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Published in: BMC Medicine 1/2022

Open Access 01-12-2022 | Vaccination | Research article

Impact of a delayed second dose of mRNA vaccine (BNT162b2) and inactivated SARS-CoV-2 vaccine (CoronaVac) on risks of all-cause mortality, emergency department visit, and unscheduled hospitalization

Authors: Carlos King Ho Wong, Xi Xiong, Kristy Tsz Kwan Lau, Celine Sze Ling Chui, Francisco Tsz Tsun Lai, Xue Li, Esther Wai Yin Chan, Eric Yuk Fai Wan, Ivan Chi Ho Au, Benjamin John Cowling, Cheuk Kwong Lee, Ian Chi Kei Wong

Published in: BMC Medicine | Issue 1/2022

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Abstract

Background

Safety after the second dose of the SARS-CoV-2 vaccine remains to be elucidated, especially among individuals reporting adverse events after their first dose. This study aims to evaluate the impact of a delayed second dose on all-cause mortality and emergency services.

Methods

A territory-wide, retrospective cohort of people who had completed two doses of mRNA (BNT162b2) or inactivated SARS-CoV-2 (CoronaVac) vaccine between February 23 and July 3, 2021, in Hong Kong was analyzed, with linkage to electronic health records retrieved from the Hong Kong Hospital Authority. Vaccine recipients were classified as receiving a second dose within recommended intervals (21–28 days for BNT162b2; 14–28 days for CoronaVac) or delayed. Study outcomes were all-cause mortality, emergency department (ED) visits, and unscheduled hospitalizations within 28 days after the second dose of vaccination.

Results

Among 417,497 BNT162b2 and 354,283 CoronaVac second dose recipients, 3.8% and 28.5% received the second dose beyond the recommended intervals (mean 34.4 and 31.8 days), respectively. During the study period, there were < 5 daily new cases of COVID-19 infections in the community. Delaying the second dose was not associated with all-cause mortality (hazard ratio [HR] = 1.185, 95% CI 0.478–2.937, P = 0.714), risk of ED visit (HR = 0.966, 95% CI 0.926–1.008, P = 0.113), and risk of unscheduled hospitalization (HR = 0.956, 95% CI 0.878–1.040, P = 0.294) compared to that within the recommended interval for CoronaVac recipients. No statistically significant differences in all-cause mortality (HR = 4.438, 95% CI 0.951–20.701, P = 0.058), ED visit (HR = 1.037, 95% CI 0.951–1.130, P = 0.411), and unscheduled hospitalization (HR = 1.054, 95% CI 0.867–1.281, P = 0.597) were identified between people who received a second dose of BNT162b2 within and beyond the recommended intervals.

Conclusions

No significant association between delayed second dose of BNT162b2 or CoronaVac and all-cause mortality, ED visit, and unscheduled hospitalization was observed in the present cohort. Regardless of the recommended or delayed schedule for SARS-CoV-2 vaccination, a second dose of both vaccines should be administered to obtain better protection against infection and serious disease. The second dose should be administered within the recommended interval following the manufacturer’s product information, until further studies support the benefits of delaying vaccination outweighing the risks.
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Literature
1.
go back to reference Kyriakidis NC, López-Cortés A, González EV, Grimaldos AB, Prado EO. SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates. NPJ Vaccines. 2021;6(1):28.PubMedPubMedCentralCrossRef Kyriakidis NC, López-Cortés A, González EV, Grimaldos AB, Prado EO. SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates. NPJ Vaccines. 2021;6(1):28.PubMedPubMedCentralCrossRef
2.
go back to reference Kadire SR, Wachter RM, Lurie N. Delayed second dose versus standard regimen for COVID-19 vaccination. N Engl J Med. 2021;384(9):e28.PubMedCrossRef Kadire SR, Wachter RM, Lurie N. Delayed second dose versus standard regimen for COVID-19 vaccination. N Engl J Med. 2021;384(9):e28.PubMedCrossRef
3.
go back to reference Tauh T, Mozel M, Meyler P, Lee SM, Mas M. What is the evidence for extending the SARS-CoV-2 (COVID-19) vaccine dosing schedule. BC Med J. 2021;63:67–70. Tauh T, Mozel M, Meyler P, Lee SM, Mas M. What is the evidence for extending the SARS-CoV-2 (COVID-19) vaccine dosing schedule. BC Med J. 2021;63:67–70.
