Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 39
Filter
1.
Lancet Infect Dis ; 21(10): 1383-1394, 2021 10.
Article in English | MEDLINE | ID: covidwho-1621119

ABSTRACT

BACKGROUND: Given the scale of the ongoing COVID-19 pandemic, the development of vaccines based on different platforms is essential, particularly in light of emerging viral variants, the absence of information on vaccine-induced immune durability, and potential paediatric use. We aimed to assess the safety and immunogenicity of an MF59-adjuvanted subunit vaccine for COVID-19 based on recombinant SARS-CoV-2 spike glycoprotein stabilised in a pre-fusion conformation by a novel molecular clamp (spike glycoprotein-clamp [sclamp]). METHODS: We did a phase 1, double-blind, placebo-controlled, block-randomised trial of the sclamp subunit vaccine in a single clinical trial site in Brisbane, QLD, Australia. Healthy adults (aged ≥18 to ≤55 years) who had tested negative for SARS-CoV-2, reported no close contact with anyone with active or previous SARS-CoV-2 infection, and tested negative for pre-existing SARS-CoV-2 immunity were included. Participants were randomly assigned to one of five treatment groups and received two doses via intramuscular injection 28 days apart of either placebo, sclamp vaccine at 5 µg, 15 µg, or 45 µg, or one dose of sclamp vaccine at 45 µg followed by placebo. Participants and study personnel, except the dose administration personnel, were masked to treatment. The primary safety endpoints included solicited local and systemic adverse events in the 7 days after each dose and unsolicited adverse events up to 12 months after dosing. Here, data are reported up until day 57. Primary immunogenicity endpoints were antigen-specific IgG ELISA and SARS-CoV-2 microneutralisation assays assessed at 28 days after each dose. The study is ongoing and registered with ClinicalTrials.gov, NCT04495933. FINDINGS: Between June 23, 2020, and Aug 17, 2020, of 314 healthy volunteers screened, 120 were randomly assigned (n=24 per group), and 114 (95%) completed the study up to day 57 (mean age 32·5 years [SD 10·4], 65 [54%] male, 55 [46%] female). Severe solicited reactions were infrequent and occurred at similar rates in participants receiving placebo (two [8%] of 24) and the SARS-CoV-2 sclamp vaccine at any dose (three [3%] of 96). Both solicited reactions and unsolicited adverse events occurred at a similar frequency in participants receiving placebo and the SARS-CoV-2 sclamp vaccine. Solicited reactions occurred in 19 (79%) of 24 participants receiving placebo and 86 (90%) of 96 receiving the SARS-CoV-2 sclamp vaccine at any dose. Unsolicited adverse events occurred in seven (29%) of 24 participants receiving placebo and 35 (36%) of 96 participants receiving the SARS-CoV-2 sclamp vaccine at any dose. Vaccination with SARS-CoV-2 sclamp elicited a similar antigen-specific response irrespective of dose: 4 weeks after the initial dose (day 29) with 5 µg dose (geometric mean titre [GMT] 6400, 95% CI 3683-11 122), with 15 µg dose (7492, 4959-11 319), and the two 45 µg dose cohorts (8770, 5526-13 920 in the two-dose 45 µg cohort; 8793, 5570-13 881 in the single-dose 45 µg cohort); 4 weeks after the second dose (day 57) with two 5 µg doses (102 400, 64 857-161 676), with two 15 µg doses (74 725, 51 300-108 847), with two 45 µg doses (79 586, 55 430-114 268), only a single 45 µg dose (4795, 2858-8043). At day 57, 67 (99%) of 68 participants who received two doses of sclamp vaccine at any concentration produced a neutralising immune response, compared with six (25%) of 24 who received a single 45 µg dose and none of 22 who received placebo. Participants receiving two doses of sclamp vaccine elicited similar neutralisation titres, irrespective of dose: two 5 µg doses (GMT 228, 95% CI 146-356), two 15 µg doses (230, 170-312), and two 45 µg doses (239, 187-307). INTERPRETATION: This first-in-human trial shows that a subunit vaccine comprising mammalian cell culture-derived, MF59-adjuvanted, molecular clamp-stabilised recombinant spike protein elicits strong immune responses with a promising safety profile. However, the glycoprotein 41 peptide present in the clamp created HIV diagnostic assay interference, a possible barrier to widespread use highlighting the criticality of potential non-spike directed immunogenicity during vaccine development. Studies are ongoing with alternative molecular clamp trimerisation domains to ameliorate this response. FUNDING: Coalition for Epidemic Preparedness Innovations, National Health and Medical Research Council, Queensland Government, and further philanthropic sources listed in the acknowledgments.


