For more information: www.cdc.gov/COVID19

Risk/Benefit assessment of thrombotic 

thrombocytopenic events after 

Janssen COVID-19 vaccines: 

Applying Evidence to Recommendation 

Framework

ACIP COVID-19 Vaccines

Sara Oliver MD, MSPH

ACIP Meeting

April 23, 2021
Evidence to Recommendations Framework
 Structure to describe information considered in moving from evidence

to ACIP vaccine recommendations

 Provide transparency around the impact of additional factors on 

deliberations when considering a recommendation

Evidence to Recommendations (EtR) Framework

3
 Should vaccination with the Janssen COVID-19 vaccine 

(1 dose) be recommended for persons 18 years of age and older 

under an Emergency Use Authorization?

Evidence to Recommendations (EtR) Framework

Policy Question

4
Evidence to Recommendations (EtR) Framework: 

Previous Janssen COVID-19 vaccine Recommendations 

EtR DomainQuestion

Public Health Problem • Is the problem of public health importance?

Benefits and Harms

• How substantial are the desirable anticipated effects?

• How substantial are the undesirable anticipated effects?

• Do the desirable effects outweigh the undesirable effects?

Values

• Does the target population feel the desirable effects are large relative to the

_ undesirable effects?

• Is there important variability in how patients value the outcomes?

Acceptability • Is the intervention acceptable to key stakeholders?

Feasibility • Is the intervention feasible to implement?

Resource Use • Is the intervention a reasonable and efficient allocation of resources?

Equity • What would be the impact of the intervention on health equity? 5
EtR Domain

Question

Public Health 

Problem

• Recent COVID-19 Epidemiology

• Thrombosis after COVID-19 Disease

• Cerebral Venous Sinus Thrombosis (CVST)

• Heparin Induced Thrombocytopenia (HIT)

• AstraZeneca COVID-19 vaccines: Available global data 

Benefits and 

Harms

• Benefits of Janssen COVID-19 vaccine

• Harms of Janssen COVID-19 vaccine: 

Estimated cases of TTS after Janssen COVID-19 vaccine

• Benefit/Risk Assessment of COVID-19 vaccines 

Evidence to Recommendations (EtR) Framework: 

Adaptation to Risk/Benefit assessment for Janssen COVID-19 vaccine recommendations 

6
EtR Domain

Question

Values and

Acceptability

• Intent to receive 1-dose COVID-19 vaccine

• Intent to receive Janssen COVID-19 vaccine over time 

Feasibility

• Jurisdictional use of Janssen COVID-19 vaccine

Possible impact of Janssen COVID-19 vaccine policy options

Equity

• Possible impact of Janssen COVID-19 vaccine policy options in 

disproportionately affected populations 

Resource Use • No information available

Evidence to Recommendations (EtR) Framework: 

Adaptation to Risk/Benefit assessment for Janssen COVID-19 vaccine recommendations 

7
EtR Domain: Public Health Problem
• Recent COVID-19 Epidemiology

– COVID-19 cases, hospitalization and deaths, stratified by age, sex, race and ethnicity 

• Cerebral Venous Sinus Thrombosis (CVST)

• Heparin Induced Thrombocytopenia (HIT) 

• Thrombosis after COVID-19 Disease

• AstraZeneca COVID-19 vaccines

– Review of available global data

Public Health Problem:

9
Trends in Number of COVID-19 Cases in the US

https://covid.cdc.gov/covid-data-tracker/#trends_dailytrendscases

0

50000

100000

150000

200000

250000

300000

350000

Jan 22 2020 Apr 21 2020 Jul 20 2020 Oct 18 2020 Jan 16 2021 Apr 16 2021

Number of COVID-19 Cases

January 21, 2020 – April 17, 2021

Apr 17 2021

10
0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

Jan 22 2020 Apr 21 2020 Jul 20 2020 Oct 18 2020 Jan 16 2021 Apr 16 2021

Number of COVID-19 Deaths

Trends in Number of COVID-19 Deaths in the US

https://covid.cdc.gov/covid-data-tracker/#trends_dailytrendscases

Apr 17 2021

January 21, 2020 – April 17, 2021

11
COVID-19 Incidence Rates, by State

40.2 – 75.8

83.2 – 102.8

110.6 – 146.6

149.8 – 218.4

233.4 – 519.8

US COVID-19 7-Day Case Rate per 100,000, by State

https://covid.cdc.gov/covid-data-tracker/#cases_casesper100klast7days 12
COVID-19 Incidence by State

40.2 – 75.8

83.2 – 102.8

110.6 – 146.6

149.8 – 218.4

233.4 – 519.8

US COVID-19 7-Day Case Rate per 100,000, by State

0

200

400

600

800

Jan 22

2020

Apr 21

2020

Jul 20

2020

Oct 18

2020

Jan 16

2021

Apr 16

2021

7-Day Rate per 

100,000

Michigan

https://covid.cdc.gov/covid-data-tracker/#cases_casesper100klast7days 13
SARS-CoV-2 Variants Circulating in the United States

