key: cord-1054472-5se32jae authors: Andrews, N.; Stowe, J.; Kirsebom, F.; Toffa, S.; Rickeard, T.; Gallagher, E.; Gower, C.; Kall, M.; Groves, N.; O'Connell, A.-M.; Simons, D.; Blomquist, P. B.; Dabrera, G.; Myers, R.; Ladhani, S. N.; Amirthalingam, G.; Gharbia, S.; Barrett, J. C.; Elson, R.; Ferguson, N.; Zambon, M.; Campbell, C. N.; Brown, K.; Hopkins, S.; Chand, M.; Ramsay, M.; Lopez Bernal, J. title: Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern date: 2021-12-14 journal: nan DOI: 10.1101/2021.12.14.21267615 sha: 5962bd2f3c99c3569df9c3ebf3871efd42b123ba doc_id: 1054472 cord_uid: 5se32jae Abstract Background A rapid increase in cases due to the SARS-CoV-2 Omicron (B.1.1.529) variant in highly vaccinated populations has raised concerns about the effectiveness of current vaccines. Methods We used a test-negative case-control design to estimate vaccine effectiveness (VE) against symptomatic disease caused by the Omicron and Delta variants in England. VE was calculated after primary immunisation with two BNT162b2 or ChAdOx1 doses, and at 2+ weeks following a BNT162b2 booster. Results Between 27 November and 06 December 2021, 581 and 56,439 eligible Omicron and Delta cases respectively were identified. There were 130,867 eligible test-negative controls. There was no effect against Omicron from 15 weeks after two ChAdOx1 doses, while VE after two BNT162b2 doses was 88.0% (95%CI: 65.9 to 95.8%) 2-9 weeks after dose 2, dropping to between 34 and 37% from 15 weeks post dose 2.From two weeks after a BNT162b2 booster, VE increased to 71.4% (95%CI: 41.8 to 86.0%) for ChAdOx1 primary course recipients and 75.5% (95%CI: 56.1 to 86.3%) for BNT162b2 primary course recipients. For cases with Delta, VE was 41.8% (95%CI: 39.4-44.1%) at 25+ weeks after two ChAdOx1 doses, increasing to 93.8% (95%CI: 93.2-94.3%) after a BNT162b2 booster. With a BNT162b2 primary course, VE was 63.5% (95%CI: 61.4 to 65.5%) 25+ weeks after dose 2, increasing to 92.6% (95%CI: 92.0-93.1%) two weeks after the booster. Conclusions Primary immunisation with two BNT162b2 or ChAdOx1 doses provided no or limited protection against symptomatic disease with the Omicron variant. Boosting with BNT162b2 following either primary course significantly increased protection. A r a p i d i n c r e a s e i n c a s e s d u e t o t h e S A R S -C o V -2 O m i c r o n ( B . 1 . 1 . 5 2 9 ) v a r i a n t i n h i g h l y v a c c i n a t e d p o p u l a t i o n s h a s r a i s e d c o n c e r n s a b o u t t h e e f f e c t i v e n e s s o f c u r r e n t v a c c i n e n . C O V I D -1 9 , O m i c r o n , D e l t a , V a c c i n e E f f e c t i v e n e s s , T e s t N e g a t i v e C a s e C o n t r o l , I m m u n i s a t i o n Introduction O n 2 6 N o v e m b e r 2 0 2 1 t h e W o r l d H e a l t h O r g a n i z a t i o n T e c h n i c a l A d v i s o r y G r o u p o n S A R S -C o V -2 V i r u s E v o l u t i o n n a m e d t h e B . 1 . 1 . 5 2 9 C O V I D -1 9 v a r i a n t , f i r s t d e t e c t e d i n B o t s w a n a a n d S o u t h A f r i c a , a s t h e O m i c r o n v a r i a n t o f c o n c e r n . ( 1 ) T h i s c l a s s i f i c a t i o n w a s b a s e d o n a r a p i d i n c r e a s e i n c o n f i r m e d S A R S -C o V -2 i n f e c t i o n i n S o u t h A f r i c a , c o i n c i d i n g w i t h a n i n c r e a s e i n d e t e c t i o n s o f t h e O m i c r o n v a r i a n t , i d e n t i f i c a t i o n o f a n u m b e r o f c o n c e r n i n g m u t a t i o n s a n d e a r l y e v i d e n c e o f a n i n c r e a s e d r i s k o f r e i n f e c t i o n i n r e c e n t l y -i n f e c t e d i n d i v i d u a l V I D -1 9 v a c c i n e s a r e h i g h l y e f f e c t i v e a g a i n s t s y m p t o m a t i c d i s e a s e a n d , m o r e s o , a g a i n s t s e v e r e d i s e a s e a n d f a t a l o u t c o m e s w i t h t h e o r i g i n a l s t r a i n a s w e l l a s t h e A l p h a v a r i a n t t h a t p r e d o m i n a t e d i n e a r l y 2 0 2 1 . ( 8 -1 4 ) M o d e s t r e d u c t i o n s i n v a c c i n e e f f e c t i v e n e s s a g a i n s t i n f e c t i o n a n d m i l d d i s e a s e h a v e b e e n o b s e r v e d w i t h B e t a a n d D e l t a v a r i a n t s , a l t h o u g h e f f e c t i v e n e s s a g a i n s t s e v e r e d i s e a s e h a s r e m a i n e d h i g h f o r a t l e a s t 6 m o n t h s a f t e r p r i m a r y i m m u n i s a t i o n w i t h t w o C O V I D -1 9 v a c c i n e d o s e s . ( 1 5 -1 8 ) W a n i n g o f p r o t e c t i o n h a s b e e n o b s e r v e d w i t h t i m e s i n c e v a c c i n a t i . