不活化ワクチン(CoronaVac) の効果(チリの調査)

//Background//---
 Currently, the epidemiological situation of SARS-CoV-2 infection in India is severe. India plays a vital role in equal vaccine distribution for the world including low-middle income countries, because their production capacity like Astrazeneca vaccine is huge. However, they urgently need to vaccinate the persons of their countries as soon as possible in order to alleviate SARS-CoV-2 pandemic in India. Therefore, distribution of vaccine to low-middle countries from India gets stack up. On the other hand, a total of 22 primarily low and middle-income counties have approved the CoronaVac vaccine (Sinovac COVID-19 vaccine) produced in China for emergency use(1). For equal distribution, evaluating the large-scale epidemiological vaccine efficacy and safety is urgently needed.
 Alejandro Jara, Eduardo A. Undurraga, Cecilia González, M.D et al. evaluate effectiveness of an inactivated SARS-CoV-2 vaccine (CoronaVac vaccine) in Chile in the large-scale(1). I hope to share a part of these contents with the global important readers.
 
//Vaccine information//---
Inactivated SARS-CoV-2 vaccine (CoronaVAc: Sinovac COVID-19 vaccine)
(Previous clinical trial)
*Phase 1-2 trials(2-4)--The vaccine was safe and immunogenic in most patient 14 days after receipt of the second dose.
*Phase 3 clinical trials in Brazil, Chile, Indonesia and Turkey
(NCT04456595, NCT04651790, NCT04508075, and NCT04582344, respectively).
--Efficacy 50.7% in Brazil, 65.3% in Indonesia, 91.3% in Turkey(5-7).
 
//Condition(1)//---
Place: Chile
Period: From 2/February, 2021 to 1/May, 2021
Participant number: 10.2 million persons
Age: 16 years old or older
 
//Result(1)//---
(Definition)
Partial immunization (≥14 days after receipt of the first dose and before receipt of the second dose)
Full immunization (≥14 days after receipt of the second dose).
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(Infection) Infection cases / Total number
Unvaccinated: 185,633 / 614,868,240
Partial immunization: 20,865 / 69,788,352 -- Efficacy 15.5%
Fully immunization: 12,286 / 91,671,797 -- Efficacy 65.9%
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(Hospitalization) Hospitalization cases / Total number
Unvaccinated: 18,034 / 620,894,706
Partial immunization: 3,370 / 70,690,796 -- Efficacy 37.4%
Fully immunization: 1,462 / 92,445,333 -- Efficacy 87.5%
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(Admission to ICU) Severe cases / Total number
Unvaccinated: 6,359 / 621,226,431
Partial immunization: 1,154 / 70,836,597 -- Efficacy 44.7%
Fully immunization: 360 / 92,622,083 -- Efficacy 90.3%
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(Death) Death cases / Total number
Unvaccinated: 2,786 / 621,426,477
Partial immunization: 847 / 70,845,187 -- Efficacy 45.7%
Fully immunization: 409 / 92,514,261 -- Efficacy 86.3%
 
//Adverse events(1)(See S1.5)//---
Headache (988), reactions at the site of injection (914), itching (333), nausea (307), fatigue (283), myalgias (278), general malaise (271), diarrhea (258), fever (200), dizziness (178), vomiting (161), urticarial reactions (144), unspecified rash (122), odynophagia (121), dyspnea (121), arthralgias (94), chills (91), erythema (84), anaphylaxis (69), and abdominal pain (56).
*():Notification per 100,000
*Serious adverse event: 2.3 per 100,000
 
//Discussion//---
 The vaccination of fully immunization (After booster dose) has higher efficacy than partly immunization cases. Therefore, immune function specific to SARS-CoV-2 could be enhanced from this epidemiological data. Furthermore, this vaccine is more effective against severe symptom like hospitalization and ICU admission. Therefore, medical burden is expected to be significantly reduced through broad vaccination. On adverse events, we need to carefully evaluate and analyze them including the serious cases.
 
//Support(1)//---
Supported by grants from the Agencia Nacional de Investigación y Desarrollo (ANID) Millennium Science Initiative Program, Millennium Nucleus Center for the Discovery of Structures in Complex Data (MIDAS) (NCN17_059, to Dr. Jara), and Millennium Initiative for Collaborative Research in Bacterial Resistance (MICROB-R) (NCN17_081, to Drs. Undurraga and Araos); the Advanced Center for Chronic Diseases, ANID Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP) (15130011, to Dr. Araos); and the Research Center for Integrated Disaster Risk Management ANID FONDAP (15110017, to Dr. Undurraga).
 
