Safety of Simultaneous versus Sequential 

Administration of mRNA COVID-19 and

Quadrivalent Inactivated Influenza (IIV4) 

Vaccines: A Randomized Placebo Controlled Trial

(ClinicalTrials.gov ID: NCT05028361)

Emmanuel “Chip” Walter MD, MPH

ACIP October 25, 2023
Disclaimer

• The findings and conclusions in this presentation are 

those of the presenter and do not necessarily 

represent the official position of the Centers for 

Disease Control and Prevention

• Mention of a product or company name is for 

identification purposes only and does not constitute 

endorsement by CDC

• This study was supported by the CDC Clinical 

Immunization Safety Assessment (CISA) Project 

2
Study Rationale

• Influenza and COVID-19 vaccines are recommended 

for persons 6 months of age and older to prevent 

illness and complications resulting from these 

infections.*

• Available data support the simultaneous 

administration of these vaccines as currently ACIP 

recommended.

• However, there are limited data from placebo- controlled studies (none from the US) evaluating the 

safety of simultaneous administration of influenza and 

mRNA COVID-19 vaccines.

3

*Clinical Guidance for COVID-19 Vaccination | CDC and Prevention and Control of Seasonal Influenza with Vaccines: Recommendations 

of the Advisory Committee on Immunization Practices — United States, 2023–24 Influenza Season | MMWR (cdc.gov)
Design, Population, Recruitment

• Design: prospective, randomized, 

placebo-controlled, observer-blind 

study

• Population: non-pregnant persons aged 

≥5 years if receiving primary two-dose 

mRNA COVID-19 vaccine series or 

persons aged ≥12 years if receiving a 

booster mRNA COVID-19 vaccine dose 

and intending to receive a quadrivalent 

inactivated influenza vaccine (IIV4)*

• Recruitment: 3 CISA sites – Duke 

University, Cincinnati Children’s 

Hospital Medical Center (CCHMC), and 

John Hopkins University (JHU) during 

the 2021-2022 and 2022-2023 

influenza seasons 

4

Simultaneous

Sequential

a

*Persons ≥65 years received High-Dose IIV4 (Fluzone High-Dose Quadrivalent); those <65 years received standard dose IIV4 (FluLaval or Fluzone Quadrivalent) 
Study Aims and Objectives: 

Primary objective: To compare the proportion of participants with moderate or more severe fever, chills, myalgia, or arthralgia (RE)* 

in the group receiving IIV4 simultaneously with mRNA COVID-19 

vaccine at Vaccination Visit 1 (Simultaneous group) with the group 

receiving IIV4 alone one to two weeks later at Vaccination Visit 2 

(Sequential group) following both Vaccination Visit 1 and 2

– Primary outcome: considered present if participant has at least one of 

the RE symptoms on at least one day during days 1 to 7 following Visit 

1 and/or Visit 2 

Hypothesis: The proportion of participants with moderate or more severe fever, chills, myalgia or arthralgia will be non-inferior (not 

higher) in the Simultaneous group versus the Sequential group

5

*RE: reactogenicity event 
Secondary Objectives

• To compare the proportion of participants with RE in the 

Simultaneous group versus the Sequential group following 

Vaccination Visit 1 and 2 separately

• To describe the proportions of participants in each group with 

solicited local and systemic reactogenicity events according to 

severity grade after vaccination visits

• To describe the proportions of participants in each group 

experiencing at least one serious adverse event and a description 

of these events

6
Study Aims and Objectives: 

Exploratory Objectives

• To further characterize and describe the proportion of participants 

in each group with local or systemic reactogenicity events of 

greater severity 

• To describe the proportion of participants each group experiencing 

at least one unsolicited adverse event and one adverse event of 

special interest and to characterize these events

• To compare the change of health-related quality of life (HRQOL) 

from baseline in both groups following the Vaccination Visit 1 

7
Study Procedures Summary

• After randomization (1:1) to either the simultaneous or 

sequential group and a baseline blood draw, participants 

received study influenza vaccine or placebo according to 

assignment 

• Solicited Reactogenicity: Days 1-7* after V1, V2, V3a 

• Unsolicited Adverse Events: Days 1-7 after V1, V2, V3a 

• Health-Related Quality of Life (HRQOL): Days 1-7 after V1 

only

• Adverse Events of Special Interest (AESIs): Days 1-121 

• Serious Adverse Events (SAEs): Days 1-121

• Blood draws for immunogenicity: baseline and post- vaccination (data not yet available) 

