Covid-19 Vaccine Update: Global Landscape, Safety, and Efficacy PDF

COVID-19 Vaccine Update: Global Landscape, Safety and Efficacy Elizabeth A. Talbot, MD Deputy State Epidemiologist, NH DHHS Professor, Infectious Diseases and International Health, Dartmouth We are now in the transition phase of the pandemic, but it is not over BLUF: Summary Vaccines are our best to...

COVID-19 Vaccine Update: Global Landscape, Safety and Efficacy Elizabeth A. Talbot, MD Deputy State Epidemiologist, NH DHHS Professor, Infectious Diseases and International Health, Dartmouth We are now in the transition phase of the pandemic, but it is not over BLUF: Summary Vaccines are our best tool to mitigate morbidity and mortality mRNA vaccines are most commonly-used globally, safe, and effective, even in Omicron era Vaccine hesitancy continues to be our collective challenge Current Global Epidemic World Health Organization >13 Billion Doses Administered >5B Persons Fully Vaccinated Covid World Vaccination Tracker - The New York Times (nytimes.com) COVID-19 vaccines (who.int) Regional Disparities Covid World Vaccination Tracker (nytimes.com) COVID-19 vaccines (who.int) Global Vaccine Landscape WHO provided EUL to these 10 vaccines which met criteria for safety and efficacy: AstraZeneca/Oxford vaccine Johnson and Johnson Moderna Pfizer/BionTech Sinopharm Sinovac COVAXIN Covovax Nuvaxovid CanSino Some nations assessed other vaccines for use in their countries Most important messaging: Take whatever vaccine is made available to you first, even if you have already had COVID-19 SAGE accepts 2 heterologous doses of WHO EUL COVID-19 vaccines as a complete primary series Current vaccines provide strong protection against serious illness and death caused by Omicron and Delta variants Being fully vaccinated will help reduce the likelihood of new variants emerging WHO and CDC Resources to Understand COVID-19 Vaccine Presentations Focus on mRNA Vaccines WHO: Who Should Get Vaccinated? Vaccines with EUL are safe for most people >18y, including those with pre-existing conditions, such as autoimmune disorders If you are immunocompromised, you should be prioritized for additional dose after 1 to 3 months If you are pregnant, want to get pregnant in the future or are breastfeeding, get vaccinated – Many vaccinated while pregnant or breastfeeding, and no safety concerns have been identified for them or their babies – Getting vaccinated while pregnant proven to protect your baby; this may also be the case if you get vaccinated while breastfeeding Children can be safely vaccinated, EULs vary Current U.S. Vaccine Recommendations Everyone >6m should complete a COVID-19 vaccine primary series: 2 or 3 doses depending on age, immunocompromised status – Pfizer or Moderna mRNA vaccines for persons 6+ months of age – Novavax is also available for people 12+ years of age Everyone >5y who has completed at least primary series should receive one bivalent Omicron booster https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html Uptake Declining Reasons Adults Do Not Get COVID-19 Vaccine October 2022 https://scholars.unh.edu/cgi/viewcontent.cgi?article=1714&context=survey_center_polls Parental Reasons for Not Vaccinating Children February 2022 https://scholars.unh.edu/cgi/viewcontent.cgi?article=1689&context=survey_center_polls mRNA Vaccine Safety Critical knowledge to support uptake U.S. Safety Monitoring Systems VAERS: Providers are required report all serious adverse events (including deaths) that occur after vaccination, regardless of whether or not they are plausibly associated with vaccination Designed as an early warning system to detect potential safety signals Cannot establish causality V-safe: Voluntary smartphone-based system that uses text messaging and web-based surveys to monitor for COVID-19 vaccine side effects Expected overrepresentation from those with side effects https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00054-8/fulltext Dec 2020 – Jun 2021: 298+ million doses administered in U.S. 56% Pfizer-BioNTech, 44% Moderna Analysis of safety in persons >16y from VAERS and v-safe Serious side effects were rare Local injection-site and systemic side effects were common Usually mildmoderate, occurred within 1-2d of vaccination, then resolved quickly Side effects were more common after dose #2 than #1 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00054-8/fulltext Side effects slightly more common with Moderna vs. PfizerBioNTech VAERS Reports Summary 340,522 adverse events 92% were non-serious Headache, fatigue, fever/chills, pain 7% were serious Dyspnea, fever, fatigue, headache, chest pain 1% deaths 4,471 deaths “No unusual patterns in cause of death among the death reports” Median age 76 years (IQR 66-86 years) 18% of deaths had death certificate or autopsy report COVID-19: 13% Heart diseases: 47% Myocarditis and Pericarditis Myocarditis/pericarditis have multiple causes including infection, inflammatory