A randomized clinical trial of a booster dose with low versus standard dose of AZD1222 in adult after 2 doses of inactivated vaccines

BackgroundImmunogenicity of inactivated SARS-CoV-2 vaccine has waning antibody over time. With the emergence of the SARS-CoV-2 delta variant, which requires higher neutralizing antibody to prevent infection, a booster dose is needed. ObjectiveTo evaluate immunogenicity and reactogenicity of standard- versus low-dose ChAdOx1 nCoV-19 vaccine booster after CoronaVac in healthy adults. MethodsA double-blinded, randomized, controlled trial of adult, aged 18-59 years, with completion of 2-dose CoronaVac at 21-28 days apart for more than 2 months was conducted. Participants were randomized to receive AZD1222 (Oxford/AstraZeneca) intramuscularly; standard dose (SD, 5x1010 viral particles) or low dose (LD, 2.5x1010 viral particles). Surrogate virus neutralization test (sVNT) against wild type and delta variant, and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG) were compared as geometric mean ratio (GMR) at day 14 and 90 between LD and SD arms. ResultsFrom July-August 2021, 422 adults with median age of 44 (IQR 36-51) years were enrolled. The median interval from CoronaVac to AZD1222 booster was 77 (IQR 64-95) days. At baseline, geometric means (GMs) of sVNT against delta variant and anti-S-RBD IgG were 18.1%inhibition (95%CI 16.4-20.0) and 111.5 (105.1-118.3) BAU/ml. GMs of sVNT against delta variant and anti-S-RBD IgG in SD were 95.6%inhibition (95%CI 94.3-97.0) and 1975.1 (1841.7-2118.2) BAU/ml at day 14, and 89.4%inhibition (86.4-92.4) and 938.6 (859.9-1024.4) BAU/ml at day 90, respectively. GMRs of sVNT against delta variant and anti-S-RBD IgG in LD compared to SD were 1.00 (95%CI 0.98-1.02) and 0.84 (0.76-0.93) at day 14, and 0.98 (0.94-1.03) and 0.89 (0.79-1.00) at day 90, respectively. LD recipients had significantly lower rate of fever (6.8%vs25.0%) and myalgia (51.9%vs70.7%) compared to SD. ConclusionHalf-dose AZD1222 booster after 2-dose inactivated SARS-CoV-2 vaccination had non-inferior immunogenicity, yet lower systemic reactogenicity. Fractional low-dose AZD1222 booster should be considered especially in resource-constrained settings. Highlights- Low dose AZD1222 could boost comparable immunity to standard dose in healthy adult who completed 2 doses of inactivated SARS-CoV-2 vaccines. - Less reactogenicity occurred in low-dose AZD1222 booster than standard-dose recipients. Thai Clinical Trials Registry (thaiclinicaltrials.org): TCTR20210722003

Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac

BackgroundCurrently, booster dose is needed after 2 doses of inactivated COVID-19 vaccine. With limited resource and shortage of COVID-19 vaccine, intradermal(ID) administration might be a potential dose-sparing strategy. ObjectiveTo determine antibody response and reactogenicity of ID ChAdOx1 nCoV-19 vaccine(AZD1222,Oxford/AstraZeneca) as a booster dose after completion of 2-dose CoronaVac(SV) in healthy adult. MethodsThis is a prospective cohort study of adult aged 18-59 years who received 2-dose SV at 14-35 days apart for more than 2 months. Participants received ID AZD1222 at fractional low dose(1x1010 viral particles,0.1ml). Antibody responses were evaluated by surrogate virus neutralization test(sVNT) against wild type and delta variant and anti-spike-receptor-binding-domain immunoglobulin G(anti-S-RBD IgG) at prior, day14 or 28, and day90 post booster. Solicited reactogenicity was collected during 7 days post-booster. Primary endpoint was the differences of sVNT against delta strain [≥]80%inhibition at day14 and 90 compared with the parallel cohort study of 0.5-ml intramuscular(IM) route. ResultsFrom August2021, 100 adults with median(IQR) age of 46(41-52) years participated. At baseline, geometric means(GMs) of sVNT against delta strain prior to booster were 22.4%inhibition(95%CI 18.7-26.9) and of anti-S-RBD IgG were 109.3(95.4-125.1)BAU/ml. GMs of sVNT against delta strain were 92.9%inhibition(95%CI 87.7-98.3) at day14 and 73.1%inhibition(66.7-80.2) at day90 post ID booster. The differences of proportion of participants with sVNT to delta strain[≥]80%inhibition in ID recipients versus IM were +4.2%(95%CI-2.0to10.5) at day14, and -37.3%(-54.2to-20.3) at day90. Anti-S-RBD IgG GMs were 2037.1(95%CI1770.9-2343.2) at day14 and 744.6(650.1-852.9) BAU/ml at day90, respectively. Geometric mean ratios(GMRs) of anti-S-RBD IgG were 0.99(0.83-1.20) at day14, and 0.82(0.66-1.02) at day90. Only 18% reported feverish, compared with 37% of IM(p=0.003). Only 18% reported feverish, compared with 37% of IM(p=0.003). Common reactogenicity was erythema(55%) at injection site while 7% reported blister. ConclusionLow-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity. HighlightsO_LIIntradermal AZD1222 booster vaccine gave comparable short-term immunogenicity but lower 90-day immunogenicity with conventional intramuscular vaccine. C_LIO_LILower systemic but higher local reactogenicity was found in intradermal AZD1222 booster vaccine. C_LIO_LIBlister and pruritus could be seen after intradermal AZD1222 booster vaccine. C_LI