4.
go back to reference Voysey M, Costa Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet. 2021;397(10277):881–91.PubMedPubMedCentralCrossRef Voysey M, Costa Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet. 2021;397(10277):881–91.PubMedPubMedCentralCrossRef
5.
go back to reference Flaxman A, Marchevsky NG, Jenkin D, Aboagye J, Aley PK, Angus B, et al. Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002). Lancet. 2021;398(10304):981–90.PubMedPubMedCentralCrossRef Flaxman A, Marchevsky NG, Jenkin D, Aboagye J, Aley PK, Angus B, et al. Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002). Lancet. 2021;398(10304):981–90.PubMedPubMedCentralCrossRef
6.
go back to reference Zeng G, Wu Q, Pan H, Li M, Yang J, Wang L, et al. Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials. Lancet Infect Dis. 2021. https://doi.org/10.1016/S1473-3099(21)00681-2. Online ahead of print. Zeng G, Wu Q, Pan H, Li M, Yang J, Wang L, et al. Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials. Lancet Infect Dis. 2021. https://​doi.​org/​10.​1016/​S1473-3099(21)00681-2. Online ahead of print.
7.
go back to reference Moghadas SM, Vilches TN, Zhang K, Nourbakhsh S, Sah P, Fitzpatrick MC, et al. Evaluation of COVID-19 vaccination strategies with a delayed second dose. PLoS Biol. 2021;19(4):e3001211.PubMedPubMedCentralCrossRef Moghadas SM, Vilches TN, Zhang K, Nourbakhsh S, Sah P, Fitzpatrick MC, et al. Evaluation of COVID-19 vaccination strategies with a delayed second dose. PLoS Biol. 2021;19(4):e3001211.PubMedPubMedCentralCrossRef
8.
go back to reference Romero-Brufau S, Chopra A, Ryu AJ, Gel E, Raskar R, Kremers W, et al. Public health impact of delaying second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent based modeling study. BMJ. 2021;373:n1087.PubMedCrossRef Romero-Brufau S, Chopra A, Ryu AJ, Gel E, Raskar R, Kremers W, et al. Public health impact of delaying second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent based modeling study. BMJ. 2021;373:n1087.PubMedCrossRef
9.
go back to reference Zhang M-X, Zhang T-T, Shi G-F, Cheng F-M, Zheng Y-M, Tung T-H, et al. Safety of an inactivated SARS-CoV-2 vaccine among healthcare workers in China. Expert Rev Vaccines. 2021;20(7):891–8.PubMedCrossRef Zhang M-X, Zhang T-T, Shi G-F, Cheng F-M, Zheng Y-M, Tung T-H, et al. Safety of an inactivated SARS-CoV-2 vaccine among healthcare workers in China. Expert Rev Vaccines. 2021;20(7):891–8.PubMedCrossRef
10.
go back to reference 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. 2021;11(3):249.PubMedPubMedCentralCrossRef 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. 2021;11(3):249.PubMedPubMedCentralCrossRef
11.
go back to reference Hervé C, Laupèze B, Del Giudice G, Didierlaurent AM, Tavares Da Silva F. The how’s and what’s of vaccine reactogenicity. NPJ Vaccines. 2019;4(1):39.PubMedPubMedCentralCrossRef Hervé C, Laupèze B, Del Giudice G, Didierlaurent AM, Tavares Da Silva F. The how’s and what’s of vaccine reactogenicity. NPJ Vaccines. 2019;4(1):39.PubMedPubMedCentralCrossRef
12.
