Safety and immunogenicity following a homologous booster dose of CoronaVac in children and adolescents.

Data on safety and immunity elicited by a third booster dose of inactivated COVID-19 vaccine in children and adolescents are scarce. Here we conducted a study based on a double-blind, randomised, placebo-controlled phase 2 clinical trial (NCT04551547) to assess the safety and immunogenicity of a third dose of CoronaVac. In this study, 384 participants in the vaccine group were assigned to two cohorts. One received the third dose at a 10-months interval (cohort 1) and the other one at a 12-months interval (cohort 2). The primary endpoint is safety and immunogenicity following a third dose of CoronaVac. The secondary endpoint is antibody persistence following the primary two-dose schedule. Severities of local and systemic adverse reactions reported within 28 days after dose 3 were mild and moderate in both cohorts. A third dose of CoronaVac increased GMTs to 681.0 (95%CI: 545.2-850.7) in cohort 1 and 745.2 (95%CI: 577.0-962.3) in cohort 2. Seropositivity rates against the prototype were 100% on day 28 after dose 3. Seropositivity rates against the Omicron variant were 90.6% (cohort 1) and 91.5% (cohort 2). A homologous booster dose of CoronaVac is safe and induces a significant neutralising antibody levels increase in children and adolescents.

Association among resilience, post-traumatic stress disorder, and somatization in frontline healthcare workers in COVID-19: The mediating role of perceived stress

Background Frontline healthcare workers were at a high risk of infection and developing mental health problems during the outbreak of coronavirus disease 2019 (COVID-19). It is important to monitor the symptoms of post-traumatic stress disorder (PTSD) and somatization among frontline healthcare workers in China. Aim This study aimed to investigate PTSD, somatization, resilience, and perceived stress among frontline healthcare workers fighting against COVID-19 and examine the mediating effects of perceived stress on resilience in both PTSD and somatization. Methods The study was conducted from December 2021 to February 2022 through an online survey of frontline healthcare workers fighting against COVID-19. The survey included questions regarding socio-demographic information, resilience (10-item Conner–Davidson Resilience Scale, CD-RISC-10), perceived stress (14-item Perceived Stress Scale, PSS), PTSD (Checklist-Civilian Version, PCL-C), and somatization (Symptom Checklist-90). The PROCESS macro for SPSS was used to examine the mediating effects of perceived stress. Results Approximately 14.9% of healthcare workers had possible PTSD (PCL-C score of ≥ 44), and 41.04% of the workers had low resilience (CD-RISC-10 score of ≤ 25.5). Approximately 54.05% of healthcare workers were symptomatic, and 14.7% had a moderate or higher degree of somatization with sleep-related problems as the most common symptom. Perceived stress was negatively correlated with resilience (r = –0.527, p < 0.001) and positively correlated with PTSD (r = 0.505, p < 0.001) and somatization (r = 0.361, p < 0.001). In addition, perceived stress mediated the relationship between resilience and PTSD [indirect b = –0.382;bootstrapped confidence interval (CI), –0.454, –0.319] and somatization (indirect effect b = –0.159;bootstrapped CI, –0.199, –0.123). Conclusion The prevalence of PTSD and somatic symptoms indicates that the mental health of frontline healthcare workers deserves more attention. Resilience is negatively associated with PTSD and somatization, and the relationship among resilience, PTSD, and somatization is mediated by perceived stress. Strategies for reducing perceived stress and increasing resilience may help to prevent and alleviate PTSD and somatization.

Visual Social Media and Black Activism: Exploring How Using Instagram Influences Black Activism Orientation and Racial Identity Ideology Among Black Americans

During the civil unrest emphasizing the Black Lives Matter movement amid the COVID-19 pandemic, Instagram was widely adopted by activists, journalists, and the general audience to disseminate and gather information about critical social issues and protests. Through a survey sampling Black Instagram users (N = 402), this study examined how Black people?s use of Instagram and its specific features?Instagram Carousel, Instagram Live, Instagram Story, standard post, and comment section?influenced their Black activism orientation, in-app activism engagement, and Black racial identity ideology. The results indicated that, along with Instagram use, Instagram network politicalness, diversity, and authenticity are also important predictors.

