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Vaccine effectiveness of BNT162b2 and CoronaVac against SARS-CoV-2 Omicron BA.2 infection, hospitalisation, severe complications, cardiovascular disease and mortality in patients with diabetes mellitus: A case control study

  • Author Footnotes
    1 Co-first authors with equal contributions.
    Eric Yuk Fai Wan
    Footnotes
    1 Co-first authors with equal contributions.
    Affiliations
    Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China

    Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China

    Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Author Footnotes
    1 Co-first authors with equal contributions.
    Anna Hoi Ying Mok
    Footnotes
    1 Co-first authors with equal contributions.
    Affiliations
    Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Author Footnotes
    1 Co-first authors with equal contributions.
    Vincent Ka Chun Yan
    Footnotes
    1 Co-first authors with equal contributions.
    Affiliations
    Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Boyuan Wang
    Affiliations
    Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Ran Zhang
    Affiliations
    Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Sabrina Nan Hong
    Affiliations
    Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Celine Sze Ling Chui
    Affiliations
    Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China

    School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China

    School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Xue Li
    Affiliations
    Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China

    Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China

    Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Carlos King Ho Wong
    Affiliations
    Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China

    Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China

    Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Francisco Tsz Tsun Lai
    Affiliations
    Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China

    Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China
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  • Kathryn Choon Beng Tan
    Affiliations
    Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Chak Sing Lau
    Affiliations
    Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
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  • Ian Chi Kei Wong
    Correspondence
    Corresponding author at: Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L02-57 2/F, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
    Affiliations
    Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China

    Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China

    Research Department of Practice and Policy, School of Pharmacy, University College London, London, United Kingdom

    Aston Pharmacy School, Aston University, Birmingham B4 7ET, United Kingdom

    Department of Pharmacy, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
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  • Esther Wai Yin Chan
    Correspondence
    Corresponding author at: Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L02-56 2/F, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
    Affiliations
    Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China

    Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China

    Department of Pharmacy, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China

    The University of Hong Kong Shenzhen Institute of Research and Innovation, Shenzhen, China
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  • Author Footnotes
    1 Co-first authors with equal contributions.
Published:August 17, 2022DOI:https://doi.org/10.1016/j.jinf.2022.08.008

      Highlight

      • There was a dose-response relationship between the number of vaccine doses received and vaccine effectiveness.
      • Three doses of BNT162b2 were more effective inreducing infection than three doses of CoronaVac, but the effectiveness against other outcomes, such as mortality, was similar between these two vaccines.
      • Vaccination reduces the risk of post-infection cardiovascular disease incidents in DM patients.
      Dear Editor,
      In this journal, Yin and Li et al. (2022) examined the antibody efficacy of CoronaVac (an inactivated vaccine) and suggested that two doses of CoronaVac were insufficient in eliciting adequate antibody response against SARS-CoV-2 Omicron variant
      • Yin Y.
      • Li X.
      • Qian C.
      • Cheng B.
      • Lu F.
      • Shen T.
      Antibody efficacy of inactivated vaccine boosters (CoronaVac) against Omicron variant from a 15-month follow-up study.
      . We in turn investigated the real-world effectiveness of the two vaccines that were employed in Hong Kong, namely CoronaVac and BNT162b2, in a group of patients with diabetes mellitus (DM), given their heightened susceptibility to COVID-19 infection and complications; yet limited literature is available for this specific population.
      This case-control study extracted data using the population-level electronic health databases from the Hong Kong Hospital Authority (HA) and the Department of Health (DH) of the Government of the Hong Kong Special Administrative Region, China, and enrolled DM patients aged ≥12 years, who had received zero to three doses of BNT162b2 or CoronaVac, during January to March 2022. This period was principally driven by the Omicron BA.2 variant

      Mesfin Y., Chen D., Bond H., Lam V., Cheung J., Wong J., et al. Epidemiology of infections with SARS-CoV-2 Omicron BA. 2 variant in Hong Kong, January-March 2022. medRxiv. 2022.