*Day 1 is the vaccination day 8
Statistical Methods

• Full Analysis Population 2

– All randomized and vaccinated participants

– Participant characteristics and adverse event outcomes

• Full Analysis Population 1

– All participants who are randomized, vaccinated, and provide at least one day of complete data on the 

symptom diary

– Reactogenicity outcomes

• Statistical Testing

– Primary outcome was conducted at the one-sided alpha 0.025 level using the upper bound of a stratified by site 

Newcombe binomial confidence interval with Cochran-Mantel-Haenszel (CMH) weighting of the difference with 

a noninferiority margin of 10%. 

– Comparisons of proportions between the simultaneous and sequential groups used an exact Mantel-Haenszel 

statistic in a stratified analysis by site to control for the randomization blocks at the two-sided alpha 0.05 level. 

Study site adjusted odds ratios and corresponding 95% confidence intervals for proportions were also 

calculated. 

– The changes in HRQOL after Visit 1 were evaluated using Mann-Whitney U tests. For the HRQOL comparisons 

we used a two-sided alpha at the 0.05 level. 

– Summary statistics were used to describe REs, AEs, SAEs and AESIs. 95% confidence intervals of the 

difference between vaccination groups were calculated.

9
Study Consort Diagram

10
Demographics / Enrollment Site

Characteristic Simultaneous (n=169) Sequential (n=166) Total (N=335)

Sex: Female 96 (56.8%) 115 (69.3%) 211 (63.0%)

Male 73 (43.2%) 51 (30.7%) 124 (37.0%)

Race: White Only 123 (72.8%) 113 (68.1%) 236 (70.4%)

Black Only 31 (18.3%) 33 (19.9%) 64 (19.1%) 

Other 15 (8.9%) 20 (12.0%) 35 (10.4%)

Ethnicity: Hispanic 12 (7.1%) 9 (5.4%) 21 (6.3%)

Age (yrs): 5 to <12 4 (2.4%) 2 (1.2%) 6 (1.8%)

12 to <18 11 (6.5%) 13 (7.8%) 24 (7.2%)

18 to <65 146 (86.4%) 143 (86.1%) 289 (86.3%)

>=65 8 (4.7%) 8 (4.8%) 16 (4.8%)

Site: CCHMC 67 (39.6%) 63 (38.0%) 130 (38.8%)

Duke 79 (46.7%) 81 (48.8%) 160 (47.8%)

JHU 23 (13.6%) 22 (13.3%) 45 (13.4%)

11
Season, COVID-19 Vaccine Received, 

Vaccination and COVID-19 History

Characteristic Simultaneous (n=169) Sequential (n=166) Total (N=335)

Season: 2021-2022 37 (21.9%) 36 (21.7%) 73 (21.8%)

2022-2023 132 (78.1%) 130 (78.3%) 262 (78.2%)

COVID-19 Vaccine Brand:

Pfizer-BioNTech Monovalent 34 (20.1%) 35(21.1%) 69 (20.6%)

Pfizer-BioNTech Bivalent 130 (76.9%) 125 (75.3%) 255 (76.1%)

Moderna Monovalent 4 (2.4%) 4 (2.4%) 8 (2.4%)

Moderna Bivalent 1 (0.6%) 2 (1.2%) 3 (0.9%)

Prior COVID-19 Vaccine

Yes 165 (97.6%) 166 (100.0%) 331 (98.8%)

Prior COVID-19 and/or 

+ nucleocapsid ab 

Yes 96 (56.8%) 95 (57.2%) 191 (57.0%)