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint r e g i o n ) , r i s k g r o u p s t a t u s , c l i n i c a l l y e x t r e m e l y v u l n e r a b l e s t a t u s , a n d h e a l t h / s o c i a l c a r e w o r k e r w e r e a l s o e x t r a c t e d f r o m t h e N I M S . B o o s t e r d o s e s w e r e i d e n t i f i e d a s a t h i r d d o s e g i v e n a t l e a s t 1 4 0 d a y s a f t e r a s e c o n d d o s e a n d a d m i n i s t e r e d a f t e r 1 3 S e p t e m b e r 2 0 2 1 . I n d i v i d u a l s w i t h f o u r o r m o r e d o s e s o f v a c c i n e , h e t e r o l o g o u s p r i m a r y s c h e d u l e o r f e w e r t h a n 1 9 d a y s b e t w e e n t h e i r f i r s t a n d s e c o n d d o s e w e r e e x c l u d e d . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint 3 0 2 3 S A R S - C o V - 2 T e s t i n g P C R t e s t i n g f o r S A R S C o V - 2 i n E no w d e v i c e . S A R S - C o V - 2 l a t e r a l f l o w t e s t s ( L F T ) a r e f r e e l y a v a i l a b l e t o a l l m e m b e r s o f t h e p o p u l a t i o n f o r r e g u l a r h o m e t e s t i n g . D a t a o n a l l p o s i t i v e P C R a n d L F T t e s t s , a n d o n n e g a t i v e P i l l a r 2 P C R t e s t s f r o m s y m p t o m a t i c i n d i v i d u a l s w i t h a n o n s e t d a t e a f t e r 1 6 t h O c t o b e r 2 0 2 0 w e r e e x t r a c t e d u p t o 6 t h D e c e m b e r 2 0 2 1 . I n d i v i d u a l s w h o r e p o r t e d s y m p t o m s a n d w e r e t e s t e d i n P i l l a r 2 b e t w e e n N o v e m b e r 2 7 t h a n d D e c e m b e r 3 r d 2 0 2 1 w e r e i n c l u d e d i n t h e a n a l y s i s . A n y n e g a t i v e t e s t s t a k e n w i t h i n 7 d a y s o f a p r e v i o u s n e g a t i v e t e s t , The copyright holder for this this version posted December 14, 2021. ; https://doi.org/10.1101/2021.12.14.21267615 doi: medRxiv preprint Results W i t h i n s e q u e n c e d c a s e s f r o m P i l l a r 2 t e s t i n g w h e r e S -g e n e t e s t i n g w a s d o n e t h e p r o p o r t i o n o f S g e n e n e g a t i v e t e s t s t h a t w e r e s e q u e n c e d a s O m i c r o n w a s 6 / 1 s h o w n h e r e , m o d e r a t e t o h i g h v a c c i n e e f f e c t i v e n e s s a g a i n s t m i l d i n f e c t i o n o f 7 0 -7 5 % w a s s e e n i n t h e e a r l y p e r i o d a f t e r a b o o s t e r d o s e o f B N T 1 6 2 b 2 f o l l o w i n g e i t h e r C h A d O x 1 -S o r B N T 1 6 2 b 2 a s a p r i m a r y c o u r s . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 14, 2021. ; https://doi.org/10.1101/2021.12.14.21267615 doi: medRxiv preprint T h e l a r g e s c a l e o f t e s t i n g a n d s e q u e n c i n g i n t h e U K , a s w e l l a s t h e u s e o f a n a t i o n a l v a c c i n a t i o n r e g i s t e r h a s e n a b l e d r a p i d e v a l u a t i o n o f v a c c i n e e f f e c t i v e n e s s a g a i n s t s y m p t o m a t i c i n f e c t i o n w i t h t h e O m i c r o n v a r i a n t . N e v e r t h e l e s s , t h e r e a r e s o m e l i m i t a t i o n s a n d f i n d i n g s s h o u l d b e i n t e r p r e t e d w i t h c a u t i o n . D u r i n g t h i s e a r l y p e r i o d o f c i r c u l a t i o n o f t h e n e w v a r i a n t , a l a r g e p r o p o r t i o n o f c a s e s o c c u r r e d a m o n g t r a v e l l e r s . I n d i v i d u a l s w h o r e p o r t e d t r a v e l i n t h e p r e c e d i n g t w o w e e k s w e r e e x c l u d e d f r o m t h i s a n a l y s i s , h o w e v e r , t h i s m a y n o t e x c l u d e a l l t r a v e l l e r s a n d w i l l n o t e x c l u d e c o n t a c t s o f t r a v e l l e r s . T h i s g r o u p i s l i k e l y t o h a v e d i f f e r e n t e x p o s u r e t o t h e w i d e r p o p u l a t i o n a n d m a y a l s o h a v e d i f f e r e n t l e v e l s o f v a c c i n e c o v e r a . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 14, 2021. ; https://doi.org/10.1101/2021.12.14.21267615 doi: medRxiv preprint Acknowledgements W e t h a n k t h e U K H e a l t h S e c u r i t y A g e n c y ( U K H S A ) c o v i d -1 9 D a t a S c i e n c e T e a m , U K H S A O u t b r e a k S u r v e i l l a n c e T e a m , N H S E n g l a n d , N H S D i g i t a l , a n d N H S T e s t a n d T r a c e f o r t h e i r r o l e s i n d e v e l o p i n g a n d m a n a g i n g t h e C O V I D -1 9 t e s t i n g , v a r i a n t i d e n t i f i c a t i o n a n d v a c c i n a t i o n s y s t e m s a n d d a t a s e t s a s w e l l a s r e p o r t i n g N H S v a c c i n a t o r s , N H S l a b o r a t o r i e s , U K H S A l a b o r a t o r i e s , a n d l i g h t h o u . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 14, 2021. ; https://doi.org/10.1101/2021.12.14.21267615 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 14, 2021. ; https://doi.org/10.1101/2021.12.14.21267615 doi: medRxiv preprint Table 1: Descriptive characteristics of positive and negative test results in individuals tested for SARS-CoV-2 in England for the study population C a t e g o r y O v e r a l l D e l t a O m i c r o n N e g a t i v e n % n % n % n % 1 8 7 , 8 8 7 1 0 0 5 6 , 4 3 9 3 0 . 0 5 8 1 0 . 3 1 3 0 , 8 6 7 6 9 . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 14, 2021. ; https://doi.org/10.1101/2021.12.14.21267615 doi: medRxiv preprint 1 5 4 0 -4 4 2 4 , 9 7 3 1 3 . 3 8 , 6 2 3 1 5 . 3 5 1 8 . 8 1 6 , 2 9 9 1 2 . 5 4 5 -4 9 2 0 , 2 1 7 1 0 . 8 7 , 6 2 6 1 3 . 5 5 3 9 . 1 1 2 , 5 3 8 9 . 6 5 0 -5 4 1 6 , 0 1 4 8 . 5 5 , 8 8 3 1 0 . 4 3 2 5 . 5 1 0 , 0 9 9 7 . 7 5 5 -5 9 1 2 , 3 3 4 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 14, 2021. ; https://doi.org/10.1101/2021.12.14.21267615 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 14, 2021. ; https://doi.org/10.1101/2021.12.14.21267615 doi: medRxiv preprint SARS-CoV-2 Variant of Concern who.int: World Health Organization European Centre for Disease Prevention and Control. Implications of the further emergence and spread of the SARS-CoV-2 B.1.1.529 variant of concern (Omicron) for the EU/EEA -first update 2021 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and monoclonal antibodies Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nature medicine Neutralizing Antibodies Correlate with Protection from SARS-CoV-2 in Humans during a Fishery Vessel Outbreak with a High Attack Rate Reinfection with new variants of SARS-CoV-2 after natural infection: a prospective observational cohort in 13 care homes in England. The Lancet Healthy longevity Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The Lancet Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study. The Lancet Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines in preventing SARS-CoV-2 infection among health care personnel, first responders, and other essential and frontline workerseight US locations BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. The New England journal of medicine Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK Duration of Protection of COVID-19 Vaccines Against Mild and Severe Disease Partial resistance of SARS-CoV-2 Delta variants to vaccine-elicited antibodies and convalescent sera. iScience Waning immunity of the BNT162b2 vaccine: A nationwide study from Israel Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection in a large cohort Correlation of SARS-CoV-2 Breakthrough Infections to Time-from-vaccine Effectiveness of BNT162b2 (Comirnaty, Pfizer-BioNTech) COVID-19 booster vaccine against covid-19 related symptoms in England: test negative casecontrol study Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel SARS-CoV-2 variants of concern and variants under investigation in England: Omicron VOC-21NOV-01 (B.1.1.529) update on cases, S gene target failure and risk assessment 2021