Archived 19: National Advisory Committee on Immunization (NACI) rapid response: Additional dose of COVID-19 vaccine in immunocompromised individuals following 1- or 2- dose primary series [2021-09-10]

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Preamble

The National Advisory Committee on Immunization (NACI) is an External Advisory Body that provides the Public Health Agency of Canada (PHAC) with independent, ongoing and timely medical, scientific, and public health advice in response to questions from PHAC relating to immunization.

In addition to burden of disease and vaccine characteristics, PHAC has expanded the mandate of NACI to include the systematic consideration of programmatic factors in developing evidence-based recommendations to facilitate timely decision-making for publicly funded vaccine programs at provincial and territorial levels.

The additional factors to be systematically considered by NACI include: economics, ethics, equity, feasibility, and acceptability. Not all NACI Statements will require in-depth analyses of all programmatic factors. While systematic consideration of programmatic factors will be conducted using evidence-informed tools to identify distinct issues that could impact decision-making for recommendation development, only distinct issues identified as being specific to the vaccine or vaccine-preventable disease will be included.

This statement contains NACI's independent advice and recommendations, which are based upon the best current available scientific knowledge. This document is being disseminated for information purposes. People administering the vaccine should also be aware of the contents of the relevant product monograph. Recommendations for use and other information set out herein may differ from that set out in the product monographs of the Canadian manufacturers of the vaccines. Manufacturer(s) have sought approval of the vaccines and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs. NACI members and liaison members conduct themselves within the context of PHAC's Policy on Conflict of Interest, including yearly declaration of potential conflict of interest.

Background

Immunocompromised individuals, including those receiving immunosuppressive therapy, are a very heterogeneous population some of whom may respond differently to vaccines and thus require unique considerations regarding immunization. To date, people with moderately to severely compromised immune systems have been observed to generally have lower antibody responses and lower vaccine effectiveness from Coronavirus disease 2019 (COVID-19) vaccines than immunocompetent individuals, although this varies depending on the underlying condition or immunosuppressive agents. Individuals with various conditions associated with immunocompromise were excluded from the manufacturer-conducted randomized controlled COVID-19 vaccine efficacy trials and it is uncertain what vaccination strategy will most optimally protect these individuals from illness and severe outcomes due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.

There is currently a resurgence of COVID-19 cases in some regions of Canada fuelled by the highly transmissible Delta variant that was declared a global variant of concern by the World Health Organization in May 2021. The Delta variant has been observed to increase the risk of infections due to its higher transmissibility. Breakthrough infections (infection in fully vaccinated people) have occurred with the Delta variant. This may be due to some degree of evasion of vaccine-induced immunity or waning of vaccine-induced immunity over time, or poor immune response to initial vaccine doses (as might occur amongst those who are moderately or severely immunocompromised). Delta has also been shown to be more virulent compared to previous strains resulting in a higher percentage of cases requiring hospital care, most notably in unvaccinated individuals, but also to some extent in vaccinated individuals when compared to the Alpha variantFootnote 1. In order to reduce the risk of breakthrough infections among vulnerable groups several countries including Israel, the United States, France, Germany, the United Kingdom, Denmark and Norway have implemented, or are planning to implement, the administration of third doses of COVID-19 vaccine in some immunocompromised populations.

NACI previously preferentially recommended that a complete COVID-19 vaccine series (defined as a 2-dose series) with an mRNA COVID-19 vaccine should be offered to individuals in the authorized age group who are immunocompromised due to disease or treatment. Recent studies have demonstrated that some people who do not respond after two doses, particularly those who are moderately to severely immunocompromised, develop antibodies after a third dose of an mRNA vaccine; and that there are increases in antibody titres following a third dose for some of those who do respond to an initial primary series. There is increasing evidence that antibody titres are related to vaccine effectiveness, (including against viral variants) and may relate to the duration of protection and protection against severe disease. However, a correlate of protection has not yet been defined.

The additional or third dose being considered for moderately to severely immunocompromised persons should be distinguished from that of a booster dose. The intent of a booster dose is to restore protection that may have waned over time in individuals who responded adequately to an initial 1- or 2-dose primary vaccine series. Additional doses beyond the standard primary vaccine series, such as discussed in this statement, provide an opportunity for individuals who may not have achieved an adequate level of protection from the standard primary vaccine series to develop a better immune response.

Guidance objective

The objective of this guidance document is to provide advice on the use of an additional dose of a COVID-19 vaccine following receipt of a standard 1- or 2-dose primary series in moderately to severely immunocompromised individuals in Canada.

Methods

NACI has reviewed direct and indirect evidence available up to August 11, 2021 on efficacy/effectiveness, safety and immunogenicity of the standard 1- or 2- dose primary series, and the safety and immunogenicity of an additional dose of COVID-19 vaccine following a standard primary series in individuals who are immunocompromised due to disease or treatment. As of August 11, 2021 no data on the efficacy/effectiveness of an additional dose after a primary series of COVID-19 vaccine was available. There were thus only immunogenicity and safety data. NACI also reviewed a summary report from the PHAC Public Health Ethics Consultative Group (PHECG) on ethical considerations related to the provision of third doses of COVID-19 vaccines prepared on August 12, 2021.

Following a comprehensive review of available evidence, NACI approved the recommendations outlined below on September 1, 2021.

Details of NACI's evidence-informed recommendation development process can be found elsewhereFootnote 2Footnote 3.

Defining immunocompromised individuals

To operationalize guidance for this population, NACI has reviewed a number of sources to identify which immunocompromised populations would likely benefit most from an additional dose of COVID-19 vaccine at this time. These sources have included evidence available in published and grey literature, the Canadian Immunization Guide chapter on Immunization of Immunocompromised Persons, and eligibility criteria for additional doses of COVID-19 vaccine in immunocompromised people currently being used by other jurisdictions. In addition, the clinical expertise of the committee informed the definition of immunocompromised individuals for the recommendations outlined in this statement.

Summary of evidence

Burden of illness in Canada

Immunocompromised individuals, including those receiving immunosuppressive therapy, are at increased risk for prolonged infection and serious complications from SARS-CoV-2 infection. Canadian surveillance data collected since December 2020 indicates that the proportion of COVID-19 cases that are hospitalized or admitted into intensive care unit (ICU), without adjusting for age, is 4-5 times higher than for the general population amongst individuals 12 years of age and older who are reporting either immunodeficiency or malignancy than amongst the general populationFootnote 4. This was also observed when data was limited to Delta-specific cases reported since March, 2021Footnote 5.

Summary of evidence on 2-dose COVID-19 vaccine series in immunocompromised individuals

Effectiveness of a 2-dose COVID-19 vaccine series in immunocompromised individuals

Although the evidence is limited, observational studies show a reduction in vaccine effectiveness against SARS-CoV-2 infection and COVID-19 disease in immunocompromised adults when compared to the general population (based on use of the vaccines as per the manufacturers' schedules). A pooled analysis of three large population-based cohort studiesFootnote 6Footnote 7Footnote 8 estimated vaccine effectiveness against any SARS-CoV-2 infection after the second dose in immunocompromised persons to be 79% (95% confidence interval (CI): 69 - 91%), compared to vaccine effectiveness after the second dose in the general population of 90% (95% CI: 86 - 95%)Footnote 9. Another pooled analysis of two large case-control studiesFootnote 10Footnote 11 also against infection estimated vaccine effectiveness to be 88% (95% CI: 83 - 93%) in immunocompromised persons and 91% (95% CI: 84 - 98%) in the general populationFootnote 9. The criteria for being considered immunocompromised was not defined in these studies, and these analyses do not provide sufficient data to determine vaccine effectiveness for specific immunocompromising conditions or treatments.