https://covid.cdc.gov/covid-data-tracker/#variant-proportions

Variant Proportions, January 3 - March 27, 2021

14

B.1.1.7 - 45%

P.1 - 2%

B.1.351 - <1%

B.1.429 - 7%

B.1.526 - 16%
https://covid.cdc.gov/covid-data-tracker/#global-counts-rates

Global COVID-19 Incidence Rates

Global cases of COVID-19 reported per 100,000 population in the past 7 days

15
Trends in Number of COVID-19 Cases in the US

https://covid.cdc.gov/covid-data-tracker/#trends_dailytrendscases

0

50000

100000

150000

200000

250000

300000

350000

Jan 22 2020 Apr 21 2020 Jul 20 2020 Oct 18 2020 Jan 16 2021 Apr 16 2021

Number of COVID-19 Cases

January 21, 2020 – April 17, 2021

Apr 17 2021

Focus on recent epi,

March 1–April 17 

16
https://covid.cdc.gov/covid-data-tracker/#demographics

COVID-19 Incidence Rates, by Age Group and Sex

COVID-19 Incidence Rate per 100,000 Population, by Age Group and Sex

March 1, 2021 – April 17, 2021

0 200 400 600 800 1000 1200

18 - 29 Years

30 - 49 Years

50 - 64 Years

65+ Years

COVID-19 Incidence Rate per 100,000 Population

Female

Male

17
https://covid.cdc.gov/covid-data-tracker/#demographics

COVID-19 Hospitalization Rates, by Age Group and Sex

COVID-19 Hospitalization Rate per 100,000 Population, by Age Group and Sex

March 1, 2021 – April 17, 2021

0 5 10 15 20 25 30 35 40 45 50

18 - 29 Years

30 - 49 Years

50 - 64 Years

65+ Years

COVID-19 Hospitalization Rate per 100,000 Population

Female

Male

18
https://covid.cdc.gov/covid-data-tracker/#demographics

COVID-19 Mortality Rates, by Age Group and Sex

COVID-19 Mortality Rate per 100,000 Population, by Age Group and Sex

March 1, 2021 – April 17, 2021

0 2 4 6 8 10 12 14

18 - 29 Years

30 - 49 Years

50 - 64 Years

65+ Years

COVID-19 Mortality Rate per 100,000 Population

Female

Male

19
https://covid.cdc.gov/covid-data-tracker/#demographics

COVID-19 Incidence Rates, by Race/Ethnicity

COVID-19 Incidence Rate per 100,000 Population by Race/Ethnicity

March 1, 2021 – April 17, 2021

0 100 200 300 400 500 600 700 800 900

Asian, Non-Hispanic

American Indian/Alaska Native, Non-Hispanic

White, Non-Hispanic

Black, Non-Hispanic

Native Hawaiian/Other Pacific Islander, Non-Hispanic

Hispanic/Latino

Multiple/Other, Non-Hispanic

COVID-19 Incidence Rate per 100,000 Population 20
https://covid.cdc.gov/covid-data-tracker/#demographics

COVID-19 Mortality Rate, by Race/Ethnicity

COVID-19 Mortality Rate per 100,000 Population by Race/Ethnicity

March 1, 2021 – April 17, 2021

0 0.5 1 1.5 2 2.5 3 3.5

American Indian/Alaska Native, Non-Hispanic

Asian, Non-Hispanic

White, Non-Hispanic

Hispanic/Latino

Black, Non-Hispanic

Native Hawaiian/Other Pacific Islander, Non-Hispanic

Multiple/Other, Non-Hispanic

COVID-19 Mortality Rate per 100,000 Population

21
 Incidence

– Cumulative incidence rate for adults: 710.9 per 100,000 population

– Younger females (18-29 years) have the highest incidence of new infections

 Hospitalization

– Cumulative hospitalization rate for adults: 20.6 per 100,000 population

– Most hospitalizations still occur in persons aged ≥ 65 years

• Proportion of hospitalizations occurring in persons aged ≥65 years declining

 Mortality

– Cumulative mortality rate: 3.0 per 100,000 population

– Most COVID-19 deaths still occur in persons aged ≥ 65 years

• Proportion of deaths occurring in persons aged ≥65 years declining

Summary of the COVID-19 Epidemiology

March 1–April 17, 2021

https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html . https://gis.cdc.gov/grasp/COVIDNet/COVID19_5.html . https://covid.cdc.gov/covid-datatracker/#trends_totalandratedeathssevendayrate 22
 Cerebral Venous Sinus Thrombosis (CVST) incidence: 14.5−28.5 per million U.S population

– Incidence increasing in recent years (4% annually)

– Higher in women aged 18–49 years

– Risk factors (e.g. hereditary thrombophilia, oral contraceptives, obesity) identified in up 

to 85% of cases

– Mortality ~5-10%

 Splanchnic Vein Thrombosis (SVT) incidence: 84‒179 per million U.S. population

– Incidence higher among men

– Risk increases with age

 Incidence with thrombocytopenia much lower than without thrombocytopenia

– CVST with thrombocytopenia: 0.7‒1.6 per million U.S. population

Epidemiology of Cerebral Venous Sinus Thrombosis (CVST) and 

Splanchnic Vein Thrombosis (SVT)

23

Data source: Health Care Utilization Project (HCUP) National Inpatient Sample (NIS) for 2018 and Marketscan Treatment Pathways (Continuously-enrolled Commercial 

Insurance and Medicaid) for 2019

Otite et al. Neurology 2020; 95: e2200-e2213. 2020; Silvis et al. Nat Rev Neurol 13, 555–565 (2017). Silvis et al. Semin Thromb Hemost 2016;42:622–631.;
 Heparin-induced thrombocytopenia (HIT) occurs in 0.5% to 1% of patients exposed to 

unfractionated heparin for medical and surgical indications

– Incidence: 23‒45 per million total U.S. population* 

 Of patients with HIT, thrombosis occurs in about 20%−64% (called HITT)