go back to reference Kadali RAK, Janagama R, Peruru S, Malayala SV. Side effects of BNT162b2 mRNA COVID-19 vaccine: a randomized, cross-sectional study with detailed self-reported symptoms from healthcare workers. Int J Infect Dis. 2021;106:376–81.PubMedPubMedCentralCrossRef Kadali RAK, Janagama R, Peruru S, Malayala SV. Side effects of BNT162b2 mRNA COVID-19 vaccine: a randomized, cross-sectional study with detailed self-reported symptoms from healthcare workers. Int J Infect Dis. 2021;106:376–81.PubMedPubMedCentralCrossRef
13.
go back to reference Diaz GA, Parsons GT, Gering SK, Meier AR, Hutchinson IV, Robicsek A. Myocarditis and pericarditis after vaccination for COVID-19. JAMA. 2021;326(12):1210–2.PubMedPubMedCentralCrossRef Diaz GA, Parsons GT, Gering SK, Meier AR, Hutchinson IV, Robicsek A. Myocarditis and pericarditis after vaccination for COVID-19. JAMA. 2021;326(12):1210–2.PubMedPubMedCentralCrossRef
14.
go back to reference García-Grimshaw M, Ceballos-Liceaga SE, Hernández-Vanegas LE, Núñez I, Hernández-Valdivia N, Carrillo-García DA, et al. Neurologic adverse events among 704,003 first-dose recipients of the BNT162b2 mRNA COVID-19 vaccine in Mexico: a nationwide descriptive study. Clin Immunol. 2021;229:108786.PubMedPubMedCentralCrossRef García-Grimshaw M, Ceballos-Liceaga SE, Hernández-Vanegas LE, Núñez I, Hernández-Valdivia N, Carrillo-García DA, et al. Neurologic adverse events among 704,003 first-dose recipients of the BNT162b2 mRNA COVID-19 vaccine in Mexico: a nationwide descriptive study. Clin Immunol. 2021;229:108786.PubMedPubMedCentralCrossRef
15.
go back to reference Wan EYF, Chui CSL, Lai FTT, Chan EWY, Li X, Yan VKC, et al. Bell’s palsy following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines: a case series and nested case-control study. Lancet Infect Dis. 2022;22(1):64–72.PubMedCrossRef Wan EYF, Chui CSL, Lai FTT, Chan EWY, Li X, Yan VKC, et al. Bell’s palsy following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines: a case series and nested case-control study. Lancet Infect Dis. 2022;22(1):64–72.PubMedCrossRef
17.
go back to reference Kim T, Park SY, Yu S, Park JW, Lee E, Jeon MH, et al. Impacts of side effects to BNT162b2 and the first dose of ChAdOx1 anti-SARS-CoV-2 vaccination on work productivity, the need for medical attention, and vaccine acceptance: a multicenter survey on healthcare workers in referral teaching hospitals in the Republic of Korea. Vaccines. 2021;9(6):648.PubMedPubMedCentralCrossRef Kim T, Park SY, Yu S, Park JW, Lee E, Jeon MH, et al. Impacts of side effects to BNT162b2 and the first dose of ChAdOx1 anti-SARS-CoV-2 vaccination on work productivity, the need for medical attention, and vaccine acceptance: a multicenter survey on healthcare workers in referral teaching hospitals in the Republic of Korea. Vaccines. 2021;9(6):648.PubMedPubMedCentralCrossRef
18.
go back to reference McMurry R, Lenehan P, Awasthi S, Silvert E, Puranik A, Pawlowski C, et al. Real-time analysis of a mass vaccination effort confirms the safety of FDA-authorized mRNA COVID-19 vaccines. Med. 2021;2(8):965–78 e965.PubMedCrossRef McMurry R, Lenehan P, Awasthi S, Silvert E, Puranik A, Pawlowski C, et al. Real-time analysis of a mass vaccination effort confirms the safety of FDA-authorized mRNA COVID-19 vaccines. Med. 2021;2(8):965–78 e965.PubMedCrossRef
19.