Subject(s)
Adjuvants, Immunologic/pharmacology , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Squalene/immunology , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Australia , Female , Healthy Volunteers , Humans , Male , Pandemics/prevention & control , Polysorbates , Vaccination/adverse effects , Young Adult
2.
Gut ; 70(5): 865-875, 2021 05.
Article in English | MEDLINE | ID: covidwho-1388530

ABSTRACT

OBJECTIVE: Antitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections. DESIGN: Antibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4ß7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020. RESULTS: Rates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2-5.6) vs 37.0 (15.2-76.1), p<0.0001). CONCLUSIONS: Infliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy. TRIAL REGISTRATION NUMBER: ISRCTN45176516.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation/immunology , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , SARS-CoV-2/immunology , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies , Serologic Tests , United Kingdom/epidemiology
3.
Chin Med J (Engl) ; 134(11): 1289-1298, 2021 Apr 28.
Article in English | MEDLINE | ID: covidwho-1343718

ABSTRACT

BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 µg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 µg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-µg vaccine (n = 24), 10-µg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-µg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-µg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-µg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-µg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-µg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , COVID-19 Vaccines , Double-Blind Method , Humans , Vaccines, Inactivated/adverse effects
4.
JAMA ; 326(1): 35-45, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1318655

ABSTRACT

Importance: Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed. Objective: To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines. Design, Setting, and Participants: Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively. Interventions: Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 µg/dose; n = 13 459) and HB02 (4 µg/dose; n = 13 465) strains or an aluminum hydroxide (alum)-only control (n = 13 458); they received 2 intramuscular injections 21 days apart. Main Outcomes and Measures: The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose. Results: Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase-polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (P < .001 for both). Two severe cases of COVID-19 occurred in the alum-only group and none occurred in the vaccine groups. Adverse reactions 7 days after each injection occurred in 41.7% to 46.5% of participants in the 3 groups; serious adverse events were rare and similar in the 3 groups (WIV04: 64 [0.5%]; HB02: 59 [0.4%]; alum-only: 78 [0.6%]). Conclusions and Relevance: In this prespecified interim analysis of a randomized clinical trial, treatment of adults with either of 2 inactivated SARS-CoV-2 vaccines significantly reduced the risk of symptomatic COVID-19, and serious adverse events were rare. Data collection for final analysis is pending. Trial Registration: ClinicalTrials.gov Identifier: NCT04510207; Chinese Clinical Trial Registry: ChiCTR2000034780.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Adult , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Datasets as Topic , Double-Blind Method , Female , Humans , Injections, Intramuscular , Male , Middle Aged , Middle East , Vaccines, Inactivated/immunology
5.
Pharmacy (Basel) ; 9(1)2021 Mar 03.
Article in English | MEDLINE | ID: covidwho-1308394

ABSTRACT

Vaccinations are a safe and effective way to protect against infectious diseases. The World Health Organization estimates vaccines have saved more lives than any other interventions and every year about two to three million deaths are averted worldwide through immunization. To improve vaccination coverage, pharmacists have been increasingly involved in immunization roles in their communities-as advocates, educators, and immunizers. Community pharmacy-based vaccination services have increased both in the number of immunization providers and the number of sites where patients can receive immunizations. In Canada, health care is under provincial legislation-and so, there are distinct differences in scope of pharmacist practice across the country. Prior to the COVID-19 outbreak in early 2020, in Québec, Canada's second-largest province, pharmacists did not have the authority to administer vaccines. To help prepare pharmacists in Québec to become immunizers, we developed and deployed a series of accredited workshops. In these facilitated workshops, pharmacists were able to share best practices that may lead to providing effective vaccination services, identify common competency gaps, discuss effective patient communication skills, and determine how to target the most vulnerable population groups. Participants were also asked to evaluate the workshop. Our results indicate the evaluation was very reliable in measuring participant satisfaction (Cronbach's α = 0.94) and pharmacists commented that the workshops' learning outcomes exceeded their expectations, and the topics covered were relevant and applicable. The evaluation also asked participants to identify weaknesses of training, so future educational interventions can be planned accordingly. We believe this work will contribute to the continual growth and advancement of the pharmacy profession in Canada.

6.
Eur Respir J ; 59(1)2022 01.
Article in English | MEDLINE | ID: covidwho-1277909

ABSTRACT

BACKGROUND: Rapid tests to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell responses are urgently needed to decipher protective immunity and aid monitoring vaccine-induced immunity. METHODS: Using a rapid whole blood assay requiring a minimal amount of blood, we measured qualitatively and quantitatively SARS-CoV-2-specific CD4 T-cell responses in 31 healthcare workers using flow cytometry. RESULTS: 100% of COVID-19 convalescent participants displayed a detectable SARS-CoV-2-specific CD4 T-cell response. SARS-CoV-2-responding cells were also detected in 40.9% of participants with no COVID-19-associated symptoms or who tested PCR-negative. Phenotypic assessment indicated that, in COVID-19 convalescent participants, SARS-CoV-2 CD4 responses displayed an early differentiated memory phenotype with limited capacity to produce interferon (IFN)-γ. Conversely, in participants with no reported symptoms, SARS-CoV-2 CD4 responses were enriched in late differentiated cells, coexpressing IFN-γ and tumour necrosis factor-α and also Granzyme B. CONCLUSIONS: This proof-of-concept study presents a scalable alternative to peripheral blood mononuclear cell-based assays to enumerate and phenotype SARS-CoV-2-responding T-cells, thus representing a practical tool to monitor adaptive immunity due to natural infection or vaccine trials.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Leukocytes, Mononuclear , Phenotype , T-Lymphocytes
7.
Rheumatol Int ; 41(8): 1441-1445, 2021 08.
Article in English | MEDLINE | ID: covidwho-1274816