Six-month follow-up of a booster dose of CoronaVac in two single-centre phase 2 clinical trials.

Determining the duration of immunity induced by booster doses of CoronaVac is crucial for informing recommendations for booster regimens and adjusting immunization strategies. In two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, immunogenicity and safety of four immunization regimens are assessed in adults aged 18 to 59 years and one immunization regimen in adults aged 60 years and older, respectively. Serious adverse events occurring within 6 months after booster doses are recorded as pre-specified secondary endpoints, geometric mean titres (GMTs) of neutralising antibodies one year after the 3-dose schedule immunization and 6 months after the booster doses are assessed as pre-specified exploratory endpoints, GMT fold-decreases in neutralization titres are assessed as post-hoc analyses. Neutralising antibody titres decline approximately 4-fold and 2.5-fold from day 28 to day 180 after third doses in adults aged 18-59 years of age and in adults aged 60 years and older, respectively. No safety concerns are identified during the follow-up period. There are increases in the magnitude and duration of humoral response with homologous booster doses of CoronaVac given 8 months after a primary two-dose immunization series, which could prolong protection and contribute to building our wall of population immunity. Trial number: NCT04352608 and NCT04383574.

Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials.

BACKGROUND: Large-scale vaccination against COVID-19 is being implemented in many countries with CoronaVac, an inactivated vaccine. We aimed to assess the immune persistence of a two-dose schedule of CoronaVac, and the immunogenicity and safety of a third dose of CoronaVac, in healthy adults aged 18 years and older. METHODS: In the first of two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, adults aged 18-59 years in Jiangsu, China, were initially allocated (1:1) into two vaccination schedule cohorts: a day 0 and day 14 vaccination cohort (cohort 1) and a day 0 and day 28 vaccination cohort (cohort 2); each cohort was randomly assigned (2:2:1) to either a 3 µg dose or 6 µg dose of CoronaVac or a placebo group. Following a protocol amendment on Dec 25, 2020, half of the participants in each cohort were allocated to receive an additional dose 28 days (window period 30 days) after the second dose, and the other half were allocated to receive a third dose 6 months (window period 60 days) after the second dose. In the other phase 2 trial, in Hebei, China, participants aged 60 years and older were assigned sequentially to receive three injections of either 1·5 µg, 3 µg, or 6 µg of vaccine or placebo, administered 28 days apart for the first two doses and 6 months (window period 90 days) apart for doses two and three. The main outcomes of the study were geometric mean titres (GMTs), geometric mean increases (GMIs), and seropositivity of neutralising antibody to SARS-CoV-2 (virus strain SARS-CoV-2/human/CHN/CN1/2020, GenBank accession number MT407649.1), as analysed in the per-protocol population (all participants who completed their assigned third dose). Our reporting is focused on the 3 µg groups, since 3 µg is the licensed formulation. The trials are registered with ClinicalTrials.gov, NCT04352608 and NCT04383574. FINDINGS: 540 (90%) of 600 participants aged 18-59 years were eligible to receive a third dose, of whom 269 (50%) received the primary third dose 2 months after the second dose (cohorts 1a-14d-2m and 2a-28d-2m) and 271 (50%) received a booster dose 8 months after the second dose (cohorts 1b-14d-8m and 2b-28d-8m). In the 3 µg group, neutralising antibody titres induced by the first two doses declined after 6 months to near or below the seropositive cutoff (GMT of 8) for cohort 1b-14d-8m (n=53; GMT 3·9 [95% CI 3·1-5·0]) and for cohort 2b-28d-8m (n=49; 6·8 [5·2-8·8]). When a booster dose was given 8 months after a second dose, GMTs assessed 14 days later increased to 137·9 (95% CI 99·9-190·4) for cohort 1b-14d-8m and 143·1 (110·8-184·7) 28 days later for cohort 2b-28d-8m. GMTs moderately increased following a primary third dose, from 21·8 (95% CI 17·3-27·6) on day 28 after the second dose to 45·8 (35·7-58·9) on day 28 after the third dose in cohort 1a-14d-2m (n=54), and from 38·1 (28·4-51·1) to 49·7 (39·9-61·9) in cohort 2a-28d-2m (n=53). GMTs had decayed to near the positive threshold by 6 months after the third dose: GMT 9·2 (95% CI 7·1-12·0) in cohort 1a-14d-2m and 10·0 (7·3-13·7) in cohort 2a-28d-2m. Similarly, in adults aged 60 years and older who received booster doses (303 [87%] of 350 participants were eligible to receive a third dose), neutralising antibody titres had declined to near or below the seropositive threshold by 6 months after the primary two-dose series. A third dose given 8 months after the second dose significantly increased neutralising antibody concentrations: GMTs increased from 42·9 (95% CI 31·0-59·4) on day 28 after the second dose to 158·5 (96·6-259·2) on day 28 following the third dose (n=29). All adverse reactions reported within 28 days after a third dose were of grade 1 or 2 severity in all vaccination cohorts. There were three serious adverse events (2%) reported by the 150 participants in cohort 1a-14d-2m, four (3%) by 150 participants from cohort 1b-14d-8m, one (1%) by 150 participants in each of cohorts 2a-28d-2m and 2b-28d-8m, and 24 (7%) by 349 participants from cohort 3-28d-8m. INTERPRETATION: A third dose of CoronaVac in adults administered 8 months after a second dose effectively recalled specific immune responses to SARS-CoV-2, which had declined substantially 6 months after two doses of CoronaVac, resulting in a remarkable increase in the concentration of antibodies and indicating that a two-dose schedule generates good immune memory, and a primary third dose given 2 months after the second dose induced slightly higher antibody titres than the primary two doses. FUNDING: National Key Research and Development Program, Beijing Science and Technology Program, and Key Program of the National Natural Science Foundation of China. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial.