go back to reference Li X, Tong X, Yeung WWY, Kuan P, Yum SHH, Chui CSL, et al. Two-dose COVID-19 vaccination and possible arthritis flare among patients with rheumatoid arthritis in Hong Kong. Ann Rheum Dis. 2022;81(4):564–8.PubMedCrossRef Li X, Tong X, Yeung WWY, Kuan P, Yum SHH, Chui CSL, et al. Two-dose COVID-19 vaccination and possible arthritis flare among patients with rheumatoid arthritis in Hong Kong. Ann Rheum Dis. 2022;81(4):564–8.PubMedCrossRef
20.
21.
go back to reference Lai FTT, Huang L, Chui CSL, Wan EYF, Li X, Wong CKH, et al. Multimorbidity and adverse events of special interest associated with COVID-19 vaccines in Hong Kong. Nat Commun. 2022;13(1):411.PubMedPubMedCentralCrossRef Lai FTT, Huang L, Chui CSL, Wan EYF, Li X, Wong CKH, et al. Multimorbidity and adverse events of special interest associated with COVID-19 vaccines in Hong Kong. Nat Commun. 2022;13(1):411.PubMedPubMedCentralCrossRef
22.
go back to reference Lai FTT, Li X, Peng K, Huang L, Ip P, Tong X, et al. Carditis after COVID-19 vaccination with a messenger RNA vaccine and an inactivated virus vaccine: a case-control study. Ann Intern Med. 2022. https://doi.org/10.7326/M21-3700. Online ahead of print. Lai FTT, Li X, Peng K, Huang L, Ip P, Tong X, et al. Carditis after COVID-19 vaccination with a messenger RNA vaccine and an inactivated virus vaccine: a case-control study. Ann Intern Med. 2022. https://​doi.​org/​10.​7326/​M21-3700. Online ahead of print.
23.
go back to reference Sing CW, Tang CTL, Chui CSL, Fan M, Lai FTT, Li X, et al. COVID-19 vaccines and risks of hematological abnormalities: nested case-control and self-controlled case series study. Am J Hematol. 2022;97(4):470–80.PubMedPubMedCentralCrossRef Sing CW, Tang CTL, Chui CSL, Fan M, Lai FTT, Li X, et al. COVID-19 vaccines and risks of hematological abnormalities: nested case-control and self-controlled case series study. Am J Hematol. 2022;97(4):470–80.PubMedPubMedCentralCrossRef
24.
go back to reference Wan EYF, Chui CSL, Wang Y, Ng VWS, Yan VKC, Lai FTT, et al. Herpes zoster related hospitalization after inactivated (CoronaVac) and mRNA (BNT162b2) SARS-CoV-2 vaccination: a self-controlled case series and nested case-control study. Lancet Reg Health West Pac. 2022;21:100393.PubMedCrossRef Wan EYF, Chui CSL, Wang Y, Ng VWS, Yan VKC, Lai FTT, et al. Herpes zoster related hospitalization after inactivated (CoronaVac) and mRNA (BNT162b2) SARS-CoV-2 vaccination: a self-controlled case series and nested case-control study. Lancet Reg Health West Pac. 2022;21:100393.PubMedCrossRef
25.
go back to reference 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. https://doi.org/10.1111/joim.13453. Online ahead of print. 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. https://​doi.​org/​10.​1111/​joim.​13453. Online ahead of print.
27.