      , and these databases have previously been applied in several COVID-19 pharmacovigilance studies
      • Wan E.Y.F.
      • Chui C.S.L.
      • Lai F.T.T.
      • Chan E.W.Y.
      • Li X.
      • Yan V.K.C.
      • 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.
      • Wan E.Y.F.
      • Chui C.S.L.
      • Wang Y.
      • Ng V.W.S.
      • Yan V.K.C.
      • Lai F.T.T.
      • 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.
      • Wan E.Y.F.
      • Wang Y.
      • Chui C.S.L.
      • Mok A.H.Y.
      • Xu W.
      • Yan V.K.C.
      • et al.
      Safety of an inactivated, whole-virion COVID-19 vaccine (CoronaVac) in people aged 60 years or older in Hong Kong: a modified self-controlled case series.
      • Wan E.Y.F.
      • Chui C.S.L.
      • Ng V.W.S.
      • Wang Y.
      • Yan V.K.C.
      • Lam I.C.H.
      • et al.
      mRNA (BNT162b2) COVID-19 vaccination increased risk of Bell's palsy: a nested case control and self-controlled case series study.
      . Those who had a previous COVID-19 infection before the index date or had received the fourth dose of COVID-19 vaccine were excluded from the analysis. Each Polymerase Chain Reaction (PCR)-confirmed COVID-19 case was matched with up to 10 controls based on age, gender, and index date for each outcome independently. This study evaluated the vaccine effectiveness (VE) of each dose of BNT162b2 and CoronaVac against any COVID-19 infection, COVID-19-related hospital admission, ICU admission, incident cardiovascular disease (CVD), and all-cause mortality within 28 days after COVID-19 infection during the local outbreak dominated by Omicron BA.2 sublineage. VE was calculated using (1 - adjusted odds ratio (OR)) x 100%, where the adjusted OR was estimated using conditional logistic regression, adjusted for chronic comorbidities including hypertension, cancer, chronic kidney disease, respiratory disease, coronary heart disease, stroke, heart failure, and dementia, along with the use of chronic medications.
      A total of 82,587 cases of COVID-19 infection, 10,241 cases of COVID-19 related hospital admission, 539 cases of ICU admission, 135 cases of post-infection incident CVD, and 2898 cases of all-cause mortality were identified. A positive dose-response relationship, between the number of BNT162b2 or CoronaVac doses received and VE, was demonstrated. The characteristics of cases and controls are summarized in Table 1. Table 2 shows the VE for each outcome. A positive dose-response relationship between the number of BNT162b2 or CoronaVac doses received and VE was demonstrated found. VE amongst DM patients against COVID-19 infection after the first dose of BNT162b2 and CoronaVac were 28.4% (95% CI: 24.8 - 31.7) and −6.1% (95% CI: −9.0 - −3.2), respectively. Highest VE against COVID-19 infection was observed in people who received three doses of BNT162b2 [54.8% (95% CI: 53.1 - 56.5) and three doses of CoronaVac [21.2% (95% CI: 18.6 - 23.6)] when compared to those who received fewer doses. VE was higher in terms of other outcomes, reaching 91.7% (95% CI: 89.9 - 93.2) and 86.1% (95% CI: 84.0 - 87.9) against COVID-19 related hospital admission; 87.1% (95% CI: 73.1 - 93.8) and 94.9% (95% CI:86.1 - 98.1) against ICU admission; 91.1% (95% CI: 61.2 - 98.0) and 46.3% (95% CI: −15.8 - 75.1) against incident CVD; and 98.4% (95% CI: 96.1 - 99.3) and 96.1% (95% CI: 93.6 - 97.6) against all-cause mortality in three-dose BNT162b2 recipients and three-dose CoronaVac recipients respectively, in comparison with unvaccinated DM patients. Patients who received two doses of CoronaVac with BNT162b2 as a booster had higher VE against COVID-19 infection [40.8% (95% CI: 37.7 - 43.8)] but had similar VE against hospitalisation, CVD and mortality compared to those who received three doses of CoronaVac. Due to a small number of people who received CoronaVac after two doses of BNT162b2 (n = 313), the VE against different outcomes between heterologous and homologous boosters in people receiving BNT162b2 could not be compared as the primary series.
      Table 1Baseline characteristics of cases and controls. ICU: intensive care unit. All parameters are expressed in either number (percentage) or mean (SD).
      Baseline characteristicsInfectionHospitalisationICU admission or ventilatory supportCVDAll-cause mortality
      CasesControlsCasesControlsCasesControlsCasesControlsCasesControls
      Number of individuals82,587329,56010,241100,32053952521351335289828,056
      Age, years67.82 (12.51)67.84 (12.41)77.69 (12.13)77.69 (11.79)76.13 (12.26)76.30 (11.75)76.67 (11.74)76.34 (11.75)82.86 (9.88)82.70 (9.55)
