Comparative effectiveness of two- and three-dose schedules involving AZD1222 and BNT162b2 in people with kidney disease

Comparative effectiveness of two- and three-dose schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study

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How to cite: Comparative effectiveness of two- and three-dose schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study The OpenSAFELY Collaborative, Edward PK Parker, Elsie MF Horne, William J Hulme, John Tazare, Bang Zheng, Edward J Carr, Fiona Loud, Susan Lyon, Viyaasan Mahalingasivam, Brian MacKenna, Amir Mehrkar, Miranda Scanlon, Shalini Santhakumaran, Retha Steenkamp, Ben Goldacre, Jonathan AC Sterne, Dorothea Nitsch, Laurie A Tomlinson, The LH&W NCS (or CONVALESCENCE) Collaborative medRxiv 2022.11.16.22282396; doi: https://doi.org/10.1101/2022.11.16.22282396

Lay summary

Since the early stages of the COVID-19 pandemic, it has been clear that people with moderate-to-severe kidney disease are particularly vulnerable to the harmful effects of this virus. As a result, these individuals were among the first to be offered COVID-19 vaccines in England, and have since been offered additional doses to give them further protection.

Most of the population received initial doses of one of two vaccines: ‘AZ’ (AstraZeneca AZD1222, also called ChAdOx1-S or Vaxzevria) and ‘BNT’ (Pfizer BNT162b2, an RNA vaccine). Several laboratory studies have shown that the immune response may be weaker in people with moderate-to-severe kidney disease following two doses of the AstraZeneca AZ vaccine compared with having two doses of the Pfizer BNT vaccine. When BNT was used as a third dose, this appeared to reduce the gap in immunity levels. However, it was not known whether these laboratory findings would hold true for real-life protection against COVID-19.

In the present study, we compared the risk of COVID-19 among people with moderate-severe kidney disease in England who received different combinations of AZ and BNT over the course of the pandemic. GP records were used to identify people with stage 3–5 chronic kidney disease (CKD) and the UK Renal Registry was used to identify dialysis patients and kidney transplant recipients.

Findings

Most people with moderate-to-severe kidney disease had received two doses of either AZ or BNT before the onset of the Delta wave of the pandemic in the spring of 2021. Over the course of this wave, we found that AZ recipients were more likely than BNT recipients to experience COVID-19-related infection, hospitalisation, and death. The difference between the two vaccines was the same for different stages of kidney disease, including stage 3 CKD, stage 4–5 CKD, dialysis patients, and kidney transplant recipients.

Third doses of BNT were given in England from September 2021 onwards, which appeared to level the playing field in our study population. We saw similar rates of mild and severe COVID-19 after the third dose, regardless of whether people had previously received AZ or BNT for their initial two doses. Most cases of COVID-19 after these third doses occurred after mid-December 2021, when the Omicron variant was dominant. Our study combined data from ‘third primary doses’ (given to highly immunosuppressed individuals) and ‘booster doses’ (offered to all adults).

Conclusions

Combining high quality healthcare data from different sources can provide valuable opportunities for new and important analyses. Our findings highlight the value of additional doses of BNT (and probably other RNA vaccines such as Moderna mRNA-1273/Spikevax) in people with moderate-to-severe kidney disease. These additional doses have the potential to compensate for differences in protection that may exist after initial vaccination doses. Where possible, achieving high coverage with RNA vaccines during booster campaigns is likely to reduce the burden of COVID-19 in people with kidney disease.