34.
go back to reference Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med. 2020;383(27):2603–15.PubMedCrossRef Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med. 2020;383(27):2603–15.PubMedCrossRef
35.
go back to reference Tanriover MD, Doganay HL, Akova M, Guner HR, Azap A, Akhan S, et al. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet. 2021;398(10296):213–22.PubMedPubMedCentralCrossRef Tanriover MD, Doganay HL, Akova M, Guner HR, Azap A, Akhan S, et al. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet. 2021;398(10296):213–22.PubMedPubMedCentralCrossRef
37.
go back to reference Desai RJ, Franklin JM. Alternative approaches for confounding adjustment in observational studies using weighting based on the propensity score: a primer for practitioners. BMJ. 2019;367:l5657.PubMedCrossRef Desai RJ, Franklin JM. Alternative approaches for confounding adjustment in observational studies using weighting based on the propensity score: a primer for practitioners. BMJ. 2019;367:l5657.PubMedCrossRef
38.
go back to reference Kriss JL, Reynolds LE, Wang A, Stokley S, Cole MM, Harris LQ, et al. COVID-19 vaccine second-dose completion and interval between first and second doses among vaccinated persons - United States, December 14, 2020-February 14, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(11):389–95.PubMedPubMedCentralCrossRef Kriss JL, Reynolds LE, Wang A, Stokley S, Cole MM, Harris LQ, et al. COVID-19 vaccine second-dose completion and interval between first and second doses among vaccinated persons - United States, December 14, 2020-February 14, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(11):389–95.PubMedPubMedCentralCrossRef
40.
go back to reference Abdi H. The Bonferonni and `idák corrections for multiple comparisons; 2006. Abdi H. The Bonferonni and `idák corrections for multiple comparisons; 2006.
41.
go back to reference Amirthalingam G, Bernal JL, Andrews NJ, Whitaker H, Gower C, Stowe J, et al. Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England. Nat Commun. 2021;12(1):7217.PubMedPubMedCentralCrossRef Amirthalingam G, Bernal JL, Andrews NJ, Whitaker H, Gower C, Stowe J, et al. Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England. Nat Commun. 2021;12(1):7217.PubMedPubMedCentralCrossRef
42.
go back to reference Li J, Chen W, Chen M, Bai S, Yuan Q, Wu J. Immunogenicity of inactivated COVID-19 vaccines at different vaccination intervals. Hum Vaccines Immunother. 2021;17(10):3310–3.CrossRef Li J, Chen W, Chen M, Bai S, Yuan Q, Wu J. Immunogenicity of inactivated COVID-19 vaccines at different vaccination intervals. Hum Vaccines Immunother. 2021;17(10):3310–3.CrossRef
43.
go back to reference Parry H, Bruton R, Stephens C, Bentley C, Brown K, Amirthalingam G, et al. Extended interval BNT162b2 vaccination enhances peak antibody generation. NPJ Vaccines. 2022;7(1):14.PubMedPubMedCentralCrossRef Parry H, Bruton R, Stephens C, Bentley C, Brown K, Amirthalingam G, et al. Extended interval BNT162b2 vaccination enhances peak antibody generation. NPJ Vaccines. 2022;7(1):14.PubMedPubMedCentralCrossRef
44.
go back to reference Payne RP, Longet S, Austin JA, Skelly DT, Dejnirattisai W, Adele S, et al. Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine. Cell. 2021;184(23):5699–714 e5611.PubMedPubMedCentralCrossRef Payne RP, Longet S, Austin JA, Skelly DT, Dejnirattisai W, Adele S, et al. Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine. Cell. 2021;184(23):5699–714 e5611.PubMedPubMedCentralCrossRef
45.
go back to reference Chen M, Yuan Y, Zhou Y, Deng Z, Zhao J, Feng F, et al. Safety of SARS-CoV-2 vaccines: a systematic review and meta-analysis of randomized controlled trials. Infect Dis Poverty. 2021;10(1):94.PubMedPubMedCentralCrossRef Chen M, Yuan Y, Zhou Y, Deng Z, Zhao J, Feng F, et al. Safety of SARS-CoV-2 vaccines: a systematic review and meta-analysis of randomized controlled trials. Infect Dis Poverty. 2021;10(1):94.PubMedPubMedCentralCrossRef
47.