ABSTRACT

Patients with rheumatic and musculoskeletal (RMD) diseases may be at higher risks for COVID-19 infection. Data on the safety of the adenoviral vector-borne ChAdOx1 nCoV-19 and the heat-inactivated BBV152 Vaccines in this group are limited. 724 patients with RMD who had received at least one dose of either the ChAdOx1 or the BBV152 were audited to find out post-vaccination adverse effect (AE) or disease flares. The AE rates in patients with autoimmune rheumatic disease (AIRD) were compared with those with non-AIRD RMDs. The mean age of the cohort was 59.9 (± 10.43) years with a female (n = 581; 80.24%) majority. 523 (70.8%) had AIRD. The ChAdOx1 and the BBV152 vaccines were received by 624 (86.18%) and 77 (10.63%), respectively. 23 (3.17%) were unaware of which vaccine they had received. 238 (32.87%) of patients had at least one comorbidity. 436 (60.22%) participants [306 (59.64%) of those with AIRD and 130 (61.61%) with other RMDs] had at least one adverse effect (AE). Four patients reported flare of arthritis that resolved within 5 days. No patient had any severe AE or required hospitalization. All AEs were self-limiting. Both the ChAdOx1 and the BBV152 vaccines appear safe in RMDs. AEs do not differ between patients with AIRD or non-AIRD. This information can help negate vaccine hesitancy amongst all stakeholders.


Subject(s)
Autoimmunity , COVID-19 Vaccines/administration & dosage , Rheumatic Diseases/immunology , Aged , Autoimmunity/drug effects , COVID-19 Vaccines/adverse effects , Cross-Sectional Studies , Female , Humans , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Rheumatic Diseases/diagnosis , Rheumatic Diseases/drug therapy , Vaccination , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects
8.
Eur J Epidemiol ; 36(7): 753-762, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1265532

ABSTRACT

The Human Immunomics Initiative (HII), a joint project between the Harvard T.H. Chan School of Public Health and the Human Vaccines Project (HVP), focuses on studying immunity and the predictability of immuneresponsiveness to vaccines in aging populations. This paper describes the hypotheses and methodological approaches of this new collaborative initiative. Central to our thinking is the idea that predictors of age-related non-communicable diseases are the same as predictors for infectious diseases like COVID-19 and influenza. Fundamental to our approach is to differentiate between chronological, biological and immune age, and to use existing large-scale population cohorts. The latter provide well-typed phenotypic data on individuals' health status over time, readouts of routine clinical biochemical biomarkers to determine biological age, and bio-banked plasma samples to deep phenotype humoral immune responses as biomarkers of immune age. The first phase of the program involves 1. the exploration of biological age, humoral biomarkers of immune age, and genetics in a large multigenerational cohort, and 2. the subsequent development of models of immunity in relation to health status in a second, prospective cohort of an aging population. In the second phase, vaccine responses and efficacy of licensed COVID-19 vaccines in the presence and absence of influenza-, pneumococcal- and pertussis vaccines routinely offered to elderly, will be studied in older aged participants of prospective population-based cohorts in different geographical locations who will be selected for representing distinct biological and immune ages. The HII research program is aimed at relating vaccine responsiveness to biological and immune age, and identifying aging-related pathways crucial to enhance vaccine effectiveness in aging populations.


Subject(s)
Aging/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/diagnosis , COVID-19/prevention & control , Clinical Protocols , Female , Health Status , Humans , Immunity, Humoral , Male , Middle Aged , Phenotype , Program Development , Research Design , Young Adult
9.
BMC Public Health ; 21(1): 1103, 2021 06 09.
Article in English | MEDLINE | ID: covidwho-1262501

ABSTRACT

BACKGROUND: There are no pharmacological interventions currently available to prevent the transmission of SARS-CoV-2 or to treat COVID-19. The development of vaccines against COVID-19 is essential to contain the pandemic. we conducted a cross-sectional survey of Shanghai residents to understand residents' willingness to be vaccinated with any future COVID-19 vaccines and take measures to further improve vaccination coverage. METHODS: We conducted a cross-sectional survey using self-administered anonymous questionnaires from 1 July to 8 September 2020. The main outcome was willingness of participants, and any children or older individuals living with them, to receive future COVID-19 vaccines. Logistic regression analyses were used to explore potential factors associated with vaccination willingness. RESULTS: A total of 1071 participants were asked about their willingness to receive future COVID-19 vaccines, for themselves and at least 747 children and 375 older individuals (≥60 years old) living with them. The highest proportion of expected willingness to vaccinate was among participants (88.6%), followed by children (85.3%) and older individuals (84.0%). The main reasons for reluctance to vaccinate among 119 participants were doubts regarding vaccine safety (60.0%) and efficacy (28.8%). Participants with a self-reported history of influenza vaccination were more likely to accept COVID-19 vaccines for themselves [adjusted odds ratio (OR) = 1.83; 95% confidence interval (CI): 1.19-2.82], their children (adjusted OR = 2.08; 95%CI: 1.30-3.33), and older individuals in their household (adjusted OR = 2.12; 95%CI: 1.14-3.99). Participants with older individuals in their families were less willing to vaccinate themselves (adjusted OR = 0.59; 95%CI: 0.40-0.87) and their children (adjusted OR = 0.58; 95%CI: 0.38-0.89). CONCLUSIONS: Participants were more reluctant to accept COVID-19 vaccines for older individuals living with them. The presence of older individuals in the home also affected willingness of participants and their children to be vaccinated.