Immunogenicity of a 2-dose mRNA COVID-19 vaccine series in immunocompromised individuals

The impact of immunocompromise on seroconversion after vaccination varies according to specific conditions and/or immunosuppressive therapy. Not all immunocompromised populations have been studied in detail. Some studies have shown that immunogenicity is substantially decreased in some immunocompromised adults when compared to healthy vaccine recipientsFootnote 9. This notably included individuals with malignancy (solid and hematological)Footnote 12Footnote 13Footnote 14Footnote 15Footnote 16Footnote 17Footnote 18Footnote 19Footnote 20Footnote 21Footnote 22Footnote 23Footnote 24Footnote 25Footnote 26Footnote 27Footnote 28Footnote 29Footnote 30Footnote 31Footnote 32Footnote 33Footnote 34Footnote 35Footnote 36Footnote 37Footnote 38Footnote 39Footnote 40Footnote 41Footnote 42Footnote 43Footnote 44Footnote 45Footnote 46Footnote 47Footnote 48Footnote 49Footnote 50Footnote 51Footnote 52Footnote 53Footnote 54Footnote 55, multiple sclerosis when treated with immunosuppressive therapyFootnote 56Footnote 57Footnote 58, solid organ transplant recipientsFootnote 10Footnote 15Footnote 41Footnote 50Footnote 59Footnote 60Footnote 61Footnote 62Footnote 63Footnote 64Footnote 65Footnote 66Footnote 67Footnote 68Footnote 69Footnote 70Footnote 71Footnote 72Footnote 73Footnote 74Footnote 75Footnote 76Footnote 77Footnote 78Footnote 79Footnote 80Footnote 81Footnote 82Footnote 83Footnote 84Footnote 85Footnote 86Footnote 87Footnote 88Footnote 89Footnote 90Footnote 91Footnote 92Footnote 93Footnote 94Footnote 95Footnote 96Footnote 97Footnote 98Footnote 99, and those with primary immune deficiencyFootnote 50Footnote 100Footnote 101Footnote 102.

The clinical significance of this difference in seroconversion and its impact on vaccine effectiveness is not known.

Safety of a 2-dose COVID-19 vaccine series in immunocompromised individuals

The safety profile of mRNA vaccines in real-world observational studies in this population has been comparable to what has been observed in the general population, with no unexpected or serious safety signals to date, including no worsening of an immunocompromising condition that has been attributed to the vaccine.

Summary of evidence on an additional dose of COVID-19 vaccine following a 2-dose series

Efficacy/effectiveness of an additional COVID-19 vaccine dose following a 2-dose primary series in immunocompromised individuals

There are currently no data on the efficacy/effectiveness of an additional dose of a COVID-19 vaccine following a 1- or 2-dose primary series in individuals with immunocompromising conditions.

Immunogenicity of an additional dose of COVID-19 vaccines following a 2-dose primary series in immunocompromised individuals

Emerging evidence indicates that humoral immune responses increase after a third dose of mRNA COVID-19 vaccine is administered to adults with immunocompromising conditions, although the degree of increase varies between studies and according to the type of immunocompromising condition or treatment. From 10 studiesFootnote 103Footnote 104Footnote 105Footnote 106Footnote 107Footnote 108Footnote 109Footnote 110Footnote 111Footnote 112 evaluating 2,075 patients, including one randomized-controlled trialFootnote 112, the overall pooled increase in the proportion of immunosuppressed individuals who seroconverted after an additional dose was 13% (95%CI: 5% - 22%)Footnote 9. These studies assessed seroconversion in solid organ transplant recipients, and individuals with hematologic malignancies, and individuals receiving hemodialysis. The greatest increase in proportion of those who seroconverted after the third dose was in solid organ transplant recipients. In the majority of studies, all three doses were mRNA vaccines. Some individuals received the AstraZenecaFootnote 113 or Janssen COVID-19 vaccineFootnote 105Footnote 106Footnote 107Footnote 108 as their third dose, however data specific to these vaccines as additional dose is not available. In some studies, although the increase in proportion of those who seroconverted was small, median antibody titers increased after the third dose compared to after the second dose. There was a significant amount of heterogeneity between studies due to differences in the populations that were studied. Given the limited size of the studies available to date and the lack of a defined immunological correlate of protection, there are limitations to interpreting the significance of these results.

Safety of an additional dose following a 2-dose primary series in immunocompromised individuals

In ten studies in adults, (five in solid organ transplant patientsFootnote 105Footnote 107Footnote 110Footnote 111Footnote 114, three in patients on dialysis Footnote 104Footnote 106Footnote 108, one in patients with non-hematologic cancerFootnote 115 and one in patients with hematologic cancerFootnote 109), the reactogenicity of a third dose of COVID-19 vaccine was similar to that of prior doses. In nearly all studies, the third dose was an mRNA vaccine, with the exception of one study where Janssen was also used for some study participations as an additional dose following a 2-dose mRNA COVID-19 vaccine primary seriesFootnote 105. However, there are no data specific to the Janssen COVID-19 vaccine when used as an additional dose in this population. No worsening of underlying disease was reported after immunization, however a few cases of graft versus host disease or organ rejection were reported. Without unvaccinated controls however, it is not possible at this time to determine if receipt of a third COVID-19 vaccine dose could potentially be associated with an increased risk of rejection in this population. No serious adverse events were deemed to be associated with the vaccine. Limitations of these studies include small sample sizes, short follow up periods and heterogeneous populations/vaccine schedules. Due to the small size of these studies and limited follow-up times, the impact of additional doses on rare adverse events in these populations are unknown.

The risk of myocarditis and/or pericarditis following receipt of an mRNA COVID-19 vaccine is currently reported more commonly after second doses compared to first doses. The risk of myocarditis and/or pericarditis associated with an additional dose of an mRNA vaccine, including when given to immunocompromised individuals, is unknown at this time. NACI is continuing to monitor the evidence and will update recommendations as information becomes available.

For further information, please refer to NACI's Recommendations on the use of COVID-19 vaccines.

Additional information and considerations

Timing of the additional dose

There is currently limited data to determine the optimal interval between the initial 1- or 2-dose series or with an additional dose. Dosing intervals between the second and third doses varied across studies, ranging from 28 days to 127 days, with the majority of studies having assessed an interval of 2 to 3 months between dosesFootnote 104Footnote 105Footnote 106Footnote 107Footnote 108Footnote 110Footnote 111Footnote 112. A longer interval between the second and third doses, such as that used in most of the studies, is likely to result in better immune response. However, delaying the third dose increases the period of time during which the immunocompromised individual may be sub-optimally protected and could leave the immunocompromised individual susceptible to SARS-CoV-2 infection while waiting to be vaccinated with the additional dose.

In general, NACI recommends that immunocompromised individuals be immunized at the time when when maximum immune response can be anticipated:

Vaccine product considerations

Studies assessing additional doses in immunocompromised individuals have primarily used mRNA vaccines, for both the initial primary series and additional dose. There are very limited data on the Janssen vaccine, and no data on the AstraZeneca COVID-19 vaccine as an additional dose in this population at this time. No safety concerns have been identified with additional doses following a homologous and heterologous 1- or 2-dose primary series in the evidence available to date.

In a meta-analysis of 22 studiesFootnote 15Footnote 16Footnote 17Footnote 27Footnote 42Footnote 46Footnote 53Footnote 58Footnote 75Footnote 87Footnote 97Footnote 116Footnote 117Footnote 118Footnote 119Footnote 120Footnote 121Footnote 122Footnote 123Footnote 124Footnote 125Footnote 126 assessing seroconversion after the initial 2-dose series in immunocompromised and dialysis populations, Pfizer-BioNTech had slightly lower pooled rates of seroconversion than Moderna with relative risk of 0.94 (95% CI = 0.91 to 0.97) with moderate heterogeneity between studies (I2 = 65%, χ2 = 59.6, p˂0.0001)Footnote 9. A proportion of this heterogeneity was due to the Pfizer-BioNTech vaccine lower pooled rate of seroconversion in solid organ transplant patients in particular.

Ethics and Equity Considerations

Evidence has shown that some immunocompromised individuals have a reduced immune response to the use of the COVID-19 vaccines as per the manufacturers' schedules. Although some reduction in vaccine effectiveness has been identified when compared to the general population, the extent of the loss is unclear due to the limited evidence in this population and heterogeneous nature of immunocompromising conditions and treatments. Vaccination strategies aimed at protecting these vulnerable populations have also varied across studies and jurisdictions Although waiting for vaccine effectiveness data for this population would increase the certainty of this recommendation, an assessment of the benefits and harms given the available evidence on immunogenicity and safety supports offering an additional dose in order to optimize direct protection from vaccine if possible, despite the limited evidence. The additional dose provides an opportunity to attain protective immunity against COVID-19 and thus contribute to equity since a three-dose schedule may be required for an effective primary vaccine series in this population. It will be necessary to ensure a robust informed consent process that clearly communicates both what is known and unknown about the risks and benefits of receiving a third dose (including the off-label status of NACI's recommendation).

