125742 45 S211 M5 glatman freedman a 2021

Document text

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 27, No. 11, November 2021 2919In May 2021, the US Food and Drug Administration 
and the European Medicines Agency expanded 
H[LVWLQJ DXWKRUL]DWLRQ IRU %17E YDFFLQH 3À]HU%LR17HFK KWWSVZZZSÀ]HUFRP DJDLQVW VHYHUHacute respiratory syndrome coronavirus 2 (SARS-CoV-2) to include its use in adolescents 12–15 years of age (1,2 2Q -XQH   WKH ,VUDHO 0LQLVWU\ RIHealth declared the availability of BNT162b2 vaccine for adolescents 12–15 years of age (3) as a 2-dose regi-men, given 21 days apart. By August 26, 2021, a total of 277,218 adolescents (46.1% of those eligible) had received 1 dose of the vaccine and 187,707 (31.2%) KDGUHFHLYHGGRVHV)LJXUHSDQHO$,QPLG-XQH2021, after a month of extremely low SARS-CoV-2 ac-tivity in Israel, 2 local outbreaks erupted (4–6). These outbreaks marked the beginning of a new widespread SARS-CoV-2 outbreak in Israel (Figure 1, panel B), dominated by the B.1.617.2 (Delta) variant, which ac-FRXQWHGIRU²RIWKHVHTXHQFHGYLUXVHVGXULQJ-XO\ DQG $XJXVW  7). We analyzed effectiveness of this vaccine among adolescents who had been vac-cinated in the early stages of this outbreak in Israel. The study was approved by the superior ethical com-mittee of the Israel Ministry of Health and included exemption from informed consent.
The Study
We performed a nationwide retrospective cohort VWXG\ WR HVWLPDWH YDFFLQH HIIHFWLYHQHVV DJDLQVW 3&5FRQÀUPHG 6$56&R9 LQIHFWLRQV DPRQJ DGROHVFHQWIsrael residents 12–15 years of age who had received WKH VHFRQG YDFFLQH GRVH GXULQJ -XO\ ²  7KHdata sources used are described in detail elsewhere (8). We estimated vaccine effectiveness and 95% CIs by using (1 – incidence rate ratio)  u 100 for 1–7, 8–14, 15–21, and 22–28 days after the second vaccine dose. Incidence rate ratio denotes the ratio of the rate of 3&5FRQÀUPHG 6$56&R9 LQIHFWLRQV LQ WKH YDFFLnated and unvaccinated groups.
We excluded from analysis adolescents who had 
KDG D GRFXPHQWHG 6$56&R9²SRVLWLYH 3&5 UHVXOWbefore the evaluation periods, regardless of their vac-cination status. When several positive SARS-CoV-2 test results were documented for the same person GXULQJ WKH VWXG\ SHULRG ZH LQFOXGHG RQO\ WKH ÀUVWresult in our analysis.
We determined the number of unvaccinated con-
WUROV IRU HDFK GDWH GXULQJ -XO\ ²  E\ RPLWting the number of fully vaccinated adolescent Israel residents 12–15 years of age who had received the second BNT162b2 vaccine dose on a particular date from the total number of Israel residents who did not have a documented SARS-CoV-2–positive test result and had not received only a single vaccine dose by that date. We expressed the denominators of the vac-cinated and unvaccinated groups in person-days.
After administration of the second vaccine dose, 
crude vaccine effectiveness against laboratory-con-ÀUPHG 6$56&R9 LQIHFWLRQ ZDV   &,Eff ectiveness of BNT162b2 
Vaccine in Adolescents during 
Outbreak of SARS-CoV-2 Delta 
Variant Infection, Israel, 2021
Aharona Glatman-Freedman, Yael Hershkovitz, Zalman Kaufman, 
Rita Dichtiar, Lital Keinan-Boker, Michal Bromberg
Author affi   liations: The Israel Center for Disease Control, 
Ramat Gan, Israel (A. Glatman-Freedman, Y. Hershkovitz, 
Z. Kaufman, R. Dichtiar, L. Keinan-Boker, M. Bromberg); Tel Aviv University, Tel Aviv, Israel (A. Glatman-Freedman, M. Bromberg) ; 
Haifa University, Haifa, Israel (L. Keinan-Boker)
DOI: https://doi.org/10.3201/eid2711.211886In Israel, the BNT162b2 vaccine against severe acute re-
spiratory syndrome coronavirus 2 was approved for use in adolescents in June 2021, shortly before an outbreak of B.1.617.2 (Delta) variant–dominant infection. We eval-uated short-term vaccine eff  ectiveness and found the vaccine to be highly eff  ective among this population in 
this setting.
090177e198c5d54c\Final\Final On: 03-Dec-2021 22:30 (GMT)
FDA-CBER-2022-5812-0071305
DISPATCHES
2920  Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 27, No. 11, November 2021²LQWKHÀUVWZHHN&,²
91.2%) in the second week, 91.2% (87.4%–93.8%) in the third week, and 88.2% (95% CI 85.0%–90.7%) in the fourth week (Table; Figure 2). Vaccine effectiveness GLIIHUHG VLJQLÀFDQWO\ EHWZHHQ WKH ÀUVW DQG VXEVH-TXHQWZHHNVEXWZHIRXQGQRVWDWLVWLFDOO\VLJQLÀFDQWdifferences in vaccine effectiveness among the second, third, and fourth weeks. Because of the small number of cases of SARS-CoV-2 infection among vaccinated adolescents, we could not adjust for weekly vac-cine effectiveness evaluation. However, adjustments for sex and epidemiologic week for days 8–28 after the second dose combined demonstrated adjusted  vaccine effectiveness of 91.5% (95% CI 88.2%–93.9%) against SARS-CoV-2 infection (Table). We did not estimate vaccine effectiveness against symptomatic diseases because epidemiologic investigation was performed for 42% of vaccinated and 40% of unvac-cinated adolescents in our cohort.
As of August 26, 2021, none of the vaccinated 
adolescents who became SARS-CoV-2–positive on days 1–28 after the the second vaccine dose had been hospitalized. By that same date, among unvaccinated adolescents, 7 (0.38%) of 1,825 who tested positive for SARS-CoV-2 on days 1–7 after vaccinated adolescents had received their second vaccine dose and 26 (0.32%) 
Figure 1.  Vaccine doses among 
adolescents and total severe 
acute respiratory syndrome coronavirus 2 infections, Israel, June 1–August 26, 2021. A) Daily frequency of administration of first and second dose of BNT162b2 vaccine (Pfizer-BioNTech, https://www.pfizer.com) among adolescents 12–15 years of age. B) Daily cases of severe acute respiratory syndrome coronavirus 2 infection in persons of all ages.
 
