National Center for Immunization & Respiratory Diseases

Enhanced safety monitoring for COVID-19 vaccines 

in early phase vaccination

Tom Shimabukuro, MD, MPH, MBA

CDC COVID-19 Vaccine Planning Unit (VPU) 

Vaccine Safety Team

September 22, 2020
COVID-19 vaccine safety monitoring in early recipients

 Challenge

– During the early phase of a national COVID-19 vaccination program, initial 

doses may be distributed to specific groups such as healthcare personnel and 

other essential workers

– In this scenario, activities to enhance traditional vaccine safety monitoring 

systems (e.g., VAERS) will be necessary

 Response

– Prepare traditional monitoring systems

– Conduct active surveillance in early recipients through smartphone- and 

email-based web surveys

– Obtain vaccination and safety monitoring data from healthcare facility and 

long-term care facility surveillance
Vaccine Adverse Event Reporting System (VAERS) 

The U.S. early warning safety monitoring system
+

Co-managed by

CDC and FDA

Vaccine Adverse Event 

Reporting System

http://vaers.hhs.gov
Covered populations for COVID-19: Entire U.S. population

 VAERS has all 320 

million U.S. residents 

as a covered 

population for safety 

monitoring

 i.e., all ages, races, 

states, healthy 

people, those with 

co-morbidities, etc.

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

2015 2016 2017 2018 2019

US Reports Foreign Reports

VAERS total reports received by year
VAERS timeliness

 VAERS serves as the nation’s early warning system to detect possible 

safety issues with U.S. vaccines

 VAERS traditionally has provided initial data on the safety profile of new 

vaccines when they are introduced for use in the population

 COVID-19 vaccine report processing times

– Death reports: 1 day

– Reports classified as serious: 3 days

– Reports classified as non-serious: 5 days

 CDC and FDA receive updated datasets daily
VAERS analysis for COVID-19 reports

 FDA scientists review all VAERS reports classified as serious 

 Attempts are made to follow-up on all serious* reports to 

get medical records and other medical documentation

 CDC scientists will review VAERS reports for adverse events 

of special interest (AESI)

 CDC and FDA coordinate on analysis of VAERS data and both 

agencies conduct data mining

*Based on the Code of Federal Regulations if one of the following is reported: death, life-threatening illness, hospitalization or prolongation of 

hospitalization, permanent disability, congenital anomaly or birth defect (FDA routinely reviews all serious reports)
Preliminary list of VAERS AESIs

 COVID-19 disease

 Death

 Vaccination during pregnancy

 Guillain-Barré syndrome (GBS) 

 Other clinically serious neurologic AEs (group AE)

– Acute disseminated encephalomyelitis (ADEM)

– Transverse myelitis (TM)

– Multiple sclerosis (MS)

– Optic neuritis (ON)

– Chronic inflammatory demyelinating polyneuropathy (CIDP)

– Encephalitis

– Myelitis

– Encephalomyelitis

– Meningoencephalitis

– Meningitis

– Encepholapathy

– Ataxia

 Seizures / convulsions

 Stroke

 Narcolepsy / cataplexy

 Autoimmune disease

 Anaphylaxis

 Non-anaphylactic allergic reactions

 Acute myocardial infarction

 Myocarditis / pericarditis

 Thrombocytopenia

 Disseminated intravascular coagulation (DIC)

 Venous thromboembolism (VTE)

 Arthritis and arthralgia (not osteoarthritis or 

traumatic arthritis)

 Kawasaki disease

 Multisystem Inflammatory Syndrome in 

Children (MIS-C)
Experience from H1N1
Enhanced monitoring programs to meet 

the challenge of COVID-19
Vaccine safety assessment for essential workers (V-SAFE) 

 V-SAFE is a smartphone-based text, text-to-web survey, and email-to-web 

survey active surveillance program for early vaccine recipients

– Uses contact information (phone numbers) from the registration process for 

COVID-19 vaccination of essential workers – up to 20+ million people during the 

first few months of a vaccination program

– Conducts health checks on vaccine recipients via text messages and email

• Daily for first week post-vaccination

• Weekly thereafter for 6 weeks post-vaccination

– Active telephone follow-up will be conducted with a person reporting a clinically 

important* adverse event during any V-SAFE health check

• A VAERS report will be taken during telephone follow-up, if appropriate

*Refer to slide 14
1. Text messages or email from CDC 

with follow-up – daily 1st week 

post-vaccination and weekly 

thereafter out to 6 weeks

VAERS call center

2. Any clinically 

important event(s) 

reported by 

vaccinated person

Healthcare workers, 

essential workers, etc. 

3. Follow-up on clinically important event, 

complete a VAERS report if appropriate

This Photoby Unknown Author is licensed under CC BY-SA

Vaccine safety assessment for essential workers (V-SAFE) 

This Photo by Unknown Author is licensed under CC BY-SA
Defines 

clinically 

important
Smartphone-based monitoring

 CDC has validated the basic text messaging collection methods for vaccine 

safety monitoring*

 Smartphone-based safety monitoring of early COVID-19 vaccine recipients 

will allow estimation of:

– Rates of local and systemic reactogenicity

– Rates of clinically important adverse events following immunization

 Smartphone-based safety monitoring of early COVID-19 vaccine recipients 

will allow comparison of observed rates of adverse events:

– With background rates in the population

– With known rates following other types vaccinations (e.g., flu)

*Stockwell et al. A multi-site feasibility study to assess fever and wheezing in children after influenza vaccines using text messaging. Vaccine. 2017; 35(50):6941-6948.

Stockwell et al. Feasibility of Text Message Influenza Vaccine Safety Monitoring During Pregnancy. Am J Prev Med. 2017; 53(3):282-289.
Enhanced VAERS reporting using National Healthcare 

Safety Network (NHSN) sites

 COVID-19 vaccine safety surveillance and facilitated VAERS 

reporting for healthcare workers and LTCF residents
NHSN modules for COVID-19 vaccination

 NHSN sites will track weekly vaccine doses administered by dose number 

(i.e., denominator) in healthcare workers and LTCF residents

 NHSN sites are well positioned to identify adverse events among COVID 19 

vaccine recipients at their sites (i.e., numerator)

– VAERS staff will match reports in VAERS to NHSN sites using facility address 

information (i.e., identify reports originating from NHSN facilities)

– Allows for calculation of crude overall reporting rates and adverse eventspecific reporting rates
Established monitoring systems in a 

general vaccination program
Established monitoring systems and timeliness

 VAERS

– Reports received and processed within days of program implementation 

 Clinical Immunization Safety Assessment (CISA) Project: case reviews

 Vaccine Safety Datalink (VSD) and VA electronic health record monitoring

– Data available within a couple weeks of encounter with medical system

 FDA CMS data monitoring, includes 650K nursing home residents

– Data may be available within several weeks of an encounter with medical 

system

 FDA BEST and Sentinel and large insurer/payer databases*

– Data availability variable depending on source (couple weeks to several months)

*Biologics Effectiveness and Safety (BEST) System.
Summary
Summary

 VAERS will play an important role in characterizing the safety profile of 

COVID-19 vaccine(s) in the early stages of a vaccination program 

– Signal detection is of paramount importance

but

‒ VAERS data can also provide reassurance if no concerning safety 

signals are detected 

 Additional systems such as V-SAFE and NHSN will enhance traditional 

vaccine safety monitoring systems, such as VAERS

 Traditional large-linked database systems (VSD, CMS, VA EHR etc.) will 

quickly accumulate safety data when vaccines become widely available
Questions?