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Booster protection against Omicron infection in a highly vaccinated cohort

Authors:

• Caroline G. Tai, PhD, MPH, IQVIA, Durham, North Carolina

• Lisa L. Maragakis, MD, MPH, Division of Infectious Diseases, Department of Medicine, Johns Hopkins

University School of Medicine, Baltimore, Maryland

• Sarah Connolly, PhD, MPH, IQVIA, Durham, North Carolina

• John DiFiori, MD, Hospital for Special Surgery, and the National Basketball Association, New York,

New York

• Leroy Sims, MD, National Basketball Association, New York, New York

• Eleanor Adams, MD, MPH, National Basketball Association, New York, New York

• Deverick J. Anderson, MD, Duke Center for Antimicrobial Stewardship and Infection Prevention,

Durham, North Carolina

• Michael H. Merson, M.D., Duke Global Health Institute, Durham, North Carolina

• David D. Ho, MD, Aaron Diamond AIDS Research Center, Columbia University Vagelos College of

Physicians and Surgeons, New York, New York

• * Yonatan Grad MD, PhD, Harvard TH Chan School of Public Health.

• * Christina DeFilippo Mack, PhD, MSPH, FISPE, IQVIA, Durham, North Carolina

*These authors are joint senior authors on this work

NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
medRxiv preprint doi: https://doi.org/10.1101/2022.02.24.22271347; this version posted February 26, 2022. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.

ABSTRACT

Background: Evaluation of COVID-19 vaccine booster effectiveness is essential as new variants of SARS-CoV-
2 emerge. Data support the effectiveness of boosters in preventing severe disease and hospitalization;

however, the real-world impact on reducing incident SARS-CoV-2 infections across specific variants is not yet

clear.

Objectives: Assess the impact of COVID-19 boosters on protection against SARS-CoV-2 infection in a real-
world setting from a highly vaccinated (99%) population curated from a linked database with test results,

vaccination history, patient demographics, and genomic sequencing information from the National

Basketball Association (NBA).

Methods: In this population, 1,613 fully vaccinated staff and players (median age 34.5 years, 88% male) who
tested at least once between 1 December 2021 and 5 January 2022, were analyzed. Individuals were tested

at the time of reporting any symptom, regardless of severity, after known exposure per self-report or

contact tracing and/or during enhanced surveillance. Boosted individuals (n=1260) were compared to fully

vaccinated and booster eligible individuals (n=162), defined as 2 months post-JNJ-78436735 or 5-months

post-second dose of mRNA vaccine. Individuals not yet eligible for a booster and those who recovered from

COVID-19 between 1 November and 30 November, 2021 (n=25) were examined in secondary analyses but

excluded from the primary comparison. Individuals who were not fully vaccinated (n=27) or who received a

booster within 14 days during or prior to the observation period (n=916) were excluded.

Results: In this closely monitored population, fully vaccinated booster-eligible individuals were 2.6 times
more likely (RR = 2.6, 95% CI: 2.2 to 3.0, p<0.0001) to have a confirmed COVID-19 infection than boosted

individuals. Secondary analysis including non-boosted individuals with recent vaccination or recent SARS-

CoV-2 infection found that non-boosted individuals were at greater risk of infection compared with boosted

individuals (RR = 2.1, 95% CI: 1.8 to 2.4, p<0.001). Results were similar when stratified by primary

vaccination type with overlapping confidence intervals. No hospitalizations or deaths were observed in this

cohort. Genetic sequencing confirmed 93% of infections to be Omicron (among n=330 sequenced).

Conclusions: These results highlight the protective benefit of boosters against incident SARS-CoV-19

infection, not only for severe symptoms and death. Assessment of booster effectiveness remains vital for

COVID-19 vaccines as new variants of SARS-CoV-2 emerge, as there is still uncertainty around performance

in real-world settings. These data are needed to convince the general public that boosters remain effective

at preventing in the spread of COVID-19.

medRxiv preprint doi: https://doi.org/10.1101/2022.02.24.22271347; this version posted February 26, 2022. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.

Manuscript

Evaluation of COVID-19 vaccine booster effectiveness is essential as new variants of SARS-CoV-2

emerge. Data support the effectiveness of boosters in preventing severe disease and hospitalization;

however, the impact on reducing incident SARS-CoV-2 infections is not yet clear [1-3]. Data from the

National Basketball Association (NBA) assessed the impact of COVID-19 boosters on protection against

SARS-CoV-2 infection in a highly vaccinated (99%) population.