//Approval for the research protocol(1)//---
The research protocol was approved by the Comité Ético Científico Clínica Alemana Universidad del Desarrollo. The study was considered exempt from informed consent; no human health risks were identified. Research analysts are employees of the Chilean Ministry of Health; our use of data follows Chilean law 19.628 on private data protection.
 
//Gratitude(1)//---
We thank the attendees of the WHO meeting and working group for suggestions and comments; Drs. Ira Longini (University of Florida), Daniel Cohen (Tel Aviv University), Richard Peto (University of Oxford), Elizabeth Miller (Public Health England), and Myron M. Levine (University of Maryland); Drs. Catterina Ferreccio (Pontificia Universidad Católica de Chile), Ximena Aguilera (Universidad del Desarrollo), Maria T. Valenzuela (Universidad de Los Andes), Pablo Vial (Universidad del Desarrollo), Gonzalo Valdivia (Pontificia Universidad Católica de Chile), Fernando Otaiza (Ministerio de Salud), and Alvaro Erazo (Pontificia Universidad Católica de Chile), from the Chilean Covid-19 Advisory Group, for advice on the study design and interpretation of results; and Drs. José R. Zubizarreta (Harvard University) and Erika M.C. D’Agata (Brown University) for thoughtful suggestions.
 
(Reference)
(1)
Alejandro Jara, Ph.D., Eduardo A. Undurraga, Ph.D., Cecilia González, M.D., Fabio Paredes, M.Sc., Tomás Fontecilla, M.Sc., Gonzalo Jara, B.S.E., Alejandra Pizarro, M.D., Johanna Acevedo, M.S., Katherinne Leo, B.S.E., Francisco Leon, M.B.A., Carlos Sans, B.S.E., Paulina Leighton, B.S.E., Pamela Suárez, B.S.E., Heriberto García-Escorza, M.S., and Rafael Araos, M.D.
Effectiveness of an Inactivated SARS-CoV-2 Vaccine in Chile
The New England Journal of Medicine July 7, 2021
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Author Affiliations
From the Ministry of Health (A.J., C.G., F.P., T.F., G.J., A.P., J.A., K.L., F.L., C.S., P.L., P.S., H.G.-E., R.A.), Facultad de Matemáticas (A.J.) and Escuela de Gobierno (E.A.U.), Pontificia Universidad Católica de Chile, Millennium Nucleus Center for the Discovery of Structures in Complex Data (A.J.), Millennium Initiative for Collaborative Research in Bacterial Resistance (E.A.U., R.A.), the Research Center for Integrated Disaster Risk Management (E.A.U.), Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo (R.A.), and the Advanced Center for Chronic Diseases (R.A.) — all in Santiago, Chile; and the CIFAR Azrieli Global Scholars Program, CIFAR, Toronto (E.A.U.).
(2)
Gao Q, Bao L, Mao H, et al.
Development of an inactivated vaccine candidate for SARS-CoV-2.
Science 2020; 369: 77-81.
(3)
Zhang Y, Zeng G, Pan H, et al.
Safety, tolerability, and immunogenicity of an inactivated  SARS-CoV-2  vaccine  in  healthy adults  aged  18-59  years:  a  randomised, double-blind,  placebo-controlled,  phase 1/2 clinical trial.
Lancet Infect Dis 2021; 21: 181-92.
(4)
Wu Z, Hu Y, Xu M, et al.
Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised,  double-blind,  placebo-controlled,  phase  1/2  clinical  trial. 
Lancet Infect Dis 2021; 21: 803-12.
(5)
Cohen J, Moutinho S.
Third time’s the charm? Brazil scales back efficacy claims for COVID-19 vaccine from China.
Science. January 12, 2021
(https://www . sciencemag . org/  news/  2021/  01/  third - time - s - charm - brazil - scales - back - efficacy - claims - covid - 19 - vaccine - china).
(6)
Baraniuk C.
What do we know about China’s covid-19 vaccines?
BMJ 2021; 373: n912.
(7)
Sinovac.
Summary of clinical trial data of Sinovac’s COVID-19 vaccine (CoronaVac).2021.  (In  Chinese) 
(http://www . sinovacbio . com/  ?optionid=  754&auto_id=  927).