CLINICAL CONSIDERATIONS for COVID-19 VACCINATION February 26, 2021 CONTINUING EDUCATION

CLINICAL CONSIDERATIONS FOR COVID-19 VACCINATION February 26, 2021 CONTINUING EDUCATION

• The link for the evaluation of today’s program is: https://www.surveymonkey.com/r/Vaccine-Part1

• Please be sure to access the link, complete the evaluation form, and request your certificate. The evaluation process will remain open two weeks following the webcast. Your certificate will be emailed to you when the evaluation process closes after the 2-week process.

• If you have any questions please contact Dorothy Aldridge ([email protected])

Ohio Hospital Association | ohiohospitals.org | 2 SUBMITTING QUESTIONS

Ohio Hospital Association | ohiohospitals.org | 3 TOOLKIT

Ohio Hospital Association | ohiohospitals.org | 4 Joseph Gastaldo, MD System Medical Director, Infectious Diseases Medical Director of Quality & Safety OhioHealth Riverside Methodist Hospital

Ohio Hospital Association | ohiohospitals.org | 5 SARS-CoV-2 Vaccines February 26, 2021 (slides subject to change)

Joseph Gastaldo, MD System Medical Director, Infectious Diseases Medical Director of Quality & Safety, OhioHealth Riverside Methodist Hospital [email protected] To End this Pandemic … • Get Vaccinated the moment it’s your turn • All available vaccines (and the new J/J candidate) are safe & extremely effective in preventing severe COVID illness, hospitalization, & death • Please talk to anyone / everyone on how we can all assist in ending this pandemic

How We Arrived to Safe & Effective COVID-19 Vaccines • Money: Financial risk removed / improved efficiencies • Science: SARS in 2003 & MERS in 2012 → spike protein • Technology: Genetic Sequencing • Technology: Vaccine platforms in “trials” since the 1970s • Technology: Newer approved vaccine platforms: Shingrix • COVID-19 activity: measuring an endpoint easier COVID-19 Vaccine Trails • Scientific Integrity: performed the same way compared to previous vaccine trials • Same review process: 3 independent review boards • Same transparency of FDA & CDC Authorization / Recommendation Process

Advisory Data and Safety Monitoring Committee on Vaccine Trial Boards Immunization External Experts Practices (ACIP) Open to Public External Experts

Vaccines & Related Biologic Products Advisory Committee CDC FDA (VRBPAC) Recommends Authorizes Open to Public • Dose, storage, clinical External Experts considerations Also reviews Manufacturing • specific populations Process Vaccine Timeline … • 1/10/2020: RNA sequencing became available • 1/15/2020: NIH / Moderna form partnership • 12/2020: Pfizer & Moderna vaccines • 12/2020: AZ adenovirus vaccine in UK • 2/26/2021: FDA review of J/J trial • Spring, 2021: AZ & Novavax vaccines ? • Later 2021: Sanofi vaccine ? What We Need to Know • Vaccine landscape is complicated • It is more than just producing vaccines • Many vaccine types will be authorized “best vaccine to get is the one which is accessible” • Who is recommended to get vaccinated will evolve over time; demand >> supply recommendations may change COVID-19 Vaccine Messaging

• Acceptance: hesitancy, trust, misinformation

• (For Now) vaccination does not change mitigation; recommendations based on science & data • Reactogenicity / vaccination side effects • It will take time to vaccinate everyone • Vaccine prioritization defined by ODH 2021: Learning Continues • duration (durability) of immunity • vaccination impact on asymptomatic infection & transmission • preferred vaccines for different populations • pregnancy / lactation / below < 16 years old • pharmacovigilance post-vaccination • monitoring for viral drift (mutations)→ Variants

Variant → Mutation: Do Not Fear • RNA viruses: prone to replication errors • SARS CoV2: has mutated since discovery • SARS CoV2: genetic selection / pressure • Variants: found by genetic sequencing 3 Variants Under Investigation (VUI)

• B.1.1.7 → E484K mutation: first identified in the UK • B.1.351: first identified in South Africa • P.1: first identified in Brazil • All 3 variants identified in the US (>30 states) • Other variants too So What ? changes in spike protein → receptor binding domain (RBD) Spike protein → immune response • Changes in the spike protein → higher affinity to receptor → higher viral load → spreads more efficiently → more contagious • ? associated with higher severity of illness • OhioHealth lab PCR testing: will detect • Mitigation strategies remain effective Vaccines → spike protein • Vaccine Immune Escape is a gradual process • Lab studies: “some” reduction in neutralization activity of antibodies • Neutralizing Ab titer information thus far reassuring • Implications for real world effectiveness unclear • Needs to be studied → modify vaccines prn • ? booster (likely modified, more strains) likely needed My concern … • It is expected that B.1.1.7 variant → predominant strain ~ March, 2021 • more people will need to be vaccinated to reach herd immunity • “things will feel better”; COVID fatigue → de-escalation • Persons with vaccine hesitancy will feel complacent Vaccine Candidates & Authorized / Recommended Vaccines Phase III Trial Vaccine candidates Authorized Vaccines • Moderna & Pfizer: mRNA (“fragile”; kept frozen) • AstraZeneca & J&J: replication defective viral vector (refrigeration) • Novavax & Sanofi: recombinant spike protein with immune adjuvant (refrigeration) Vaccine Summary

mRNA & viral vector vaccines • takes advantage of the process that cells use to make proteins; in order to trigger an immune response • In oncology & other infections, these vaccines have been used in clinical trials • Does not contain a live virus; does not become part of cellular DNA; spike protein is degraded