Subject(s)
COVID-19 , Influenza Vaccines , Vaccines , COVID-19 Vaccines , Child , China/epidemiology , Cross-Sectional Studies , Humans , Middle Aged , SARS-CoV-2 , Vaccination
10.
N Engl J Med ; 385(3): 239-250, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1246454

ABSTRACT

BACKGROUND: Until very recently, vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had not been authorized for emergency use in persons younger than 16 years of age. Safe, effective vaccines are needed to protect this population, facilitate in-person learning and socialization, and contribute to herd immunity. METHODS: In this ongoing multinational, placebo-controlled, observer-blinded trial, we randomly assigned participants in a 1:1 ratio to receive two injections, 21 days apart, of 30 µg of BNT162b2 or placebo. Noninferiority of the immune response to BNT162b2 in 12-to-15-year-old participants as compared with that in 16-to-25-year-old participants was an immunogenicity objective. Safety (reactogenicity and adverse events) and efficacy against confirmed coronavirus disease 2019 (Covid-19; onset, ≥7 days after dose 2) in the 12-to-15-year-old cohort were assessed. RESULTS: Overall, 2260 adolescents 12 to 15 years of age received injections; 1131 received BNT162b2, and 1129 received placebo. As has been found in other age groups, BNT162b2 had a favorable safety and side-effect profile, with mainly transient mild-to-moderate reactogenicity (predominantly injection-site pain [in 79 to 86% of participants], fatigue [in 60 to 66%], and headache [in 55 to 65%]); there were no vaccine-related serious adverse events and few overall severe adverse events. The geometric mean ratio of SARS-CoV-2 50% neutralizing titers after dose 2 in 12-to-15-year-old participants relative to 16-to-25-year-old participants was 1.76 (95% confidence interval [CI], 1.47 to 2.10), which met the noninferiority criterion of a lower boundary of the two-sided 95% confidence interval greater than 0.67 and indicated a greater response in the 12-to-15-year-old cohort. Among participants without evidence of previous SARS-CoV-2 infection, no Covid-19 cases with an onset of 7 or more days after dose 2 were noted among BNT162b2 recipients, and 16 cases occurred among placebo recipients. The observed vaccine efficacy was 100% (95% CI, 75.3 to 100). CONCLUSIONS: The BNT162b2 vaccine in 12-to-15-year-old recipients had a favorable safety profile, produced a greater immune response than in young adults, and was highly effective against Covid-19. (Funded by BioNTech and Pfizer; C4591001 ClinicalTrials.gov number, NCT04368728.).


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Adolescent , Adult , Age Factors , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Child , Female , Humans , Immunoglobulin G/blood , Injections, Intramuscular/adverse effects , Male , Pain/etiology , Treatment Outcome , Young Adult
11.
BMC Public Health ; 21(1): 998, 2021 05 27.
Article in English | MEDLINE | ID: covidwho-1244916

ABSTRACT

BACKGROUND: COVID-19 was first detected in Lebanon on February 21, 2020; it reached its peak in January 2021, with a total number of 418,448 confirmed cases and 5380 deaths (until March 15, 2021). Gaining insight into factors regarding willingness or refusal for vaccination might guide our goals in raising the awareness and target efforts to increase acceptance of the COVID-19 vaccine and maximize the uptake. Therefore, this study aims to assess the intent to receive the COVID-19 vaccine among Lebanese adults and the factors associated with vaccine refusal. METHODS: We conducted a cross-sectional study during November-December 2020 among Lebanese adults from all Lebanese regions using a survey tool with closed-ended questions that included sociodemographic data and questions about vaccine hesitancy, knowledge, attitude, practice, and fear of COVID-19. We used the snowball technique to collect the data because of the COVID-19 imposed lockdown. RESULTS: Of the 579 participants, 21.4% were willing to receive the vaccine, 40.9% refused, and the remainder were unsure of their response. More vaccine hesitancy (adjusted odds ratio (aOR) = 1.06; 95% CI 1.03-1.09) was significantly associated with more odds of disagreeing/ strongly disagreeing on receiving the COVID-19 vaccine compared to being neutral. More vaccine hesitancy (aOR = 0.95; 95% CI 0.91-0.99), female gender compared to males (aOR = 0.53; 95% CI 0.32-0.87), and being married compared to single (aOR = 0.53; 95% CI 0.29-0.98) were significantly associated with lower odds of agreeing/strongly agreeing on receiving the COVID-19 vaccine compared to being neutral. CONCLUSION: Overall, our findings revealed a high percentage of people (40%) who strongly disagreed with receiving the vaccine, mainly females, married participants, and those who have a general vaccine hesitancy. Moreover, no significant association was found with knowledge, attitude, or prevention practice regarding COVID-19. Targeted efforts are necessary to increase acceptance of a COVID-19 vaccine among the Lebanese population to control the COVID-19 pandemic. Further studies with a larger sample size are warranted to validate our results and provide better insights into the underlying reasons for refusing vaccination.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Attitude , Communicable Disease Control , Cross-Sectional Studies , Female , Humans , Lebanon , Male , Pandemics , SARS-CoV-2 , Vaccination
12.
JAMA ; 326(1): 35-45, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1242692

