NACI rapid response: Updated guidance on COVID-19 vaccination timing for individuals previously infected with SARS-CoV-2

Publication: February 4, 2022

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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.

Introduction

Currently, infection rates across Canada are at unprecedented levels due to the highly transmissible Omicron variant, which is partially evasive to immunity conferred by COVID-19 vaccines or a previous SARS-CoV-2 infection. Due to widespread circulation of the Omicron variant, many Canadians seeking COVID-19 vaccination (for primary series or booster doses) will have a history of SARS-CoV-2 infection. While there is a paucity of evidence to inform recommendations on optimal intervals between SARS-CoV-2 infection and COVID-19 vaccination, NACI is providing updated guidance on suggested intervals based on immunological principles, the available evidence, and expert opinion. This guidance may change as additional evidence emerges regarding the extent and duration of immunological protection conferred by infection with Omicron and future variants.

Methods

On February 25, March 10, April 1, June 29, and November 23, 2021, and January 18, 2022, NACI reviewed available evidence on vaccine safety, immunogenicity, and effectiveness of COVID-19 vaccination (primary series and/or booster dose) with respect to previous infection, as well as ethics, equity, feasibility, and acceptability of guidance.

Following a comprehensive review and discussion, NACI approved this updated guidance on COVID-19 vaccines (primary series and booster doses) for individuals with a history of previous SARS-CoV-2 infection on January 31, 2022.

NACI continues to review the evidence on the use of COVID-19 vaccines and will update its recommendations as needed. Details of NACI's evidence-informed recommendation development process can be found elsewhereFootnote 1Footnote 2.

Recommendations

NACI continues to recommend that COVID-19 vaccines should be offered to individuals with previous SARS-CoV-2 infection without contraindications to the vaccine.

Updates are presented in the table below regarding the timing of vaccinations for those with recent SARS-CoV-2 infection. These are added to previous recommendations.

Interim guidance on suggested intervals between previous SARS-CoV-2 infection and COVID-19 vaccination

NACI acknowledges the current high incidence rate of COVID-19 in Canada and internationally, as well as the limitations of the evidence on optimal timing between COVID-19 vaccine doses (primary series and booster doses) and previous SARS-CoV-2 infection. While there are insufficient clinical or real-world data at this time to inform guidance on an optimal interval between infection and subsequent vaccination, NACI has considered available data, basic principles of vaccinology and immunology, and expert opinion informed by knowledge of other viral diseases, and issued the following updated guidance on suggested intervals between previous SARS-CoV-2 infection and COVID-19 vaccination:

Table 1. Suggested intervals between previous SARS-CoV-2 infectionFootnote a and COVID-19 vaccination
SARS-CoV-2 infectionFootnote a timing relative to COVID-19 vaccination Population Suggested interval between SARS-CoV-2 infectionFootnote a and vaccination (clinical discretion is advised)Footnote bFootnote c
Infection prior to initiationFootnote c or completion of primary vaccination series Individuals 5 years of age and older who are not considered moderately to severely immunocompromised and with no previous history of multisystem inflammatory syndrome in children (MIS-C) Receive the vaccine 8 weeks after symptom onset or positive test (if asymptomatic)Footnote b
Individuals 5 years of age and older who are moderately to severely immunocompromised and with no previous history of MIS-C Receive the vaccine dose 4 to 8 weeks after symptom onset or positive test (if asymptomatic)Footnote b
Individuals 5 years of age and older with a previous history of MIS-C (regardless of immunocompromised status) Receive the vaccine dose when clinical recovery has been achieved or ≥90 days since the onset of MIS-C,  whichever is longer
Infection after primary seriesFootnote d but before booster dose Individuals 12 years of age and older currently eligible for a booster dose 3 months after symptom onset or positive test (if asymptomatic)Footnote b and provided it is at least 6 months from completing the primary series

Footnotes

Footnote 1

Previous infection can be defined in different ways based on jurisdictional policies and access to testing. The following suggestion can be considered to define previous infection with SARS-CoV-2:

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Footnote 2

These suggested intervals are based on immunological principles and expert opinion, and may change as evidence on COVID-19, variants of concern (VOCs), and COVID-19 vaccines emerge. When considering whether or not to administer vaccine doses following the suggested intervals outlined in this table, biological and social risk factors for exposure (e.g., local epidemiology, circulation of VOCs, living settings) and severe disease should also be taken into account. These intervals are a guide and clinical discretion is advised.