Recommendations

  1. For those who have not yet been immunized, NACI recommends that moderately to severely immunocompromisedFootnote * individuals in the authorized age groups should be immunized with a primary series of three doses of an authorized mRNA vaccine. (Strong NACI Recommendation)
  2. For those moderately to severely immunocompromisedFootnote * individuals in the authorized age groups who have previously received a 1- or 2-dose complete primary COVID-19 vaccine series (with a homologous or heterologous schedule using mRNA or viral vector vaccines), NACI recommends that an additional dose of an authorized mRNA COVID-19 vaccine should be offered. (Strong NACI Recommendation)
    • 2a. An additional dose of a viral vector vaccine should only be considered when other authorized COVID-19 vaccines are contraindicated or inaccessible. Informed consent for an additional dose of viral vector vaccine should include discussion about the lack of evidence on the use of an additional dose of viral vector COVID-19 vaccine in this population. (Discretionary NACI Recommendation)

For guidance on the timing of vaccination for transplant recipients and those requiring immunosuppressive therapies, for a more fulsome list of conditions leading to primary immunodeficiency, and for further information on immunosuppressive therapies, refer to Immunization of Immunocompromised Persons in the Canadian Immunization Guide (CIG), Part 3 - Vaccination of Specific Populations.

Additional considerations, summary of evidence and rationale

Refer to Recommendations on the Use of COVID-19 vaccines for further information on COVID-19 vaccines.

Research priorities

What is the optimal product, vaccine doses, interval between doses, and number of doses for immunocompromised individuals to ensure protection against SARS-CoV-2?

What is the efficacy/effectiveness of additional doses in immunocompromised individuals including:

If adequate protection in immunocompromised individuals can be achieved with an additional dose, then what is the duration of this protection in immunocompromised individuals and will a booster dose/series be required?

What are the adaptive and innate immunity thresholds for protection in immunocompromised individuals?

What is the risk of myocarditis/pericarditis following an additional dose of an mRNA vaccine, including in immunocompromised individuals?

Further immunological evidence is needed in the following areas to inform efficacy/effectiveness predictions:

Additional research priorities are listed in NACI's statement on Recommendations for the use of COVID-19 vaccines.

References

Footnote *

Moderately to severely immunosuppressed includes individuals with the following conditions:

  • Active treatment for solid tumour or hematologic malignancies
  • Receipt of solid-organ transplant and taking immunosuppressive therapy
  • Receipt of chimeric antigen receptor (CAR)-T-cell therapy or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppression therapy)
  • Moderate to severe primary immunodeficiency (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome)
  • Stage 3 or advanced untreated HIV infection and those with acquired immunodeficiency syndrome
  • Active treatment with the following categories of immunosuppressive therapies: anti-B cell therapies (monoclonal antibodies targeting CD19, CD20 and CD22), high-dose systemic corticosteroids (refer to the CIG for suggested definition of high dose steroids), alkylating agents, antimetabolites, or tumor-necrosis factor (TNF) inhibitors and other biologic agents that are significantly immunosuppressive.

Return to footnote * referrer

Footnote 1

Public Health Agency of Canada (PHAC) Emerging Science Group (ESG). Living summary of SARS-CoV-2 variants of concern: The Delta variant (B.1.617.2) profile, Highlights up to July 29, 2021. Ottawa (ON): PHAC; 2021 Jul.

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Footnote 2

Ismail SJ, Langley JM, Harris TM, Warshawsky BF, Desai S, FarhangMehr M. Canada's National Advisory Committee on Immunization (NACI): Evidence-based decision-making on vaccines and immunization. Vaccine. 2010;28:A58,63. doi: 10.1016/j.vaccine.2010.02.035.

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Footnote 3

Ismail SJ, Hardy K, Tunis MC, Young K, Sicard N, Quach C. A framework for the systematic consideration of ethics, equity, feasibility, and acceptability in vaccine program recommendations. Vaccine. 2020 Aug 10;38(36):5861,5876. doi: 10.1016/j.vaccine.2020.05.051.

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Footnote 4

Public Health Agency of Canada (PHAC). Surveillance and Epidemiology Division, Centre for Immunization and Respiratory Infectious Diseases, Infectious Disease Prevention and Control Branch. Data cut-off August 7, 2021. Ottawa (ON): PHAC; 2021 Aug 30.

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Footnote 5

Public Health Agency of Canada (PHAC). Surveillance and Epidemiology Division, Centre for Immunization and Respiratory Infectious Diseases, Infectious Disease Prevention and Control Branch. Data cut-off August 14, 2021. Ottawa (ON): PHAC; 2021 Sep 3.

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Footnote 6

Barda N, Dagan N, Balicer RD. BNT162b2 mRNA Covid-19 Vaccine in a nationwide mass vaccination setting. Reply. N Engl J Med. 2021 May 20;384(20):1970. doi: 10.1056/NEJMc2104281.

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Footnote 7

Chodick G, Tene L, Rotem RS, Patalon T, Gazit S, Ben-Tov A, et al. The effectiveness of the TWO-DOSE BNT162b2 vaccine: analysis of real-world data. Clin Infect Dis. 2021 May 17:ciab438. doi: 10.1093/cid/ciab438.

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Footnote 8

Whitaker HJ, Tsang RSM, Byford R, Andrews NJ, Sherlock J, Pillai PS, et al. Pfizer-BioNTech and Oxford AstraZeneca COVID-19 vaccine effectiveness and immune response among individuals in clinical risk groups. Preprint posted on khub. 2021 Jul 9. https://khub.net/documents/135939561/430986542/RCGP+VE+riskgroups+paper.pdf/a6b54cd9-419d-9b63-e2bf-5dc796f5a91f.

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Footnote 9

Moayyedi P, Fernandes A, Yuan C, Farbod Y, Pittayanon R, Kanno T. The effects of vaccination in immunocompromised people. Rapid review of research studies on immunogenicity, safety, and efficacy/effectiveness of COVID-19 vaccines in immunocompromised individuals (unpublished draft). Toronto (ON): SPOR Evidence Alliance; 2021 Aug 25.

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Footnote 10

Young-Xu Y, Korves C, Roberts J, Powell EI, Zwain GM, Smith J, et al. Coverage and effectiveness of mRNA COVID-19 vaccines among veterans. medRxiv. 2021 Jul 14. doi: 10.1101/2021.06.14.21258906.

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Footnote 11

Tenforde MW, Patel MM, Ginde AA, Douin DJ, Talbot HK, Casey JD, et al. Effectiveness of SARS-CoV-2 mRNA vaccines for preventing Covid-19 hospitalizations in the United States. medRxiv. 2021 Jul 8. doi: 10.1101/2021.07.08.21259776.

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Footnote 12

Palich R, Veyri M, Vozy A, Marot S, Gligorov J, Benderra MA, et al. High seroconversion rate but low antibody titers after two injections of BNT162b2 (Pfizer-BioNTech) vaccine in patients treated with chemotherapy for solid cancers. Ann Oncol. 2021 Jun 22. doi: 10.1016/j.annonc.2021.06.018.

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Footnote 13

Scurr MJ, Zelek WM, Lippiatt G, Somerville M, Burnell SEA, Capitani L, et al. Whole blood-based measurement of SARS-CoV-2-specific T cell responses reveals asymptomatic infection and vaccine efficacy in healthy subjects and patients with solid organ cancers. medRxiv. 2021 Jun 3. doi: 10.1101/2021.06.02.21258218.

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Footnote 14

Barrière J, Chamorey E, Adjtoutah Z, Castelnau O, Mahamat A, Marco S, et al. Impaired immunogenicity of BNT162b2 anti-SARS-CoV-2 vaccine in patients treated for solid tumors. Ann Oncol. 2021 Aug;32(8):1053,1055. doi: 10.1016/j.annonc.2021.04.019.