Table.  Effectiveness of BNT162B2 vaccine against PCR- confirmed SARS- CoV-2 infection in adolescents 12 –15 years of age after 
receipt of second dose, Israel, 2021*  
Period Days after 
second doseUnvaccinated,  
SARS- CoV-2–
positive, no.Unvaccinated 
person -daysVaccinated, 
SARS- CoV-2–
positive, no.Vaccinated 
person -daysCrude vaccine 
effectiveness 
(95% CI)Adjusted vaccine 
effectiveness 
(95% CI)
Week 1 1–7 1,825 10,148,829 53 673,129 55.3 (41.3–66.0) NA
Week 2 8–14 2,923 9,750,816 26 672,790 87.1 (81.0 –91.2) NA
Week 3  15–21 4,906 9,386,429 31 672,624 91.2 (87.4–93.8) NA
Week 4 22–28 7,510 8,905,457 67 672,328 88.2 (85.0–90.7) NA
Weeks 2– 4 8–28 8,144 13,623,714 124 2,034,591 89.8 (87.8–91.5) 91.5 (88.2–93.9)
*BNT162B2 vaccine, Pfizer -BioNTech (https://www.pfizer.c om) NA, not applicable; SARS- CoV-2, severe acute respiratory syndrome coronavirus 2.    
      