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Footnote 3

For individuals who have not had any previous doses, they may receive their first dose after acute symptoms of COVID-19 have resolved and they are no longer infectious, or they may follow these suggested intervals. Individual benefit/risk assessment and clinical discretion are advised as per footnote “b”. These suggested waiting times are intended to minimize the risk of transmission of COVID-19 at an immunization venue and to enable monitoring for COVID-19 vaccine adverse events without potential confounding from symptoms of COVID-19 or other co-existing illnesses.

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Footnote 4

The primary series is outlined in the Canadian Immunization Guide. Note that for moderately to severely immunocompromised individuals who were immunized with a primary series that includes one additional dose, a booster dose would be subsequent to that immunocompromised primary series.

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For further information on NACI’s recommendations on the use of COVID-19 vaccines, please refer to the COVID-19 vaccine chapter in the Canadian Immunization Guide (CIG) as well as additional NACI statements on the use of COVID-19 vaccines.

NACI will continue to review the evidence as it emerges and update guidance on the use of COVID-19 vaccines in individuals with a history of SARS-CoV-2 infection as needed.

Rationale, summary of evidence, and additional considerations

Unknowns:

NACI will continue to evaluate evidence to inform on suggested intervals between previous SARS-CoV-2 infection and COVID-19 vaccination as data emerges and will update their guidance as warranted.

For further information on NACI’s recommendations on the use of COVID-19 vaccines, please refer to the COVID-19 vaccine chapter in the Canadian Immunization Guide (CIG) as well as additional NACI statements on the use of COVID-19 vaccines.

Abbreviations

COVID-19
Coronavirus disease 2019
MIS-C
Multisystem inflammatory syndrome in children
NACI
National Advisory Committee on Immunization
PHAC
Public Health Agency of Canada
VOC
Variant of concern

Acknowledgments

This statement was prepared by: N Forbes, R Krishnan, S Ismail, M Salvadori, B Warshawsky, K Young, MC Tunis, B Sander, R Harrison, and S Deeks on behalf of NACI

NACI gratefully acknowledges the contribution of: C Jensen, L Coward, E Wong, J Zafack, SH Lim, E Tarrataca, K Ramotar, and N St-Pierre

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

Liaison representatives: L Bill / M Nowgesic (Canadian Indigenous Nurses Association), 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), D Fell (Canadian Association for Immunization Research and Evaluation), S Funnell (Indigenous Physicians Association of Canada), J Hu (College of Family Physicians of Canada), M Lavoie (Council of Chief Medical Officers of Health), D Moore (Canadian Paediatric Society), M Naus (Canadian Immunization Committee), A Ung (Canadian Pharmacists Association).

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), D MacDonald (COVID-19 Epidemiology and Surveillance, PHAC), 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), N Brousseau, Y-G Bui, S Deeks, K Dooling, K Hildebrand, M Miller, M Murti, J Papenburg, D Smith, and S Vaughan.

PHAC participants: NK Abraham, N Alluqmani, L Coward, N Forbes, C Jensen, CY Jeong, A Jirovec, A Killikelly, R Krishnan, SH Lim, N Mohamed, J Montroy, A Nam, S Pierre, R Pless, M Salvadori, A Sinilaite, A Stevens, R Stirling, E Tice, A Tuite, MC Tunis, B Warshawsky, E Wong, R Ximenes, MW Yeung, J Zafack.

References

Footnotes

Footnote 1

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 2

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 3

Zhong D, Xiao S, Debes AK, Egbert ER, Caturegli P, Colantuoni E, et al. Durability of Antibody Levels After Vaccination With mRNA SARS-CoV-2 Vaccine in Individuals With or Without Prior Infection. JAMA. 2021 Dec 28;326(24):2524,2526. doi: 10.1001/jama.2021.19996.