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Footnote 15

Haidar G, Agha M, Lukanski A, Linstrum K, Troyan R, Bilderback A, et al. Immunogenicity of COVID-19 vaccination in immunocompromised patients: An observational, prospective cohort study interim analysis. medRxiv. 2021 Jun 30. doi: 10.1101/2021.06.28.21259576.

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Footnote 16

Addeo A, Shah PK, Bordry N, Hudson RD, Albracht B, Di Marco M, et al. Immunogenicity of SARS-CoV-2 messenger RNA vaccines in patients with cancer. Cancer cell. 2021 Aug 9;39(8):1091,1098.e2. doi: 10.1016/j.ccell.2021.06.009.

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Footnote 17

Thakkar A, Gonzalez-Lugo JD, Goradia N, Gali R, Shapiro LC, Pradhan K, et al. Seroconversion rates following COVID-19 vaccination among patients with cancer. Cancer Cell. 2021 Aug 9;39(8):1081,1090.e2. doi: 10.1016/j.ccell.2021.06.002.

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Footnote 18

Terpos E, Zagouri F, Liontos M, Sklirou AD, Koutsoukos K, Markellos C, et al. Low titers of SARS-CoV-2 neutralizing antibodies after first vaccination dose in cancer patients receiving checkpoint inhibitors. J Hematol Oncol. 2021 May 31;14(1):86,doi: 10.1186/s13045-021-01099-x.

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Footnote 19

Shroff RT, Chalasani P, Wei R, Pennington D, Quirk G, Schoenle MV, et al. Immune responses to COVID-19 mRNA vaccines in patients with solid tumors on active, immunosuppressive cancer therapy. medRxiv. 2021 May 14. doi: 10.1101/2021.05.13.21257129.

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Footnote 20

Monin L, Laing AG, Muñoz-Ruiz M, McKenzie DR, Del Molino Del Barrio I, Alaguthurai T, et al. Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study. Lancet Oncol. 2021 Jun;22(6):765,778. doi: 10.1016/S1470-2045(21)00213-8.

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Footnote 21

Massarweh A, Eliakim-Raz N, Stemmer A, Levy-Barda A, Yust-Katz S, Zer A, et al. Evaluation of seropositivity following BNT162b2 messenger RNA vaccination for SARS-CoV-2 in patients undergoing treatment for cancer. JAMA Oncol. 2021 Aug 1;7(8):1133,1140. doi: 10.1001/jamaoncol.2021.2155.

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Footnote 22

Benda M, Mutschlechner B, Ulmer H, Grabher C, Severgnini L, Volgger A, et al. Serological SARS-CoV-2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID-19 vaccine in haematological and oncological patients. Br J Haematol. 2021 Aug 3. doi: 10.1111/bjh.17743.

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Footnote 23

Shrotri M, Fragaszy E, Geismar C, Nguyen V, Beale S, Braithwaite I, et al. Spike-antibody responses to ChAdOx1 and BNT162b2 vaccines by demographic and clinical factors (Virus Watch study). medRxiv. 2021 May 20. doi: 10.1101/2021.05.12.21257102.

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Footnote 24

Iacono D, Cerbone L, Palombi L, Cavalieri E, Sperduti I, Cocchiara RA, et al. Serological response to COVID-19 vaccination in patients with cancer older than 80 years. J Geriatr Oncol. 2021 Jun 11. doi: 10.1016/j.jgo.2021.06.002.

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Footnote 25

Goshen-Lago T, Waldhorn I, Holland R, Szwarcwort-Cohen M, Reiner-Benaim A, Shachor-Meyouhas Y, et al. Serologic status and toxic effects of the SARS-CoV-2 BNT162b2 vaccine in patients undergoing treatment for cancer. JAMA Oncol. 2021 Jul 8. doi: 10.1001/jamaoncol.2021.2675.

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Footnote 26

Buttiron Webber T, Provinciali N, Musso M, Ugolini M, Boitano M, Clavarezza M, et al. Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment. SSRN Preprint. 2021 Aug 9. doi: 10.2139/ssrn.3901796.

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Footnote 27

Agha M, Blake M, Chilleo C, Wells A, Haidar G. Suboptimal response to COVID-19 mRNA vaccines in hematologic malignancies patients. medRxiv. 2021 Apr 7. doi: 10.1101/2021.04.06.21254949.

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Footnote 28

Bird S, Panopoulou A, Shea RL, Tsui M, Saso R, Sud A, et al. Response to first vaccination against SARS-CoV-2 in patients with multiple myeloma. Lancet Haematol. 2021 Jun;8(6):e389,e392. doi: 10.1016/S2352-3026(21)00110-1.

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Footnote 29

Cohen D, Hazut Krauthammer S, Cohen YC, Perry C, Avivi I, Herishanu Y, et al. Correlation between BNT162b2 mRNA Covid-19 vaccine-associated hypermetabolic lymphadenopathy and humoral immunity in patients with hematologic malignancy. Eur J Nucl Med Mol Imaging. 2021 May 8:1,10. doi: 10.1007/s00259-021-05389-x.

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Footnote 30

Diefenbach C, Caro J, Koide A, Grossbard M, Goldberg JD, Raphael B, et al. Impaired humoral immunity to SARS-CoV-2 vaccination in non-Hodgkin lymphoma and CLL patients. medRxiv. 2021 Jun 3. doi: 10.1101/2021.06.02.21257804.

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Footnote 31

Ghione P, Gu JJ, Attwood K, Torka P, Goel S, Sundaram S, et al. Impaired humoral responses to COVID-19 vaccination in patients with lymphoma receiving B-cell directed therapies. Blood. 2021 Jun 29;138(9):811,814. doi: 10.1182/blood.2021012443.

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Footnote 32

Harrington P, de Lavallade H, Doores KJ, O'Reilly A, Seow J, Graham C, et al. Single dose of BNT162b2 mRNA vaccine against SARS-CoV-2 induces high frequency of neutralising antibody and polyfunctional T-cell responses in patients with myeloproliferative neoplasms. Leukemia. 2021 May 22:1,5. doi: 10.1038/s41375-021-01300-7.

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Footnote 33

Harrington P, Doores KJ, Radia D, O'Reilly A, Lam HPJ, Seow J, et al. Single dose of BNT162b2 mRNA vaccine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induces neutralising antibody and polyfunctional T-cell responses in patients with chronic myeloid leukaemia. Br J Haematol. 2021 Jun 3. doi: 10.1111/bjh.17568.

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Footnote 34

Herishanu Y, Avivi I, Aharon A, Shefer G, Levi S, Bronstein Y, et al. Efficacy of the BNT162b2 mRNA COVID-19 Vaccine in patients with chronic lymphocytic leukemia. Blood. 2021 Apr 16. doi: 10.1182/blood.2021011568.

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Footnote 35

Lim SH, Campbell N, Johnson M, Joseph-Pietras D, Collins GP, O'Callaghan A, et al. Antibody responses after SARS-CoV-2 vaccination in patients with lymphoma. Lancet Haematol. 2021 Aug;8(8):e542,e544. doi: 10.1016/S2352-3026(21)00199-X.

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Footnote 36

Herzog Tzarfati K, Gutwein O, Apel A, Rahimi-Levene N, Sadovnik M, Harel L, et al. BNT162b2 COVID-19 vaccine is significantly less effective in patients with hematologic malignancies. Am J Hematol. 2021 Jun 29. doi: 10.1002/ajh.26284.

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Footnote 37

Terpos E, Trougakos IP, Gavriatopoulou M, Papassotiriou I, Sklirou AD, Ntanasis-Stathopoulos I, et al. Low neutralizing antibody responses against SARS-CoV-2 in elderly myeloma patients after the first BNT162b2 vaccine dose. Blood. 2021 Apr 16. doi: 10.1182/blood.2021011904.

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Footnote 38

Roeker LE, Knorr DA, Thompson MC, Nivar M, Lebowitz S, Peters N, et al. COVID-19 vaccine efficacy in patients with chronic lymphocytic leukemia. Leukemia. 2021 Sep;35(9):2703,2705. doi: 10.1038/s41375-021-01270-w.