ABSTRACT

Importance: Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed. Objective: To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines. Design, Setting, and Participants: Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively. Interventions: Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 µg/dose; n = 13 459) and HB02 (4 µg/dose; n = 13 465) strains or an aluminum hydroxide (alum)-only control (n = 13 458); they received 2 intramuscular injections 21 days apart. Main Outcomes and Measures: The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose. Results: Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase-polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (P < .001 for both). Two severe cases of COVID-19 occurred in the alum-only group and none occurred in the vaccine groups. Adverse reactions 7 days after each injection occurred in 41.7% to 46.5% of participants in the 3 groups; serious adverse events were rare and similar in the 3 groups (WIV04: 64 [0.5%]; HB02: 59 [0.4%]; alum-only: 78 [0.6%]). Conclusions and Relevance: In this prespecified interim analysis of a randomized clinical trial, treatment of adults with either of 2 inactivated SARS-CoV-2 vaccines significantly reduced the risk of symptomatic COVID-19, and serious adverse events were rare. Data collection for final analysis is pending. Trial Registration: ClinicalTrials.gov Identifier: NCT04510207; Chinese Clinical Trial Registry: ChiCTR2000034780.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Adult , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Datasets as Topic , Double-Blind Method , Female , Humans , Injections, Intramuscular , Male , Middle Aged , Middle East , Vaccines, Inactivated/immunology
13.
Medicina (Kaunas) ; 57(5)2021 Apr 30.
Article in English | MEDLINE | ID: covidwho-1217097

ABSTRACT

Background and objectives: The whole world is spending an extraordinary effort by implementing various measures to control and prevent the COVID-19 pandemic. The effectiveness of the preventive measures is greatly influenced by the public's knowledge, attitudes, and practices (KAP) towards the disease. In this study, KAP values and some characteristic features of people recovered from COVID-19 were determined by conducting a questionnaire survey. Materials and Methods: The questionnaire survey was conducted between 1 and 10 January 2021 on people who recovered from COVID-19 in a total of 150 different locations in Turkey. The questionnaire consisted of 46 questions: 14 for determining demographic and some characteristic features of the participants, and 32 for determining their knowledge, attitudes, and practices. The data obtained were evaluated using descriptive statistics, chi-squared tests, t-tests, and one-way analysis of variance (ANOVA). Results: It was determined that 63% of the participants had at least one chronic illness, 3.9% suffered from the disease twice, and 45.2% changed their smoking habits. The average knowledge score of the participants about COVID-19 was calculated as 10.25 (SD = 2.37; range 0-15). The participants were found to have a high level of knowledge about the symptoms and prevention methods in general, and positive changes in post-illness attitudes and behaviors. However, there was a great instability regarding the drugs and vaccines used in the treatment of COVID-19. Conclusions: This was the first study carried out in Turkey to determine knowledge, attitudes, practices, and some characteristic features of people who recovered from COVID-19. It was suggested that health authorities in the country need to develop more effective strategies and policies to find out permanent solutions in order to control and prevent the COVID-19 pandemic by taking into account the concerns of the public, particularly with regards to the drugs used in the treatment and vaccination.


Subject(s)
COVID-19 , Pandemics , Cross-Sectional Studies , Health Knowledge, Attitudes, Practice , Humans , SARS-CoV-2 , Surveys and Questionnaires , Turkey
14.
Diabetes Metab Syndr ; 15(3): 987-992, 2021.
Article in English | MEDLINE | ID: covidwho-1213148

ABSTRACT

BACKGROUND AND AIMS: The success of the COVID-19 vaccination program is dependent on people's knowledge and attitude regarding the vaccination program. Higher vaccine acceptance can be ensured by strengthening the facilitators and limiting the barriers being observed among the general population. MATERIAL AND METHODS: Indexed study is a cross-sectional web-based survey using a pre-validated questionnaire to assess knowledge, barriers and facilitators of COVID-19 vaccine and vaccination programme administered on adults across India using a Google online survey platform. RESULTS: A total of 1294 responses (age: 38.02 ± 13.34 years) were collected. Most of the participants had limited knowledge regarding the eligibility of vaccines in vulnerable population groups such as people with allergies (57.89%) and immune-compromised patients (62.98%), pregnant and lactating women (41.89%) and patients with chronic illness (34.78%). Older participants (>45 years) were more willing to take the COVID-19 vaccine (p < 0.001) as they believed the vaccine is not harmful and considered it as societal responsibility. Younger participants (<45 years) and those residing in urban settings raised concerns on the availability of the vaccine and authenticity of the vaccine (p < 0.001). CONCLUSION: There is a scope for improvement in people's knowledge regarding COVID-19 vaccine and the vaccination programme by addressing the barriers and facilitators which can improve the participants' turnover at vaccination centres.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Communication Barriers , Health Knowledge, Attitudes, Practice , Health Literacy , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/psychology , Cross-Sectional Studies , Female , Health Literacy/organization & administration , Health Literacy/statistics & numerical data , Humans , India/epidemiology , Male , Middle Aged , Patient Acceptance of Health Care/psychology , Patient Acceptance of Health Care/statistics & numerical data , Pregnancy , Preventive Health Services/organization & administration , SARS-CoV-2/immunology , Surveys and Questionnaires , Vaccination/psychology , Vaccination/statistics & numerical data , Young Adult
15.
J Parkinsons Dis ; 11(3): 1057-1065, 2021.
Article in English | MEDLINE | ID: covidwho-1211799