 Immune mediated ― antibodies against platelet factor 4 (PF4) & heparin

 Risk factors for developing thrombosis

– Genetic polymorphisms 

– Lower platelet count (and earlier fall in count)

– Higher titer of anti-heparin/PF4 antibodies

– Prior surgery (cardiac, orthopedic, trauma)

– Cardiovascular disease

 Limited case series published on HIT occurring after COVID-19

Heparin-Induced Thrombocytopenia with Thrombosis (HITT)

* Source: HCUP NIS 2018 and Marketscan (Continuously-enrolled Commercial Insurance and Medicaid) for 2019, unable to distinguish autoimmune HIT vs heparin-induced HIT

Arepally et al. 2021. https://www.ahajournals.org/doi/epub/10.1161/ATVBAHA.120.315445; Nand et al. 1998 https://doi.org/10.1002/(SICI)1096-8652(199709)56:1<12::AIDAJH3>3.0.CO;2-5; Fabris et al 2002. https://onlinelibrary.wiley.com/doi/epdf/10.1046/j.1365-2796.2002.01021.x ; Greinacher et al. 2005. https://www.thiemeconnect.com/products/ejournals/abstract/10.1160/TH04-12-0825 24
 Systematic review, meta-analysis of CVST among patients hospitalized for COVID-19

– Estimates between 0.03% and 0.08% of hospitalized COVID-19 patients

 Estimated risk of 5−6 cases of CVST per million SARS-COV-2 infections*

 CVST + thrombocytopenia in COVID-19 patients is extremely rare

 Pathology appears different than TTS after COVID-19 vaccines

– PF4/heparin specific antibodies negative by ELISA or platelet functional assay for 

confirmed COVID-19 patients (n=222), including 10 with thromboembolic 

complications

CVST associated with COVID-19

* Data source: Premier Healthcare Database, January 2020-January 2021

Acronyms: Cerebral Venous Sinus Thrombosis (CVST), Thrombosis with Thrombocytopenia Syndrome (TTS)

Katsanos et al. (2020) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753413/ ; Baldini et al. (2021) https://doi.org/10.1111/ene.14727; Mowla et al. (2020) 

https://doi.org/10.1016/j.jns.2020.117183; Greinacher et al. Research Square preprint (Apr 9, 2021): https://www.researchsquare.com/article/rs-404769/v1 25
 Recent study using electronic health records (81m patients, mostly U.S.) to estimate 

CVST & portal vein thrombosis (PVT) incidence in 513,284 COVID-19 cases

– Highest baseline CVST incidence observed over any 2-week period: 0.41 per million people

– CVST incidence 2 weeks after COVID-19 diagnosis (among hospitalized): 39 per million

– CVST incidence higher after COVID-19 diagnosis than after mRNA vaccines (4.1 per million) 

or after influenza disease (0.0 per million)

– Mortality was 20% for CVST and 19% for PVT

Limitations

– Unable to assess incidence of CVST after adenovirus vector vaccines (Janssen, AstraZeneca)

– Did not provide rates of CVST + thrombocytopenia

• Limited ability to directly compare to rates of CVST + thrombocytopenia after vaccines 

reported in US or Europe

CVST associated with COVID-19

Acronyms: Cerebral Venous Sinus Thrombosis (CVST), Portal Vein Thrombosis (PVT)

Taquet et al. Open Science preprint (April 15 2021): https://osf.io/a9jdq/ 26
 As of 4 April 2021, 169 cases of CVST & 53 cases of splanchnic vein thrombosis 

reported to EudraVigilance. ~34 million people vaccinated in EEA & UK by this date. 

– EU ~10 cases per million (1 case per 100,000) vaccinated adults

• Higher in younger adults compared to older adults

– Most of cases in women aged <60 years within 2 weeks of receiving 1st vaccine dose

 European Medicines Agency concluded benefit/risk ratio still favorable to use vaccine

– Causal association plausible

– Unable to identify definitive cause, but possibly similar to heparin-induced thrombocytopenia

– No specific risk factors to date (epidemiology may be related to vaccine delivery)

– Added unusual blood clots with low platelets to the label as very rare side effect

Thrombosis with Thrombocytopenia Syndrome (TTS) after 

AstraZeneca vaccine in Europe

https://www.who.int/news/item/16-04-2021-global-advisory-committee-on-vaccine-safety-(gacvs)-review-of-latest-evidence-of-rare-adverse-blood-coagulation-events-withastrazeneca-covid-19-vaccine-(vaxzevria-and-covishield)

https://www.ema.europa.eu/en/news/astrazenecas-covid-19-vaccine-ema-finds-possible-link-very-rare-cases-unusual-blood-clots-low-blood

https://www.ema.europa.eu/en/documents/prac-recommendation/signal-assessment-report-embolic-thrombotic-events-smq-covid-19-vaccine-chadox1-s-recombinant_en.pdf 27
 Through April 14: 168 reports of blood clotting with low platelets 

– 77 CVST with thrombocytopenia; 91 in other major veins with thrombocytopenia

– 93 women, 75 men, aged 18‒93 years

– 32 deaths 

– Most cases occurred after first vaccine dose; one case occurred after second dose

 Rate: 7.9 per million (21.2 million AZ doses given)