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Footnote 39

Pimpinelli F, Marchesi F, Piaggio G, Giannarelli D, Papa E, Falcucci P, et al. Fifth-week immunogenicity and safety of anti-SARS-CoV-2 BNT162b2 vaccine in patients with multiple myeloma and myeloproliferative malignancies on active treatment: preliminary data from a single institution. J Hematol Oncol. 2021 May 18;14(1):81,021-01090-6. doi: 10.1186/s13045-021-01090-6.

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Footnote 40

Pimpinelli F, Marchesi F, Piaggio G, Giannarelli D, Papa E, Falcucci P, et al. Lower response to BNT162b2 vaccine in patients with myelofibrosis compared to polycythemia vera and essential thrombocythemia. J Hematol Oncol. 2021 Jul 29;14(1):119,021-01130-1. doi: 10.1186/s13045-021-01130-1.

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Footnote 41

Peled Y, Ram E, Lavee J, Sternik L, Segev A, Wieder-Finesod A, et al. BNT162b2 vaccination in heart transplant recipients: Clinical experience and antibody response. J Heart Lung Transplant. 2021 Aug;40(8):759,762. doi: 10.1016/j.healun.2021.04.003.

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Footnote 42

Van Oekelen O, Gleason CR, Agte S, Srivastava K, Beach KF, Aleman A, et al. Highly variable SARS-CoV-2 spike antibody responses to two doses of COVID-19 RNA vaccination in patients with multiple myeloma. Cancer Cell. 2021 Aug 9;39(8):1028,1030. doi: 10.1016/j.ccell.2021.06.014.

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Footnote 43

Maneikis K, Šablauskas K, Ringelevičiūtė U, Vaitekėnaitė V, Čekauskienė R, Kryžauskaitė L, et al. Immunogenicity of the BNT162b2 COVID-19 mRNA vaccine and early clinical outcomes in patients with haematological malignancies in Lithuania: a national prospective cohort study. Lancet Haematol. 2021 Aug;8(8):e583,e592. doi: 10.1016/S2352-3026(21)00169-1.

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Footnote 44

Ghandili S, Schönlein M, Lütgehetmann M, Schulze Zur Wiesch J, Becher H, Bokemeyer C, et al. Post-vaccination anti-SARS-CoV-2-antibody response in patients with multiple myeloma correlates with low CD19+ b-lymphocyte count and anti-CD38 treatment. Cancers (Basel). 2021 Jul 28;13(15):3800. doi: 10.3390/cancers13153800.

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Footnote 45

Guglielmelli P, Mazzoni A, Maggi L, Kiros ST, Zammarchi L, Pilerci S, et al. Impaired response to first SARS-CoV-2 dose vaccination in myeloproliferative neoplasm patients receiving ruxolitinib. Am J Hematol. 2021 Jul 31. doi: 10.1002/ajh.26305.

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Footnote 46

Stampfer SD, Goldwater MS, Jew S, Bujarski S, Regidor B, Daniely D, et al. Response to mRNA vaccination for COVID-19 among patients with multiple myeloma. Leukemia. 2021 Jul 29:1,8. doi: 10.1038/s41375-021-01354-7.

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Footnote 47

Gurion R, Rozovski U, Itchaki G, Gafter-Gvili A, Leibovitch C, Raanani P, et al. Humoral serologic response to the BNT162b2 vaccine is abrogated in lymphoma patients within the first 12 months following treatment with anti-CD2O antibodies. Haematologica. 2021 Jul 29. doi: 10.3324/haematol.2021.279216.

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Footnote 48

Benjamini O, Rokach L, Itchaki G, Braester A, Shvidel L, Goldschmidt N, et al. Safety and efficacy of BNT162b mRNA Covid19 Vaccine in patients with chronic lymphocytic leukemia. Haematologica. 2021 Jul 29. doi: 10.3324/haematol.2021.279196.

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Footnote 49

Re D, Barrière J, Chamorey E, Delforge M, Gastaud L, Petit E, et al. Low rate of seroconversion after mRNA anti-SARS-CoV-2 vaccination in patients with hematological malignancies. Leuk Lymphoma. 2021 Jul 26:1,3. doi: 10.1080/10428194.2021.1957877.

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Footnote 50

Ramanathan M, Murugesan K, Yang LM, Costales C, Bulterys PL, Schroers-Martin J, et al. Cell-mediated and humoral immune response to 2-dose SARS-CoV2 mRNA vaccination in immunocompromised patient population. medRxiv. 2021 Jul 23. doi: 10.1101/2021.07.21.21260921.

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Footnote 51

Charmetant X, Espi M, Benotmane I, Heibel F, Buron F, Gautier-Vargas G, et al. Comparison of infected and vaccinated transplant recipients highlights the role of Tfh and neutralizing IgG in COVID-19 protection. medRxiv. 2021 Jul 24. doi: 10.1101/2021.07.22.21260852.

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Footnote 52

Gavriatopoulou M, Terpos E, Kastritis E, Briasoulis A, Gumeni S, Ntanasis-Stathopoulos I, et al. Low neutralizing antibody responses in WM, CLL and NHL patients after the first dose of the BNT162b2 and AZD1222 vaccine. Clin Exp Med. 2021 Jul 20:1,5. doi: 10.1007/s10238-021-00746-4.

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Footnote 53

Greenberger LM, Saltzman LA, Senefeld JW, Johnson PW, DeGennaro LJ, Nichols GL. Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies. Cancer cell. 2021 Aug 9;39(8):1031,1033. doi: 10.1016/j.ccell.2021.07.012.

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Footnote 54

Ehmsen S, Asmussen A, Jeppesen SS, Nilsson AC, Østerlev S, Vestergaard H, et al. Antibody and T cell immune responses following mRNA COVID-19 vaccination in patients with cancer. Cancer Cell. 2021 Aug 9;39(8):1034,1036. doi: 10.1016/j.ccell.2021.07.016.

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Footnote 55

Fox TA, Kirkwood AA, Enfield L, O'Reilly M, Arulogun S, D'Sa S, et al. Low seropositivity and sub-optimal neutralisation rates in patients fully vaccinated against COVID-19 with B cell malignancies. medRxiv. 2021 Jul 19. doi: 10.1101/2021.07.19.21260762.

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Footnote 56

Achiron A, Mandel M, Dreyer-Alster S, Harari G, Magalashvili D, Sonis P, et al. Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies. Ther Adv Neurol Disord. 2021 Apr 22;14:doi: 10.1177/17562864211012835.

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Footnote 57

Apostolidis SA, Kakara M, Painter MM, Goel RR, Mathew D, Lenzi K, et al. Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy. medRxiv. 2021 Jun 30. doi: 10.1101/2021.06.23.21259389.

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Footnote 58

Guerrieri S, Lazzarin S, Zanetta C, Nozzolillo A, Filippi M, Moiola L. Serological response to SARS-CoV-2 vaccination in multiple sclerosis patients treated with fingolimod or ocrelizumab: an initial real-life experience. J Neurol. 2021 Jun 26:1,5. doi: 10.1101/2021.06.23.21259389.

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Footnote 59

Miele M, Busà R, Russelli G, Sorrentino MC, Di Bella M, Timoneri F, et al. Impaired anti-SARS-CoV-2 humoral and cellular immune response induced by Pfizer-BioNTech BNT162b2 mRNA vaccine in solid organ transplanted patients. Am J Transplant. 2021 Aug;21(8):2919,2921. doi: 10.1111/ajt.16702.

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Footnote 60

Cucchiari D, Egri N, Bodro M, Herrera S, Del Risco-Zevallos J, Casals-Urquiza J, et al. Cellular and humoral response after MRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients. Am J Transplant. 2021 Aug;21(8):2727,2739. doi: 10.1111/ajt.16701.

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Footnote 61

Husain SA, Tsapepas D, Paget KF, Chang JH, Crew RJ, Dube GK, et al. Postvaccine anti-SARS-CoV-2 spike protein antibody development in kidney transplant recipients. Kidney Int Rep. 2021 Jun;6(6):1699,1700. doi: 10.1016/j.ekir.2021.04.017.

