cdc.gov/coronavirus

CDC COVID-19 Vaccine Effectiveness Studies

Katherine Fleming-Dutra, MD

Vaccine Effectiveness Team

COVID-19 Response

May 12, 2021
2

Need for post-authorization vaccine effectiveness (VE) 

estimates

▪ Real-world effectiveness may differ from efficacy under trial conditions due to 

implementation differences in:

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–

–

–

–

Adherence to cold chain requirements 

Broader population eligible to receive the vaccine

For 2-dose regimens, timing and coverage of second dose

▪ Build on evidence from clinical trials, specifically for:

Groups experiencing disproportionate impact of COVID-19

Severe disease

SARS-CoV-2 infection and transmission

Duration of protection
3

CDC COVID-19 VE policy priorities: results of internal 

and external input

Timeline after introduction Priority

Immediate • Does vaccine protect against symptomatic disease as expected?

Subsequent • VE against key outcomes

▪ Severe disease

▪ Non-severe disease 

▪ Infection and transmission

• VE in groups experiencing disproportionate impact of COVID-19

▪ Adults aged ≥65 years, including those in long-term care facilities (LTCFs) 

▪ People with key underlying conditions (e.g., immunocompromising 

conditions, obesity, diabetes)

▪ Racial and ethnic minority groups experiencing disproportionate impact

• VE for regimen-related questions for 2 dose products

▪ Single-dose and prolonged intervals; mixed-dose schedules (>1 product) 

• Viral evolution: Do genome changes impact VE?

Later stage • Duration of protection

• Comparison of VE across products
COVID-19 mRNA vaccine effectiveness 

literature globally
5

COVID-19 mRNA VE literature caveats

▪ The literature is rapidly evolving and growing exponentially.

▪ Wide variety of methods, populations, definitions are used.

▪ Most literature is currently in pre-print form, with few peer-reviewed 

publications.

▪ Quality varies widely. 

▪ Meta-analyses and formal comparisons are not appropriate at this time due 

to these caveats.
Figure courtesy of Dr. Minal Patel, World Health Organization, Individual studies results only, VOC=variant of concern 6

VE literature for 2 doses of Pfizer-BioNTech vaccine
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VE literature for 2 doses of mRNA vaccine

Figure courtesy of Dr. Minal Patel, World Health Organization, Individual studies results only, VOC=variant of concern
CDC vaccine effectiveness studies: 

Published literature
https://www.cdc.gov/mmwr/volumes/70/wr/mm7011e3.htm?s_cid=mm7011e3_w
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VE against infection among residents of 2 skilled 

nursing facilities

COVID-19 immunization status with 

Pfizer-BioNTech vaccine

Vaccine effectiveness 

against infection

% (95% confidence interval [CI])

Partially immunized: ≥14 days after 

first dose through dose 2 + 7 days 63 (33–79) 

Partially immunized with exclusion of 

prior SARS-CoV-2 infection 60 (30–77)

Partially immunized: ≥14 days after 

first dose through dose 2 + 0 days 66 (29–83)

Partially immunized: ≥14 days after 

first dose through dose 2 + 14 days 60 (33–77)

0 20 40 60 80 100

Vaccine Effectiveness (%)

https://www.cdc.gov/mmwr/volumes/70/wr/mm7011e3.htm?s_cid=mm7011e3_w
https://www.cdc.gov/mmwr/volumes/70/wr/mm7013e3.htm?s_cid=mm7013e3_w
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Interim VE against infection 

COVID-19 immunization status 

with mRNA vaccines

Adjusted vaccine 

effectiveness against 

infection*,†

% (95% confidence interval [CI])

Partially immunized (≥14 days after 

dose 1 through receipt of dose 2) 80 (59–90)

Fully immunized

(≥14 days after dose 2) 90 (68–97)

* Vaccine effectiveness was estimated using a Cox proportional hazards model accounting for timevarying immunization status.

† Hazard ratio is adjusted for study site

0 20 40 60 80 100

Vaccine Effectiveness (%)

https://www.cdc.gov/mmwr/volumes/70/wr/mm7013e3.htm?s_cid=mm7013e3_w
https://www.cdc.gov/mmwr/volumes/70/wr/mm7018e1.htm?s_cid=mm7018e1_w
14

Interim VE against hospitalization among adults aged 

≥65 years

0 20 40 60 80 100

COVID-19 immunization 

status with mRNA vaccines

Adjusted vaccine 

effectiveness against 

hospitalization

% (95% confidence 

interval [CI])

Full vaccination 94 (44–99)

Partial or full vaccination 71 (44–85)

Partial vaccination 64 (28–82)

