key: cord-0902760-ylebkep1
authors: Tartof, Sara Y; Slezak, Jeff M; Puzniak, Laura; Hong, Vennis; Xie, Fagen; Ackerson, Bradley K; Valluri, Srinivas R; Jodar, Luis; McLaughlin, John M.
title: Immunocompromise and durability of BNT162b2 vaccine against severe outcomes due to omicron and delta variants
date: 2022-05-06
journal: Lancet Respir Med
DOI: 10.1016/s2213-2600(22)00170-9
sha: 3904307ca8c4e897cd8faeacc06ff01c54ad19c5
doc_id: 902760
cord_uid: ylebkep1

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Immunocompromise and durability of BNT162b2 vaccine against severe outcomes due to omicron and delta variants

Our previous data showed early signs of waning effectiveness of the BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine against omicron (B.1.1.529) variant-related hospital and emergency department admission 3 months or longer after receipt of a third dose in US adults aged 18 years and older. 1 The omicron-specific data in that report were from Dec 1, 2021, through to Feb 6, 2022-a period that included the first half of the omicron wave.

Given that the US Food and Drug Administration initially authorised a third dose of the vaccine for individuals aged 65 years and older and individuals at high risk of severe COVID-19 on Sept 22, 2021, initial study estimates of vaccine effectiveness at 3 months or longer after a third dose were enriched for high-risk populations, including patients who are immunocompromised and have suppressed response to vaccination due to their conditions.

To provide additional context, we have updated our analysis with data up to March 18, 2022, and stratified our findings by immunocompromised status. Briefly, immunocompromised status, defined using previously published criteria, 2 included diagnosis of leukaemia, lymphoma, congenital immunodeficiencies, asplenia or hyposplenia, HIV/AIDS, history of haematopoietic stem cell or solid organ transplantation, or receipt of immunosuppressive medication. Our updated findings primarily show two things. First, that the waning effectiveness against omicron-related hospitalisation noted at 3 months or longer after a third dose of vaccine during the initial study period (data cutoff of Feb 6, 2022) was not as pronounced after excluding individuals who were immunocompromised (original vaccine effectiveness ≥3 months after a third dose of 55% [95% CI 28−71] against omicronrelated hospitalisation vs 74% [52−86] after excluding individuals who were immunocompromised). Second, extending the analysis period up to March 18, 2022 (after more of the general population became eligible for booster doses on Nov 29, 2021) further attenuated evidence of waning vaccine effectiveness after a third dose. Specifically, after extending the analysis period, waning of effectiveness against omicron-related outcomes was no longer apparent, particularly in the immunocompetent population. Among immunocompetent individuals, effectiveness at 3 months or longer after a third dose of BNT162b2 against omicronrelated hospital admission was 86% (95% CI 81−90) and against emergency department admission was 76 (70−81) from Dec 1, 2021, to March 18, 2022 (table) .

High-risk patients, particularly those who are immunocompromised, have weaker initial immune responses to vaccination and have more pronounced waning of vaccineinduced immunity against severe outcomes than do other patients. 2 In initial analyses (data cutoff of Feb 6, 2022), patients who were immunocompromised comprised 48% of the study population who were analysed at 3 months or longer In summary, our updated findings suggest that waning effectiveness against hospital and emergency department admission after receiving a third dose of BNT162b2 vaccine is likely nuanced; that it is likely occurring for some high-risk individuals and in some settings (as was initially identified), but not in others. Despite emerging evidence from Israel showing that a fourth dose improves protection against severe outcomes, including hospitalisation and death, in the general older adult population, 5-7 more data are needed to fully understand long-term

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