ABSTRACT

BACKGROUND: Patients with Parkinson's disease (PD) are at higher risk of vaccine-preventable respiratory infections. However, advanced, homebound individuals may have less access to vaccinations. In light of COVID-19, understanding barriers to vaccination in PD may inform strategies to increase vaccine uptake. OBJECTIVE: To identify influenza and pneumococcal vaccination rates, including barriers and facilitators to vaccination, among homebound and ambulatory individuals with PD and related disorders. METHODS: Cross-sectional US-based study among individuals with PD, aged > 65 years, stratified as homebound or ambulatory. Participants completed semi-structured interviews on vaccination rates and barriers, and healthcare utilization. RESULTS: Among 143 participants, 9.8% had missed all influenza vaccinations in the past 5 years, and 32.2% lacked any pneumococcal vaccination, with no between-group differences. Homebound participants (n = 41) reported difficulty traveling to clinic (p < 0.01) as a vaccination barrier, and despite similar outpatient visit frequencies, had more frequent emergency department visits (31.7% vs. 9.8%, p < 0.01) and hospitalizations (14.6% vs. 2.9%, p = 0.03). Vaccine hesitancy was reported in 35% of participants, vaccine refusal in 19%, and 13.3% reported unvaccinated household members, with no between-group differences. Nearly 13% thought providers recommended against vaccines for PD patients, and 31.5% were unsure of vaccine recommendations in PD. CONCLUSION: Among a sample of homebound and ambulatory people with PD, many lack age-appropriate immunizations despite ample healthcare utilization. Many participants were unsure whether healthcare providers recommend vaccinations for people with PD. In light of COVID-19, neurologist reinforcement that vaccinations are indicated, safe, and recommended may be beneficial.


Subject(s)
Facilities and Services Utilization/statistics & numerical data , Health Knowledge, Attitudes, Practice , Health Services Accessibility/statistics & numerical data , Parkinson Disease , Patient Acceptance of Health Care/statistics & numerical data , Vaccination/statistics & numerical data , Aged , Aged, 80 and over , COVID-19/prevention & control , Cross-Sectional Studies , Female , Humans , Influenza Vaccines , Male , Mobility Limitation , Pneumococcal Vaccines , United States
16.
Lancet ; 397(10286): 1725-1735, 2021 05 08.
Article in English | MEDLINE | ID: covidwho-1201329

ABSTRACT

BACKGROUND: BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK from December, 2020. We aimed to determine the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in a cohort of health-care workers undergoing regular asymptomatic testing. METHODS: The SIREN study is a prospective cohort study among staff (aged ≥18 years) working in publicly-funded hospitals in the UK. Participants were assigned into either the positive cohort (antibody positive or history of infection [indicated by previous positivity of antibody or PCR tests]) or the negative cohort (antibody negative with no previous positive test) at the beginning of the follow-up period. Baseline risk factors were collected at enrolment, symptom status was collected every 2 weeks, and vaccination status was collected through linkage to the National Immunisations Management System and questionnaires. Participants had fortnightly asymptomatic SARS-CoV-2 PCR testing and monthly antibody testing, and all tests (including symptomatic testing) outside SIREN were captured. Data cutoff for this analysis was Feb 5, 2021. The follow-up period was Dec 7, 2020, to Feb 5, 2021. The primary outcomes were vaccinated participants (binary ever vacinated variable; indicated by at least one vaccine dose recorded by at least one of the two vaccination data sources) for the vaccine coverage analysis and SARS-CoV-2 infection confirmed by a PCR test for the vaccine effectiveness analysis. We did a mixed-effect logistic regression analysis to identify factors associated with vaccine coverage. We used a piecewise exponential hazard mixed-effects model (shared frailty-type model) using a Poisson distribution to calculate hazard ratios to compare time-to-infection in unvaccinated and vaccinated participants and estimate the impact of the BNT162b2 vaccine on all PCR-positive infections (asymptomatic and symptomatic). This study is registered with ISRCTN, number ISRCTN11041050, and is ongoing. FINDINGS: 23 324 participants from 104 sites (all in England) met the inclusion criteria for this analysis and were enrolled. Included participants had a median age of 46·1 years (IQR 36·0-54·1) and 19 692 (84%) were female; 8203 (35%) were assigned to the positive cohort at the start of the analysis period, and 15 121 (65%) assigned to the negative cohort. Total follow-up time was 2 calendar months and 1 106 905 person-days (396 318 vaccinated and 710 587 unvaccinated). Vaccine coverage was 89% on Feb 5, 2021, 94% of whom had BNT162b2 vaccine. Significantly lower coverage was associated with previous infection, gender, age, ethnicity, job role, and Index of Multiple Deprivation score. During follow-up, there were 977 new infections in the unvaccinated cohort, an incidence density of 14 infections per 10 000 person-days; the vaccinated cohort had 71 new infections 21 days or more after their first dose (incidence density of eight infections per 10 000 person-days) and nine infections 7 days after the second dose (incidence density four infections per 10 000 person-days). In the unvaccinated cohort, 543 (56%) participants had typical COVID-19 symptoms and 140 (14%) were asymptomatic on or 14 days before their PCR positive test date, compared with 29 (36%) with typical COVID-19 symptoms and 15 (19%) asymptomatic in the vaccinated cohort. A single dose of BNT162b2 vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. INTERPRETATION: Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort was vaccinated when the dominant variant in circulation was B1.1.7 and shows effectiveness against this variant. FUNDING: Public Health England, UK Department of Health and Social Care, and the National Institute for Health Research.