      Sex, male44,435 (53.8)177,349 (53.8)5679 (55.5)55,850 (55.7)314 (58.3)3052 (58.1)68 (50.4)672 (50.3)1725 (59.5)16,828 (60.0)
      HbA1c,% (mmol/mol)6.96 (53) (1.19)6.91 (52) (1.07)6.94 (52) (1.38)6.91 (52) (1.12)7.04 (53) (1.54)6.92 (52) (1.14)7.13 (54) (1.25)6.90 (52) (1.00)6.92 (52) (1.46)6.92 (52) (1.17)
      Charlson Comorbidity Index3.61 (1.89)3.56 (1.81)5.32 (2.14)5.10 (2.02)5.22 (2.16)5.04 (2.10)4.30 (1.67)4.16 (1.48)6.30 (2.13)5.98 (1.99)
      Pre-existing comorbidities
      Hypertension55,905 (67.7)228,158 (69.2)7359 (71.9)78,251 (78.0)384 (71.2)4021 (76.6)79 (58.5)961 (72.0)2143 (73.9)23,086 (82.3)
      Cancer3680 (4.5)12,546 (3.8)947 (9.2)9161 (9.1)39 (7.2)491 (9.3)5 (3.7)50 (3.7)297 (10.2)3245 (11.6)
      Chronic Kidney Disease4497 (5.4)19,617 (6.0)1729 (16.9)16,151 (16.1)114 (21.2)885 (16.9)12 (8.9)78 (5.8)666 (23.0)6614 (23.6)
      Respiratory disease3006 (3.6)9698 (2.9)826 (8.1)5736 (5.7)41 (7.6)294 (5.6)2 (1.5)35 (2.6)282 (9.7)2351 (8.4)
      Coronary Heart Disease8235 (10.0)29,217 (8.9)1791 (17.5)12,930 (12.9)103 (19.1)722 (13.7)0 (0.0)0 (0.0)721 (24.9)4530 (16.1)
      Stroke7873 (9.5)27,910 (8.5)2203 (21.5)16,319 (16.3)111 (20.6)818 (15.6)0 (0.0)0 (0.0)877 (30.3)5986 (21.3)
      Heart Failure3373 (4.1)9111 (2.8)1349 (13.2)7153 (7.1)73 (13.5)413 (7.9)0 (0.0)0 (0.0)560 (19.3)3240 (11.5)
      Dementia917 (1.1)1756 (0.5)501 (4.9)1771 (1.8)27 (5.0)93 (1.8)5 (3.7)5 (0.4)234 (8.1)857 (3.1)
      Medication use
      Oral anti-diabetic drugs62,696 (75.9)254,833 (77.3)7333 (71.6)73,019 (72.8)384 (71.2)3831 (72.9)109 (80.7)996 (74.6)1921 (66.3)19,380 (69.1)
      Insulin10,795 (13.1)31,178 (9.5)2662 (26.0)11,649 (11.6)154 (28.6)688 (13.1)25 (18.5)120 (9.0)1606 (55.4)3643 (13.0)
      Renin-angiotensin-system agents44,554 (53.9)180,751 (54.8)5630 (55.0)58,366 (58.2)306 (56.8)3032 (57.7)82 (60.7)744 (55.7)1468 (50.7)16,290 (58.1)
      Beta-blockers23,306 (28.2)91,318 (27.7)3788 (37.0)31,887 (31.8)218 (40.4)1744 (33.2)48 (35.6)387 (29.0)1151 (39.7)9155 (32.6)
      Calcium channel blockers47,403 (57.4)193,345 (58.7)6232 (60.9)65,400 (65.2)327 (60.7)3399 (64.7)77 (57.0)882 (66.1)1745 (60.2)18,574 (66.2)
      Diuretics9895 (12.0)29,073 (8.8)2902 (28.3)14,343 (14.3)168 (31.2)814 (15.5)19 (14.1)135 (10.1)1211 (41.8)5023 (17.9)
      Nitrates6064 (7.3)16,781 (5.1)1533 (15.0)8436 (8.4)87 (16.1)426 (8.1)13 (9.6)46 (3.4)544 (18.8)2928 (10.4)
      Lipid-lowering agents59,383 (71.9)246,231 (74.7)7134 (69.7)75,808 (75.6)364 (67.5)3909 (74.4)89 (65.9)969 (72.6)1854 (64.0)20,822 (74.2)
      Oral anticoagulants2907 (3.5)8238 (2.5)887 (8.7)5166 (5.1)48 (8.9)259 (4.9)7 (5.2)40 (3.0)299 (10.3)1993 (7.1)
      Antiplatelets19,532 (23.7)70,071 (21.3)4321 (42.2)31,051 (31.0)236 (43.8)1639 (31.2)35 (25.9)211 (15.8)1511 (52.1)10,058 (35.8)
      Immunosuppressants646 (0.8)1811 (0.5)210 (2.1)561 (0.6)13 (2.4)38 (0.7)2 (1.5)4 (0.3)197 (6.8)143 (0.5)
      Table 2Vaccine effectiveness against COVID-19-related outcomes and mortality amongst individuals with different vaccination status. VE: vaccine effectiveness; CI: confidence interval; REF: reference level; CVD: cardiovascular disease; B-B-C: two doses of BNT162b2 followed by CoronaVac; C C-B: two doses of CoronaVac followed by BNT162b2; NA: Not available due to insufficient number; ICU: intensive care unit. Vaccine effectiveness was adjusted by HbA1c, comorbidities (hypertension, cancer, chronic kidney disease, respiratory disease, coronary heart disease, stroke, heart failure, dementia), chronic medication uses in the past 90 days (renin-angiotensin-system agents, beta-blockers, calcium channel blockers, diuretics, nitrates, lipid-lowering agents, oral anticoagulants, antiplatelets, immunosuppressants, oral anti-diabetic drugs, and insulin).
      OutcomeUnvaccinated1 dose only2 doses only3 doses
      BNT162b2CoronaVacAll BNT162b2All CoronaVacAll BNT162b2All CoronaVacB-B-CC-C-B
      Infection
      Case16,707242412,09013,33623,60843397992672024
      Control56,59611,48639,65359,42183,07332,65934,75924611,667
      VE%REF27.8−7.322.1−0.354.219.812.139.9
      (95% CI)(24.2 - 31.2)(−10.3 - −4.4)(20.0 - 24.2)(−2.7 - 2.1)(52.4 - 55.9)(17.2 - 22.3)(−15.8 - 33.3)(36.6 - 42.9)
      Hospitalisation
      Case512231021516391633109229048
      Control27,368320715,89112,64524,96860527975442170
      VE%REF51.024.474.264.291.485.4NA89.5
      (95% CI)(44.5 - 56.8)(19.9 - 28.7)(71.7 - 76.4)(61.8 - 66.4)(89.5 - 92.9)(83.2 - 87.3)(85.9 - 92.2)
      ICU admission or ventilatory support
      Case2712112023908501
      Control142119485269512663103852127