 Benefits continue to outweigh risks ― stronger evidence for a link of vaccine to extremely 

rare blood clots with lower platelets, but more work needed 

– Careful consideration be given to those at higher risk of blood clots because of medical 

conditions or pregnancy

– Continue to give second doses, except to those with blood clots and low platelets after first dose

 Recommended ages 18−29 years at low risk of infections be offered other vaccines

UK decision on use of AstraZeneca vaccine ― April 14, 2021

https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting

https://www.gov.uk/government/news/mhra-issues-new-advice-concluding-a-possible-link-between-covid-19-vaccine-astrazeneca-and-extremely-rare-unlikely-to-occur-blood-clots

https://www.gov.uk/government/publications/use-of-the-astrazeneca-covid-19-vaccine-jcvi-statement/jcvi-statement-on-use-of-the-astrazeneca-covid-19-vaccine-7-april-2021 28
 Reviewed evidence on 8 U.S. reports of serious cases of unusual blood clots with low 

levels of blood platelets, one of which had a fatal outcome. Over 7 million U.S. 

people had received Janssen vaccine, as of 13 April 2021

 Cases reviewed very similar to cases occurring with AstraZeneca COVID-19 vaccine

 Concluded that a warning about unusual blood clots with low blood platelets should 

be added to the product information for Janssen COVID-19 vaccine 

 Very rare event, and the overall benefits of Janssen COVID-19 vaccine in preventing 

COVID-19 outweigh the risks of side effects

 Emphasized importance of healthcare provider awareness

EMA’s safety committee (PRAC) meeting on U.S. TTS cases 

after Janssen vaccine, April 20, 2021

https://www.ema.europa.eu/en/news/covid-19-vaccine-janssen-ema-finds-possible-link-very-rare-cases-unusual-blood-clots-low-blood 29
Public Health Problem:

30

COVID-19

CVST after 

COVID-19

HIT CVST

TTS after AZ 

vaccine

Hospitalization:

200 per million population

Death:

30 per million population

5-6 per million 

SARS-COV-2 infections 

14.5‒28.5 per million 

population

UK:

7.9 per million 

vaccinated population

EU:

10 per million 

vaccinated population

CVST + 

Thrombocytopenia

0.7‒1.6 per million 

population

23‒45 per million 

population

Acronyms: Cerebral Venous Sinus Thrombosis (CVST), Heparin-Induced Thrombocytopenia (HIT), Thrombosis with Thrombocytopenia Syndrome (TTS) 
EtR Domain: Benefits and Harms
• Benefits of Janssen COVID-19 vaccine

– Prevention of COVID-19 cases, hospitalizations and deaths

• Harms of Janssen COVID-19 vaccine 

– Estimated cases of TTS after Janssen COVID-19 vaccine, by age and gender

• Benefit and Risk summary 

Benefits and Harms:

32
 The clinical trial demonstrated efficacy against symptomatic, laboratory-confirmed 

COVID-19. The overall efficacy was 66.3% (95% CI: 59.9%, 71.8%)

 Vaccine efficacy against COVID-19 associated hospitalization was 93% (95% CI: 71%, 98%)

 Higher efficacy against severe outcomes than for any symptomatic COVID-19

– VE against deaths due to COVID-19: 100%

 Efficacy against severe disease† remained high across world regions (73-82%*), 

suggesting protection against severe illness with variant strains

Benefits of the Janssen COVID-19 vaccine

33

†Definition: Respiratory Rate ≥ 30, Heart Rate ≥125, SpO2≤ 93% on room air at sea level or PaO2/FIO2< 300 mm Hg; OR respiratory failure or Acute Respiratory Distress Syndrome 

(ARDS), defined as needing high-flow oxygen, non-invasive or mechanical ventilation, or ECMO; OR evidence of shock (systolic blood pressure <90mmHg, diastolic BP<60mmHg or 

requiring vasopressors); OR significant acute renal, hepatic or neurologic dysfunction; OR admission to an intensive care unit or death

*Assessed ≥ 14 days post vaccination
 Similar efficacy for across age, sex, race, and ethnicity categories, and those 

with underlying medical conditions at ≥14 days post-vaccination 

64.7

76.5

66.4

65.6

67.6

63.7

64.2

67.6

0 20 40 60 80 100

Vaccine Efficacy (%)

Benefits of the Janssen COVID-19 vaccine

Age 18-64 years 

Age ≥65 years 

Non-Hispanic/Latino

Hispanic/Latino 

White

Black

With comorbidities

Without comorbidities

34
 Vaccine shipment and storage (3 months) at refrigerator temperatures (2-8oC)*

– Refrigerator-stable vaccine could facilitate the availability of the Janssen COVID-19 

vaccine in many community settings and mobile sites

 Single-dose series

 Easier to reach some disproportionately affected groups such as: homeless, rural 

residents, justice-involved, disabled, homebound, or with no/limited access to 

healthcare

35

Benefits of the Janssen COVID-19 vaccine

* Long-term storage at standard freezer temperatures (-20oC)
36

Potential Harms of the Janssen COVID-19 vaccine

 7.98 million vaccine doses administered*and 15 confirmed TTS cases as of April 21, 2021

– Additional potential TTS cases under review, including potential male cases

Females Males

Age group Cases Doses admin Reporting rate† Cases* Doses admin Reporting rate†

18-49 years old 13 1,866,294 7.0 per million 0 1,977,330 0 per million

50+ years old 2 2,125,239 0.9 per million 0 2,010,144 0 per million

* Source of doses administered: https://covid.cdc.gov/covid-data-tracker/#vaccinations; Some age- and sex-specific doses administered data were imputed

† Reporting rate = TTS cases per 1 million Janssen COVID-19 vaccine doses administered 

* One TTS case occurred in the Phase 3 trial in a male aged 18-49 years. 