Vaccine Effectiveness (%)

https://www.cdc.gov/mmwr/volumes/70/wr/mm7018e1.htm?s_cid=mm7018e1_w
https://www.cdc.gov/mmwr/volumes/70/wr/mm7017e2.htm?s_cid=mm7017e2_w
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VE against symptomatic disease in a Kentucky skilled 

nursing facility with a SARS-CoV-2 R.1 lineage variant 

outbreak 

COVID-19 immunization status with 

Pfizer-BioNTech vaccine

Adjusted vaccine 

effectiveness against 

symptomatic disease

% (95% confidence 

interval [CI])

Residents who were fully immunized 

(≥14 days after dose 2) 87 (66–95)

Healthcare personnel who were fully 

immunized (≥14 days after dose 2) 87 (46–97)

0 20 40 60 80 100

Vaccine Effectiveness (%)

https://www.cdc.gov/mmwr/volumes/70/wr/mm7017e2.htm?s_cid=mm7017e2_w
Additional ongoing CDC VE assessments
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VE priority Prospective data collection

Electronic health record (EHR) and claims 

analyses (coordination across US gov)

Immediate priority

Does vaccine work as expected to 

prevent symptomatic disease?

Test-negative design case-control among healthcare personnel 

Subsequent priorities

Older adults, including residents 

of long-term care facilities (LTCFs)

Case-control among adults ≥65 years (COVID-NET linked to 

CMS); National Healthcare Safety Network (NHSN)

CMS cohort (FDA, CMS)

EHR data sets (CDC, VA, FDA)

Infection and transmission Prospective longitudinal cohorts, including among healthcare 

personnel and frontline workers; case-ascertained household 

cohorts for transmission

Severe disease/hospitalization Test-negative design (for adults and children); conventional 

case-control using hospitalized controls; screening method

EHR data sets (CDC, VA, FDA); 

retrospective cohort or test-negative design

Non-severe disease Test-negative design among outpatients Potentially using EHR data sets

Those with key underlying 

conditions (e.g., 

immunocompromised)

Captured in above studies CMS (FDA, CMS); 

EHR data sets (CDC, VA, FDA)

Racial and ethnic groups 

disproportionately affected by 

COVID-19

Captured in above studies; test-negative design in American 

Indian and Alaska Native populations 

CMS (FDA, CMS); EHR data sets (CDC, VA, 

FDA); exploring IHS EHR (IHS)

Vaccine impact Ecologic analyses of disease incidence/seroprevalence and vaccination coverage; comparisons of expected 

vaccine impact from models with observed impact

Current VE assessments
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VE priority Prospective data collection

Electronic health record (EHR) and claims 

analyses (coordination across US gov)

Immediate priority

Does vaccine work as expected to 

prevent symptomatic disease?

Test-negative design case-control among healthcare personnel 

Subsequent priorities

Older adults, including residents 

of long-term care facilities (LTCFs) 

Case-control among adults ≥65 years (COVID-NET linked to 

CMS); National Healthcare Safety Network (NHSN)

CMS cohort (FDA, CMS)

EHR data sets (CDC, VA, FDA)

Infection and transmission Prospective longitudinal cohorts, including among healthcare 

personnel and frontline workers; case-ascertained household 

cohorts for transmission

Severe disease/hospitalization Test-negative design (for adults and children); conventional 

case-control using hospitalized controls; screening method

EHR data sets (CDC, VA, FDA); 

retrospective cohort or test-negative design

Non-severe disease Test-negative design among outpatients Potentially using EHR data sets

Those with key underlying 

conditions (e.g., 

immunocompromised)

Captured in above studies CMS (FDA, CMS); 

EHR data sets (CDC, VA, FDA)

Racial and ethnic groups 

disproportionately affected by 

COVID-19

Captured in above studies; test-negative design in American 

Indian and Alaska Native populations 

CMS (FDA, CMS); EHR data sets (CDC, VA, 

FDA); exploring IHS EHR (IHS)

Vaccine impact Ecologic analyses of disease incidence/seroprevalence and vaccination coverage; comparisons of expected 

vaccine impact from models with observed impact

Current VE assessments including children
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OVERCOMING2: VE against COVID-19 or Multisystem 

Inflammatory Syndrome in Children (MIS-C) among 

hospitalized children <19 years

▪ Based on an intensive care unit (ICU) network assessing influenza VE against 

critical illness in pediatric patients (aged <19 years)

▪ During 2020: Overcoming enrolled all MIS-C patients and ICU patients with 

COVID-19 at ~57 US pediatric hospitals 

▪ Primary objectives: 

• VE against any hospitalized COVID-19 and MIS-C

– Two control groups (test-negative acute respiratory illness and 

non-acute respiratory illness hospitalizations)

• VE by subgroup: variant, vaccine type, age, race/ethnicity, sex, time 

since vaccination, partial vaccination 
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Do viral genome changes impact VE?

▪ Selected prospective platforms will collect specimens from cases, where possible, 

for whole genome sequencing.

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–

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Will not be performed in real time

May not be powered for variant-specific VE assessments

▪ Vaccine evaluation unit is assessing vaccine breakthrough cases with 

hospitalization or death.