      VE%REF44.616.182.358.186.394.8NA95.9
      (95% CI)(8.6 - 66.4)(−7.9 - 34.7)(72.1 - 88.8)(45.0 - 68.1)(71.5 - 93.4)(85.8 - 98.1)(70.3 - 99.4)
      CVD
      Case46227163021002
      Control29643174198357113124030
      VE%REF69.4−3.150.348.490.946.3NA52.3
      (95% CI)(−35.8 - 93.1)(−77.5 - 40.1)(5.1 - 73.9)(10.8 - 70.2)(60.2 - 97.9)(−16.0 - 75.1)(−116.6 - 89.5)
      All-cause mortality
      Case1938505475528451801
      Control88988625092283466401343191118458
      VE%REF67.844.790.374.898.294.9NA98.7
      (95% CI)(55.8 - 76.5)(37.6 - 51.1)(86.9 - 92.9)(70.7 - 78.3)(95.5 - 99.3)(91.6 - 96.9)(90.4 - 99.8)
      This study specifically evaluates the real-world effectiveness of an mRNA (BNT162b2) and an inactivated virus (CoronaVac) COVID-19 vaccine against the Omicron BA.2 variant in a DM population. A clear dose-response relationship between the number of vaccine doses received and the magnitude of VE against COVID-19 infection, infection-related complications, and mortality has also been demonstrated. The low VE against COVID-19 infection of two-dose CoronaVac in this study was consistent with the findings from Yin and Li et al. (2022), which revealed a low level of neutralizing antibody against Omicron in healthy volunteers after two doses of CoronaVac
      • Yin Y.
      • Li X.
      • Qian C.
      • Cheng B.
      • Lu F.
      • Shen T.
      Antibody efficacy of inactivated vaccine boosters (CoronaVac) against Omicron variant from a 15-month follow-up study.
      . Nonetheless, we noted a relatively high VE against severe COVID-19 disease, all-cause mortality, and incident CVD in booster dose BNT162b2 and CoronaVac recipients, suggesting that adaptive immunity, apart from humoral immunity, might have a more important role in this regard
      • Khoury D.S.
      • Cromer D.
      • Reynaldi A.
      • Schlub T.E.
      • Wheatley A.K.
      • Juno J.A.
      • et al.
      Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.
      .
      Another key finding of our study is the effect of vaccination on reducing the risk of developing cardiovascular complications after COVID-19 infection. This reinforced the importance of vaccination in the DM population, and booster shots are necessary to further boost the protection against COVID-19 complications. On the other hand, we observed that a heterologous booster dose of BNT162b2 after two doses of CoronaVac may be more effective than three doses of CoronaVac in our DM population. This is in line with prior studies which revealed a higher rise in antibody concentrations in BNT162b2 booster recipients as opposed to homologous booster recipients after two doses of CoronaVac in Brazil
      • Costa Clemens S.A.
      • Weckx L.
      • Clemens R.
      • Almeida Mendes A.V.
      • Ramos Souza A.
      • Silveira M.B.
      • 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.
      ,
      • Cerqueira-Silva T.
      • Katikireddi S.V.
      • de Araujo Oliveira V.
      • Flores-Ortiz R.
      • Júnior J.B.
      • Paixão E.S.
      • et al.
      Vaccine effectiveness of heterologous CoronaVac plus BNT162b2 in Brazil.
      and Hong Kong
      • Cheng S.
      • Mok C.K.P.
      • Leung Y.W.
      • Ng S.S.
      • Chan K.C.
      • Ko F.W.
      • et al.
      Neutralizing antibodies against the SARS-CoV-2 Omicron variant following homologous and heterologous CoronaVac or BNT162b2 vaccination.
      . Given that limited people received heterologous boosters in this study, further studies are warranted to confirm our findings. By and large, both homologous and heterologous boosters were effective in protecting against severe COVID-19 diseases in the DM population.
      There were several limitations in this study. Only patients with positive PCR and RAT results were required to report to the DH. Hence, we could not apply a test-negative case-control study design to the current dataset. There is a possibility that people with asymptomatic COVID-19 infections could be misclassified as controls, leading to bias in the estimates towards null. Meanwhile, we defined the need for ventilatory support merely based on the procedure codes recorded in the electronic database, hence may have been underestimated. ICU admissions may have been limited by bed availability, which were fully occupied during the peak of the outbreak. Lastly, we did not consider the effect of different health-seeking behaviours in T2DM patients on the risk of catching COVID-19 infection.
      Overall, booster shots should be encouraged to reduce morbidity and mortality after COVID-19 infection in patients with diabetes.