12
Primary Outcome 

Proportions with moderate or more severe fever, chills, myalgia, or arthralgia 

(RE) in participants in sequential versus simultaneous group 

13

Moderate or more severe fever, chills, myalgia, or arthralgia following Visit 1 and/or Visit 2

No Yes Non-inferiority Test 10% Margin*

Group N % N % Diff Lower 

95% CI

Upper 

95% CI

p-value

Simultaneous 125 74.40 43 25.60

Sequential 114 68.67 52 31.33 -0.0563 -0.1517 0.0404 0.0007

Ho: Sim-Seq ≥ 0.10 (10%)

Conclusion: The rate of moderate or more server fever, chills, myalgia, or 

arthralgia in simultaneous group is considered not worse/not higher than 

the rate in sequential group and the noninferiority criteria was met. The 

upper limit of the 95% confidence interval (CI) of the difference for Sim 

minus Seq was 4.0% and the noninferiority margin was 10%; therefore, the 

null hypothesis of inferiority was rejected. 

*Site-stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel (CMH) weighting of the difference 
Objective: To compare the proportion of participants with 

moderate or more severe fever, chills, myalgia, or arthralgia in the 

Simultaneous versus the Sequential Group following the first 

vaccination visit

Secondary Objective

14

Moderate or more severe fever, chills, myalgia, or arthralgia following Visit 1 

No Yes

Group N % N % Odds Ratio (95%CI) p-value*

Simultaneous 128 76.19 40 23.81

Sequential 119 71.69 47 28.31 0.80 (0.49, 1.30) 0.3851

*Exact Mantel-Haenszel statistic in a stratified analysis by site 
Objective: To compare the proportion of participants with 

moderate or more severe fever, chills, myalgia, or arthralgia in the 

Simultaneous versus the Sequential Group following the second 

vaccination visit

Secondary Objective

15

Moderate or more severe fever, chills, myalgia, or arthralgia following Visit 2 

No Yes

Group N % N % Odds Ratio (95%CI) p-value*

Simultaneous 163 97.02 5 2.98

Sequential 157 94.58 9 5.42 0.54 (0.18, 1.63) 0.2886

*Exact Mantel-Haenszel statistic in a stratified analysis by site 
Percent With Injection Site Reaction 

Visit 1

16

More ≥ moderate pain and swelling in sequential group* More ≥ moderate pain in simultaneous group*

*95% CI of difference in proportions between does not contain zero

0

20

40

60

80

100

 Sim Seq Sim Seq Sim Seq Sim Seq

Pain Swelling Erythema Axillary Swelling

and Tenderness

Percent

Solicited Event and Group

Injection Site Reactions Visit 1

COVID-19 Vaccine

Mild Moderate Severe Life Threatening

0

20

40

60

80

100

Sim Seq Sim Seq Sim Seq Sim Seq

Pain* Swelling Erythema Axillary Swelling

and Tenderness*

Percent

Solicited Event and Group

Injection Site Reactions Visit 1

Influenza Vaccine or Placebo

Mild Moderate Severe Life Threatening

*95% CI of difference does not contain zero

*95% CI of difference in proportions between does not contain zero
17

Percent With Injection Site Reaction 

Visit 2

More ≥ moderate pain and axillary swelling/ tenderness in sequential group*

*95% CI of difference in proportions between does not contain zero

0

20

40

60

80

100

Sim Seq Sim Seq Sim Seq Sim Seq

Pain* Swelling* Erythema Axillary Swelling and

Tenderness*

Percent

Solicited Event and Group

Injection Site Reactions Visit 2

Influenza Vaccine or Placebo

Mild Moderate Severe Life Threatening

*95% CI of difference does not contain zero
18

Percent With Systemic Reaction 

Visit 1

No differences in ≥ moderate systemic symptoms

0

20

40

60

80

100

Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq

Fever Chills Fatigue Myalgia Headache Arthralgia Nausea &

Vomiting

Diarrhea

Percent

Solicited Event and Group

Systemic Reactions Visit 1

Mild Moderate Severe Life Threatening
19

Percent With Systemic Reaction 

Visit 2

No differences in ≥ moderate systemic symptoms

0

20

40

60

80

100

Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq

Fever Chills* Fatigue* Myalgia* Headache Arthralgia Nausea &

Vomiting

Diarrhea*

Percent

Solicited Event and Group

Systemic Reactions Visit 2

Mild Moderate Severe Life Threatening

*95% CI of difference does not contain zero
Objective: To describe the proportions of participants in the 