Acronyms: Thrombosis with Thrombocytopenia Syndrome (TTS)
Type of analysis Objective

2. Direct

(1-month period)

• Quantify direct age and sex-specific benefits and harms, per 

million Janssen vaccine doses

Summary of Different Risk-Benefit Analyses

37

Population Level Risk-Benefit Analysis

Type of analysis Objective

1. Population 

(6-month period)

• Quantify COVID-19 infections, hospitalizations, and 

deaths averted under different assumptions about resumption 

of Janssen vaccination

• Quantify population-level, age-specific benefits and harms of 

resuming vaccination with Janssen COVID-19 vaccine

Individual Level Risk-Benefit Analysis
Modeled Janssen COVID-19 Vaccine Scenarios

 Objective: Quantify COVID-19 infections, hospitalizations, and deaths under 

different assumptions about resumption of Janssen vaccination

 In all scenarios we assume continued use of mRNA vaccines

 Evaluated the following scenarios:

– Janssen vaccination not resumed

– Janssen vaccination resumed on April 24th for all adults aged 18+ years

• 50% of pre-pause J&J administration rate (in 18+ age group)

• 100% of pre-pause J&J administration rate (in 18+ age group)

– Janssen vaccination resumed on April 24th in adults aged 50+ years only

• 50% of pre-pause J&J administration rate (in 50+ age group)

• 100% of pre-pause J&J administration rate (in 50+ age group)

38
Model Overview & Assumptions

 Compartmental model used to simulate incident infections, hospitalizations, and 

deaths over the course of the epidemic in the US

– Stratified by age, essential-worker status, and underlying conditions

– Calibrated to observations through Spring 2021. Future activity based on 

external scenarios.

 Two vaccine types: mRNA and Janssen (VE informed by RCTs)

– Immunity develops 14 days after administration

– 28 days between mRNA doses

 No loss to follow-up or delays in administration

 No waning of immunity over time

39
Modeled Time to Complete Vaccination for All Intending 

Adults

Multiple assumptions:

• Vaccine intent in each age 

group remains same

• Administration of mRNA 

vaccines continues at the 

same rate as before pause 

• In practice, pace of 

administration may slow as 

those experiencing barriers 

to access and/or greater 

hesitancy comprise a greater 

share of the unvaccinated 

40
Modeling Transmission Scenarios

 Calibrated assuming no 

interruption of Janssen 

vaccination under two 

scenarios reflecting 

continued level of nonpharmaceutical 

interventions (i.e., low 

transmission and 

moderate transmission)

 Calibrated to Round 4 of 

the COVID-19 Scenario 

Hub

41
Percent Change* in Outcomes 6 Months Post-Pause,

by Janssen Resumption Strategy

* compared to a scenario in which administration of 

the J&J vaccine does not resume

Moderate Transmission

42
Percent Change* in Outcomes 6 Months Post-Pause,

by Janssen Resumption Strategy

* Compared to a scenario in which administration of the J&J vaccine does not resume

Moderate Transmission Low Transmission

There is a benefit of resuming Janssen vaccination in terms of infections, hospitalizations and deaths 

prevented under different epidemiologic assumptions

43
44

Population Risk-benefit assessment

 Quantify age-specific risks and benefits of resuming vaccination with Janssen 

COVID-19 vaccine

– Risks: Number of TTS

– Benefits: Prevention of COVID-19-related hospitalizations, 

ICU admissions, and deaths

Acronyms: Thrombosis with Thrombocytopenia Syndrome (TTS)
Population Risk-Benefit Inputs

 Estimates from compartmental model

– Numbers of hospitalizations and deaths due to COVID-19

– Number of persons estimated to receive Janssen COVID-19 vaccine 

after pause

– Conditions: Low and moderate transmission; 50% and 100% of prior 

vaccination rate; Resuming in ages 18+ and 50+, vs no resumption

– 6-month time horizon

 ICU admissions per hospitalization (CDC Pandemic Planning Scenarios)

 Counts of TTS cases by age (CDC data)

 Numbers vaccinated with Janssen COVID-19 vaccine, by age, before pause 

(CDC data)

Acronyms: Thrombosis with Thrombocytopenia Syndrome (TTS) 45
Benefits and harms of resuming vaccination for 

ages ≥18 years vs. ≥50 years over 6-month period

Moderate transmission; Vaccination resumed at 50% of rate before pause

1 Based on observed cases adjudicated as of 4/21/2021

NOTE: in Phase III RCT, one male in 18-49 year age group experienced TTS; not included in this analysis

Acronyms: Thrombosis with Thrombocytopenia Syndrome (TTS)

0 200 400 600 800 1000 1200

18-49 years

50-64 years

>=65 years

Resume vaccination: age 18+

26 TTS in 9.8M vaccinations

Prevent 1,435 deaths, 2,236 ICU admissions 

24 TTS

2 TTS

Deaths averted ICU admissions averted

46
Benefits and harms of resuming vaccination for 

ages ≥18 years vs. ≥50 years over 6-month period

Moderate transmission; Vaccination resumed at 50% of rate before pause

1 Based on observed cases adjudicated as of 4/21/2021

NOTE: in Phase III RCT, one male in 18-49 year age group experienced TTS; not included in this analysis

