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. 2023 Mar 1;6(3):e232598.
doi: 10.1001/jamanetworkopen.2023.2598.

Estimation of COVID-19 mRNA Vaccine Effectiveness and COVID-19 Illness and Severity by Vaccination Status During Omicron BA.4 and BA.5 Sublineage Periods

Ruth Link-Gelles  1 , Matthew E Levy  2 , Karthik Natarajan  3   4 , Sarah E Reese  2 , Allison L Naleway  5 , Shaun J Grannis  6   7 , Nicola P Klein  8 , Malini B DeSilva  9 , Toan C Ong  10 , Manjusha Gaglani  11   12 , Emily Hartmann  13 , Monica Dickerson  1 , Edward Stenehjem  14 , Anupam B Kharbanda  15 , Jungmi Han  3 , Talia L Spark  2 , Stephanie A Irving  5 , Brian E Dixon  6   16 , Ousseny Zerbo  8 , Charlene E McEvoy  9 , Suchitra Rao  10 , Chandni Raiyani  11 , Chantel Sloan-Aagard  13   17 , Palak Patel  1 , Kristin Dascomb  14 , Anne-Catrin Uhlemann  18 , Margaret M Dunne  2 , William F Fadel  6   16 , Ned Lewis  8 , Michelle A Barron  10 , Kempapura Murthy  11 , Juan Nanez  13 , Eric P Griggs  1 , Nancy Grisel  14 , Medini K Annavajhala  18 , Akintunde Akinseye  2 , Nimish R Valvi  6 , Kristin Goddard  8 , Mufaddal Mamawala  11 , Julie Arndorfer  14 , Duck-Hye Yang  2 , Peter J Embí  6   19 , Bruce Fireman  8 , Sarah W Ball  2 , Mark W Tenforde  1
Affiliations

Estimation of COVID-19 mRNA Vaccine Effectiveness and COVID-19 Illness and Severity by Vaccination Status During Omicron BA.4 and BA.5 Sublineage Periods

Ruth Link-Gelles et al. JAMA Netw Open. .

Abstract

Importance: Recent SARS-CoV-2 Omicron variant sublineages, including BA.4 and BA.5, may be associated with greater immune evasion and less protection against COVID-19 after vaccination.

Objectives: To evaluate the estimated vaccine effectiveness (VE) of 2, 3, or 4 doses of COVID-19 mRNA vaccination among immunocompetent adults during a period of BA.4 or BA.5 predominant circulation; and to evaluate the relative severity of COVID-19 in hospitalized patients across Omicron BA.1, BA.2 or BA.2.12.1, and BA.4 or BA.5 sublineage periods.

Design, setting, and participants: This test-negative case-control study was conducted in 10 states with data from emergency department (ED) and urgent care (UC) encounters and hospitalizations from December 16, 2021, to August 20, 2022. Participants included adults with COVID-19-like illness and molecular testing for SARS-CoV-2. Data were analyzed from August 2 to September 21, 2022.

Exposures: mRNA COVID-19 vaccination.

Main outcomes and measures: The outcomes of interest were COVID-19 ED or UC encounters, hospitalizations, and admission to the intensive care unit (ICU) or in-hospital death. VE associated with protection against medically attended COVID-19 was estimated, stratified by care setting and vaccine doses (2, 3, or 4 doses vs 0 doses as the reference group). Among hospitalized patients with COVID-19, demographic and clinical characteristics and in-hospital outcomes were compared across sublineage periods.

Results: During the BA.4 and BA.5 predominant period, there were 82 229 eligible ED and UC encounters among patients with COVID-19-like illness (median [IQR] age, 51 [33-70] years; 49 682 [60.4%] female patients), and 19 114 patients (23.2%) had test results positive for SARS-CoV-2; among 21 007 hospitalized patients (median [IQR] age, 71 [58-81] years; 11 209 [53.4%] female patients), 3583 (17.1 %) had test results positive for SARS-CoV-2. Estimated VE against hospitalization was 25% (95% CI, 17%-32%) for receipt of 2 vaccine doses at 150 days or more after receipt, 68% (95% CI, 50%-80%) for a third dose 7 to 119 days after receipt, and 36% (95% CI, 29%-42%) for a third dose 120 days or more (median [IQR], 235 [204-262] days) after receipt. Among patients aged 65 years or older who had received a fourth vaccine dose, VE was 66% (95% CI, 53%-75%) at 7 to 59 days after vaccination and 57% (95% CI, 44%-66%) at 60 days or more (median [IQR], 88 [75-105] days) after vaccination. Among hospitalized patients with COVID-19, ICU admission or in-hospital death occurred in 21.4% of patients during the BA.1 period vs 14.7% during the BA.4 and BA.5 period (standardized mean difference: 0.17).