Simultaneous and Sequential vaccination groups experiencing at 

least one serious adverse event and a description of these 

events

Secondary Objective

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At Least One Serious Adverse Event

No Yes

Group N % N % Difference (Sim-Seq) (95%CI)

Simultaneous 168 99.41 1 0.59

Sequential 165 99.40 1 0.60 -0.01 (-1.66, 1.64)
SAE Descriptions

21

Group Vaccine Onset 

since Visit 

1 

Sex Age 

group

Category Relatedness Description

Sequential Pfizer-BioNTech 

Bivalent

14 days Female 50-64 Hospitalization/

prolongation of 

existing 

hospitalization

Unlikely related Small bowl obstruction with 

incarcerated ventral hernia

Past medical history (PMH): 

abdominal surgeries and cancer

Simultaneous Pfizer-BioNTech 

Monovalent

19 Weeks Female 18-49 

years 

Other important

medical event

Not related Spontaneous abortion occurring at 

16 weeks gestation 

PMH: COVID-19 illness (mild) 9 

weeks after visit 1; 

(Note: Participant did not report 

being pregnant or intention of 

becoming pregnant at enrollment)
• Objective: To describe the proportion of participants in Simultaneous and 

Sequential groups experiencing at least one unsolicited adverse event 

and one adverse event of special interest and to characterize these events

Exploratory Objective

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At Least One Unsolicited Adverse Event within 7 Days of a Vaccination Visit (Preliminary)

No Yes Percent Yes

Group N % N % 95% CI Difference (Sim-Seq)

(95%CI)

Simultaneous 148 87.57 21 12.43 (7.86, 18.37)

Sequential 150 90.36 16 9.64 (5.61, 15.18) 2.79 (-3.91, 9.49)

• AEs within 7 days of vaccine (n=45)

– 29 simultaneous group in 21 participants (3 possibly related)

– 16 sequential group in 16 participants (1 related, 2 possibly related)
• Objective: To describe the proportion of participants in Simultaneous and 

Sequential groups experiencing at least one unsolicited adverse event and one 

adverse event of special interest and to characterize these events

Exploratory Objective

23

At Least One Adverse Event of Special Interest

No Yes Percent Yes

Group N % N % 95% CI Difference (Sim-Seq)

(95%CI)

Simultaneous 150 88.76 19 11.24 (6.91, 17.00)

Sequential 157 94.58 9 5.42 (2.51, 10.04) 5.82 (-0.06, 11.70)

• AESIs (n=28)

– 29 COVID-19 illnesses (unrelated): Sim Group* (n=18) Seq Group* (n=9) 

– 1 allergic type reaction (possibly related): Sim Group (n=1)

*One person in each group reported 2 COVID-19 illness events
Exploratory Objective

• Objective: To compare the change of health-related quality of life (HRQOL) from 

baseline in the Simultaneous versus Sequential groups following the Vaccination 

Visit 1

24
Limitations

• Most data come from use of bivalent Pfizer-BioNTech 

mRNA COVID-19 vaccine during one season

– Very little use of Moderna mRNA vaccine

• Very few children ages 5-11 years and older adults ≥65 years enrolled

• Enrollment limited by COVID-19 pandemic; enrolled ~70% of target 

• Study too small to detect rare adverse events 

• People known to be pregnant not included; a future 

CISA study assessing safety of simultaneous influenza 

and COVID-19 vaccines during pregnancy is planned 

25
Summary

• Simultaneous administration of influenza and mRNA COVID-19 vaccines is well tolerated 

when compared to sequential administration 

– Occurrence of moderate or more severe fever, chills, myalgia, or arthralgia was not 

higher in the simultaneous (25.6%) vs. sequential (31.3%) group

– No significant differences in occurrence of adverse events within 7 days, adverse 

events of special interest, serious adverse events, and HRQOL 

• As previously observed in other studies injection site and systemic reactions were 

associated with mRNA COVID-19 vaccine and influenza vaccine; most reactions were mild 

or moderate

– Most frequent injection site reactions after either vaccine were pain and axillary swelling/tenderness 