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Footnote 62

Schmidt T, Klemis V, Schub D, Schneitler S, Reichert MC, Wilkens H, et al. Cellular immunity predominates over humoral immunity after the first dose of COVID-19 vaccines in solid organ transplant recipients. medRxiv. 2021 May 14. doi: 10.1101/2021.05.07.21256809.

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Footnote 63

Ben-Dov I, Oster Y, Tzukert K, Alster T, Bader R, Israeli R, et al. Impact of tozinameran (BNT162b2) mRNA vaccine on kidney transplant and chronic dialysis patients: 3-5 months followup. medRxiv. 2021 Jul 17. doi: 10.1101/2021.06.12.21258813.

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Footnote 64

Benotmane I, Gautier-Vargas G, Cognard N, Olagne J, Heibel F, Braun-Parvez L, et al. Weak anti-SARS-CoV-2 antibody response after the first injection of an mRNA COVID-19 vaccine in kidney transplant recipients. Kidney Int. 2021 Jun;99(6):1487,1489. doi: 10.1016/j.kint.2021.03.014.

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Footnote 65

Bertrand D, Hamzaoui M, Lemée V, Lamulle J, Hanoy M, Laurent C, et al. Antibody and T cell response to SARS-CoV-2 messenger RNA BNT162b2 vaccine in kidney transplant recipients and hemodialysis patients. J Am Soc Nephrol. 2021 Sep;32(9):2147,2152. doi: 10.1681/ASN.2021040480.

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Footnote 66

Chavarot N, Ouedrani A, Marion O, Leruez-Ville M, Vilain E, Baaziz M, et al. Poor anti-SARS-CoV-2 humoral and T-cell responses after 2 injections of mRNA vaccine in kidney transplant recipients treated with belatacept. Transplantation. 2021 Sep 1;105(9):e94,e95. doi: 10.1097/TP.0000000000003784.

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Footnote 67

Danthu C, Hantz S, Dahlem A, Duval M, Ba B, Guibbert M, et al. Humoral response after SARS-CoV-2 mRNA vaccination in a cohort of hemodialysis patients and kidney transplant recipients. J Am Soc Nephrol. 2021 Sep;32(9):2153,2158. doi: 10.1681/ASN.2021040490.

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Footnote 68

Firket L, Descy J, Seidel L, Bonvoisin C, Bouquegneau A, Grosch S, et al. Serological response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients depends on prior exposure to SARS-CoV-2. Am J Transplant. 2021 Jun 21. doi: 10.1111/ajt.16726.

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Footnote 69

Grupper A, Rabinowich L, Schwartz D, Schwartz IF, Ben-Yehoyada M, Shashar M, et al. Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus. Am J Transplant. 2021 Apr 18. doi: 10.1111/ajt.16615.

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Footnote 70

Havlin J, Svorcova M, Dvorackova E, Lastovicka J, Lischke R, Kalina T, et al. Immunogenicity of BNT162b2 mRNA COVID-19 vaccine and SARS-CoV-2 infection in lung transplant recipients. J Heart Lung Transplant. 2021 Aug;40(8):754,758. doi: 10.1016/j.healun.2021.05.004.

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Footnote 71

Itzhaki Ben Zadok O, Shaul AA, Ben-Avraham B, Yaari V, Ben Zvi H, Shostak Y, et al. Immunogenicity of the BNT162b2 mRNA vaccine in heart transplant recipients - a prospective cohort study. Eur J Heart Fail. 2021 May 8. doi: 10.1002/ejhf.2199.

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Footnote 72

Marinaki S, Adamopoulos S, Degiannis D, Roussos S, Pavlopoulou ID, Hatzakis A, et al. Immunogenicity of SARS-CoV-2 BNT162b2 vaccine in solid organ transplant recipients. Am J Transplant. 2021 Aug;21(8):2913,2915. doi: 10.1111/ajt.16607.

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Footnote 73

Marion O, Del Bello A, Abravanel F, Couat C, Faguer S, Esposito L, et al. Safety and immunogenicity of anti-SARS-CoV-2 messenger RNA vaccines in recipients of solid organ transplants. Ann Intern Med. 2021 May 25. doi: 10.7326/M21-1341.

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Footnote 74

Mazzola A, Todesco E, Drouin S, Hazan F, Marot S, Thabut D, et al. Poor antibody response after two doses of SARS-CoV-2 vaccine in transplant recipients. Clin Infect Dis. 2021 Jun 24. doi: 10.1093/cid/ciab580.

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Footnote 75

Narasimhan M, Mahimainathan L, Clark AE, Usmani A, Cao J, Araj E, et al. Serological response in lung transplant recipients after two doses of SARS-CoV-2 mRNA vaccines. Vaccines (Basel). 2021 Jun 30;9(7):708. doi: 10.3390/vaccines9070708.

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Footnote 76

Rabinowich L, Grupper A, Baruch R, Ben-Yehoyada M, Halperin T, Turner D, et al. Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients. J Hepatol. 2021 Aug;75(2):435,438. doi: 10.1016/j.jhep.2021.04.020.

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Footnote 77

Ram R, Hagin D, Kikozashvilli N, Freund T, Amit O, Bar-On Y, et al. Safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients after allogeneic HCT or CD19-based CART therapy-A single-center prospective cohort study. Transplant Cell Ther. 2021 Sep;27(9):788,794. doi: 10.1016/j.jtct.2021.06.024.

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Footnote 78

Rincon-Arevalo H, Choi M, Stefanski A, Halleck F, Weber U, Szelinski F, et al. Impaired antigen-specific memory B cell and plasma cell responses including lack of specific IgG upon SARS-CoV-2 BNT162b2 vaccination among kidney transplant and dialysis patients. medRxiv. 2021 Apr 20. doi: 10.1101/2021.04.15.21255550.

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Footnote 79

Rozen-Zvi B, Yahav D, Agur T, Zingerman B, Ben-Zvi H, Atamna A, et al. Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study. Clin Microbiol Infect. 2021 Aug;27(8):1173.e1,1173.e4. doi: 10.1016/j.cmi.2021.04.028.

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Footnote 80

Sattler A, Schrezenmeier E, Weber UA, Potekhin A, Bachmann F, Straub-Hohenbleicher H, et al. Impaired humoral and cellular immunity after SARS-CoV-2 BNT162b2 (tozinameran) prime-boost vaccination in kidney transplant recipients. J Clin Invest. 2021 Jul 15;131(14):e150175. doi: 10.1172/JCI150175.

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Footnote 81

Shostak Y, Shafran N, Heching M, Rosengarten D, Shtraichman O, Shitenberg D, et al. Early humoral response among lung transplant recipients vaccinated with BNT162b2 vaccine. Lancet Respir Med. 2021 Jun;9(6):e52,e53. doi: 10.1016/S2213-2600(21)00184-3.

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Footnote 82

Yi SG, Knight RJ, Graviss EA, Nguyen DT, Ghobrial RM, Gaber AO, et al. Kidney transplant recipients rarely show an early antibody response following the first COVID-19 vaccine administration. Transplantation. 2021 Mar 19. doi: 10.1097/TP.0000000000003764.

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Footnote 83

Midtvedt K, Tran T, Parker K, Marti HP, Stenehjem AE, Gøransson LG, et al. Low immunization rate in kidney transplant recipients also after dose 2 of the BNT162b2 vaccine: Continue to keep your guard up! Transplantation. 2021 Aug 1;105(8):e80,e81. doi: 10.1097/TP.0000000000003856.

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Footnote 84

Di Meo A, Miller JJ, Fabros A, Brinc D, Hall V, Pinzon N, et al. Evaluation of three anti-SARS-CoV-2 serologic immunoassays for post-vaccine response. J Appl Lab Med. 2021 Aug 3. doi: 10.1093/jalm/jfab087.

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Footnote 85

Del Bello A, Abravanel F, Marion O, Couat C, Esposito L, Lavayssière L, et al. Efficiency of a boost with a third dose of anti-SARS-CoV-2 messenger RNA-based vaccines in solid organ transplant recipients. Am J Transplant. 2021 Jul 31. doi: 10.1111/ajt.16775.