In this population, 1613 fully vaccinated (as defined by CDC guidelines[4]) staff and players (median age

34.5 years, 88% male) who tested at least once between Dec 1, 2021 and Jan 5, 2022, were analyzed

(Table 1). Individuals were tested at the time of reporting any symptom, regardless of severity, after

known exposure per self-report or contact tracing and/or during enhanced surveillance. Boosted

individuals (n=1260) were compared to fully vaccinated and booster eligible individuals (n=162), defined

as 2 months post-JNJ-78436735 or 5-months post-second dose of mRNA vaccine [4]. Individuals not yet

eligible for a booster and those who recovered from COVID-19 between Nov 1 and Nov 30, 2021 (n=25)

were examined in secondary analyses but excluded from the primary comparison. Individuals who were

not fully vaccinated (n=27) or who received a booster within 14 days during or prior to the observation

period (n=916) were excluded.

In this closely monitored population[5], fully vaccinated booster-eligible individuals were 2.6 times more

likely (RR = 2.6, 95% CI: 2.2 to 3.0, p<0.0001) to have a confirmed COVID-19 infection than boosted

individuals. Secondary analysis including non-boosted individuals with recent vaccination or recent

SARS-CoV-2 infection found that non-boosted individuals were at greater risk of infection compared

with boosted individuals (RR = 2.1, 95% CI: 1.8 to 2.4, p<0.001). Results were similar when stratified by

primary vaccination type with overlapping confidence intervals (Table 1). No hospitalizations or deaths

were observed in this cohort. Genetic sequencing confirmed the Omicron variant to be the dominant,
medRxiv preprint doi: https://doi.org/10.1101/2022.02.24.22271347; this version posted February 26, 2022. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.

nearly exclusive variant, in this sample period, with 93% confirmed to be Omicron (among n=339 with

genomic sequencing).

Overall, this study is a younger, healthier cohort compared to the U.S. population, precluding

generalizability. There was more frequent testing among the non-boosted group (Table 1, median

number of tests per person) and as daily surveillance testing was not performed, it is possible that some

asymptomatic cases or unreported symptomatic cases were not detected. These results highlight the

protective benefit of boosters against SARS-CoV-19 infection, specifically reducing incident infection

with the Omicron variant.

medRxiv preprint doi: https://doi.org/10.1101/2022.02.24.22271347; this version posted February 26, 2022. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.

Table 1: Booster protection against SARS-CoV-2 infection, Dec 1, 2021 - Jan 5, 2022
Population Characteristics Overall Boosted Non-Boosted
a
Total number of fully vaccinated individuals 1613 1267 346

(180 booster eligible)

Male, % 88% 87% 93%

Median age, years (IQR) 34.5 (27.8 - 46.4) 37.6 (30.0 - 48.7) 27.1 (23.6 - 32.3)

Median number of tests per individual (IQR) 14.0 (8.0 - 22.0) 14.0 (8.0 - 22.0) 16.0 (9.0 - 23.0)

Individuals with recent infections during Nov

25 (2%) 7 (1%) 18 (5%)
1, 2021 – Nov 30, 2021, # (%)

b
Individuals with COVID-19 during

observation period Dec 1, 2021 – Jan 5, 479 (30%) 304 (24%) 175 (51%)

2022, # (%)

Primary Vaccination Type, # (%)

mRNA 1262 (78%) 965 (76%) 297 (86%)

Viral vector 351 (22%) 302 (24%) 49 (14%)

Comparisons: Risk Ratio (95% CI) P-value

Non-boosted, but booster eligible (n=162) versus boosted
2.6 (2.2, 3.0) p<0.0001
(n=1260), excluding recent infections in Nov 2021

Stratified by primary vaccination type:

mRNA 2.8 (2.3, 3.3)

Viral Vector 2.3 (1.8, 2.9)

Non-boosted (n=346) versus boosted (n=1267) 2.1 (1.8, 2.4) p<0.0001

Stratified by primary vaccination type:

mRNA 2.26 (1.92, 2.67)

Viral Vector 2.01 (1.53, 2.64)

Footnotes:
a
Fully vaccinated was defined as two doses of an mRNA vaccine (BNT162b2 or mRNA-1273) or 1 dose of

JNJ-78436735 per CDC guidelines [4].

b
Diagnostic testing for COVID-19 was conducted via a molecular test using mid-turbinate swab with the

Cue Health system or Mesa Accula test platform or pooled nasal oropharyngeal swab with the Roche

cobas platform to detect the presence RNA of SARS-CoV-2. All positive tests were confirmed with a

subsequent test on a Roche cobas platform.

medRxiv preprint doi: https://doi.org/10.1101/2022.02.24.22271347; this version posted February 26, 2022. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.

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