Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons

Chaguza, Chrispin; Coppi, Andreas; Earnest, Rebecca; Ferguson, David; Kerantzas, Nicholas; Warner, Frederick; Young, H. Patrick; Breban, Mallery I.; Billig, Kendall; Koch, Robert Tobias; Pham, Kien; Kalinich, Chaney C.; Ott, Isabel M.; Fauver, Joseph R.; Hahn, Anne M.; Tikhonova, Irina; Castaldi, Christopher; Kumar, Bony De; Pettker, Christian M.; Warren, Joshua L.; Weinberger, Daniel M; Landry, Marie L.; Peaper, David R.; Schulz, Wade; Vogels, Chantal B.F.; Grubaugh, Nathan D.

doi:10.1101/2022.01.22.22269660

Cited by 25 publications

(34 citation statements)

References 18 publications

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“…(16) We used the TaqPath assay to select tests as cases and controls since its S-gene probe, which fails for Omicron (BA.1) but not for Delta, allows for prediction of an Omicron infection when the primary circulating variants are Omicron and Delta. (17)…”

Section: Methodsmentioning

confidence: 99%

“…A case of Omicron infection was a positive SARS-CoV-2 RT-PCR test with SGTF, defined as: 1] an ORF1ab Ct value of < 30 and S-gene Ct – ORF1ab Ct value ≥5; or 2] ORF1ab Ct value <30 and S-gene Ct value ≥40. (17,20) An eligible control was a negative SARS-CoV-2 RT-PCR test collected ≥7 days prior to a positive test or the end of the study period (to account for non-resulted cases). Our sample included all eligible cases and up to three negative tests (controls) per person during the study period.…”

Section: Methodsmentioning

confidence: 99%

“…1,19 While a new sub-lineage of the Omicron variant (BA.2) has been detected in the US without SGTF, sequencing data from YNHH showed 100% agreement between SGTF and whole genome sequence-defined Omicron through December 2021. (17) In January 2022, we observed a small number (184) of positive tests that did not have SGTF and were not included as cases in the analyses. Our sample is overly representative of mild cases of SARS-CoV-2 infection since TaqPath testing was primarily employed in the YNHH outpatient setting.…”

Section: Limitationsmentioning

confidence: 99%

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Effectiveness of Primary and Booster COVID-19 mRNA Vaccination against Omicron Variant SARS-CoV-2 Infection in People with a Prior SARS-CoV-2 Infection

Lind

Robertson

Silva

et al. 2022

Preprint

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ImportanceThe benefit of primary and booster vaccination in people who experienced prior SARS-CoV-2 infection remains unclear.ObjectiveTo estimate the effectiveness of a primary (two-dose) and booster (third dose) vaccination against Omicron infection among previously infection people.DesignTest-negative case-control study.SettingYale New Haven Health System facilities serving southern Connecticut communities.ParticipantsVaccine eligible people who received SARS-CoV-2 RT-PCR testing between November 1, 2021, and January 31, 2022.ExposureCOVID-19 mRNA primary and booster vaccination.Main Outcomes and MeasuresWe conducted two analyses, each with an outcome of Omicron BA.1 variant infection (S-gene target failure defined) and each stratified by prior SARS-CoV-2 infection status. We estimated the effectiveness of primary vaccination during the period before and during booster eligibility (14-149 and ≥150 days, respectively, after 2nd dose) and of booster vaccination (≥14 days after booster dose). To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds among boosted and booster eligible people.ResultsOverall, 10,676 cases and 119,397 controls were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 6.1% and 7.8% had a prior infection. The effectiveness of primary vaccination 14-149 days after 2nd dose was 36.1% (95% CI, 7.1-56.1%) and 28.5% (95% CI, 20.0-36.2%) for people with and without prior infection, respectively. The effectiveness of booster vaccination was 45.8% (95% CI, 20.0-63.2%) and 56.9% (95% CI, 52.1-61.2%) in people with and without prior infection, respectively. The odds ratio comparing boosted and booster eligible people with prior infection was 0.83 (95% CI, 0.56-1.23), whereas the odds ratio comparing boosted and booster eligible people without prior infection was 0.51 (95% CI, 0.46-0.56).Conclusions and RelevancePrimary vaccination provided significant but limited protection against Omicron BA.1 infection among people with and without prior infection. While booster vaccination was associated with additional protection in people without prior infection, it was not associated with additional protection among people with prior infection. These findings support primary vaccination in people regardless of prior infection status but suggest that infection history should be considered when evaluating the need for booster vaccination.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Limitationsmentioning

confidence: 99%

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Effectiveness of Primary and Booster COVID-19 mRNA Vaccination against Omicron Variant SARS-CoV-2 Infection in People with a Prior SARS-CoV-2 Infection