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Footnote 86

Hod T, Ben-David A, Olmer L, Levy I, Ghinea R, Mor E, et al. Humoral response of renal transplant recipients to the BNT162b2 SARS-CoV-2 mRNA vaccine using both RBD IgG and neutralizing antibodies. Transplantation. 2021 Jul 6. doi: 10.1097/TP.0000000000003889.

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Footnote 87

Stumpf J, Siepmann T, Lindner T, Karger C, Schwöbel J, Anders L, et al. Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine. Lancet Reg Health Eur. 2021 Jul 23. doi: 10.1016/j.lanepe.2021.100178.

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Footnote 88

Herrera S, Colmenero J, Pascal M, Escobedo M, Castel MA, Sole-González E, et al. Cellular and humoral immune response after mRNA-1273 SARS-CoV-2 vaccine in liver and heart transplant recipients. Am J Transplant. 2021 Jul 22. doi: 10.1111/ajt.16768.

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Footnote 89

Easdale S, Shea R, Ellis L, Bazin J, Davis K, Dallas F, et al. Serologic responses following a single dose of SARS-Cov-2 vaccination in allogeneic stem cell transplantation recipients. Transplant Cell Ther. 2021 Jul 19. doi: 10.1016/j.jtct.2021.07.011.

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Footnote 90

Boyarsky BJ, Barbur I, Chiang TP, Ou MT, Greenberg RS, Teles AT, et al. SARS-CoV-2 messenger RNA vaccine immunogenicity in solid organ transplant recipients with prior COVID-19. Transplantation. 2021 Jul 19. doi: 10.1097/TP.0000000000003900.

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Footnote 91

Ali H, Ngo D, Aribi A, Arslan S, Dadwal S, Marcucci G, et al. Safety and tolerability of SARS-CoV2 emergency-use authorized vaccines for allogeneic hematopoietic stem cell transplant recipients. Transplant Cell Ther. 2021 Jul 15. doi: 10.1016/j.jtct.2021.07.008.

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Footnote 92

Redjoul R, Le Bouter A, Beckerich F, Fourati S, Maury S. Antibody response after second BNT162b2 dose in allogeneic HSCT recipients. Lancet. 2021 Jul 24;398(10297):298,299. doi: 10.1016/S0140-6736(21)01594-4.

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Footnote 93

Prendecki M, Thomson T, Clarke CL, Martin P, Gleeson S, De Aguiar RC, et al. Comparison of humoral and cellular responses in kidney transplant recipients receiving BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines. medRxiv. 2021 Jul 14. doi: 10.1101/2021.07.09.21260192.

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Footnote 94

Schramm R, Costard-Jäckle A, Rivinius R, Fischer B, Müller B, Boeken U, et al. Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients. Clin Res Cardiol. 2021 Aug;110(8):1142,1149. doi: 10.1007/s00392-021-01880-5.

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Footnote 95

Korth J, Jahn M, Dorsch O, Anastasiou OE, Sorge-Hädicke B, Eisenberger U, et al. Impaired humoral response in renal transplant recipients to SARS-CoV-2 vaccination with BNT162b2 (Pfizer-BioNTech). Viruses. 2021 Apr 25;13(5):756. doi: 10.3390/v13050756.

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Footnote 96

Holden IK, Bistrup C, Nilsson AC, Hansen JF, Abazi R, Davidsen JR, et al. Immunogenicity of SARS-CoV-2 mRNA vaccine in solid organ transplant recipients. J Intern Med. 2021 Jul 8. doi: 10.1111/joim.13361.

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Footnote 97

Cao J, Liu X, Muthukumar A, Gagan J, Jones P, Zu Y. Poor humoral response in solid organ transplant recipients following complete mRNA SARS-CoV-2 vaccination. Clin Chem. 2021 Aug 6. doi: 10.1093/clinchem/hvab149.

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Footnote 98

Hall VG, Ferreira VH, Ierullo M, Ku T, Marinelli T, Majchrzak-Kita B, et al. Humoral and cellular immune response and safety of two-dose SARS-CoV-2 mRNA-1273 vaccine in solid organ transplant recipients. Am J Transplant. 2021 Aug 4. doi: 10.1111/ajt.16766.

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Footnote 99

Rashidi-Alavijeh J, Frey A, Passenberg M, Korth J, Zmudzinski J, Anastasiou OE, et al. Humoral response to SARS-Cov-2 vaccination in liver transplant recipients-A single-center experience. Vaccines (Basel). 2021 Jul 4;9(7):738. doi: 10.3390/vaccines9070738.

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Footnote 100

Salinas AF, Mortari EP, Terreri S, Quintarelli C, Pulvirenti F, Cecca SD, et al. SARS-CoV-2 vaccine induced atypical immune responses in antibody defects: everybody does their best. medRxiv. 2021 Jun 28. doi: 10.1101/2021.06.24.21259130.

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Footnote 101

Hagin D, Freund T, Navon M, Halperin T, Adir D, Marom R, et al. Immunogenicity of Pfizer-BioNTech COVID-19 vaccine in patients with inborn errors of immunity. J Allergy Clin Immunol. 2021 Sep;148(3):739,749. doi: 10.1016/j.jaci.2021.05.029.

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Footnote 102

Nadesalingam A, Cantoni D, Wells DA, Aguinam ET, Ferrari M, Smith P, et al. Paucity and discordance of neutralising antibody responses to SARS-CoV-2 VOCs in vaccinated immunodeficient patients and health-care workers in the UK. Lancet Microbe. 2021 Sep;2(9):e416,e418. doi: 10.1016/S2666-5247(21)00157-9.

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Footnote 103

Ducloux D, Colladant M, Chabannes M, Yannaraki M, Courivaud C. Humoral response after 3 doses of the BNT162b2 mRNA COVID-19 vaccine in patients on hemodialysis. Kidney Int. 2021 Sep;100(3):702,704. doi: 10.1016/j.kint.2021.06.025.

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Footnote 104

Longlune N, Nogier MB, Miedougé M, Gabilan C, Cartou C, Seigneuric B, et al. High immunogenicity of a messenger RNA based vaccine against SARS-CoV-2 in chronic dialysis patients. Nephrol Dial Transplant. 2021 May 31. doi: 10.1093/ndt/gfab193.

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Footnote 105

Werbel WA, Boyarsky BJ, Ou MT, Massie AB, Tobian AAR, Garonzik-Wang JM, et al. Safety and immunogenicity of a third dose of SARS-CoV-2 vaccine in solid organ transplant recipients: A case series. Ann Intern Med. 2021 Jun 15. doi: 10.7326/L21-0282.

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Footnote 106

Espi M, Charmetant X, Barba T, Pelletier C, Koppe L, Chalencon E, et al. Justification, safety, and efficacy of a third dose of mRNA vaccine in maintenance hemodialysis patients: a prospective observational study. medRxiv. 2021 Jul 6. doi: 10.1101/2021.07.02.21259913.

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Footnote 107

Massa F, Cremoni M, Gerard A, Grabsi H, Rogier L, Blois M, et al. Safety and cross-variant immunogenicity of a three-dose COVID-19 mRNA vaccine regimen in kidney transplant recipients. SSRN- Lancet prepublication. 2021 Jul 22. doi: 10.2139/ssrn.3890865.

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Footnote 108

Frantzen L, Thibeaut S, Moussi-Frances J, Indreies M, Kiener C, Saingra Y, et al. COVID-19 vaccination in haemodialysis patients: Good things come in threes…. Nephrol Dial Transplant. 2021 Jul 20. doi: 10.1093/ndt/gfab224.

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Footnote 109

Re D, Seitz-Polski B, Carles M, Brglez V, Graça D, Benzaken S, et al. Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients with lymphoid malignancies. Research square - prepublication. 2021 Jul 21. doi: 10.21203/rs.3.rs-727941/v1.

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Footnote 110

Benotmane I, Gautier G, Perrin P, Olagne J, Cognard N, Fafi-Kremer S, et al. Antibody response after a third dose of the mRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients with minimal serologic response to 2 doses. JAMA. 2021 Jul 23. doi: 10.1001/jama.2021.12339.

