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Two Doses of SARS-CoV-2 Vaccines Reduce Risk of Death Due to COVID-19 in Solid Organ Transplant Recipients: Preliminary Outcomes From a UK Registry Linkage Analysis

Ravanan, Rommel FRCP1; Mumford, Lisa MSc1; Ushiro-Lumb, Ines FRCPath1; Callaghan, Chris FRCS1; Pettigrew, Gavin FRCS1; Thorburn, Douglas FRCP1; Gardiner, Dale FFICM1; Forsythe, John FRCS1

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doi: 10.1097/TP.0000000000003908
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Abstract

Solid organ and islet transplant (SOT) recipients have higher risk of death following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.1,2 Trials investigating SARS-CoV-2 vaccine efficacy excluded SOT recipients.3 As seen with other vaccines, immunosuppression may reduce SARS-CoV-2 vaccine efficacy. Emerging data indicate lower spike protein antibody levels following vaccination in SOT recipients.4

Registry linkage studies enable prospective tracking of new SARS-CoV-2 infections in vaccinated and unvaccinated SOT recipients. The UK transplant registry (held by NHS Blood and Transplant) records all SOT recipients, Public Health England records positive results for SARS-CoV-2 RNA in England, NHS Digital holds records of date of death, and the National Immunisation Management Service records details of all doses of SARS-CoV-2 vaccines administered in England. Linkage of these 4 registries enables analyses of outcomes of interest: demographics of vaccine uptake, testing positive for SARS-CoV-2 RNA 14 d after first or second vaccine dose, and death within 28 d of testing positive.

In the United Kingdom, SARS-CoV-2 vaccination roll out commenced on December 8, 2020, with a predefined prioritization.5 Pfizer (BNT162b2) and Oxford/AstraZeneca (ChAdOx1-S) were the predominant vaccine types deployed, and most SOT recipients received their first dose in February 2021 and the second dose approximately 10 wk later. Following linkage of the 4 registries, SOT recipients from England (n = 48 213) who were alive with a functioning graft on September 1, 2020, were followed up for outcomes of interest.

As of July 9, 2021, 82% (n = 39 727) had received both vaccine doses, 4% (1738) had received 1 dose, and 14% (6748) remained unvaccinated or contracted infection before vaccination. Vaccination uptake was lower in London (75%) and in people from Black, Asian, and mixed race and minority ethnic backgrounds (65%–75%). Table 1 shows the unadjusted case fatality ratios in vaccinated cases compared with unvaccinated cases. The mortality rate after testing positive for SARS-CoV-2 was 7.7% among recipients of 2 doses compared with approximately 12% among unvaccinated patients and recipients of only 1 dose.

TABLE 1. - Case fatality ratios for deaths within 28 d of onset in vaccinated compared with unvaccinated transplant recipients
Vaccination status (n) SARS-CoV-2 RNA positive, n Deaths in SARS-CoV-2 RNA-positive patients
N (%)
Unvaccinated (6748) 3473 438 12.6
One dose (1738) 326 39 12.0
Two doses (39 727) 143 11 7.7
SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

This study is the first published national registry–based analysis reporting on real-world vaccine efficacy in the SOT patient population and has the strengths of scale and minimal ascertainment bias. Case fatality ratio comparison methodology was used to reduce risk of bias when only mortality is reported as outcome of interest; detailed risk-adjusted analyses are currently being undertaken to evaluate risk of SARS-CoV-2 infection and related mortality in vaccinated versus unvaccinated patients and will be published in due course. The findings need to be interpreted in the context of changes in virus circulation in the community; Alpha and Delta variant surges in the United Kingdom; and the implementation, adherence to, and subsequent relaxation of government-mandated nonpharmaceutical interventions. Despite these limitations, there appears to be an early indication that vaccinated SOT recipients have a reduced risk of death from COVID-19 compared with unvaccinated SOT recipients.

We believe this information will provide some assurance to vaccinated patients and help clinical teams target interventions to encourage currently unvaccinated patients to take up the offer of both vaccine doses at the earliest opportunity.

ACKNOWLEDGMENTS

Members of the OTDT Clinical Team other than the authors already named are Ms Lisa Burnapp, MA, Mr John Casey, FRCS, Mr Ian Currie, FRCS, Dr Richard Baker, FRCP, Dr Jan Dudley, FRCPCH, Mr Marius Berman, FRCS, Mr John Asher, FRCS, Dr Dan Harvey, FICM, Mr Derek Manas, FRCS, Dr Jasvir Parmar, FRCP, Mr Andrew Butler, FRCS, Mr Steven White, FRCS, and Mr Rajamiyer Venkateswaran, FRCS. All these authors are also affiliated to NHS Blood & Transplant, UK.

REFERENCES

1. Williamson EJ, Walker AJ, Bhaskaran K, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020;584:430–436.
2. Ravanan R, Callaghan CJ, Mumford L, et al. SARS-CoV-2 infection and early mortality of waitlisted and solid organ transplant recipients in England: a national cohort study. Am J Transplant. 2020;20:3008–3018.
3. Polack FP, Thomas SJ, Kitchin N, et al.; C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603–2615.
4. Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325:2204–2206.
5. Department of Health and Social Care. Priority groups for coronavirus (COVID-19) vaccination: advice from the JCVI, 30 December 2020. Available at https://www.gov.uk/government/publications/priority-groups-for-coronavirus-covid-19-vaccination-advice-from-the-jcvi-30-december-2020. Accessed July 2021.
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