Conclusions and relevance: In this case-control study of COVID-19 vaccines and illness, VE associated with protection against medically attended COVID-19 illness was lower with increasing time since last dose; estimated VE was higher after receipt of 1 or 2 booster doses compared with a primary series alone.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Natarajan reported receiving grants from Janssen during the conduct of the study. Dr Naleway reported receiving grants from Pfizer and Vir Biotechnology outside the submitted work. Dr Klein reported receiving grants from Pfizer, Merck, GSK, and Sanofi Pasteur outside the submitted work. Dr Gaglani reported receiving grants directly from the Centers for Disease Control and Prevention (CDC) and from the CDC via subcontracts from Abt Associates and Vanderbilt University Medical Center to her institution outside the submitted work. Dr Hartmann reported receiving personal fees from Westat outside the submitted work. Dr Dixon reported receiving grants from the CDC, National Institutes of Health, Agency for Healthcare Research and Quality, and the US Department of Veterans Affairs to his institution; personal fees from Elsevier and Springer Nature; and consulting fees from Merck outside the submitted work. Dr McEvoy reported receiving grants from AstraZeneca outside the submitted work. Dr Rao reported receiving grants from GSK and serving as a consultant for Sequiris outside the submitted work. Dr Uhlemann reported receiving grants from Merck outside the submitted work. Dr Irving reported receiving grants from the CDC to her institution outside the submitted work. Dr Murthy reported receiving grants from the CDC to his institution outside the submitted work. During the conduct of the study, all Westat- and Kaiser Permanente Northern California Division of Research–affiliated authors reported receiving contractual support from the CDC via payments made to their respective institutions. Additionally, all authors affiliated with Baylor Scott & White Health, Children’s Minnesota, Columbia University Irving Medical Center, HealthPartners Institute, Intermountain Healthcare, Kaiser Permanente Center for Health Research, Regenstrief Institute, University of Colorado Anschutz Medical Campus, Paso del Norte Health Information Exchange, and Vanderbilt University Medical Center reported receiving contractual support from the CDC during the conduct of the study, via subcontracts from Westat, with payments made to their respective institutions.

Figures

Figure 1.
Figure 1.. Flowchart for the Selection of Hospitalizations
CLI indicates COVID-19–like illness; ICU, intensive care unit; VE, vaccine effectiveness.
Figure 2.
Figure 2.. mRNA COVID-19 Vaccine Effectiveness (VE) Associated With Protection Against Laboratory-Confirmed COVID-19–Associated Emergency Department or Urgent Care Encounters and Hospitalization, by Age Group, During a Period of Omicron BA.4/BA.5 Sublineage Predominance, June 19 to August 20, 2022
VE estimates were adjusted for age, geographic region, calendar time (days since January 1, 2021), and local virus circulation (percentage of SARS-CoV-2–positive test results from testing within the counties surrounding the facility on the date of the encounter) and weighted for inverse propensity to be vaccinated or unvaccinated (calculated separately for each VE estimate). Generalized boosted regression trees were used to estimate the propensity to be vaccinated based on the following sociodemographic, facility, and medical factors: age, sex, race, ethnicity, Medicaid status, calendar date, geographic region, local SARS-CoV-2 circulation on the day of each medical visit, urban-rural classification of facility, hospital type, number of hospital beds, chronic respiratory condition, chronic nonrespiratory condition, asthma, chronic obstructive pulmonary disease, other chronic lung disease, heart failure, ischemic heart disease, hypertension, other heart disease, stroke, other cerebrovascular disease, diabetes type 1, diabetes type 2, diabetes due to underlying conditions or other specified diabetes, other metabolic disease (excluding diabetes), clinical obesity, clinical underweight, kidney disease, liver disease, blood disorder, dementia, other neurological/musculoskeletal disorder, Down syndrome, and the presence of at least 1 prior molecular or rapid antigen SARS-CoV-2 test record documented in the electronic medical record at least 15 days before the medical encounter date (prevaccination, if vaccinated). VE estimates are not shown for vaccination status comparisons with CIs greater than 50 percentage points around the VE estimate. Adjusted VE could not be calculated for 1 subgroup due to lack of model convergence: hospitalizations, 50-64 years, 2 doses (14-149 days earlier). In vaccination status subgroups with fewer than 10 patients with SARS-CoV-2–positive test results, all numbers in the row were removed because of small cell sizes. ED indicates emergency department; NA, not available; UC, urgent care.
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References

    1. Steele MK, Couture A, Reed C, et al. Estimated number of COVID-19 infections, hospitalizations, and deaths prevented among vaccinated persons in the US, December 2020 to September 2021. JAMA Netw Open. 2022;5(7):e2220385. doi: 10.1001/jamanetworkopen.2022.20385 - DOI - PMC - PubMed
    1. Wang L, Kainulainen MH, Jiang N, et al. ; SSEV Bioinformatics Working Group . Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines. Nat Commun. 2022;13(1):4350. doi: 10.1038/s41467-022-31929-6 - DOI - PMC - PubMed
    1. Lauring AS, Tenforde MW, Chappell JD, et al. ; Influenza and Other Viruses in the Acutely Ill (IVY) Network . Clinical severity of, and effectiveness of mRNA vaccines against, COVID-19 from Omicron, Delta, and Alpha SARS-CoV-2 variants in the United States: prospective observational study. BMJ. 2022;376:e069761. doi: 10.1136/bmj-2021-069761 - DOI - PMC - PubMed
    1. Accorsi EK, Britton A, Fleming-Dutra KE, et al. Association between 3 doses of mRNA COVID-19 vaccine and symptomatic infection caused by the SARS-CoV-2 Omicron and Delta variants. JAMA. 2022;327(7):639-651. doi: 10.1001/jama.2022.0470 - DOI - PMC - PubMed
    1. Hachmann NP, Miller J, Collier AY, et al. Neutralization escape by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, and BA.5. N Engl J Med. 2022;387(1):86-88. doi: 10.1056/NEJMc2206576 - DOI - PMC - PubMed

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