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Footnote 4

UKHSA Variant Technical Group. SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 31 [Internet]. London (UK): UK Health Security Agency; 2021 Dec 10 [cited 2022 Feb 2]. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1042367/technical_briefing-31-10-december-2021.pdf.

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Footnote 5

Ferguson N, Ghani A, Cori A, Hogan A, Hinsley W, Volz E. Report 49: Growth, population distribution and immune escape of Omicron in England [Internet]. London (UK): Imperial College London; 2021 Dec 16 [cited 2022 Feb 2]. Available from: https://www.imperial.ac.uk/media/imperial-college/medicine/mrc-gida/2021-12-16-COVID19-Report-49.pdf.

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Footnote 6

UKHSA Variant Technical Group. SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 32 [Internet]. London (UK): UK Health Security Agency; 2021 Dec 17 [cited 2022 Feb 2]. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1042688/RA_Technical_Briefing_32_DRAFT_17_December_2021_2021_12_17.pdf.

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Footnote 7

Sheikh A, Kerr S, Woolhouse M, McMenamin J, Robertson C. Severity of Omicron variant of concern and vaccine effectiveness against symptomatic disease: national cohort with nested test negative design study in Scotland. Edinburgh Research Explorer. 2021 Dec 22. Available from: https://www.pure.ed.ac.uk/ws/portalfiles/portal/245818096/Severity_of_Omicron_variant_of_concern_and_vaccine_effectiveness_against_symptomatic_disease.pdf.

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Footnote 8

Coronavirus (COVID-19) Infection Survey, characteristics of people testing positive for COVID-19, UK: 19 January 2022 [Internet]. London (UK): Office for National Statistics; 2022 Jan 19 [cited 2022 Feb 2]. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/coronaviruscovid19infectionsurveycharacteristicsofpeopletestingpositiveforcovid19uk/19january2022.

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Footnote 9

The National Collaborating Centre for Methods and Tools. Rapid Review Update 1: What is the ongoing effectiveness, immunogenicity, and safety of COVID-19 vaccines in persons who have had a prior, confirmed COVID-19 infection? [Internet]. Hamilton (ON): McMaster University; 2021 Oct 15 [cited 2022 Feb 2]. Available from: https://www.nccmt.ca/covid-19/covid-19-rapid-evidence-service/36.

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Footnote 10

Hall V, Foulkes S, Insalata F, Saei A, Kirwan P, Atti A, et al. Effectiveness and durability of protection against future SARS-CoV-2 infection conferred by COVID-19 vaccination and previous infection; findings from the UK SIREN prospective cohort study of healthcare workers March 2020 to September 2021. medRxiv. 2021 Dec 1. https://doi.org/10.1101/2021.11.29.21267006.

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Footnote 11

Goldberg Y, Mandel M, Bar-On Y, Bodenheimer O, Freedman L, Ash N, et al. Protection and waning of natural and hybrid COVID-19 immunity. medRxiv. 2021 Dec 5. https://doi.org/10.1101/2021.12.04.21267114.

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Footnote 12

UKHSA Variant Technical Group. SARS-CoV-2 variants of concern and variants under investigation in England: Technical briefing 34 [Internet]. London (UK): UK Health Security Agency; 2022 Jan 14 [cited 2022 Feb 2]. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1050236/technical-briefing-34-14-january-2022.pdf.

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Footnote 13

Wratil PR, Stern M, Priller A, Willmann A, Almanzar G, Vogel E, et al. Three exposures to the spike protein of SARS-CoV-2 by either infection or vaccination elicit superior neutralizing immunity to all variants of concern. Nat Med. 2022 Jan 28. doi: 10.1038/s41591-022-01715-4.

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Footnote 14

Bekliz M, Adea K, Vetter P, Eberhardt CS, Hosszu-Fellous K, Vu D, et al. Neutralization of ancestral SARS-CoV-2 and variants Alpha, Beta, Gamma, Delta, Zeta and Omicron by mRNA vaccination and infection-derived immunity through homologous and heterologous variants. medRxiv. 2022 Jan 12. doi: 10.1101/2021.12.28.21268491.