BACKGROUND: A vaccine against SARS-CoV-2 for children and adolescents will play an important role in curbing the COVID-19 pandemic. Here we aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in children and adolescents aged 3-17 years. METHODS: We did a double-blind, randomised, controlled, phase 1/2 clinical trial of CoronaVac in healthy children and adolescents aged 3-17 years old at Hebei Provincial Center for Disease Control and Prevention in Zanhuang (Hebei, China). Individuals with SARS-CoV-2 exposure or infection history were excluded. Vaccine (in 0·5 mL aluminum hydroxide adjuvant) or aluminum hydroxide only (alum only, control) was given by intramuscular injection in two doses (day 0 and day 28). We did a phase 1 trial in 72 participants with an age de-escalation in three groups and dose-escalation in two blocks (1·5 µg or 3·0 µg per injection). Within each block, participants were randomly assigned (3:1) by means of block randomisation to receive CoronaVac or alum only. In phase 2, participants were randomly assigned (2:2:1) by means of block randomisation to receive either CoronaVac at 1·5 µg or 3·0 µg per dose, or alum only. All participants, investigators, and laboratory staff were masked to group allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint assessed in the per-protocol population was seroconversion rate of neutralising antibody to live SARS-CoV-2 at 28 days after the second injection. This study is ongoing and is registered with ClinicalTrials.gov, NCT04551547. FINDINGS: Between Oct 31, 2020, and Dec 2, 2020, 72 participants were enrolled in phase 1, and between Dec 12, 2020, and Dec 30, 2020, 480 participants were enrolled in phase 2. 550 participants received at least one dose of vaccine or alum only (n=71 for phase 1 and n=479 for phase 2; safety population). In the combined safety profile of phase 1 and phase 2, any adverse reactions within 28 days after injection occurred in 56 (26%) of 219 participants in the 1·5 µg group, 63 (29%) of 217 in the 3·0 µg group, and 27 (24%) of 114 in the alum-only group, without significant difference (p=0·55). Most adverse reactions were mild and moderate in severity. Injection site pain was the most frequently reported event (73 [13%] of 550 participants), occurring in 36 (16%) of 219 participants in the 1·5 µg group, 35 (16%) of 217 in the 3·0 µg group, and two (2%) in the alum-only group. As of June 12, 2021, only one serious adverse event of pneumonia has been reported in the alum-only group, which was considered unrelated to vaccination. In phase 1, seroconversion of neutralising antibody after the second dose was observed in 27 of 27 participants (100·0% [95% CI 87·2-100·0]) in the 1·5 µg group and 26 of 26 participants (100·0% [86·8-100·0]) in the 3·0 µg group, with the geometric mean titres of 55·0 (95% CI 38·9-77·9) and 117·4 (87·8-157·0). In phase 2, seroconversion was seen in 180 of 186 participants (96·8% [93·1-98·8]) in the 1·5 µg group and 180 of 180 participants (100·0% [98·0-100·0]) in the 3·0 µg group, with the geometric mean titres of 86·4 (73·9-101·0) and 142·2 (124·7-162·1). There were no detectable antibody responses in the alum-only groups. INTERPRETATION: CoronaVac was well tolerated and safe and induced humoral responses in children and adolescents aged 3-17 years. Neutralising antibody titres induced by the 3·0 µg dose were higher than those of the 1·5 µg dose. The results support the use of 3·0 µg dose with a two-immunisation schedule for further studies in children and adolescents. FUNDING: The Chinese National Key Research and Development Program and the Beijing Science and Technology Program.

