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Item BNT162b2 Protection against the Omicron Variant in Children and Adolescents(Massachusetts Medical Society, 2022) Price, Ashley M.; Olson, Samantha M.; Newhams, Margaret M.; Halasa, Natasha B.; Boom, Julie A.; Sahni, Leila C.; Pannaraj, Pia S.; Irby, Katherine; Bline, Katherine E.; Maddux, Aline B.; Nofziger, Ryan A.; Cameron, Melissa A.; Walker, Tracie C.; Schwartz, Stephanie P.; Mack, Elizabeth H.; Smallcomb, Laura; Schuster, Jennifer E.; Hobbs, Charlotte V.; Kamidani, Satoshi; Tarquinio, Keiko M.; Bradford, Tamara T.; Levy, Emily R.; Chiotos, Kathleen; Bhumbra, Samina S.; Cvijanovich, Natalie Z.; Heidemann, Sabrina M.; Cullimore, Melissa L.; Gertz, Shira J.; Coates, Bria M.; Staat, Mary A.; Zinter, Matt S.; Kong, Michele; Chatani, Brandon M.; Hume, Janet R.; Typpo, Katri V.; Maamari, Mia; Flori, Heidi R.; Tenforde, Mark W.; Zambrano, Laura D.; Campbell, Angela P.; Patel, Manish M.; Randolph, Adrienne G.; Overcoming Covid-19 Investigators; Pediatrics, School of MedicineBackground: Spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant, which led to increased U.S. hospitalizations for coronavirus disease 2019 (Covid-19), generated concern about immune evasion and the duration of protection from vaccines in children and adolescents. Methods: Using a case-control, test-negative design, we assessed vaccine effectiveness against laboratory-confirmed Covid-19 leading to hospitalization and against critical Covid-19 (i.e., leading to receipt of life support or to death). From July 1, 2021, to February 17, 2022, we enrolled case patients with Covid-19 and controls without Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2 messenger RNA vaccine) at least 14 days before illness among case patients and controls, according to time since vaccination for patients 12 to 18 years of age and in periods coinciding with circulation of B.1.617.2 (delta) (July 1, 2021, to December 18, 2021) and omicron (December 19, 2021, to February 17, 2022) among patients 5 to 11 and 12 to 18 years of age. Results: We enrolled 1185 case patients (1043 [88%] of whom were unvaccinated, 291 [25%] of whom received life support, and 14 of whom died) and 1627 controls. During the delta-predominant period, vaccine effectiveness against hospitalization for Covid-19 among adolescents 12 to 18 years of age was 93% (95% confidence interval [CI], 89 to 95) 2 to 22 weeks after vaccination and was 92% (95% CI, 80 to 97) at 23 to 44 weeks. Among adolescents 12 to 18 years of age (median interval since vaccination, 162 days) during the omicron-predominant period, vaccine effectiveness was 40% (95% CI, 9 to 60) against hospitalization for Covid-19, 79% (95% CI, 51 to 91) against critical Covid-19, and 20% (95% CI, -25 to 49) against noncritical Covid-19. During the omicron period, vaccine effectiveness against hospitalization among children 5 to 11 years of age was 68% (95% CI, 42 to 82; median interval since vaccination, 34 days). Conclusions: BNT162b2 vaccination reduced the risk of omicron-associated hospitalization by two thirds among children 5 to 11 years of age. Although two doses provided lower protection against omicron-associated hospitalization than against delta-associated hospitalization among adolescents 12 to 18 years of age, vaccination prevented critical illness caused by either variant.Item Effectiveness of BNT162b2 Vaccine against Critical Covid-19 in Adolescents(Massachusetts Medical Society, 2022) Olson, Samantha M.; Newhams, Margaret M.; Halasa, Natasha B.; Price, Ashley M.; Boom, Julie A.; Sahni, Leila C.; Pannaraj, Pia S.; Irby, Katherine; Walker, Tracie C.; Schwartz, Stephanie P.; Maddux, Aline B.; Mack, Elizabeth H.; Bradford, Tamara T.; Schuster, Jennifer E.; Nofziger, Ryan A.; Cameron, Melissa A.; Chiotos, Kathleen; Cullimore, Melissa L.; Gertz, Shira J.; Levy, Emily R.; Kong, Michele; Cvijanovich, Natalie Z.; Staat, Mary A.; Kamidani, Satoshi; Chatani, Brandon M.; Bhumbra, Samina S.; Bline, Katherine E.; Gaspers, Mary G.; Hobbs, Charlotte V.; Heidemann, Sabrina M.; Maamari, Mia; Flori, Heidi R.; Hume, Janet R.; Zinter, Matt S.; Michelson, Kelly N.; Zambrano, Laura D.; Campbell, Angela P.; Patel, Manish M.; Randolph, Adrienne G.; Pediatrics, School of MedicineBackground: The increasing incidence of pediatric hospitalizations associated with coronavirus disease 2019 (Covid-19) caused by the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United States has offered an opportunity to assess the real-world effectiveness of the BNT162b2 messenger RNA vaccine in adolescents between 12 and 18 years of age. Methods: We used a case-control, test-negative design to assess