go back to reference Menni C, Klaser K, May A, Polidori L, Capdevila J, Louca P, et al. Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study. Lancet Infect Dis. 2021;21(7):939–49.PubMedPubMedCentralCrossRef Menni C, Klaser K, May A, Polidori L, Capdevila J, Louca P, et al. Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study. Lancet Infect Dis. 2021;21(7):939–49.PubMedPubMedCentralCrossRef
48.
go back to reference Michos A, Tatsi EB, Filippatos F, Dellis C, Koukou D, Efthymiou V, et al. Association of total and neutralizing SARS-CoV-2 spike -receptor binding domain antibodies with epidemiological and clinical characteristics after immunization with the 1(st) and 2(nd) doses of the BNT162b2 vaccine. Vaccine. 2021;39(40):5963–7.PubMedPubMedCentralCrossRef Michos A, Tatsi EB, Filippatos F, Dellis C, Koukou D, Efthymiou V, et al. Association of total and neutralizing SARS-CoV-2 spike -receptor binding domain antibodies with epidemiological and clinical characteristics after immunization with the 1(st) and 2(nd) doses of the BNT162b2 vaccine. Vaccine. 2021;39(40):5963–7.PubMedPubMedCentralCrossRef
49.
go back to reference d’Arminio Monforte A, Tavelli A, Perrone PM, Za A, Razzini K, Tomasoni D, et al. Association between previous infection with SARS CoV-2 and the risk of self-reported symptoms after mRNA BNT162b2 vaccination: data from 3,078 health care workers. EClinicalMedicine. 2021;36:100914.PubMedPubMedCentralCrossRef d’Arminio Monforte A, Tavelli A, Perrone PM, Za A, Razzini K, Tomasoni D, et al. Association between previous infection with SARS CoV-2 and the risk of self-reported symptoms after mRNA BNT162b2 vaccination: data from 3,078 health care workers. EClinicalMedicine. 2021;36:100914.PubMedPubMedCentralCrossRef
50.
go back to reference Nittner-Marszalska M, Rosiek-Biegus M, Kopeć A, Pawłowicz R, Kosińska M, Łata A, et al. Pfizer-BioNTech COVID-19 vaccine tolerance in allergic versus non-allergic individuals. Vaccines. 2021;9(6):553.PubMedPubMedCentralCrossRef Nittner-Marszalska M, Rosiek-Biegus M, Kopeć A, Pawłowicz R, Kosińska M, Łata A, et al. Pfizer-BioNTech COVID-19 vaccine tolerance in allergic versus non-allergic individuals. Vaccines. 2021;9(6):553.PubMedPubMedCentralCrossRef
51.
go back to reference Ossato A, Tessari R, Trabucchi C, Zuppini T, Realdon N, Marchesini F. Comparison of medium-term adverse reactions induced by the first and second dose of mRNA BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine: a post-marketing Italian study conducted between 1 January and 28 February 2021. Eur J Hosp Pharm. 2021. https://doi.org/10.1136/ejhpharm-2021-002933. Online ahead of print. Ossato A, Tessari R, Trabucchi C, Zuppini T, Realdon N, Marchesini F. Comparison of medium-term adverse reactions induced by the first and second dose of mRNA BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine: a post-marketing Italian study conducted between 1 January and 28 February 2021. Eur J Hosp Pharm. 2021. https://​doi.​org/​10.​1136/​ejhpharm-2021-002933. Online ahead of print.