– Most frequent systemic reactions after COVID-19 vaccine, with or without influenza vaccine, were fatigue, 

myalgia, headache, chills and arthralgia 

– Receipt of influenza vaccine alone was associated chills, fatigue, myalgia and diarrhea

26
Acknowledgements

• Duke University (Duke)

– Principal Investigator: Emmanuel B. Walter, MD, MPH

– Investigators: Ken Schmader MD, Wes Rountree, MPH, Marek S. Poniewierski MD, MS, 

Rachel L. Spreng PhD

• John Hopkins University (JHU)

– Principal Investigator: Kawsar Talaat, MD

• Cincinnati Children’s Hospital Medical Center (CCHMC)

– Principal Investigator: Elizabeth Schlaudecker, MD, MPH 

– Investigator: Mary Staat, MD, MPH

• CDC

– Principal Investigator: Karen Broder, MD

– Investigators: Jonathan Duffy, MD, MPH, Oidda Museru MSN, MPH, Lisa A. Grohskopf 

MD, MPH, Anju Goel MD, MPH (contractor)

27
Extra Slides

28
Serious Adverse Event (SAE) Definition

• An SAE is defined as an AE that meets one of the following conditions:

– Results in death during the period of protocol-defined surveillance 

– Is life-threatening (defined as immediate risk of death at the time of the event)

– Requires inpatient hospitalization or prolonged hospitalization during the period of 

protocol-defined surveillance 

– Results in congenital anomaly or birth defect

– Results in a persistent or significant disability/incapacity

– Any other important medical event that may not result in death, be life threatening, or 

require hospitalization, may be considered an SAE when, based upon appropriate 

medical judgment, the event may jeopardize the participant and may require medical 

or surgical intervention to prevent one of the outcomes listed above. Examples of such 

medical events include allergic bronchospasm requiring intensive treatment in an 

emergency room or at home, blood dyscrasias or convulsions that do not result in 

inpatient hospitalization, or the development of drug dependency or drug abuse.

29
Adverse Event of Special Interest (AESI) 

Definition

• An AESI includes the following:

– COVID-19 illness 

– Multisystem inflammatory syndrome 

– Guillain-Barre syndrome

– Allergic type reactions (including anaphylaxis, hives, or facial 

and limb swelling occurring within 7 days of a vaccination visit)

– Myocarditis or pericarditis 

30
Injection Site Reactions Grading

31

Table 8. Injection-site Reactogenicity Grading 

Local Reaction to 

Injectable Product 

Mild (Grade 1) Moderate (Grade 2) Severe (Grade 3) Potentially Life Threatening 

(Grade 4)

Pain

Noticeable but does 

not interfere with 

activity

Interferes with activity 

but did not need a 

medical visit or 

absenteeism [i.e. 

missing work or 

school]

Significant; prevents 

daily activity and/or 

resulted in medical visit 

and/or absenteeism [i.e. 

missing work or school]

Requires an emergency room (ER) 

visit or hospitalization

Induration/Swelling

(≥ 12 years of age) 2.5 – 5 cm 5.1 – 10 cm > 10 cm Requires an emergency room (ER) 

visit or hospitalization

Induration/Swelling

(< 12 years of age) 0.5 – 2 cm 2.0 -7.0 cm > 7 cm Requires an emergency room (ER) 

visit or hospitalization

Erythema/Redness

(≥ 12 years of age) 2.5 – 5 cm 5.1 – 10 cm > 10 cm Requires an emergency room (ER) 

visit or hospitalization

Erythema/Redness

(< 12 years of age) 0.5 – 2 cm 2.0 -7.0 cm > 7 cm Requires an emergency room (ER) 

visit or hospitalization

Axillary (underarm) 

swelling or tenderness 

ipsilateral to side of 

injection Noticeable but does 

not interfere with 

activity

Interferes with activity 

but did not need a 

medical visit or 

absenteeism [i.e. 