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.

BACKGROUND: A vaccine against COVID-19 is urgently needed for older adults, in whom morbidity and mortality due to the disease are increased. We aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in adults aged 60 years and older. METHODS: We did a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial of CoronaVac in healthy adults aged 60 years and older in Renqiu (Hebei, China). Vaccine or placebo was given by intramuscular injection in two doses (days 0 and 28). Phase 1 comprised a dose-escalation study, in which participants were allocated to two blocks: block 1 (3 µg inactivated virus in 0·5 mL of aluminium hydroxide solution per injection) and block 2 (6 µg per injection). Within each block, participants were randomly assigned (2:1) using block randomisation to receive CoronaVac or placebo (aluminium hydroxide solution only). In phase 2, participants were randomly assigned (2:2:2:1) using block randomisation to receive either CoronaVac at 1·5 µg, 3 µg, or 6 µg per dose, or placebo. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint was seroconversion rate at 28 days after the second injection (which was assessed in all participants who had received the two doses of vaccine according to their random assignment, had antibody results available, and did not violate the trial protocol). Seroconversion was defined as a change from seronegative at baseline to seropositive for neutralising antibodies to live SARS-CoV-2 (positive cutoff titre 1/8), or a four-fold titre increase if the participant was seropositive at baseline. This study is ongoing and is registered with ClinicalTrials.gov (NCT04383574). FINDINGS: Between May 22 and June 1, 2020, 72 participants (24 in each intervention group and 24 in the placebo group; mean age 65·8 years [SD 4·8]) were enrolled in phase 1, and between June 12 and June 15, 2020, 350 participants were enrolled in phase 2 (100 in each intervention group and 50 in the placebo group; mean age 66·6 years [SD 4·7] in 349 participants). In the safety populations from both phases, any adverse reaction within 28 days after injection occurred in 20 (20%) of 100 participants in the 1·5 µg group, 25 (20%) of 125 in the 3 µg group, 27 (22%) of 123 in the 6 µg group, and 15 (21%) of 73 in the placebo group. All adverse reactions were mild or moderate in severity and injection site pain (39 [9%] of 421 participants) was the most frequently reported event. As of Aug 28, 2020, eight serious adverse events, considered unrelated to vaccination, have been reported by seven (2%) participants. In phase 1, seroconversion after the second dose was observed in 24 of 24 participants (100·0% [95% CI 85·8-100·0]) in the 3 µg group and 22 of 23 (95·7% [78·1-99·9]) in the 6 µg group. In phase 2, seroconversion was seen in 88 of 97 participants in the 1·5 µg group (90·7% [83·1-95·7]), 96 of 98 in the 3 µg group (98·0% [92·8-99·8]), and 97 of 98 (99·0% [94·5-100·0]) in the 6 µg group. There were no detectable antibody responses in the placebo groups. INTERPRETATION: CoronaVac is safe and well tolerated in older adults. Neutralising antibody titres induced by the 3 µg dose were similar to those of the 6 µg dose, and higher than those of the 1·5 µg dose, supporting the use of the 3 µg dose CoronaVac in phase 3 trials to assess protection against COVID-19. FUNDING: Chinese National Key Research and Development Program and Beijing Science and Technology Program.