Subject(s)
COVID-19 Vaccines/supply & distribution , Health Personnel , Occupational Diseases/prevention & control , Occupational Exposure/prevention & control , RNA, Messenger , COVID-19 Vaccines/administration & dosage , Cohort Studies , England , Humans , Prospective Studies , Treatment Outcome
17.
N Engl J Med ; 384(24): 2273-2282, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1196904

ABSTRACT

BACKGROUND: Many pregnant persons in the United States are receiving messenger RNA (mRNA) coronavirus disease 2019 (Covid-19) vaccines, but data are limited on their safety in pregnancy. METHODS: From December 14, 2020, to February 28, 2021, we used data from the "v-safe after vaccination health checker" surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS) to characterize the initial safety of mRNA Covid-19 vaccines in pregnant persons. RESULTS: A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases). CONCLUSIONS: Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.


Subject(s)
COVID-19 Vaccines/adverse effects , Pregnancy , Abortion, Spontaneous/epidemiology , Adolescent , Adult , Adverse Drug Reaction Reporting Systems , COVID-19 Vaccines/immunology , Female , Humans , Infant, Newborn , Infant, Small for Gestational Age , Middle Aged , Premature Birth/epidemiology , Public Health Surveillance/methods , Registries , United States/epidemiology , Vaccines, Synthetic/adverse effects , Young Adult
18.
Trials ; 22(1): 276, 2021 Apr 13.
Article in English | MEDLINE | ID: covidwho-1183569

ABSTRACT

OBJECTIVES: The primary objective is to evaluate the efficacy of an inactivated and aluminium hydroxide adsorbed SARS-CoV-2 vaccine (Sinovac, China) in voluntary participants after 14 days of the second dose against RT-PCR confirmed symptomatic COVID-19 cases. The secondary objectives include evaluating the efficacy after at least one dose of the vaccine against RT-PCR confirmed symptomatic COVID-19 cases; the efficacy of two doses of the vaccine on the rates of hospitalization and death; the safety of the vaccine including adverse reactions up to one year after the 2nd dose of vaccination; and the immunogenicity of the vaccine and its duration up to 120 days. TRIAL DESIGN: This is a phase III, randomized, double-blind, placebo-controlled case driven clinical trial to assess the efficacy and safety of the vaccine. The study is planned to be carried out within two separate cohorts in voluntary participants aged between 18-59 years old. The first cohort includes healthcare professionals actively working in healthcare units, who are assumed to have higher risk of acquiring COVID-19, and the second cohort includes other immunocompetent subjects in the same age group, who are at a regular risk for COVID-19 disease. In Cohort 1, healthcare professionals will be randomized to receive two intramuscular doses of investigational product or the placebo in a 1:1 ratio and they will be monitored for 12 months by active surveillance of COVID-19. In Cohort 2, immunocompetent subjects will be randomized to receive vaccine or the placebo in a 2:1 ratio. PARTICIPANTS: Healthcare professionals of both genders, including medical doctors, nurses, cleaners, hospital technicians, and administrative personnel who work in any department of a healthcare unit and immunocompetent individuals of both genders are included. Pregnant (confirmed by positive beta-hCG test) and breastfeeding women as well as those intending to become pregnant within three months after vaccination are excluded. Other exclusion criteria include history of COVID-19 test positivity (PCR or immunoglobulin test results), any form of immunosuppressive therapy including corticosteroids within 6 months, history of bleeding disorders, asplenia, and administration of any form of immunoglobulins or blood products within 3 months. Exclusion criteria for the second dose include any serious adverse events related with the vaccine, anaphylaxis or hypersensitivity after vaccination, or any confirmed or suspected autoimmune or immunosuppressive disease (including HIV infection). Participants are only included after signing the voluntary informed consent form, ensuring cooperation in visits, undergoing screening for evaluation, and conforming to all the inclusion and exclusion criteria. All clinical sites are located in Turkey. INTERVENTION AND COMPARATOR: The vaccine was manufactured by Sinovac Research & Development Co., Ltd. It is a preparation made from a novel coronavirus (strain CZ02) grown in the kidney cell cultures (Vero Cell) of the African green monkey and contains inactivated SARS-CoV-2 virus, aluminium hydroxide, disodium hydrogen phosphate, sodium dihydrogen phosphate, and sodium chloride. A dose of 0.5 mL contains 600 SU of SARS-CoV-2 virus antigen. The placebo contains aluminium hydroxide, disodium hydrogen phosphate, sodium dihydrogen phosphate, and sodium chloride (0.5mL/dose). Scheduled visits and additional unscheduled weekly visits will be performed for the first 13 weeks and neutralizing antibody test, IgG test, T-Cell activation test, pregnancy test, and RT-PCR tests along with total antibody test will be performed. Adverse events and serious adverse events during the follow-up will be recorded on diary cards. Diary cards will collect information on the timing and severity of COVID-19 symptoms and solicited adverse events recorded by the subjects during one-year follow-up period. All serious adverse events will be managed and necessary treatment will be ensured according to the local regulations. All serious adverse events following vaccination will be reported to the ethics committee, the Ministry of Health, and the study sponsor within 24 hours of detection. MAIN OUTCOMES: The primary efficacy endpoint is the incidence of symptomatic cases of COVID-19 disease confirmed by RT-PCR two weeks after the second dose of vaccination. Secondary efficacy endpoints are the incidence of hospitalization/mortality rates among one or two dose regimens, duration of immunogenicity rates up to 120 days, the seroconversion rate, the seropositivity rate, neutralizing antibody titer, and IgG levels 14 days after each dose of vaccination. The primary safety endpoint is the severity and frequency of local and systemic adverse reactions during the period of one week after vaccination. The study would be terminated if more than 15% of the subjects have grade ≥3 adverse events related to vaccination including local reactions. RANDOMISATION: Eligible subjects will be randomized at their Study Day 0 to two study groups using an Interactive Web Response System (IWRS; developed by Omega CRO, Ankara, Turkey) in both risk groups. The IWRS system customizes the randomization algorithm. After enrolment in the study, each participant will be randomly assigned to either of the two treatment arms at a ratio of 1:1 in the high-risk group and at a ratio of 2:1 in the normal risk group. Each enrolled participant will be assigned to a code and will receive the treatment labelled with the code. BLINDING (MASKING): The trial is a double-blind study to avoid introducing bias. The blinding may be broken by the investigator in the event of a medical emergency in which knowledge of the identity of the study vaccine is critical for management of the subject's immediate treatment. The Data and Safety Monitoring Board is to be contacted in case of breaking the blinding for a study object. The blood samples will be taken from both placebo and vaccinated groups, in order not to break the blinding. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The study is planned to be carried out with two separate cohorts. The Cohort 1 includes healthcare professionals working in healthcare units and the Cohort 2 consists of immunocompetent subjects having normal risk for COVID-19 disease. The Cohort 2 will be initiated after the evaluation of the interim safety report of the Cohort 1 by the Data and Safety Monitoring Board. Both cohorts will be followed-up via RT-PCR to confirm symptomatic COVID-19 cases. If the clinical efficacy of the vaccine is shown in the Cohort 1 or 2, the subjects randomized into the placebo arm will also be vaccinated. In the Cohort 1, 588 subjects should be included in both arms with the assumption that the risk of infection with COVID-19 will be 5% for the placebo arm and 2% for the vaccine arm in the high-risk group. Considering 10% of drop-out rate and 5% of seropositivity or PCR positivity at baseline, 680 subjects should be screened at both arms of the Cohort 1. Group sample sizes of 7545 SARS-CoV-2 vaccine and 3773 placebo suits at a two-sided 95% confidence interval for the difference in population proportions with a width equal to 1.0%, when the estimated incidence rate for vaccinated group is 1.0% and the estimated incidence rate for placebo group is 2.0%. Drop-out rate is assumed to be 10% and seropositivity or PCR positivity at baseline is assumed to be 5%; accordingly, 13000 participants are needed to be enrolled totally in both cohorts. The remaining 11640 subjects will be screened in the Cohort 2 and eligible subjects will be randomized at a ratio of 2:1. TRIAL STATUS: Protocol version 6.0 - 15 October 2020. Recruitment started on 15.09.2020 and is expected to end on February 2022. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04582344 . Registered 8 October 2020 FULL PROTOCOL: The full protocol of the trial is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Animals , COVID-19 Vaccines/adverse effects , China , Chlorocebus aethiops , Clinical Trials, Phase III as Topic , Double-Blind Method , Female , Humans , Male , Pregnancy , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome , Vero Cells
19.
Lancet ; 397(10277): 881-891, 2021 03 06.
Article in English | MEDLINE | ID: covidwho-1174543