vaccine effectiveness against Covid-19 resulting in hospitalization, admission to an intensive care unit (ICU), the use of life-supporting interventions (mechanical ventilation, vasopressors, and extracorporeal membrane oxygenation), or death. Between July 1 and October 25, 2021, we screened admission logs for eligible case patients with laboratory-confirmed Covid-19 at 31 hospitals in 23 states. We estimated vaccine effectiveness by comparing the odds of antecedent full vaccination (two doses of BNT162b2) in case patients as compared with two hospital-based control groups: patients who had Covid-19-like symptoms but negative results on testing for SARS-CoV-2 (test-negative) and patients who did not have Covid-19-like symptoms (syndrome-negative). Results: A total of 445 case patients and 777 controls were enrolled. Overall, 17 case patients (4%) and 282 controls (36%) had been fully vaccinated. Of the case patients, 180 (40%) were admitted to the ICU, and 127 (29%) required life support; only 2 patients in the ICU had been fully vaccinated. The overall effectiveness of the BNT162b2 vaccine against hospitalization for Covid-19 was 94% (95% confidence interval [CI], 90 to 96); the effectiveness was 95% (95% CI, 91 to 97) among test-negative controls and 94% (95% CI, 89 to 96) among syndrome-negative controls. The effectiveness was 98% against ICU admission and 98% against Covid-19 resulting in the receipt of life support. All 7 deaths occurred in patients who were unvaccinated. Conclusions: Among hospitalized adolescent patients, two doses of the BNT162b2 vaccine were highly effective against Covid-19-related hospitalization and ICU admission or the receipt of life support. (Funded by the Centers for Disease Control and Prevention.).Item How many lives have coronavirus vaccines saved? We used state data on deaths and vaccination rates to find out(The Conversation US, Inc., 2021-10-15) Gupta, Sudmedha; Economics, School of Liberal ArtsItem Real-world Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescent(medRxiv, 2023-11-13) Wu, Qiong; Tong, Jiayi; Zhang, Bingyu; Zhang, Dazheng; Chen, Jiajie; Lei, Yuqing; Lu, Yiwen; Wang, Yudong; Li, Lu; Shen, Yishan; Xu, Jie; Bailey, L. Charles; Bian, Jiang; Christakis, Dimitri A.; Fitzgerald, Megan L.; Hirabayashi, Kathryn; Jhaveri, Ravi; Khaitan, Alka; Lyu, Tianchen; Rao, Suchitra; Razzaghi, Hanieh; Schwenk, Hayden T.; Wang, Fei; Witvliet, Margot I.; Tchetgen Tchetgen, Eric J.; Morris, Jeffrey S.; Forrest, Christopher B.; Chen, Yong; Pediatrics, School of MedicineBackground: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant's emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited. Objective: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents. Design: Comparative effectiveness research accounting for underreported vaccination in three study cohorts: adolescents (12 to 20 years) during the Delta phase, children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. Setting: A national collaboration of pediatric health systems (PEDSnet). Participants: 77,392 adolescents (45,007 vaccinated) in the Delta phase, 111,539 children (50,398 vaccinated) and 56,080 adolescents (21,180 vaccinated) in the Omicron period. Exposures: First dose of the BNT162b2 vaccine vs. no receipt of COVID-19 vaccine. Measurements: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100% with confounders balanced via propensity score stratification. Results: During the Delta period, the estimated effectiveness of BNT162b2 vaccine was 98.4% (95% CI, 98.1 to 98.7) against documented infection among adolescents, with no significant waning after receipt of the first dose. An analysis of cardiac complications did not find an increased risk after vaccination. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (95% CI, 72.2 to 76.2). Higher levels of effectiveness were observed against moderate or severe COVID-19 (75.5%, 95% CI, 69.0 to 81.0) and ICU admission with COVID-19 (84.9%, 95% CI, 64.8 to 93.5). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (95% CI, 83.8 to 87.1), with 84.8% (95% CI, 77.3 to 89.9) against moderate or severe COVID-19, and 91.5% (95% CI, 69.5 to 97.6)) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined after 4 months following the first dose and then stabilized. The analysis revealed a lower risk of cardiac complications in the vaccinated group during the Omicron variant period. Limitations: Observational study design and potentially undocumented infection. Conclusions: Our study suggests that BNT162b2 was effective for various COVID-19-related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time.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.