Lind

Robertson

Silva

et al. 2022

Preprint

Self Cite

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“… Abstract The omicron variant of SARS-CoV-2 infected very large numbers of SARS-CoV-2 vaccinated and convalescent individuals 1–3 . The penetrance of this variant in the antigen experienced human population can be explained in part by the relatively low levels of plasma neutralizing activity against Omicron in people who were infected or vaccinated with the original Wuhan-Hu-1 strain 4–7 .…”

mentioning

confidence: 99%

Increased Potency and Breadth of SARS-CoV-2 Neutralizing Antibodies After a Third mRNA Vaccine Dose

Muecksch

Wang

Cho

et al. 2022

Preprint

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The omicron variant of SARS-CoV-2 infected very large numbers of SARS-CoV-2 vaccinated and convalescent individuals. The penetrance of this variant in the antigen experienced human population can be explained in part by the relatively low levels of plasma neutralizing activity against Omicron in people who were infected or vaccinated with the original Wuhan-Hu-1 strain. The 3rd mRNA vaccine dose produces an initial increase in circulating anti-Omicron neutralizing antibodies, but titers remain 10-20-fold lower than against Wuhan-Hu-1 and are, in many cases, insufficient to prevent infection. Despite the reduced protection from infection, individuals that received 3 doses of an mRNA vaccine were highly protected from the more serious consequences of infection. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving 3 mRNA vaccine doses. We find that the 3rd dose is accompanied by an increase in, and evolution of, anti-receptor binding domain specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the 2nd vaccine dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared to antibodies obtained after the 2nd vaccine dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells that differed from the persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analyzed neutralizing antibodies in the memory compartment obtained from individuals receiving a 3rd mRNA vaccine dose neutralized Omicron. Thus, individuals receiving 3 doses of an mRNA vaccine encoding Wuhan-Hu-1, have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help explain why a 3rd dose of an mRNA vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.

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“…Recent estimates suggest that 57% of Americans were infected with Omicron due to its high transmissibility and potential for immune escape [3][4][5]10]. In our cohort of recently boosted participants, one in five reported known infection based on a positive COVID-19 diagnostic test.…”

Section: Discussionmentioning

confidence: 79%

Antibody responses to known and unknown SARS-CoV-2 infections after mRNA vaccine booster

Demonbreun

Sancilio

Vaught

et al. 2022

Preprint

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We followed a fully-vaccinated (two mRNA vaccine doses) community cohort (n=41) without prior COVID-19 diagnosis from September 2021 through March 2022 through the Omicron wave following a booster mRNA vaccination. 19.5% of participants reported a known SARS-CoV-2 infection during the Omicron wave, which was confirmed by anti-nucleocapsid IgG. An additional 36.5% also developed anti-nucleocapsid IgG after the boost, consistent with unknown, asymptomatic SARS-CoV-2 infection during this period. Infection defined by anti-nucleocapsid IgG, whether known to participant or not, increased anti-spike IgG levels, relative to those lacking anti-nucleocapsid IgG, at 120 days post-booster.

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Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons

Cited by 25 publications

References 18 publications

Effectiveness of Primary and Booster COVID-19 mRNA Vaccination against Omicron Variant SARS-CoV-2 Infection in People with a Prior SARS-CoV-2 Infection

Effectiveness of Primary and Booster COVID-19 mRNA Vaccination against Omicron Variant SARS-CoV-2 Infection in People with a Prior SARS-CoV-2 Infection

Increased Potency and Breadth of SARS-CoV-2 Neutralizing Antibodies After a Third mRNA Vaccine Dose

Antibody responses to known and unknown SARS-CoV-2 infections after mRNA vaccine booster

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