Acronyms: Thrombosis with Thrombocytopenia Syndrome (TTS)

0 200 400 600 800 1000 1200

18-49 years

50-64 years

>=65 years

Resume vaccination: age 18+

0 200 400 600 800 1000 1200

18-49 years

50-64 years

>=65 years

Resume vaccination: age 50+

26 TTS in 9.8M vaccinations

Prevent 1,435 deaths, 2,236 ICU admissions 

2 TTS in 3.6M vaccinations

Prevent 257 deaths, 779 ICU admissions 

24 TTS

2 TTS 2 TTS

Deaths averted ICU admissions averted

47
Summary of population-level risks and benefits by 

recommendation, all scenarios

Note: Benefits of vaccination apply to the whole population over a 6-month 

period, and result from direct and indirect effects.

Recommendation for all persons 

aged 18+

– Risks: Expect 26‒45 TTS cases, 

depending on uptake

– Benefits: Depend on uptake, 

amount of transmission

• 800‒3,500 fewer ICU admissions

• 600‒1,400 fewer deaths

Recommendation for all 

persons aged 50+

Risks: Expect 2‒3 TTS cases, 

depending on uptake

Benefits: Depend on uptake, 

amount of transmission

300‒1000 fewer ICU 

admissions

40‒250 fewer deaths

Acronyms: Thrombosis with Thrombocytopenia Syndrome (TTS) 48
Estimation of direct benefits and risks to vaccinated 

persons

 Evaluate direct benefits and risk, per million Janssen vaccine 

doses

Used to visualize sex differences in risk and benefits

 Calculations based on recent hospitalization incidence, VE, 

Janssen vaccinations to date, number of persons already 

vaccinated

 30-day period

49
Risks and benefits by for females, by age group

For every 1 million doses of vaccine given with current US exposure risk1

Females 18-49

* Deaths, ICU admissions, and deaths due to COVID-19

Acronyms: Thrombosis with Thrombocytopenia Syndrome (TTS) 50

601 Hospitalizations* Prevented

7 Cases of TTS

6 Deaths* Prevented

56 ICU Admissions* Prevented

297 Hospitalizations* Prevented
Risks and benefits females, by age group

For every 1 million doses of vaccine given with current US exposure risk1

Females 18-49

657 Hospitalizations* Prevented

Females 50+

1 Case of TTS

394 Deaths* Prevented

661 ICU Admissions* Prevented

2454 Hospitalizations* Prevented

* Deaths, ICU admissions, and deaths due to COVID-19

Acronyms: Thrombosis with Thrombocytopenia Syndrome (TTS) 51

601 Hospitalizations* Prevented

7 Cases of TTS

6 Deaths* Prevented

56 ICU Admissions* Prevented

297 Hospitalizations* Prevented
Risks and benefits males, by age group

For every 1 million doses of vaccine given with current US exposure risk1

1 Cases of TTS

6 Deaths* Prevented

51 ICU Admissions* Prevented

272 Hospitalizations* Prevented

Males 18-49†

†Analyses incorporated one TTS case that occurred in the Phase 3 trial in a male aged 18-49 years.

*Deaths, ICU admissions, and deaths due to COVID-19

Acronyms: Thrombosis with Thrombocytopenia Syndrome (TTS) 52
Risks and benefits males, by age group

For every 1 million doses of vaccine given with current US exposure risk1

Males 50+

0 Cases of TTS

471 Deaths* Prevented

760 ICU Admissions* Prevented

601 Hospitalizations* Prevented 2821 Hospitalizations* Prevented

Males 18-49†

†Analyses incorporated one TTS case that occurred in the Phase 3 trial in a male aged 18-49 years.

*Deaths, ICU admissions, and deaths due to COVID-19 

Acronyms: Thrombosis with Thrombocytopenia Syndrome (TTS) 53

1 Cases of TTS

6 Deaths* Prevented

51 ICU Admissions* Prevented

272 Hospitalizations* Prevented
 Population

– Takes into account direct and 

indirect (herd) effects of vaccination

– Incorporates availability of different 

vaccines

– Simulates incidence, 

hospitalizations, and deaths over 

course of pandemic

– 6-month time horizon

 Shows large population benefit of 

vaccination relative to rare TTS

 Direct

– Considers individual benefits of 

vaccination vs. individual risks

– Only considers getting Janssen 

vaccine vs. not getting a vaccine

– Short, 1-month time horizon

 Shows positive balance for 

benefits vs. risks for all age and 

sex groups

 Balance of risks and benefits 

varies by age and sex

Risk-benefit interpretations

Acronyms: Thrombosis with Thrombocytopenia Syndrome (TTS) 54
EtR Domains: Values and Acceptability
 Intent to receive 1-dose COVID-19 vaccine

– Data stratified by age, sex, race/ethnicity and income

 Intent to receive Janssen COVID-19 vaccine over time

 Effect on overall vaccine confidence

Values and Acceptability:

56
 Among unvaccinated respondents, if both a 2-dose and 1-dose COVID-19 

vaccine were available, which would you choose? Assume that both 

types of vaccines are safe.