missing work or 

school]

Significant; prevents 

daily activity and/or 

resulted in medical visit 

and/or absenteeism [i.e. 

missing work or school] 

Requires an emergency room (ER) 

visit or hospitalization
Systemic Reactions Grading

32

Table 9. Systemic Reactogenicity Grading (FDA modified)

Systemic Mild (Grade 1) Moderate (Grade 2) Severe (Grade 3) Potentially Life Threatening 

(Grade 4)

Fever (°C)

(°F)

38.0 - 38.4

100.4 - 101.1 

38.5 - 38.9 

101.2 - 102.0 

39.0 – 40.0 

102.1-104.0

> 40.0 

>104.0

Nausea/vomiting

Noticeable but does not interfere 

with activity or 1 – 2 episodes/24 

hours

Some interference with activity or 

> 2 episodes/24 hours

Significant; prevents daily activity 

and/or resulted in medical visit 

and/or absenteeism [i.e. missing 

work or school]

Requires an ER visit or 

hospitalization 

Diarrhea

Noticeable but does not interfere 

with activity or 2 – 3 loose stools/24 

hours

Some interference with activity or 

4-5 loose stools/24 hours

Significant; prevents daily activity 

and/or resulted in medical visit 

and/or absenteeism [i.e. missing 

work or school] or 6 or more 

watery stools or > 24 hours

Requires an ER visit or 

hospitalization

Headache

Noticeable but does not interfere 

with activity

Some interference with activity but 

did not need a medical visit or 

absenteeism [i.e. missing work or 

school]

Significant; prevents daily routine 

activity and/or resulted in medical 

visit and/or absenteeism [i.e. 

missing work or school]

Requires an ER visit or 

hospitalization

Fatigue

Noticeable but does not interfere 

with activity

Some interference with activity but 

did not need a medical visit or 

absenteeism [i.e. missing work or 

school]

Significant; prevents daily routine 

activity and/or resulted in medical 

visit and/or absenteeism [i.e. 

missing work or school]

Requires an ER visit or 

hospitalization

Myalgia 

Noticeable but does not interfere 

with activity

Some interference with activity but 

did not need a medical visit or 

absenteeism [i.e. missing work or 

school]

Significant; prevents daily routine 

activity and/or resulted in medical 

visit and/or absenteeism [i.e. 

missing work or school]

Requires an ER visit or 

hospitalization

Arthralgia

Noticeable but does not interfere 

with activity

Some interference with activity but 

did not need a medical visit or 

absenteeism [i.e. missing work or 

school]

Significant; prevents daily routine 

activity and/or resulted in medical 

visit and/or absenteeism [i.e. 

missing work or school]

Requires an ER visit or 

hospitalization

Chills 

Noticeable but does not interfere 

with activity

Some interference with activity but 

did not need a medical visit or 

absenteeism [i.e. missing work or 

school] 

Significant; prevents daily routine 

activity and/or resulted in medical 

visit and/or absenteeism [i.e. 

missing work or school]

Requires an ER visit or 

hospitalization
EQ-5D-5L and VAS

33
Subject Inclusion Criteria

• Persons aged ≥5 years if receiving primary two-dose mRNA COVID-19 

vaccine series or persons aged ≥12 years if receiving a booster mRNA 

COVID-19 vaccine dose according to FDA authorization or approval and ACIP recommendation. Note: receipt of an mRNA COVID-19 vaccine 

within 8 hours of enrollment is permitted

* Individuals age 5-11 receiving a booster may be enrolled in the event a booster for individuals age 5-11 is authorized or approved and recommended by the ACIP.