response, toxins, autoimmune, etc. mRNA COVID-19 vaccines associated with development of myocarditis/pericarditis COVID-19 itself can cause myocarditis/pericarditis Nearly all persons who develop myocarditis/pericarditis after COVID-19 vaccination recover Highest risk is in adolescent and young adult males Usually after dose #2, in first 7 days after vaccination https://www.cdc.gov/mmwr/volumes/71/wr/mm7144a3.htm https://www.cdc.gov/mmwr/volumes/70/wr/mm7035e5.htm https://www.cdc.gov/mmwr/volumes/71/wr/mm7114e1.htm Omicron Variants Evading immunity from original vaccines and disease https://www.nature.com/articles/d41586-022-03533-7 Omicron Variant Lineages 43.0% 15.9% 28.8% https://covid.cdc.gov/covid-data-tracker/#variant-proportions Omicron Variants Substantially Impact Vaccine Effectiveness and Durability of Immunity Antibody neutralization is lower against Omicron variants This translates into lower VE of monovalent vaccine at preventing infection and symptomatic disease VE against hospitalization and death is documented, but protection declines over time, particularly against Omicron variants The updated bivalent (‘Omicronadapted’) booster increases protection Summary: reactions are consistent and similar to reactions reported after monovalent primary and booster vaccination Vsafe VAERS 5,542 VAERS reports of 22.6 million doses of bivalent vaccine administered >95% were non-serious – Headache, fatigue, pain 65y were more likely to have an ischemic stroke in 3w following Pfizer bivalent booster compared to 22-44d after vaccination Not seen in 3 other federal vaccine safety tracking databases Pfizer’s global safety database Other countries’ monitoring systems All data to be reviewed at FDA Jan 26 meeting With Moderna bivalent booster Safety Summary Local and systemic side effects are common Patients should be counseled to expect to not feel well for 1-2 days after vaccination, but symptoms will usually subside quickly Myocarditis/pericarditis have been rarely associated with mRNA COVID19 vaccination, usually in 7d after dose #2 in male adolescents and young adults Risk is greater after COVID-19 compared with vaccination in all age groups Most will fully recover Serious vaccine side effects are rare Multiple safety surveillance systems ongoing to detect any signal Does the Bivalent Vaccine Work? 8 lab-based studies suggest the bivalent vaccine boosters targeting the Omicron BA.4/BA.5 subvariants provide broad and better protection than original vaccine boosters against severe COVID-19 outcomes Real-world data is coming in with consistent findings that the bivalent booster protects against hospitalization and death Emerging Data Showing Effectiveness US CDC’s MMWR showed bivalent booster provided 73% additional protection against COVID-19 hospitalization among immunocompetent adults >65y, compared to past monovalent Nov 2022 CDC data show – 90% reduction of hospitalizations for people >65y who had bivalent booster compared to unvaccinated – 13.5-fold increased risk of hospitalization for unvaccinated 2.5-fold risk among vaccinated without bivalent booster Israeli study found in 70d follow up after bivalent booster, 81% reduction in hospitalization among people >65y “What if I am Younger?” MMWR study of adults >18y found bivalent booster was 3857% effective against hospitalization, consistent with, but at a lower magnitude, than protection among older adults – Among 18-49yo, monthly rates of COVID-19-associated hospitalizations were 29.9 times higher in unvaccinated individuals 3.2 times higher in vaccinated individuals without bivalent booster https://covid.cdc.gov/covid-data-tracker/#covidnet-hospitalizations-vaccination https://covid.cdc.gov/covid-data-tracker/#rates-by-vaccine-status Predictions For the Future of COVID-19 Vaccines COVID-19 will continue to circulate and evolve to new variants Yearly routine boosting is likely to be important, particularly to protect against severe disease Combination vaccines (e.g., influenza + RSV) are being developed Vital strategy to incorporate COVID-19 vaccination into routine well-child and primary care appointments Booster Future? Jan 26 2023 VRBPAC Meeting Unanimous vote to “harmonize” the primary vaccine and boosters so that all COVID-19 vaccines will target circulating strains Plan that every fall will have new boosters targeting a recent strain, to be administered in influenza vaccination campaign mRNA vaccines take 90 days to generate an updated booster, Novavax needs nearly twice that Once-per-year update may not serve some populations, such as the very young who have not yet been primed, the very old, and the immunocompromised We are now in the transition phase of the pandemic, but it is not over Vaccines are our best tool to mitigate morbidity and mortality Summary mRNA vaccines are most commonly used globally, safe, and effective, even in Omicron era Vaccine hesitancy continues to be our collective challenge Thanks