52.
go back to reference Shay DK, Shimabukuro TT, DeStefano F. Myocarditis occurring after immunization with mRNA-based COVID-19 vaccines. JAMA Cardiol. 2021;6(10):1115–7.PubMedCrossRef Shay DK, Shimabukuro TT, DeStefano F. Myocarditis occurring after immunization with mRNA-based COVID-19 vaccines. JAMA Cardiol. 2021;6(10):1115–7.PubMedCrossRef
53.
go back to reference Turner PJ, Ansotegui IJ, Campbell DE, Cardona V, Ebisawa M, El-Gamal Y, et al. COVID-19 vaccine-associated anaphylaxis: a statement of the World Allergy Organization Anaphylaxis Committee. World Allergy Organ J. 2021;14(2):100517.PubMedPubMedCentralCrossRef Turner PJ, Ansotegui IJ, Campbell DE, Cardona V, Ebisawa M, El-Gamal Y, et al. COVID-19 vaccine-associated anaphylaxis: a statement of the World Allergy Organization Anaphylaxis Committee. World Allergy Organ J. 2021;14(2):100517.PubMedPubMedCentralCrossRef
54.
go back to reference Robertson JFR, Sewell HF, Stewart M. Delayed second dose of the BNT162b2 vaccine: innovation or misguided conjecture? Lancet. 2021;397(10277):879–80.PubMedPubMedCentralCrossRef Robertson JFR, Sewell HF, Stewart M. Delayed second dose of the BNT162b2 vaccine: innovation or misguided conjecture? Lancet. 2021;397(10277):879–80.PubMedPubMedCentralCrossRef
55.
go back to reference Bueno SM, Abarca K, González PA, Gálvez NMS, Soto JA, Duarte LF, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in a subgroup of healthy adults in Chile. Clin Infect Dis. 2021. https://doi.org/10.1093/cid/ciab823. Online ahead of print. Bueno SM, Abarca K, González PA, Gálvez NMS, Soto JA, Duarte LF, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in a subgroup of healthy adults in Chile. Clin Infect Dis. 2021. https://​doi.​org/​10.​1093/​cid/​ciab823. Online ahead of print.
56.
go back to reference Soysal A, Gönüllü E, Karabayır N, Alan S, Atıcı S, Yıldız İ, et al. Comparison of immunogenicity and reactogenicity of inactivated SARS-CoV-2 vaccine (CoronaVac) in previously SARS-CoV-2 infected and uninfected health care workers. Hum Vaccin Immunother. 2021;17:1–5.CrossRef Soysal A, Gönüllü E, Karabayır N, Alan S, Atıcı S, Yıldız İ, et al. Comparison of immunogenicity and reactogenicity of inactivated SARS-CoV-2 vaccine (CoronaVac) in previously SARS-CoV-2 infected and uninfected health care workers. Hum Vaccin Immunother. 2021;17:1–5.CrossRef
57.
58.
go back to reference Pérez-Then E, Lucas C, Monteiro VS, Miric M, Brache V, Cochon L, et al. Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination. Nat Med. 2022. https://doi.org/10.1038/s41591-022-01705-6. Online ahead of print. Pérez-Then E, Lucas C, Monteiro VS, Miric M, Brache V, Cochon L, et al. Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination. Nat Med. 2022. https://​doi.​org/​10.​1038/​s41591-022-01705-6. Online ahead of print.
59.
go back to reference Bar-On YM, Goldberg Y, Mandel M, Bodenheimer O, Freedman L, Alroy-Preis S, et al. Protection against COVID-19 by BNT162b2 booster across age groups. N Engl J Med. 2021;385(26):2421–30.PubMedCrossRef Bar-On YM, Goldberg Y, Mandel M, Bodenheimer O, Freedman L, Alroy-Preis S, et al. Protection against COVID-19 by BNT162b2 booster across age groups. N Engl J Med. 2021;385(26):2421–30.PubMedCrossRef
60.
go back to reference Barda N, Dagan N, Cohen C, Hernán MA, Lipsitch M, Kohane IS, et al. Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study. Lancet. 2021;398(10316):2093–100.PubMedPubMedCentralCrossRef Barda N, Dagan N, Cohen C, Hernán MA, Lipsitch M, Kohane IS, et al. Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study. Lancet. 2021;398(10316):2093–100.PubMedPubMedCentralCrossRef
61.
