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Item Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, August 2021–January 2022(Center for Disease Control, 2022-02-18) Ferdinands, Jill M.; Rao, Suchitra; Dixon, Brian E.; Mitchell, Patrick K.; DeSilva, Malini B.; Irving, Stephanie A.; Lewis, Ned; Natarajan, Karthik; Stenehjem, Edward; Grannis, Shaun J.; Han, Jungmi; McEvoy, Charlene; Ong, Toan C.; Naleway, Allison L.; Reese, Sarah E.; Embi, Peter J.; Dascomb, Kristin; Klein, Nicola P.; Griggs, Eric P.; Konatham, Deepika; Kharbanda, Anupam B.; Yang, Duck-Hye; Fadel, William F.; Grisel, Nancy; Goddard, Kristin; Patel, Palak; Liao, I-Chia; Birch, Rebecca; Valvi, Nimish R.; Reynolds, Sue; Arndorfer, Julie; Zerbo, Ousseny; Dickerson, Monica; Murthy, Kempapura; Williams, Jeremiah; Bozio, Catherine H.; Blanton, Lenee; Verani, Jennifer R.; Schrag, Stephanie J.; Dalton, Alexandra F.; Wondimu, Mehiret H.; Link-Gelles, Ruth; Azziz-Baumgartner, Eduardo; Barron, Michelle A.; Gaglani, Manjusha; Thompson, Mark G.; Fireman, Bruce; Community and Global Health, Richard M. Fairbanks School of Public HealthCDC recommends that all persons aged ≥12 years receive a booster dose of COVID-19 mRNA vaccine ≥5 months after completion of a primary mRNA vaccination series and that immunocompromised persons receive a third primary dose.* Waning of vaccine protection after 2 doses of mRNA vaccine has been observed during the period of the SARS-CoV-2 B.1.617.2 (Delta) variant predominance† (1-5), but little is known about durability of protection after 3 doses during periods of Delta or SARS-CoV-2 B.1.1.529 (Omicron) variant predominance. A test-negative case-control study design using data from eight VISION Network sites§ examined vaccine effectiveness (VE) against COVID-19 emergency department/urgent care (ED/UC) visits and hospitalizations among U.S. adults aged ≥18 years at various time points after receipt of a second or third vaccine dose during two periods: Delta variant predominance and Omicron variant predominance (i.e., periods when each variant accounted for ≥50% of sequenced isolates). Persons categorized as having received 3 doses included those who received a third dose in a primary series or a booster dose after a 2 dose primary series (including the reduced-dosage Moderna booster). The VISION Network analyzed 241,204 ED/UC encounters** and 93,408 hospitalizations across 10 states during August 26, 2021-January 22, 2022. VE after receipt of both 2 and 3 doses was lower during the Omicron-predominant than during the Delta-predominant period at all time points evaluated. During both periods, VE after receipt of a third dose was higher than that after a second dose; however, VE waned with increasing time since vaccination. During the Omicron period, VE against ED/UC visits was 87% during the first 2 months after a third dose and decreased to 66% among those vaccinated 4-5 months earlier; VE against hospitalizations was 91% during the first 2 months following a third dose and decreased to 78% ≥4 months after a third dose. For both Delta- and Omicron-predominant periods, VE was generally higher for protection against hospitalizations than against ED/UC visits. All eligible persons should remain up to date with recommended COVID-19 vaccinations to best protect against COVID-19-associated hospitalizations and ED/UC visits.Item Waning of vaccine effectiveness against moderate and severe covid-19 among adults in the US from the VISION network: test negative, case-control study(BMJ Publishing, 2022-10-03) Ferdinands, Jill M.; Rao, Suchitra; Dixon, Brian E.; Mitchell, Patrick K.; DeSilva, Malini B.; Irving, Stephanie A.; Lewis, Ned; Natarajan, Karthik; Stenehjem, Edward; Grannis, Shaun J.; Han, Jungmi; McEvoy, Charlene; Ong, Toan C.; Naleway, Allison L.; Reese, Sarah E.; Embi, Peter J.; Dascomb, Kristin; Klein, Nicola P.; Griggs, Eric P.; Liao, I-Chia; Yang, Duck-Hye; Fadel, William F.; Grisel, Nancy; Goddard, Kristin; Patel, Palak; Murthy, Kempapura; Birch, Rebecca; Valvi, Nimish R.; Arndorfer, Julie; Zerbo, Ousseny; Dickerson, Monica; Raiyani, Chandni; Williams, Jeremiah; Bozio, Catherine H.; Blanton, Lenee; Link-Gelles, Ruth; Barron, Michelle A.; Gaglani, Manjusha; Thompson, Mark G.; Fireman, Bruce; Epidemiology, School of Public HealthObjective: To estimate the effectiveness of mRNA vaccines against moderate and severe covid-19 in adults by time since second, third, or fourth doses, and by age and immunocompromised status. Design: Test negative case-control study. Setting: Hospitals, emergency departments, and urgent care clinics in 10 US states, 17 January 2021 to 12 July 2022. Participants: 893 461 adults (≥18 years) admitted to one of 261 hospitals or to one of 272 emergency department or 119 urgent care centers for covid-like illness tested for SARS-CoV-2. Main outcome measures: The main outcome was waning of vaccine effectiveness with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine during the omicron and delta periods, and the period before delta was dominant using logistic regression conditioned on calendar week and geographic area while adjusting for age, race, ethnicity, local virus circulation, immunocompromised status, and likelihood of being vaccinated. Results: 45 903 people admitted to hospital with covid-19 (cases) were compared with 213 103 people with covid-like illness who tested negative for SARS-CoV-2 (controls), and 103 287 people admitted to emergency department or urgent care with covid-19 (cases) were compared with 531 168 people with covid-like illness who tested negative for SARS-CoV-2. In the omicron period, vaccine effectiveness against covid-19 requiring admission to hospital was 89% (95% confidence interval 88% to 90%) within two months after dose 3 but waned to 66% (63% to 68%) by four to five months. Vaccine effectiveness of three doses against emergency department or urgent care visits was 83% (82% to 84%) initially but waned to 46% (44% to 49%) by four to five months. Waning was evident in all subgroups, including young adults and individuals who were not immunocompromised; although waning was morein people who were immunocompromised. Vaccine effectiveness increased among most groups after a fourth dose in whom this booster was recommended. Conclusions: Effectiveness of mRNA vaccines against moderate and severe covid-19 waned with time after vaccination. The findings support recommendations for a booster dose after a primary series and consideration of additional booster doses.