Seroprevalence of Hospital Staff in Province with Zero COVID-19 cases

BACKGROUNDCOVID-19 seroprevalence data has been scarce, especially in less developed countries with a relatively low infection rate. METHODSA locally developed rapid immunoglobulin M (IgM) / immunoglobulin G (IgG) test kit was used for screening hospital staff in Ranong hospital which located in a province with zero COVID-19 prevalence in Thailand from April 17 to May 17, 2020. A total of 844 participants were tested; 82 of which were tested twice with one month apart. (Thai Clinical Trials Registry: TCTR20200426002) RESULTSOverall, 0.8% of the participants (7 of 844) had positive IgM, none had positive IgG. Female staff seemed to have higher IgM seropositive than male staff (1.0% vs. 0.5%). None of the participants with a history of travel to the high-risk area or a history of close contact with PCR-confirmed COVID-19 case had developed antibodies against SARS-CoV-2. Among 844 staff, 811 had no symptom and six of them developed IgM seropositive (0.7%) while 33 had minor symptoms and only one of them developed IgM seropositive (3.0%). No association between IgM antibody against SARS-CoV-2 status and gender, history of travel to a high-risk area, history of close contact with PCR-confirmed COVID-19 case, history of close contact with suspected COVID-19 case, presence of symptoms within 14 days, or previous PCR status was found. None of the hospital staff developed IgG against SARS-CoV-2. CONCLUSIONCOVID-19 antibody test could detect a substantial number of hospital staffs who could be potential silent spreaders in a province with zero COVID-19 cases. Antibody testing should be encouraged for mass screening, especially in asymptomatic healthcare workers. TRIAL REGISTRATIONThis study was approved by the Institutional Review Board of Chulalongkorn University (IRB No.236/63) and the Institutional Review Board of Ranong Hospital. (Thai Clinical Trials Registry: TCTR20200426002) FUNDINGNone.

COVID-19 Antibody in Thai Community Hospitals

BackgroundCOVID-19 seroprevalence data has been scarce, especially in less developed countries with a relatively low infection rate. MethodsA locally developed rapid IgM/IgG test kit was used for screening hospital staff and patients who required procedural treatment or surgery in 52 hospitals in Thailand from April 8 to June 26, 2020. A total of 857 participants were tested--675 were hospital staff and 182 were pre-procedural patients. (Thai Clinical Trials Registry: TCTR20200426002) ResultsOverall, 5.5% of the participants (47 of 857) had positive immunoglobulin M (IgM), 0.2% (2 of 857) had positive immunoglobulin G (IgG) and IgM. Hospitals located in the Central part of Thailand had the highest IgM seroprevalence (11.9%). Preprocedural patients had a higher rate of positive IgM than the hospital staff (12.1% vs. 3.7%). Participants with present upper respiratory tract symptoms had a higher rate of positive IgM than those without (9.6% vs. 4.5%). Three quarters (80.5%, 690 of 857) of the participants were asymptomatic, of which, 31 had positive IgM (4.5%) which consisted of 20 of 566 healthcare workers (3.5%) and 11 of 124 preprocedural patients (8.9%). ConclusionsCOVID-19 antibody test could detect a substantial number of potential silent spreaders in Thai community hospitals. Antibody testing should be encouraged for mass screening, especially in asymptomatic individuals.