Covid-19 Living Data

Trial NCT04352608, NCT04383574
Publication Zeng G, Lancet Infect Dis, 2021

Funding: Public/non profit (National Key Research and Development Program; Beijing Science and Technology Program; Key Program of the National Natural Science Foundation of China)
Conflict of interest: Yes

Methods
	RCT
	Location : Multicenter / China Follow-up duration (months): 1
	3 mcg CoronaVac booster at 2 months (n=109) Placebo at 2 months (n=52) 3 mcg CoronaVac booster at 8 months (n=197) Placebo at 8 months (n=105)
Inclusion criteria	Adults aged 18–59 years or aged >=60 years healthy able to understand and sign the Informed Consent Form voluntarily provide legal proof of identity.
Exclusion criteria	Aged 18–59 years cohort: (1) Having traveled to or lived in Wuhan or surrounding areas or communities where confirmed cases have been reported within the previous 14 days (2) Having contact with patients who were infected with COVID-19 within the previous 14 days (3) Having contact with patients who have fever and symptoms of respiratory infections from Wuhan or surrounding areas or communities where confirmed cases have been reported within the previous 14 days (4) Having been in places such as houses, offices and classrooms where over 2 cases of fever and/or symptoms of respiratory infections have been reported within the previous 14 days (5) SARS record in self-report (6) Infection with COVID-19 recorded in self-report (7) IgG or IgM screening results were positive (8) The RT-PCR test results of throat and anal swabs were positive (9) Women who are breastfeeding, pregnant, or planning to become pregnant during the study period (10) Body mass index (BMI) ≥35 kg/m2 (11) Having a history of asthma and allergy to vaccine or vaccine ingredients and having serious adverse reactions to the vaccine such as urticaria, dyspnea and angioneurotic edema (12) Subjects with congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc. (13) Subjects with autoimmune diseases or immune deficiency/immune inhibition (14) Subjects with severe chronic diseases, severe cardiovascular diseases and hypertension, diabetes, liver and kidney diseases and malignant tumors that can not be controlled by drugs (15) Subjects with serious neurological diseases or mental diseases (16) Subjects with thyropathy or having a history of thyroidectomy, subjects with an absent or dysfunctional spleen and subjects with an absent spleen or splenectomy (17) Subjects with coagulation disorders diagnosed by a doctor or significant bruising or coagulation disorder (18) Having received the immunosuppressive therapy, cytotoxic therapy, and inhale corticosteroids in the past six months (19) Subjects with abnormal laboratory test results such as in hematology and biochemistry which are beyond the range of reference values and of clinical significance in physical examination (20) Chronic alcoholics or those having a history of drug abuse (21) Subjects who have received blood products within 3 months before vaccination with the test vaccine (22) Subjects who have received other study drugs within 30 days before vaccination with the test vaccine (23) Subjects who have received live attenuated vaccines within 14 days before vaccination with the test vaccine (24) Subjects who have received subunit or inactivated vaccines within 7 days before vaccination with the test vaccine (25) Subjects having an attack of various acute or chronic diseases within 7 days (26) Subjects with axillary temperature >37.0℃ before vaccination with the test vaccine (27) Subjects who are not suitable for participating in this clinical trial according to the investigator. Aged >=60 years cohort: (1) Travel / residence history of Wuhan city and surrounding areas or other communities with case reports within 14 days prior to the entry (2) Contact with SARS-CoV-2 infected persons within 14 days prior to the netry (3) Contact patients with fever or respiratory symptoms from Wuhan city and surrounding areas, or from communities with case reports within 14 days prior to the entry (4) Two or more cases of fever and / or respiratory symptoms in a small cantact area of subjects, such as family, office, school class or other places within 14 days prior to the entry (5) History of SARS (6) History of SARS-CoV-2 infection (7) History of asthma, allergy to vaccines or vaccine ingredients, and serious adverse reactions to vaccines, such as urticaria, dyspnea, angioneuroedema (8) Congenital malformation or developmental disorder, genetic defect, severe malnutrition, etc (9) Autoimmune disease or immunodeficiency / immunosuppression (10) Serious chronic disease, serious cardiovascular disease, hypertension and diabetes that cannot be controlled by drugs, hepatorenal disease, malignant tumor, etc (11) Serious nervous system disease or psychosis (12) Thyroid disease or history of thyroidectomy, spleenlessness, functional spleenlessness, spleenlessness or splenectomy resulting from any condition (13) Diagnosed abnormal blood coagulation function or obvious bruising or blood coagulation (14) Immunosuppressive therapy, cytotoxic therapy, inhaled corticosteroids in the past 6 months (15) Long history of alcohol or drug abuse (16) Receipt of blood products in the past 3 months (17) Receipt of other investigational drugs in the past 30 days (18) Receipt of attenuated live vaccines in the past 14 days (19) Receipt of inactivated or subunit vaccines in the past 7 days (20) Acute diseases or acute exacerbation of chronic diseases in the past 7 days (21) Axillary temperature >37.0°C (22) According to the investigator's judgment, the subject has any other factors that are not suitable for the clinical trial
Interventions
	Intervention 1 IM dose of 3 mcg CoronaVac, 2 months after primary CoronaVac schedule 1 IM dose of 3 mcg CoronaVac, 8 months after primary CoronaVac schedule
	Control 1 IM dose of adjuvant, 2 months after primary CoronaVac schedule1 IM dose of adjuvant, 8 months after primary CoronaVac schedule
Participants
	Randomized 510 participants
	Characteristics of participants Type of participants: Healthy adults N=510 228 males Children: 0 Pregnant women: 0 Immunocompromized patients: 0 Mean age: Age range: NR
	Description of participants Healthy adults and older adults without suspected or laboratory-confirmed SARS-CoV-2 infections in 2 centres in China
Primary outcome
	In the register 1) Safety indexes of adverse reactions [ Time Frame: From Day 0 to Day 28 after each dose ] Incidence of adverse reactions occured from Day 0 to Day 28 after each dose 2) Immunogenicity indexes of neutralizing-antibody seroconversion rates [ Time Frame: The 14th day /the 28th day after two doses of vaccination ] The seroconversion rate of neutralizing antibodies 14 days (emergency schedule)/28 days (routine schedule) after the two-dose vaccination.
	In the report 1) Any adverse reactions within 28 days after dose three 2) geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibodies to infectious SARS-CoV-2 28 days after the third dose
Documents available	Protocol Yes. In English Statistical plan Yes Data-sharing stated: Yes, The data will be available immediately after publication and finalisation of the completed clinical study report for at least 1 year. Data accessibility: Information on how to access supporting clinical documents is available online for adults aged 18–59 years at http://www.jshealth.com/ and for adults aged 60 years and older at http://www.hebeicdc.cn/ kygz/22506.jhtml. Researchers who provide a scientifically sound proposal will be allowed access to the de-identified individual participant data. Proposals should be sent to the corresponding authors. Yuliang Zhao: yuliang_zh1@163.com, Fengcai Zhu: jszfc@vip.sina.com, Hongjie Yu: yhj@fudan.edu.cn, Weidong Yin: yinwd@sinovac.comv
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article, two study registries, protocols, statistical analysis plans and supplementary data were used in data extraction and risk of bias assessment. The article reports the results of two studies with patients 18-59 in one study and patients 60 and over in the other. The article presented interim analyses for a study with ongoing recruitment and follow-up and reports on booster vaccines in cohorts originally included in two primary schedule trials, and thus the outcomes reported as primary in the article differ slightly from the original primary outcomes. This study was updated on November 10th 2022 after publication of results at a longer follow up.