Pfizer mRNA vaccine (tozinameran) • FDA authorized & CDC recommended; >16 yo • N = 43,448 (21720 vaccine, 21728 placebo) • 49.4% females; 81.9% white, 9.8% AA, 4.4% Asian, 26.1% Hispanic, 0.8% native American, Median age: 51; Obesity 35.1%, diabetes 8.4%, pulmonary disease 7.8%, 76.7% from the US • 170 symptomatic COVID-19; 162 in placebo group, 8 in vaccine group (9 severe cases; all in placebo) “95% effective” Pfizer mRNA vaccine

• 2 doses; 21 days apart • Cold chain: frozen • Once out of freezing: stable in refrigerator for only 5 days • HCW adds diluent, making 5 doses with 1 vial • Once diluted, doses must be given within 6 hours Moderna mRNA Vaccine authorized / recommended for >18yo • >30k people; 42% deemed "high risk"; 37% from racial & ethnic minorities; 11k from communities of color; 7k >65yo; 5k <65 years with comorbid conditions; included (+) HIV volunteers • 196 cases of symptomatic COVID-19; 185 cases in the placebo group; 11 cases in the vaccinated group; 94.1% efficacy “30 severe" only in placebo group • Signals in the data that vaccine can decrease asymptomatic infection / shedding Moderna Trial reviewed by FDA Moderna mRNA Vaccine • Vaccine well tolerated

• side effects lasting <24 hours: 9.7% fatigue, 8.9% muscle pain, 5.2% joint pain, 4.5% HA • 2 doses; 28 days apart (can give 4 days earlier) • Stable at – 20 C (normal freezer) for 6 months • Stable at 4 C (normal refrigerator) for 30 days

Adenovirus Vector (inactive) Vaccines

• Adenoviruses (DNA virus) that cause common cold • Used in research for gene therapy & infections • Like mRNA vaccines, introduce genetic material • Persons can have preexisting antibodies ** • Finding a vector where people do not have preexisting immunity; ~ 70 different human types Johnson & Johnson Candidate • Uses replication defective human adenovirus type 26 (essentially non-existent seroprevalence) • N = ~ 44k • FDA to review: 2/26/2021 • Single dose; also 2 dose trial • Stored in refrigerator

Observation from J/J trial:

• 74% lower likelihood of asymptomatic transmission to others at 71 days compared to placebo • FDA cautionary statement: number of participants small; needs to be verified

Astra-Zeneca Candidate (adenovirus vector; introduces DNA → spike protein) 12/30/2020: authorized in the UK; USA review likely in spring, 2021 • Uses replication defective chimpanzee adenovirus • 2 doses (4-12 weeks apart) • storage: refrigeration for 6 months (not as fragile) • “much cheaper”, $2-4 has been quoted • Arm of study: weekly PCR testing; “signals” Astra-Zeneca Candidate Lancet, 12/8/2020: date from 4 ongoing trails: UK, Brazil, South Africa • >18 yo; vaccine vs meningococcal placebo

• Between 4/23 & 11/4: 23k enrolled; 11k included in efficacy endpoint • UK: ½ dose, then full dose: 90% efficacy • Other sites: both full doses: 62.1% efficacy • Overall efficacy: 70.4%; MORE DATA NEEDED • Well tolerated Novavax Candidate (NVXCoV2373) recombinant spike protein nanoparticle with immune adjuvant “think Shingrix vaccine”

• 2 doses; 21 days apart • Stable at 2-8 C; shipped in ready to use liquid • Evaluating a separate combined influenza & COVID vaccine • 2/15/2021: making a new vaccine → SA variant; bivalent vaccine ?

Other layers of Safety

8 week pause after trails enrolled 2 categories of Serious ADR • Hypersensitivity (allergies) reactions: within 30 minutes • Hyper Immune response: within 6 weeks FDA Ask after study enrollment: 2 month PAUSE after doses given to volunteers (FDA.gov) • Follow up duration of 8 weeks allows time for potential immune related adverse reactions to be observed & evaluated Pharmacovigilance (post vaccination surveillance) • Will be happening … mechanisms in place • CDC’s v-safe app: voluntary survey about their symptoms after vaccination • Vaccine adverse event reporting system (VAERS)

Pfizer & Moderna mRNA vaccines Clinical Considerations

No Vaccine is 100% effective

Previous h/o COVID-19: Does not change recommendations to receive vaccine • No recommended minimum interval between infection and vaccination • If desired, persons with recent documented acute SARS-CoV- 2 infection may choose to temporarily delay vaccination • The risk of reinfection, and therefore the need for vaccination, may increase with time following initial infection Pfizer: “regular” freezing / “dry” • 2 doses • 21 days apart (“ok” if 4 days earlier) • Start with Pfizer, stay with Pfizer ** • mRNA vaccines: different lipid nanoparticle Moderna: “regular” freezing / “liquid”

• 2 doses • 28 days apart (“ok” if 4 days) • Start with Moderna, stay with Moderna ** OHA collaborates with member hospitals and health systems to ensure a healthy Ohio

James Guliano, MSN, RN-BC, FACHE Vice President, Quality Programs [email protected]

— — Ohio Hospital Association