A study of solid phase competition ELISA for detection of A-type foot-and-mouth disease virus antibody

In order to evaluate the immune levels of type A FMD vaccine, the monoclonal antibody (MAb) 3D9 of FMDV prepared in our lab was used as the capture antibody, and the HRP- labeled MAb 9A9 was used as the detection antibody. A solidphase competition ELISA method (SPCE) for the detection of antibody against FMDV serotype A based on monoclonal antibodies was developed and its conditions were optimized. The results showed that the optimal concentration of MAb 3D9 was 1.16 g/mL, the optimal dilution of A- type FMDV antigen was 1:5, and the optimal dilution of HRP- labeled MAb 9A9 was 1:5000. When the serum diluted at 1:32, the critical value of the assay was determined to be 35%. The method was used to detect positive serum of type A FMDV, type O FMDV, BCV, BRV, PRRSV, PCV and CSFV, respectively. The results showed that the solid phase competition ELISA method could specifically detect type A FMDV, but had no cross- reaction with other viruses. It showed that the method established in this study has strong specificity. The sensitivity test was performed on 3 positive sera samples by VNT (virus neutralization test). The sensitivity is 1:1 024, 1:256, 1:128, respectively, indicating the method has high sensitivity. Repeatability results showed the coefficient of variation of the intra-assay and inter-assay repeated tests were less than 10%, indicating that the repeatability is good. This method was used to detect 112 serum samples along with the liquid- phase blocking ELISA method (LPBE) and VNT and analyze the correlation. The results showed the correlation coefficient between the method established in this study and LPBE and VNT was 0.901 and 0.916, respectively. It indicated that this method had a good reliability and has a higher correlation with VNT. Using the SPCE and Korean Jeno A FMDV ELISA antibody detection diagnosis kitto detect 470 clinical samples (90 sheep serum samples, 170 cow serum samples and 210 pig serum samples). The results showed the overall coincidence rate between this method and Jeno kit is 90.3%, 91.8% and 89.0%, respectively, indicating that the detection result of this method is relatively accurate. This study laid a foundation for the establishment of a method for the detection of immunity level of type A foot-and-mouth disease vaccine.

Development of solid phase competition elisa for detection ofO-type foot-and-mouth disease virus antibodies based onmonoclonal antibody

In order to detect antibodies against foot-and-mouth disease virus (FMDV), the monoclonal antibody (MAb) 3D9was used as the capture antibody, and the HRP-labeled MAb 8E8 was used as the detection antibody. After several conditions wereoptimized, the critical value of the detection was established. A solid phase competition ELISA (SPCE) method for the detecting oftype O FMDV antibodies based on monoclonal antibodies. Specific, sensitive, and reproducible tests were performed on this method. The correlation between this method and the liquid phase blocking ELISA (LPBE) method and the virus neutralization test (VNT)was compared. The results showed that the optimal dilution of MAb 3D9 was 1:25 000, the optimal dilution of inactivated type OFMDV antigen was 1:3, and the optimal dilution of MAb 8E8 was 1:5 000. When the serum was diluted at 1:32, the cut-off value of the assay was determined to be 45%. The method was used to detect reference positive serum of type A FMDV, bovinecoronavirus, bovine rotavirus, porcine reproductive and respiratory syndrome virus, porcine circovirus 2, and classical swine fevervirus, respectively. The test results were all negative and no cross-reaction occurred. After testing, when the dilution of the positivestandard serum is 1:512, the method still has good sensitivity;the coefficient of variation of the intra-assay and inter-assay repeatedtests is less than 10%, indicating that the repeatability is better. The correlation between this method and VNT and LPBE was 0.923and 0.896, respectively. This study established a new method for the detection of domestic type O FMDV antibodies in China.