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Footnote 15

Khan K, Karim F, Cele S, San JE, Lustig G, Tegally H, et al. Omicron infection enhances neutralizing immunity against the Delta variant. medRxiv. 2021 Dec 27. https://doi.org/10.1101/2021.12.27.21268439.

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Footnote 16

Suryawanshi RK, Chen IP, Ma T, Syed AM, Simoneau CR, Ciling A, et al. Limited cross-variant immunity after infection with the SARS-CoV-2 Omicron variant without vaccination. medRxiv. 2022 Jan 17 https://doi.org/10.1101/2022.01.13.22269243.

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Footnote 17

Raw RK, Rees J, Kelly CA, Wroe C, Chadwick DR. Prior COVID-19 infection is associated with increased Adverse Events (AEs) after the first, but not the second, dose of the BNT162b2/Pfizer vaccine. Vaccine. 2022 Jan 24;40(3):418,423. doi: 10.1016/j.vaccine.2021.11.090.

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Footnote 18

Krammer F, Srivastava K, Alshammary H, Amoako AA, Awawda MH, Beach KF, et al. Antibody Responses in Seropositive Persons after a Single Dose of SARS-CoV-2 mRNA Vaccine. N Engl J Med. 2021 Apr 8;384(14):1372,1374. doi: 10.1056/NEJMc2101667.

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Footnote 19

Tré-Hardy M, Cupaiolo R, Papleux E, Wilmet A, Horeanga A, Antoine-Moussiaux T, et al. Reactogenicity, safety and antibody response, after one and two doses of mRNA-1273 in seronegative and seropositive healthcare workers. J Infect. 2021 Mar 31;83(2):237,279. doi: 10.1016/j.jinf.2021.03.025.

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Footnote 20

Ebinger JE, Fert-Bober J, Printsev I, Wu M, Sun N, Prostko JC, et al. Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2. Nat Med. 2021 Apr 1;27(6):981,984. doi: 10.1038/s41591-021-01325-6.

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Footnote 21

Beatty AL, Peyser ND, Butcher XE, Cocohoba JM, Lin F, Olgin JE, et al. Analysis of COVID-19 Vaccine Type and Adverse Effects Following Vaccination. JAMA Netw Open. 2021 Dec 22;4(12):e2140364. doi: 10.1001/jamanetworkopen.2021.40364.

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Footnote 22

Lai FTT, Huang L, Peng K, Li X, Chui CSL, Wan EYF, et al. Post-Covid-19-vaccination adverse events and healthcare utilization among individuals with or without previous SARS-CoV-2 infection. J Intern Med. 2022 Jan 19. doi: 10.1111/joim.13453.

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Footnote 23

Mathioudakis AG, Ghrew M, Ustianowski A, Ahmad S, Borrow R, Papavasileiou LP, et al. Self-Reported Real-World Safety and Reactogenicity of COVID-19 Vaccines: A Vaccine Recipient Survey. Life (Basel). 2021 Mar 17;11(3):249. doi: 10.3390/life11030249.

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Footnote 24

Raw RK, Kelly CA, Rees J, Wroe C, Chadwick DR. Previous COVID-19 infection, but not Long-COVID, is associated with increased adverse events following BNT162b2/Pfizer vaccination. J Infect. 2021 Sep 1;83(3):381,412. doi: 10.1016/j.jinf.2021.05.035.

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Footnote 25

Arnold DT, Milne A, Samms E, Stadon L, Maskell NA, Hamilton FW. Are vaccines safe in patients with Long COVID? A prospective observational study. medRxiv. 2021 Mar 14. https://doi.org/10.1101/2021.03.11.21253225.

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Footnote 26

Personal communication, re: CANVAS Network, as per Julie A. Bettinger, Vaccine Evaluation Center, BC Children's Hospital, University of British Columbia following presentation to NACI on November 23, 2021.

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