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Footnote 111

Del Bello A, Abravanel F, Marion O, Couat C, Esposito L, Lavayssière L, et al. Efficiency of a boost with a third dose of anti-SARS-CoV-2 messenger RNA-based vaccines in solid organ transplant recipients. Am J Transplant. 2021 Jul 31. doi: 10.1111/ajt.16775.

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Footnote 112

Hall VG, Ferreira VH, Ku T, Ierullo M, Majchrzak-Kita B, Chaparro C, et al. Randomized trial of a third dose of mRNA-1273 vaccine in transplant recipients. N Engl J Med. 2021 Aug 11. doi: 10.1056/NEJMc2111462.

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Footnote 113

Schrezenmeier E, Rincon-Arevalo H, Stefanski A, Potekhin A, Staub-Hohenbleicher H, Choi M, et al. B and T cell responses after a third dose of SARS-CoV-2 vaccine in Kidney Transplant Recipients. medRxiv. 2021 Aug 13. doi: 10.1101/2021.08.12.21261966:2021.08.12.21261966.

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Footnote 114

Kamar N, Abravanel F, Marion O, Couat C, Izopet J, Del Bello A. Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients. N Engl J Med. 2021 Aug 12;385(7):661,662. doi: 10.1056/NEJMc2108861.

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Footnote 115

Gounant V, Ferré VM, Soussi G, Charpentier C, Flament H, Fidouh N, et al. Efficacy of SARS-CoV-2 vaccine in thoracic cancer patients: a prospective study supporting a third dose in patients with minimal serologic response after two vaccine doses. medRxiv. 2021 Aug 13. doi: 10.1101/2021.08.12.21261806.

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Footnote 116

Ruddy JA, Connolly CM, Boyarsky BJ, Werbel WA, Christopher-Stine L, Garonzik-Wang J, et al. High antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in patients with rheumatic and musculoskeletal diseases. Ann Rheum Dis. 2021 May 24.

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Footnote 117

Husain SA, Tsapepas D, Paget KF, Chang JH, Crew RJ, Dube GK, et al. Postvaccine anti-SARS-CoV-2 spike protein antibody development in kidney transplant recipients. Kidney Int Rep. 2021 Jun;6(6):1699,1700. doi: 10.1016/j.ekir.2021.04.017.

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Footnote 118

Anand S, Montez-Rath M, Han J, Garcia P, Cadden L, Hunsader P, et al. Antibody response to COVID-19 vaccination in patients receiving dialysis. J Am Soc Nephrol. 2021 Jun 11. doi: 10.1681/ASN.2021050611.

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Footnote 119

Broseta JJ, Rodríguez-Espinosa D, Rodríguez N, Mosquera MDM, Marcos MÁ, Egri N, et al. Humoral and cellular responses to mRNA-1273 and BNT162b2 SARS-CoV-2 vaccines administered to hemodialysis patients. Am J Kidney Dis. 2021 Jun 24. doi: 10.1053/j.ajkd.2021.06.002.

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Footnote 120

Spiera R, Jinich S, Jannat-Khah D. Rituximab, but not other antirheumatic therapies, is associated with impaired serological response to SARS- CoV-2 vaccination in patients with rheumatic diseases. Ann Rheum Dis. 2021 May 11. doi: 10.1136/annrheumdis-2021-220604.

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Footnote 121

Lacson E, Argyropoulos C, Manley H, Aweh G, Chin A, Salman L, et al. Immunogenicity of SARS-CoV-2 vaccine in dialysis. J Am Soc Nephrol. 2021 Aug 4. doi: 10.1681/ASN.2021040432.

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Footnote 122

Izmirly PM, Kim MY, Samanovic M, Fernandez-Ruiz R, Ohana S, Deonaraine KK, et al. Evaluation of immune response and disease status in SLE patients following SARS-CoV-2 vaccination. Arthritis Rheumatol. 2021 Aug 4. doi: 10.1002/art.41937.

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Footnote 123

Garcia P, Anand S, Han J, Montez-Rath M, Sun S, Shang T, et al. COVID19 vaccine type and humoral immune response in patients receiving dialysis. medRxiv. 2021 Aug 4. doi: 10.1101/2021.08.02.21261516.

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Footnote 124

Sormani MP, Inglese M, Schiavetti I, Carmisciano L, Laroni A, Lapucci C, et al. Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies. SSRN Preprint. 2021 Jul 20. doi: 10.2139/ssrn.3886420.

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Footnote 125

Kaiser RA, Haller MC, Apfalter P, Kerschner H, Cejka D. Comparison of BNT162b2 (Pfizer-BioNtech) and mRNA-1273 (Moderna) SARS-CoV-2 mRNA vaccine immunogenicity in dialysis patients. Kidney Int. 2021 Sep;100(3):697,698. doi: 10.1016/j.kint.2021.07.004.

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Footnote 126

Mrak D, Tobudic S, Koblischke M, Graninger M, Radner H, Sieghart D, et al. SARS-CoV-2 vaccination in rituximab-treated patients: B cells promote humoral immune responses in the presence of T-cell-mediated immunity. Ann Rheum Dis. 2021 Jul 20. doi: 10.1136/annrheumdis-2021-220781.

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Abbreviations

Abbreviation Term

CI
Confidence interval
COVID-19
Coronavirus disease 2019
NACI
National Advisory Committee on Immunization
mRNA
messenger ribonucleic acid
PHAC
Public Health Agency of Canada
SARS-CoV-2
Severe Acute Respiratory Syndrome Coronavirus 2

Acknowledgments

This statement was prepared by: E Wong, R Krishnan, K Farrah, J Montroy, N Forbes, J Zafack, R Stirling, B Warshawsky, O Baclic, K Young, M Tunis, R Harrison and S Deeks on behalf of NACI.

NACI gratefully acknowledges the contribution of: K Ramotar, N St-Pierre, A Jirovec, SH Lim, N Alluqmani, S Ismail, and the NACI Secretariat.

NACI Members: S Deeks (Chair), R Harrison (Vice-Chair), J Bettinger, N Brousseau, P De Wals, E Dubé, V Dubey, K Hildebrand, K Klein, J Papenburg, A Pham-Huy, C Rotstein, B Sander, S Smith, and S Wilson.

Former member: C Quach (Chair)

Liaison representatives: LM Bucci (Canadian Public Health Association), E Castillo (Society of Obstetricians and Gynaecologists of Canada), A Cohn (Centers for Disease Control and Prevention, United States), L Dupuis (Canadian Nurses Association), J Emili (College of Family Physicians of Canada), D Fell (Canadian Association for Immunization Research and Evaluation), M Lavoie (Council of Chief Medical Officers of Health), D Moore (Canadian Paediatric Society), M Naus (Canadian Immunization Committee), P Emberley (Canadian Pharmacists Association), L Bill (Canadian Indigenous Nurses Association), and S Funnel (Indigenous Physicians Association of Canada).

Ex-officio representatives: V Beswick-Escanlar (National Defence and the Canadian Armed Forces), E Henry (Centre for Immunization and Respiratory Infectious Diseases (CIRID), PHAC), M Lacroix (Public Health Ethics Consultative Group, PHAC), C Lourenco (Biologic and Radiopharmaceutical Drugs Directorate, Health Canada), S Ogunnaike-Cooke (CIRID, PHAC), K Robinson (Marketed Health Products Directorate, HC), G Poliquin (National Microbiology Laboratory, PHAC), and T Wong (First Nations and Inuit Health Branch, Indigenous Services Canada).

NACI High Consequence Infectious Disease Working Group

Members: R Harrison (Chair), Y-G Bui, S Deeks, K Dooling, K Hildebrand, M Miller, M Murti, J Papenburg, R Pless, S Ramanathan, N Stall, and S Vaughan.

PHAC Participants: N Abraham, L Coward, N Forbes, C Jensen, A Killikelly, R Krishnan, J Montroy, A Nam, M Patel, M Salvadori, A Sinilaite, R Stirling, E Tice, B Warshawsky, R Ximenes MW Yeung, and J Zafack.

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