 
     
 
   
   
 
    
         
   
  
   
        
          
       
   
  
  
  
   
090177e198c5d54c\Final\Final On: 03-Dec-2021 22:30 (GMT)
FDA-CBER-2022-5812-0071306
 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 27, No. 11, November 2021 2921Effectiveness of BNT162b2 Vaccine in Adolescents
of 8,144 who tested positive on days 8–28 were hos-
pitalized. Also by August 26, no vaccinated or unvac-cinated SARS-CoV-2–positive adolescents had died. 
Conclusions
The BNT162b2 vaccination campaign for adolescents 12–15 years of age in Israel coincided with the out-break of the SARS-CoV-2 Delta variant. As such, the timing enabled estimation of vaccine effectiveness against SARS-CoV-2 infection for this age group dur-ing predominant circulation of the Delta variant.
Our results demonstrate high vaccine effective-
ness against SARS-CoV-2 infection in this population starting the second week after the second vaccine dose. These estimates are somewhat lower than those that had been estimated for persons 16–39 years of age during the same time intervals after the second vaccine dose during circulation of the SARS-CoV-2 Alpha variant and wild-type virus in Israel (8). Spe-FLÀFDOO\DGMXVWHGYDFFLQHHIIHFWLYHQHVVDJDLQVW6$56CoV-2 infection for persons 16–39 years of age was 93.2% (95% CI 91.9%–94.2%) at 8–14 days, 96.7% (95% CI 95.8%–97.4%) at 15–21 days, and 96.6 (95% CI 95.7%–97.3%) at 22–28 days after receipt of the second vaccine dose. Although vaccine effectiveness estimates and 95% CIs during the circulation of the Alpha variant and the wild-type virus were adjusted for age, sex, and epidemiologic week, only minor dif-ferences in point estimates and 95% CIs were noted between crude and adjusted vaccine effectiveness (8).
7KH HIIHFWLYHQHVV HVWLPDWH RI  LQ WKH ÀUVW
ZHHN DIWHU WKH VHFRQG GRVH SUREDEO\ UHÁHFWV WKH HI-IHFW RI WKH ÀUVW YDFFLQH GRVH 7KLV HVWLPDWH LV FRQVLV-tant with previous estimates of vaccine effectiveness ²GD\VDIWHUWKHÀUVWGRVH8–10).2XU ÀQGLQJV DUH FRQVLVWHQW ZLWK WKRVH RI D UH-
FHQW VWXG\ IURP WKH 8QLWHG .LQJGRP ZKLFK GHP-onstrated vaccine effectiveness of 88.0% (95% CI 85.3%–90.1%) against symptomatic disease caused by the SARS-CoV-2 Delta variant (11), compared with vaccine effectiveness of 93.7% (95% CI 91.6%–95.3%) against disease caused by the Alpha variant among persons >16 years of age who had received 2 doses of BNT162b2 (11). However, that study addressed neither the interval between the 2 doses nor the exact interval between assessment of vaccine effectiveness and the date of the second dose ( 11).
As of September 2021, two controlled studies 
KDG DVVHVVHG YDFFLQH HIÀFDF\ LQ DGROHVFHQWV ZLWK-out specifying the SARS-CoV-2 variant (12,13). One VWXG\ UHSRUWHG %17E YDFFLQH HIÀFDF\ RI DJDLQVW ODERUDWRU\FRQÀUPHG &29,' >7 days af-
ter receipt of the second vaccine dose at 21 days after WKHÀUVWGRVH12). The other study reported that vac-FLQH HIÀFDF\ RI WKH P51$ YDFFLQH  GD\V DI-WHUWKHVHFRQGGRVHZDVGLIÀFXOWWRDVVHVVEHFDXVHRIWKHORZLQFLGHQFHRIODERUDWRU\FRQÀUPHG&29,'in the trial population (4 cases in the placebo group and 0 cases in the mRNA-1273 group) (13). Of note, the geometric mean ratio of neutralizing antibodies in adolescents receiving those vaccines was similar to or greater than that of young adults after receipt of 2 doses ( 12,13).
Behavioral and testing policy factors can poten-
tially affect estimations of vaccine effectiveness. Be-haviors that increase exposure to SARS-CoV-2 may be assumed by vaccinated or unvaccinated adolescents IRU GLIIHUHQW UHDVRQV DQG DUH GLIÀFXOW WR PHDVXUHDuring the study period, SARS-CoV-2 testing was available in Israel regardless of vaccination status.
Figure 2. Vaccine 
effectiveness against severe acute respiratory syndrome coronavirus 2 infection in adolescents 12–15 years of age, by time after second dose of BNT162b2 vaccine (Pfizer-BioNTech, https://www.pfizer.com), Israel, 2021. Error bars indicate 95% CIs. 
 
