Waning of SARS-CoV-2 booster viral-load reduction effectiveness

Levine-Tiefenbrun, Matan; Yelin, Idan; Alapi, Hillel; Herzel, Esma; Kuint, Jacob; Chodick, Gabriel; Gazit, Sivan; Patalon, Tal; Kishony, Roy

doi:10.1101/2021.12.27.21268424

Cited by 19 publications

(23 citation statements)

References 19 publications

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“…The waning of vaccine effectiveness against infection is consistent with previous observations for the second and third doses of the BNT162b2b vaccine. 10,11 Nonetheless, compared to the previously demonstrated waning pattern of the relative effectiveness of three doses compared to two doses in real-world settings – which begins around 3 months after inoculation – it appears that effectiveness of the fourth dose wanes sooner, similarly to the fact that the third dose wants sooner than the second dose. 23,11 This more rapid decline is potentially explained by a reduced effectiveness of the BNT162b2b vaccine against the Omicron variant.…”

Section: Discussionmentioning

confidence: 81%

“…1 However, the rapid spread of the Omicron variant (B.1.1.529) from late December through March 2022 9 caused a sharp increase in infection rates and COVID-19-related hospitalizations. 1 The rising incidence alongside evidence of a relatively rapid decrease in protection conferred by the third dose 10,11 prompted Israel’s decision to administer a fourth dose (a second booster). Recommendations were first given for immunosuppressed individuals on December 30, 2021, 12 and 3 days later for all individuals aged 60 or older and those at high risk of exposure (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Relative Effectiveness of Four Doses Compared to Three Dose of the BNT162b2 Vaccine in Israel

Gazit

Saciuk

Perez

et al. 2022

Preprint

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Objectives: The rapid spread of the Omicron variant (B.1.1.529) alongside evidence of a relatively rapid waning of the third dose prompted Israel to administer a fourth dose of the BNT162b2 vaccine on January 2022. Thus far, sufficient real-world evidence demonstrating the effectiveness of a fourth dose against infection and severe COVID-19 are lacking. This study examined the short-term effectiveness of a fourth dose compared to three doses over the span of 10 weeks. Design: A retrospective test-negative case-control study, performing both a matched analysis and an unmatched multiple-tests analysis. Setting: Nationally centralized database of Maccabi Healthcare Services (MHS), an Israeli national health fund that covers 2.5 million people. Participants: The study population included 97,499 MHS members aged 60 or older who were eligible to receive a fourth vaccine dose and performed at least one PCR test during the study period. Of them, 27,876 received the fourth dose and 69,623 received only three doses. Main outcomes and measures: Analyses focused on the period from January 10, 2022 (7 days after the fourth dose was first administered to eligible individuals) to March 13, 2022, an Omicron-dominant period in Israel. We evaluated two SARS-CoV-2-related outcomes: (1) breakthrough infection, defined as a positive PCR test performed 7 or more days after inoculation with the BNT162b2 vaccine; and (2) breakthrough infection resulting in a severe disease, defined as COVID-19-related hospitalization or COVID-19 associated mortality. Results: A fourth dose provided considerable additional protection against both SARS-CoV-2 infection and severe disease relative to three doses of the vaccine. However, vaccine effectiveness against infection varied over time, peaking during the third week with a VE of 64% (95% CI: 62.0%-65.9%) and declining to 29.2% (95% CI: 17.7%-39.1%) by the end of the 10-week follow-up period. Unlike VE against infection, the relative effectiveness of a fourth dose against severe COVID-19 was maintained at high level (>73%) throughout the 9-week follow-up period. Importantly, severe disease was a relatively rare event, occurring in <1% of both fourth dose and third dose only recipients. Conclusions: A fourth dose of the BNT162b2 vaccine provided considerable additional protection against both SARS-CoV-2 infection and severe disease relative to three doses of the vaccine. However, effectiveness of the fourth dose against infection wanes sooner than that of the third dose.

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Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Relative Effectiveness of Four Doses Compared to Three Dose of the BNT162b2 Vaccine in Israel

Gazit

Saciuk

Perez

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…There is, however, evidence that waning of protection against Delta variant following a booster dose of BNT162b2 is relatively rapid. 18 Allowing for a 19 This study had some limitations. There were relatively small numbers in the individual groups, but as estimated from our power calculations, the sample size was adequate to demonstrate significant difference in neutralizing antibody responses between the groups studied.…”

Section: Main Textmentioning

confidence: 99%

Neutralizing antibodies against the SARS-CoV-2 Omicron variant BA.1 following homologous and heterologous CoronaVac or BNT162b2 vaccination

Cheng

Mok

Leung

et al. 2022

Nat Med

337

301

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This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature Medicine is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

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“…However, recent contact-tracing findings, conducted in a household setting with omicron as the prevalent variant, showed no reduction in susceptibility to infection for breakthrough cases for fully-vaccinated individuals 107 . Waning vaccinal effectiveness 108 in reducing viral load (which has now been noted for the booster dose as well 109,110 can be further expected to impact the vaccinal reduction of transmission. We ran the model under two theoretical vaccine acceptance scenarios in the US (70% uptake and 100% uptake).…”

Section: Methodsmentioning

confidence: 95%

Endemicity is not a victory: the unmitigated downside risks of widespread SARS-CoV-2 transmission

Stoddard¹,

Novokhodko

Sarkar

et al. 2022

Preprint

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We have entered a new phase of the ongoing COVID-19 pandemic, as the strategy of relying solely on the current SARS-CoV-2 vaccines to bring the pandemic to an end has become infeasible. In response, public-health authorities in many countries have advocated for a strategy of using the vaccines to limit morbidity and mortality while permitting unchecked SARS-CoV-2 spread ("learning to live with the disease"). The feasibility of this strategy is critically dependent on the infection fatality rate (IFR) of COVID-19. An expectation exists, both in the lay public and in the scientific community, that future waves of the virus will exhibit decreased IFR, either due to viral attenuation or the progressive buildup of immunity. In this work, we examine the basis for that expectation, assessing the impact of virulence on transmission. Our findings suggest that large increases in virulence for SARS-CoV-2 would result in minimal loss of transmission, implying that the IFR may be free to increase or decrease under neutral evolutionary drift. We further examine the effect of changes in the IFR on the steady-state death toll under conditions of endemic COVID-19. Our modeling suggests that endemic SARS-CoV-2 implies vast transmission resulting in yearly US COVID-19 death tolls numbering in the hundreds of thousands under many plausible scenarios, with even modest increases in the IFR leading to an unsustainable mortality burden. Our findings thus highlight the critical importance of enacting a concerted strategy (involving for example global access to vaccines, therapeutics, prophylactics and nonpharmaceutical interventions) to suppress SARS-CoV-2 transmission, thereby reducing the risk of catastrophic outcomes. Our findings also highlight the importance of continued investment in novel biomedical interventions to prevent viral transmission.

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Waning of SARS-CoV-2 booster viral-load reduction effectiveness

Cited by 19 publications

References 19 publications

Relative Effectiveness of Four Doses Compared to Three Dose of the BNT162b2 Vaccine in Israel

Relative Effectiveness of Four Doses Compared to Three Dose of the BNT162b2 Vaccine in Israel

Neutralizing antibodies against the SARS-CoV-2 Omicron variant BA.1 following homologous and heterologous CoronaVac or BNT162b2 vaccination

Endemicity is not a victory: the unmitigated downside risks of widespread SARS-CoV-2 transmission

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