A collaboration with the Emerging Infections Program comparing the 

frequency of variants among vaccinated and unvaccinated persons may 

shed light.

▪ Work is part of broader CDC efforts to monitor the impact of SARS-CoV-2 

variants. 
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VE priority Prospective data collection

Electronic health record (EHR) and claims 

analyses (coordination across US gov)

Immediate priority

Does vaccine work as expected to 

prevent symptomatic disease?

Test-negative design case-control among healthcare personnel 

Subsequent priorities

Older adults, including residents 

of long-term care facilities (LTCFs) 

Case-control among adults ≥65 years (COVID-NET linked to 

CMS); National Healthcare Safety Network (NHSN)

CMS cohort (FDA, CMS)

EHR data sets (CDC, VA, FDA)

Infection and transmission Prospective longitudinal cohorts, including among healthcare 

personnel and frontline workers; case-ascertained household 

cohorts for transmission

Severe disease/hospitalization Test-negative design (for adults and children); conventional 

case-control using hospitalized controls; screening method

EHR data sets (CDC, VA, FDA); 

retrospective cohort or test-negative design

Non-severe disease Test-negative design among outpatients Potentially using EHR data sets

Those with key underlying 

conditions (e.g., 

immunocompromised)

Captured in above studies CMS (FDA, CMS); 

EHR data sets (CDC, VA, FDA)

Racial and ethnic groups 

disproportionately affected by 

COVID-19

Captured in above studies; test-negative design in American 

Indian and Alaska Native populations 

CMS (FDA, CMS); EHR data sets (CDC, VA, 

FDA); exploring IHS EHR (IHS)

Vaccine impact Ecologic analyses of disease incidence/seroprevalence and vaccination coverage; comparisons of expected 

vaccine impact from models with observed impact

Current VE assessments including genomic characterization
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Duration of protection from COVID-19 vaccines

▪ An important VE priority is to understand the duration of protection 

provided by COVID-19 vaccines.

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–

This will inform the question about the need for a booster.

It is important to take into account changes in the circulating variants 

over time. 
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VE priority Prospective data collection

Electronic health record (EHR) and claims 

analyses (coordination across US gov)

Immediate priority

Does vaccine work as expected to 

prevent symptomatic disease?

Test-negative design case-control among healthcare personnel 

Subsequent priorities

Older adults, including residents 

of long-term care facilities (LTCFs) 

Case-control among adults ≥65 years (COVID-NET linked to 

CMS); National Healthcare Safety Network (NHSN)

CMS cohort (FDA, CMS)

EHR data sets (CDC, VA, FDA)

Infection and transmission Prospective longitudinal cohorts, including among healthcare 

personnel and frontline workers; case-ascertained household 

cohorts for transmission

Severe disease/hospitalization Test-negative design (for adults and children); conventional 

case-control using hospitalized controls; screening method

EHR data sets (CDC, VA, FDA); 

retrospective cohort or test-negative design

Non-severe disease Test-negative design among outpatients Potentially using EHR data sets

Those with key underlying 

conditions (e.g., 

immunocompromised)

Captured in above studies CMS (FDA, CMS); 

EHR data sets (CDC, VA, FDA)

Racial and ethnic groups 

disproportionately affected by 

COVID-19

Captured in above studies; test-negative design in American 

Indian and Alaska Native populations 

CMS (FDA, CMS); EHR data sets (CDC, VA, 

FDA); exploring IHS EHR (IHS)

Vaccine impact Ecologic analyses of disease incidence/seroprevalence and vaccination coverage; comparisons of expected 

vaccine impact from models with observed impact

Current VE assessments including duration of protection
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CDC VE assessments in outbreak settings

▪ Residents of long-term care facilities

▪ Incarcerated and detained persons and staff in corrections facilities 

▪ Actively looking for COVID-19 outbreaks in congregate settings to assess:

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–

–

Variant-specific VE

VE for Johnson & Johnson’s Janssen vaccine

VE among adolescents and children once eligible for vaccine
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Conclusion

▪ Initial COVID-19 VE estimates from recently published reports are 

demonstrating remarkably consistent results across studies with a 

variety of methods and populations.

▪ There is an urgent need for VE data to guide vaccine policy.

▪ A broad approach, including a diversity of projects, methods, bias 

control, populations, and sample sizes strengthens our understanding of 

the true real-world performance of these vaccines. 
For more information, contact CDC

1-800-CDC-INFO (232-4636)

TTY: 1-888-232-6348 www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the 

official position of the Centers for Disease Control and Prevention.

Ensuring COVID-19 Vaccines Work: 

https://www.cdc.gov/coronavirus/2019-

ncov/vaccines/effectiveness.html

COVID-19 Vaccine Effectiveness Research: 

https://www.cdc.gov/vaccines/covid19/effectiveness-research/protocols.html