  
 
  
 
     
   
 
       
  
 
    
     
090177e198c5d54c\Final\Final On: 03-Dec-2021 22:30 (GMT)
FDA-CBER-2022-5812-0071307
DISPATCHES
2922  Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 27, No. 11, November 2021The recent rise in SARS-CoV-2 cases in Israel 
UDLVHGFRQFHUQV7KHÀUVWFRQFHUQZDVWKDW%17E
vaccine–elicited immunity was waning. Waning of spike protein antibody levels was detected over time after receipt of a second dose of SARS-CoV-2 vaccines (14). The second concern was that the vaccine was not effective against the SARS-CoV-2 Delta variant. How-HYHURXUÀQGLQJVLQGLFDWHWKDWWKH%17EYDFFLQHprovides adolescents with highly effective short-term protection against the SARS-CoV-2 Delta variant. 
A.G.-F. conceived and designed the study, led data 
DQDO\VLVDQGZURWHWKHÀUVWGUDIWRIWKHPDQXVFULSW0%oversaw the study design and analysis. Y.H. and R.D. retrieved the data. Y.H. and R.D. performed data analysis. =.SHUIRUPHGFRPSDUDWLYHHYDOXDWLRQZLWKSUHYLRXVGDWD$*)=./.%DQG0%LQWHUSUHWHGWKHGDWDDQGHGLWHGWKHÀQDOPDQXVFULSW$OODXWKRUVUHYLVHGWKHmanuscript critically for important intellectual content and DSSURYHGWKHÀQDOYHUVLRQRIWKHPDQXVFULSW
About the Author 
Dr. Glatman-Freedman is the director of the Infectious  Diseases Unit in the Israel Center for Disease Control. She LVDIÀOLDWHGDFDGHPLFDOO\ZLWKWKH6FKRRORI3XEOLF+HDOWKat Tel Aviv University. Her primary research interests are the epidemiology of respiratory viruses, syndromic surveillance, and vaccine effectiveness.
References
  1  Food and Drug Administration  Coronavirus (COVID-19) 
XSGDWH )'$DXWKRUL]HV3À]HU%LR17HFK&29,'YDFFLQH
for emergency use in adolescents in another important action LQÀJKWDJDLQVWSDQGHPLF>FLWHG$XJ@ KWWSVZZZIGDJRYQHZVHYHQWVSUHVVDQQRXQFHPHQWVFRURQDYLUXVFRYLGXSGDWHIGDDXWKRUL]HVSÀ]HUELRQWHFKFRYLG19-vaccine-emergency-use
  2  European Medicines Agency  First COVID-19 vaccine  
approved for children aged 12 to 15 in EU [cited 2021 Aug @ KWWSVZZZHPDHXURSDHXHQQHZVÀUVWFRYLG  
vaccine-approved-children-aged-12-15-eu 
  3  Israel Ministry of Health  Ministry of Health’s position 
regarding the expansion of the vaccination operation to ages ²\HDUV>FLWHG$XJ@ KWWSVZZZJRYLOHQGHSDUWPHQWVQHZV  4  Israel Ministry of Health  Coronavirus outbreak in  