– Respondents could choose 1-dose, 2-dose, either, neither

– Data collected February 2021

 Examined by age, sex, race/ethnicity, and income

– Overall, 6% exclusively preferred 1-dose vaccine

– No differences in proportion that preferred 1-dose by age, sex, or income

– Significantly more Hispanic than White respondents (11%) preferred 1-dose

Values and Acceptability:

Intent to receive 1-dose COVID-19 vaccine

Source: Combined Data from IPSOS and NORC, February 2021 (3 waves)

57
 Only 37% of respondents called the Janssen COVID-19 vaccine safe after 

the pause was announced1

– Drop of 15% in two to three days

 Americans now much less likely to prefer the Janssen COVID-19 vaccine2

– 13% decline in preference for the Janssen COVID-19 vaccine

– Declined 9% to 25% across age and race categories

Values and Acceptability:

Intent to receive Janssen COVID-19 vaccine over time

1. https://today.yougov.com/topics/politics/articles-reports/2021/04/15/johnson-johnson-vaccine-confidence

2. CVS Health Survey- COVID-19 Vaccine Brand Preferences and Hesitancy Post J&J Pause 58
Willingness to receive 

the J&J vaccine 

dropped immediately 

as a result of the pause

(Results among those who 

say “yes” they plan to get 

vaccinated but haven’t yet)

59

68%

Pfizer

56%

Moderna

19%

Janssen
 Drop in vaccine confidence does not appear to extend to the PfizerBioNTech and Moderna COVID-19 vaccines1

– 59% consider them safe

– 19% feel they are unsafe

 Recent poll did not suggest reduction in intent to be vaccinated2

– 40% more likely to receive COVID-19 vaccine compared to one month ago

– 36% report no change in intent

 A different survey found half of the unvaccinated are less inclined to 

receive COVID-19 vaccine after the pause, regardless of brand3

Values and Acceptability:

Effect on overall vaccine confidence

1. https://today.yougov.com/topics/politics/articles-reports/2021/04/15/johnson-johnson-vaccine-confidence

2. deBeaumont Foundation Poll, April 15-16, 2021. Vaccine Confidence Grows Despite J&J Pause

3. CVS Health Survey- COVID-19 Vaccine Brand Preferences and Hesitancy Post J&J Pause 60
EtR Domain: Feasibility 
Feasibility: Jurisdictions’ pre-pause use of Janssen 

vaccine

62

Populations: Focus on reaching those experiencing 

homelessness, homebound or currently incarcerated

Vaccination settings: Three core settings used by 

jurisdictions to administer Janssen vaccine

Mobile vaccination

• Temporary PODs and 

mobile vans able to reach 

transient, rural and 

homebound individuals

Student health centers

• On-campus vaccination centers with ambition 

to vaccinate students unable or less likely to 

return for second dose at end of semester 

Emergency departments

• Provided at discharge 

from urgent care or ER 

departments

• Particularly for 'safety-net' 

hospitals reaching 

transient groups

68%

64%

57%

42%

32%

28%

23%

11%

11%

0 20 40 60 80

Rural populations

Share of jurisdictions surveyed

Experiencing homelessness

College students

Those at higher risk to COVID-19

Homebound populations

Incarcerated individuals

Migrant/Seasonal populations

LTCFs

Educators

Q: Prior to the pause in administration of the Janssen vaccine, 

which populations had you focused on vaccinating with this product?

Jurisdictional survey on impacts of Janssen pause, April 18th- 21st, 2021 (n=53)
Feasibility: Impact if Janssen recommended for specific 

populations

Jurisdictions may need to reconfigure some vaccination sites, update scheduling tool, and 

have difficulty serving disproportionately affected populations

Jurisdictional survey on impacts of Janssen pause, April 18th- 21st, 2021 (n=53) 63

Providers may need to carry multiple 

vaccines, if recommendation is restricted 

by sex.

Challenging to set-up dedicated 

community PODs if Janssen recommended 

for specific groups. 

Would require IT systems update to 

internal scheduling and pre-screening 

tools.

Concerns about difficulty of 

communicating rationale for specific 

groups to public

Potential need to revise public-facing 

comms materials, provider training 

collateral, alongside re-training staff.

Expect low uptake on Janssen vaccine 

given negative publicity.

Likely to see drop in completed series for 

those "at risk of loss to follow-up" e.g., 

experiencing homelessness, seasonal 

workers.

More challenging to reduce gap in vaccine 

disparities for racial and ethnic minorities 

through mobile vaccination.

Would increase barriers to access in rural 

and hard-to-reach areas.

Changes to vaccination sites and 

schedulers might include...

Health depts. expressed concern 

about communicating change

Greater difficulty serving 

disproportionately affected 

populations
64

Feasibility: Impact if Janssen were no longer 

recommended

Jurisdictions are particularly concerned about 2nd dose management and equity

Avoid additional second dose 

management, particularly for transient 

and hard-to-reach populations

Run mobile vaccination clinics without 

need for return visits

Reduce administrative burden on 

providers

Fully vaccinate college students before 

end of school year

Convenience of single dose appeals to 

many recipients

Some individuals hesitant about 

receiving an mRNA vaccine

Possibility of second dose side effects 

causes some to favor Janssen

Some providers with lower volumes of 

patients have preference for single 

dose vaccine

Increased challenge to reach 

homebound, transient, and rural 

populations because of need to 

administer second dose

Less flexibility to use mobile 

vaccination units

Reduced ability to vaccinate upon 

ED/hospital discharge

Decreased vaccine supply from loss of 

Janssen could harm vaccine access

Janssen provided flexibility to 

jurisdictions to...