• English or Spanish literate

• Intention of receiving influenza vaccine and mRNA COVID-19 vaccine 

based on ACIP-CDC guidelines

• Willing to provide written informed consent

• Intention of being available for entire study period and complete all 

relevant study procedures, including follow-up phone calls and clinic visits

34
Subject Exclusion Criteria

• Currently pregnant, planning to become pregnant within the first three months of the study per 

participant self-report or likely to be pregnant per screening criteria as defined in protocol at Visit 1

• Prior receipt of IIV4 during the respective influenza season in which they are being enrolled

• < 9 years of age and recommended to receive two doses of IIV4 during the respective influenza 

season in which they are being enrolled 

• Prior receipt of non-mRNA COVID-19 vaccine

• Documented COVID-19 infection within 6 weeks prior to enrollment confirmed by either medical 

history or lab testing 

• History of severe allergic reaction after a previous dose of any influenza vaccine; or to an influenza 

vaccine component, including egg protein

• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g. 

anaphylaxis) to any component of an mRNA vaccine

• Receipt of any licensed inactivated vaccine within 2 weeks prior to enrollment in this study, receipt of 

any licensed live vaccine within 4 weeks prior to enrollment in this study, or receipt of Shingrix

(Zoster Vaccine Recombinant, Adjuvanted) or HEPLISAV-B (Hepatitis B Vaccine (Recombinant), 

Adjuvanted) vaccine within 6 weeks prior to enrollment in this study or planning receipt of any 

vaccines following enrollment until 6 weeks after receipt of the second dose of mRNA COVID-19 

vaccine

35
Subject Exclusion Criteria

• Has an active neoplastic disease (excluding non-melanoma skin cancer or prostate cancer that is stable in the absence of therapy) or a history of any hematologic malignancy*

*Participants with a history of malignancy may be included if, after previous treatment by surgical excision, 

chemotherapy or radiation therapy, the participant has been observed for a period that in the investigator’s 

estimation provides a reasonable assurance of sustained cure

• Thrombocytopenia, bleeding disorder, or anticoagulant use contraindicating intramuscular injection (a 

daily aspirin may be acceptable). 

• Has immunosuppression as a result of an underlying illness or medications, such as 

antirejection/transplant regimens or immunomodulatory agents. Stable HIV disease is permitted per 

the following parameters:

– Confirmed stable HIV disease defined as document viral load <50 copies/mL and CD4 count 

>200 within 6 months before enrollment, and on stable antiretroviral therapy for at least 6 

months

• Has known hepatitis B (HBV) or hepatitis C (HBC). Stable HBV or HBC are permitted per the following 

parameters:

– If known HBV: confirmed inactive chronic HBV infection: HBsAg present for ≥6 months and 

HBeAg negative, anti-HBe positive; serum HBV DNA <2000 IU/mL; persistently normal ALT or AST levels; in those who had liver biopsy, findings that confirm absence of significant 

necroinflammation

– If known HCV: evidence of sustained virological response for ≥12 weeks after treatment or without evidence of HCV RNA viremia (undetectable HCV RNA)

36
Subject Exclusion Criteria

• Use of oral, parenteral, or high-dose inhaled glucocorticoids*

*For definition of high-dose inhaled glucocorticoids, reference Appendix B.

• History of Guillain-Barré syndrome 

• Prior enrollment in this study during the 2021-22 flu season

• Anyone who is already enrolled or plans to enroll in another clinical trial with an 

investigational product during the study period.* 

*Per protocol, co-enrollment in observational or behavioral intervention studies are permitted at any time. An investigational product may be permitted for therapy of an illness condition that 

occurs during the study period e.g. COVID-19 illness.

• Hearing loss determined by the investigators to prevent successful communication over 

the phone

• History of myocarditis or pericarditis 

• History of multisystem inflammatory syndrome in children (MIS-C) or adults (MIS-A). 

• Has injury or other reason why deltoid site on both arms cannot be used for vaccinations. 

• Any condition which, in the opinion of the investigators, may pose a health risk to the 

subject or interfere with the evaluation of the study objectives. 

• Anyone who is a relative of any research study personnel. 

• Anyone who is an employee of any research study personnel. 

37