go back to reference Gardner BJ, Kilpatrick AM. Third doses of COVID-19 vaccines reduce infection and transmission of SARS-CoV-2 and could prevent future surges in some populations: a modeling study. medRxiv. 2021; 2021.2010.2025.21265500. (medRxiv preprint). Gardner BJ, Kilpatrick AM. Third doses of COVID-19 vaccines reduce infection and transmission of SARS-CoV-2 and could prevent future surges in some populations: a modeling study. medRxiv. 2021; 2021.2010.2025.21265500. (medRxiv preprint).
62.
go back to reference Ireland G, Whitaker H, Ladhani SN, Baawuah F, Subbarao S, Linley E, et al. Serological responses to COVID-19 Comirnaty booster vaccine, London, United Kingdom, September to December 2021. Euro Surveill. 2022;27(1):2101114.PubMedCentralCrossRef Ireland G, Whitaker H, Ladhani SN, Baawuah F, Subbarao S, Linley E, et al. Serological responses to COVID-19 Comirnaty booster vaccine, London, United Kingdom, September to December 2021. Euro Surveill. 2022;27(1):2101114.PubMedCentralCrossRef
63.
go back to reference Munro APS, Janani L, Cornelius V, Aley PK, Babbage G, Baxter D, et al. Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. Lancet. 2021;398(10318):2258–76.PubMedPubMedCentralCrossRef Munro APS, Janani L, Cornelius V, Aley PK, Babbage G, Baxter D, et al. Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. Lancet. 2021;398(10318):2258–76.PubMedPubMedCentralCrossRef
64.
go back to reference Costa Clemens SA, Weckx L, Clemens R, Almeida Mendes AV, Ramos Souza A, Silveira MBV, et al. Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study. Lancet. 2022;399(10324):521–9.PubMedPubMedCentralCrossRef Costa Clemens SA, Weckx L, Clemens R, Almeida Mendes AV, Ramos Souza A, Silveira MBV, et al. Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study. Lancet. 2022;399(10324):521–9.PubMedPubMedCentralCrossRef
65.
go back to reference Khong K-W, Liu D, Leung K-Y, Lu L, Lam H-Y, Chen L, et al. Antibody response of combination of BNT162b2 and CoronaVac platforms of COVID-19 vaccines against omicron variant. Vaccines. 2022;10(2):160.PubMedPubMedCentralCrossRef Khong K-W, Liu D, Leung K-Y, Lu L, Lam H-Y, Chen L, et al. Antibody response of combination of BNT162b2 and CoronaVac platforms of COVID-19 vaccines against omicron variant. Vaccines. 2022;10(2):160.PubMedPubMedCentralCrossRef
66.
go back to reference Khan NA, Al-Thani H, El-Menyar A. The emergence of new SARS-CoV-2 variant (omicron) and increasing calls for COVID-19 vaccine boosters-the debate continues. Travel Med Infect Dis. 2022;45:102246.PubMedCrossRef Khan NA, Al-Thani H, El-Menyar A. The emergence of new SARS-CoV-2 variant (omicron) and increasing calls for COVID-19 vaccine boosters-the debate continues. Travel Med Infect Dis. 2022;45:102246.PubMedCrossRef
Metadata
Title
Impact of a delayed second dose of mRNA vaccine (BNT162b2) and inactivated SARS-CoV-2 vaccine (CoronaVac) on risks of all-cause mortality, emergency department visit, and unscheduled hospitalization
Authors
Carlos King Ho Wong
Xi Xiong
Kristy Tsz Kwan Lau
Celine Sze Ling Chui
Francisco Tsz Tsun Lai
Xue Li
Esther Wai Yin Chan
Eric Yuk Fai Wan
Ivan Chi Ho Au
Benjamin John Cowling
Cheuk Kwong Lee
Ian Chi Kei Wong
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-022-02321-4

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