%LQ\DPLQD>FLWHG$XJ@ KWWSVZZZJRYLOHQGHSDUWPHQWVQHZV
  5  Israel Ministry of Health  Effective today (20 6 2021)— 
PDVNLQJUHTXLUHPHQWDWDOOVFKRROVLQ0RGL·LQDQG%LQ\DPLQD>FLWHG$XJ@ KWWSVZZZJRYLOHQ GHSDUWPHQWVQHZV
  6  Israel Ministry of Health  Home Front Command  
coronavirus testing points closed [cited 2021 Aug 23]  KWWSVZZZJRYLOHQGHSDUWPHQWVQHZV
  7  Our World in Data  SARS-CoV-2 variants in analyzed  
VHTXHQFHV,VUDHO>FLWHG$XJ@ KWWSVRXUZRUOGLQ -
GDWDRUJJUDSKHUFRYLGYDULDQWVDUHD"FRXQWU\ a,65
  8  Glatman-Freedman A, Bromberg M, Dichtiar R,  
+HUVKNRYLW]<.HLQDQ%RNHU/ 7KH%17EYDFFLQH  
effectiveness against new COVID-19 cases and complications of breakthrough cases  a nation-wide retrospective  longitudinal multiple cohort analysis using individualised GDWD (%LR0HGLFLQH  KWWSVGRLRUJ  
j ebiom 2021 103574
 'DJDQ1%DUGD1.HSWHQ(0LURQ23HUFKLN6.DW]0$
et al  BNT162b2 mRNA Covid-19 vaccine in a nationwide PDVVYDFFLQDWLRQVHWWLQJ 1(QJO-0HG ²
 &KRGLFN*7HQH/3DWDORQ7*D]LW6%HQ7RY$&RKHQ'
et al  Assessment of effectiveness of 1 dose of BNT162b2  vaccine for SARS-CoV-2 infection 13 to 24 days after  LPPXQL]DWLRQ -$0$1HWZ2SHQ H  
KWWSVGRLRUJMDPDQHWZRUNRSHQ
 /RSH]%HUQDO-$QGUHZV1*RZHU&*DOODJKHU(  
Simmons R, Thelwall S, et al  Effectiveness of Covid-19 YDFFLQHVDJDLQVWWKH%'HOWDYDULDQW 1(QJO-0HG² KWWSVGRLRUJ1(-0RD
 )UHQFN5:-U.OHLQ13.LWFKLQ1*XUWPDQ$$EVDORQ-
/RFNKDUW6HWDO 6DIHW\LPPXQRJHQLFLW\DQGHIÀFDF\RIWKH%17E&RYLGYDFFLQHLQDGROHVFHQWV 1(QJO-0HG2021;385 239–50
 $OL.%HUPDQ*=KRX+'HQJ:)DXJKQDQ9  
Coronado-Voges M, et al  Evaluation of mRNA-1273  6$56&R9YDFFLQHLQDGROHVFHQWV 1(QJO-0HG $XJ>(SXEDKHDGRISULQW@ KWWSVGRLRUJ 1(-0RD
14  Shrotri M, Navaratnam AMD, Nguyen V, Byrne T,  
Geismar C, Fragaszy E, et al ; Virus Watch Collaborative  Spike-antibody waning after second dose of BNT162b2 or &K$G2[ /DQFHW ² KWWSVGRLRUJS0140-6736(21)01642-1
Address for correspondence  Aharona Glatman-Freedman,  
The Israel Center for Disease Control, Israel Ministry of Health Gertner Institute Building, Tel Hashomer, Ramat Gan 5265601, ,VUDHOHPDLO DKDURQDIUHHGPDQ#PRKJRYLO
090177e198c5d54c\Final\Final On: 03-Dec-2021 22:30 (GMT)
FDA-CBER-2022-5812-0071308