Many individuals expressed a 

preference for Janssen

Greater difficulty serving 

disproportionately affected 

populations

Jurisdictional survey on impacts of Janssen pause, April 18th- 21st, 2021 (n=53)
EtR Domain: Equity 
Equity: Jurisdictions concerned revised recommendations 

would disproportionately affect several populations

66

40%

28%

28%

28%

17%

17%

13%

9%

6%

0 10 20 30 40

Share of jurisdictions surveyed

Experiencing homelessness

Homebound populations

Incarcerated individuals

Migrant/Seasonal populations

Rural populations

Those at higher risk to COVID-19

Racial and Ethnic Minorities

College students

LTCFs

Jurisdictions frequently raised four populations at risk of 

disproportionate impact Examples raised

Q: Which, if any, populations would be disproportionally impacted if Janssen vaccine 

was no longer recommended or recommended for only a subset of the population? Region 6 jurisdiction: "Most concerned about sub-populations 

that are difficult to reach e.g., people exp. homelessness, 

people who are working, as well as difficult geographic areas."

Region 10 jurisdiction: "...not having this vaccine would have an 

impact on trying to reduce the gap in vaccine disparities. We 

have community partners lined up to host events using the 

Janssen vaccine that are working with vulnerable populations in 

the state."

Region 2 jurisdiction: “The hardest to reach transient 

populations such as the homeless and those moving through 

substance use treatment programs, mental health treatment 

programs, etc. would be most impacted, given that they are 

among the most difficult individuals with whom to connect to 

provide second dose vaccination”

Jurisdictional survey on impacts of Janssen pause, April 18th- 21st, 2021 (n=53)
Policy Options 
Policy Options for Janssen Policy Recommendations

Do not recommend use 

of Janssen vaccine

Recommend use of Janssen 

vaccine in all adults 

≥18 years of age 

Recommend use of 

Janssen/J&J COVID-19 

vaccine in some

populations 

68
Policy Options for Janssen Policy Recommendations

69

• Recommend against use for all persons

• Reaffirm recommendations for all age and sex

– FDA to include warning statement with EUA

• Recommend vaccination only for adults ≥50 years of age

• Reaffirm recommendations for use; women aged <50 years should be aware 

of the increased risk of TTS, and may choose another COVID-19 vaccine

(i.e. mRNA vaccines)
70

Pros Cons

Recommend against use 

in all persons

• No further cases of CVST/TTS 

after Janssen vaccine

• Would remove choice from individuals

• Could lead to excess COVID-19 cases & 

deaths

• Could disproportionately impact at-risk 

populations with barriers to access or 

difficulty returning for 2nd dose

Reaffirm recommendation 

for all ages/sex

*Setting of FDA warning

• Allow for flexibility/choice

• Allow for use of the vaccine in 

harder to reach populations

• Burden on individual to understand risk; 

health dept/providers to convey risk

• May lead to more cases of TTS

• At-risk populations for COVID-19 likely at 

risk for barriers to TTS identification and 

treatment
71

Pros Cons

Recommend vaccination 

only for adults ≥50 years 

of age

• Would remove vaccine from 

most at-risk population 

(reduce TTS cases)

• Clear to communicate

• Difficult to implement (vaccination sites 

could need stock two vaccines)

• Would remove an option in a population 

with lower risk (young men)

• Could disproportionately impact at-risk 

populations 

Reaffirm recommendations 

for use; women <50 should 

be aware of increased risk, 

and may choose another 

COVID-19 vaccine

• Allow for flexibility/choice

• Allow for use of the vaccine in 

harder to reach populations, 

while still acknowledging risk 

in young women

• Could be difficult to implement 

(vaccination sites could need stock two 

vaccines)

• Could be difficult to communicate
Policy Options for Janssen Policy Recommendations

Work Group Summary

72

• Detailed discussion of risk/benefit balance difficult in many current 

vaccination settings

• Recommendations that require vaccination sites to require two types of 

vaccines would be difficult to implement

• Access to vaccines for hard-to-reach populations remains important

• Risk/benefit balance may change as the pandemic evolves and risk of 

COVID-19 disease changes
Policy Options for Janssen Policy Recommendations

Work Group Summary

73

• Work Group discussed benefits and concerns with all policy options for 

Janssen COVID-19 vaccine

• No single policy option as clear choice by Work Group

• However, many on Work Group appreciated flexibility of a broader 

recommendation for use, but acknowledgement of elevated risk in 

women <50 years of age
The Janssen COVID-19 vaccine is recommended for persons 

18 years of age and older in the U.S. population under the FDA’s 

Emergency Use Authorization

74

Previous Janssen vote: 

Question for ACIP to discuss:

 Given the review of the benefits and risks, what recommendation 

does ACIP feel is appropriate for use of the Janssen COVID-19 vaccine?
Policy Options for Janssen Policy Recommendations

75

• Recommend against use for all persons

• Reaffirm recommendations for all age and sex

– FDA to include warning statement with EUA

• Recommend vaccination only for adults ≥50 years of age

• Reaffirm recommendations for use; women aged <50 years should be aware 

of the increased risk of TTS, and may choose another COVID-19 vaccine

(i.e. mRNA 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.

Thank you