ABSTRACT

BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunization Schedule , Immunization, Secondary , Adolescent , Adult , Aged , Antibody Formation , Asymptomatic Infections , COVID-19 Vaccines/adverse effects , Humans , Middle Aged , Randomized Controlled Trials as Topic , SARS-CoV-2/immunology , Young Adult
20.
Pharm Pract (Granada) ; 19(1): 2276, 2021.
Article in English | MEDLINE | ID: covidwho-1173087

ABSTRACT

BACKGROUND: COVID-19 vaccine development is proceeding at an unprecedented pace. Once COVID-19 vaccines become widely available, it will be necessary to maximize public vaccine acceptance and coverage. OBJECTIVE: This research aimed to analyze the predictors of COVID-19 vaccine acceptance in Russia. METHODS: A cross-sectional online survey was conducted among Russian adults from September 26th to November 9th, 2020. Predictors of the intent to take up COVID-19 vaccination were explored using logistic regression. RESULTS: Out of 876 participants, 365 (41.7%) would be willing to receive the vaccine if it became available. Acceptance increased for a vaccine with verified safety and effectiveness (63.2%). Intention to receive the COVID-19 vaccine was relatively higher among males (aOR=2.37, 95% CI 1.41-4.00), people with lower monthly income (aOR=2.94, 95%CI 1.32-6.57), and with positive trust in the healthcare system (aOR=2.73, 95% CI 1.76-4.24). The Russian people were more likely to accept the COVID-19 vaccine if they believed that the vaccine reduces the risk of virus infection (aOR=8.80, 95%CI 5.21-14.87) or relieves the complications of the disease (aOR=10.46, 95%CI 6.09-17.96). Other barriers such as being unconcerned about side-effects (aOR=1.65, 95%CI 1.03-2.65) and the effectiveness and safety of the vaccination (aOR=2.55, 95%CI 1.60-4.08), also affected acceptance. CONCLUSIONS: The study showed the usefulness of the health belief model constructs in understanding the COVID-19 vaccination acceptance rate in the Russian population. This rate was influenced by sociodemographic and health-related characteristics, and health beliefs. These findings might help guide future efforts for policymakers and stakeholders to improve vaccination rates by enhancing trust in the healthcare system.

SELECTION OF CITATIONS
SEARCH DETAIL