      Ethics approval

      This study was approved by the Central Institutional Review Board of the Hospital Authority of Hong Kong (CIRB-2021–005–4) and the Department of Health Ethics Committee (LM171/2021).

      Funding

      This work was funded by a research grant from the Food and Health Bureau ; HMRF Research on COVID-19 , The Government of the Hong Kong Special Administrative Region (Principal Investigator (WP2): EWC; Ref: COVID1903011 ). We gratefully acknowledge the Centre for Health Protection, Department of Health and Hospital Authority for facilitating data access. ICKW and FTTL are partially supported by the Laboratory of Data Discovery for Health (D24H) funded by the by [email protected] administered by Innovation and Technology Commission.

      Author contributions

      Concept and design: EYFW, AHYM, VKCY, ICKW, EWC
      Acquisition, analysis, or interpretation of data: EYFW, AHYM, VKCY, BW, RZ, SNH, FTTL, CSLC, XL, CKHW, KCBT, CSL, ICKW, EWC
      Drafting of the manuscript: EYFW, AHYM, VKCY, SNH
      Critical revision of the manuscript for important intellectual content: All authors
      Statistical analysis: EYFW, VKCY, BW, RZ
      Administrative, technical, or material support: ICKW, EWC
      Supervision: ICKW, EWC

      Declaration of Competing Interest

      EYFW has received research grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, and the Hong Kong Research Grants Council, outside the submitted work. FTTL has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council and has received research grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, outside the submitted work. CSLC has received grants from the Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen; and personal fees from PrimeVigilance; outside the submitted work. XL has received research grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region; research and educational grants from Janssen and Pfizer; internal funding from the University of Hong Kong; and consultancy fees from Merck Sharp & Dohme, unrelated to this work. ICKW receives research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong Research Grants Council, the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, National Institute for Health Research in England, European Commission, and the National Health and Medical Research Council in Australia; has received speaker fees from Janssen and Medice in the previous 3 years; and is an independent non-executive director of Jacobson Medical in Hong Kong. All other authors declare no competing interests. EWC reports grants from Research Grants Council (RGC, Hong Kong), Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region; honorarium from Hospital Authority; outside the submitted work.

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