDC) (1 September 2021) Interim public health considerations for the provision of additional COVID-19 vaccine doses. Accessed 27/10/2021.

[5] European Centre for Disease Prevention and Control (ECDC) (23 September 2021) Overview of the implementation of COVID-19 vaccination strategies and deployment plans in the EU/EEA. Accessed 27/10/2-21.

[6] BMJ Best Practice (2021) Coronavirus Disease 2019 (COVID-19): Prevention. Accessed 01/11/2021.

[7] UpToDate (2021) COVID-19: Vaccines to prevent SARS-CoV-2 infection. Accessed 01/11/2021.

[8] Pouwels et al (2021) [Preprint] Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK^[1]. Accessed 01/11/2021.

[9] Whitaker et al (2021) [Preprint] Pfizer-BioNTech and Oxford AstraZeneca COVID-19 vaccine effectiveness and immune response among individuals in clinical risk groups. Accessed 01/11/2021.

[10] Israel A, Shenhar Y, Green I, Merzon E, Golan-Cohen A, Schäffer AA, Ruppin E, Vinker S, Magen E. Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection. medRxiv [Preprint]. 2021 Aug 21:2021.08.19.21262111. doi: 10.1101/2021.08.19.21262111. PMID: 34462761; PMCID: PMC8404903.

[11] Public Health England (2021) Duration of protection of COVID-19 vaccines against clinical disease. Accessed 01/11/2021.

[12] Centers for Disease Control and Prevention (United States) (2021) Underlying medical conditions associated with higher risk for severe COVID-19: Information for healthcare providers. Accessed 01/11/2021.

Produced by the members of the National Health Library and Knowledge Service Evidence Team^†. Current as at 30 September 2021. This evidence summary collates the best available evidence at the time of writing and does not replace clinical judgement or guidance. Emerging literature or subsequent developments in respect of COVID-19 may require amendment to the information or sources listed in the document.  Although all reasonable care has been taken in the compilation of content, the National Health Library and Knowledge Service Evidence Team makes no representations or warranties expressed or implied as to the accuracy or suitability of the information or sources listed in the document.  This evidence summary is the property of the National Health Library and Knowledge Service and subsequent re-use or distribution in whole or in part should include acknowledgement of the service.

Emma Quinn, Librarian, St. Luke’s General Hospital, Kilkenny [Author]; Isabelle Delaunois, Librarian, University Hospital Limerick[Author]; Margaret Morgan, Librarian, Midland Regional Hospital, Mullingar[Author]; Brendan Leen, Area Library Manager, HSE South [Editor]; NIAC Sub-Group Contributors: Dr. Geraldine Casey; Dr. Grace Kenny; Dr. Peter O’Reilly; Dr. Philippa White.