Immunogenicity, durability, and safety of an mRNA and three platform-based COVID-19 vaccines as a third dose following two doses of CoronaVac in China: A randomised, double-blinded, placebo-controlled, phase 2 trial.

Background: More effective vaccine candidates against variants of concern as a booster dose are needed in people primed with two-dose inactivated COVID-19 vaccines. Methods: This randomised, double-blinded, investigator-initiated phase 2 trial aims to evaluate immunogenicity, durability, and safety of an mRNA vaccine candidate (RQ3013) and three other platform vaccines (an adenovirus-vectored vaccine candidate [ChAdTS-S], a recombinant protein vaccine candidate [ZR202-CoV], and an inactivated vaccine [CoronaVac]) as a booster. 250 eligible volunteers, who had received a prime two-dose CoronaVac (3 to 5 weeks apart) vaccination 100-270 days before, were randomly assigned in a 1:1:1:1:1 ratio to receive a third dose of RQ3013 (30 µg mRNA per 0.15 mL), ChAdTS-S (5×1010 viral particles per 0.5 mL), ZR202-CoV (25 µg prefusion-stabilized Spike ectodomain trimer per 0.5 mL), CoronaVac (3 µg inactivated CN02 strain of SARS-CoV-2 per 0.5 mL) or placebo (0.5 mL of 0.9% sodium chloride solution) via intramuscular injection into the upper arm at a single clinical site in Kunming, China. Participants, investigators, and immunogenicity laboratory were masked to group assignment. The primary immunogenicity outcomes were geometric mean titres (GMTs) of neutralising antibodies against live SARS-CoV-2 (wild-type, delta and omicron) virus at day 0 (before vaccination), day 7, day 14 and day 28 after vaccination, as analysed in a modified intention-to-treat (mITT) population (all participants who completed their booster doses and had at least one post-dose immunogenicity data). Secondary outcomes include T cell responses against the wild-type and omicron SARS-CoV-2 Spike protein. The primary safety outcome was incidence of adverse events within 14 days after the booster vaccination. This trial is registered with ChiCTR.org.cn, ChiCTR2200057758. Findings: Between January 1, 2022, and February 28, 2022, 235 eligible participants were enrolled and vaccinated, and the primary analysis included 234 participants. At baseline, neutralising antibodies against wild-type virus, the delta, or omicron variants were low or undetectable in all groups. After the booster vaccination, GMTs of neutralising antibodies ranged from 75.4 (95% confidence interval [CI] 61.4-92.5) in CoronaVac to 950.1 (95% CI 785.4-1149.3) in RQ3013 against live wild-type SARS-CoV-2, and from 8.1 (95% CI: 6.1-10.7) in CoronaVac to 247.0 (95% CI 194.1-314.3) in RQ3013 against the omicron variant at day 14. Immunogenicities of all heterologous regimens were superior to that of homologous regimen in neutralisation against all tested SARS-CoV-2 strains, with RQ3013 showing the highest geometric mean ratios (GMRs) of 12.6, 14.7, and 31.3 against the wild-type, the delta variant and the omicron variant compared to CoronaVac at day 14 post-vaccination, respectively. Durability analysis at day 90 showed that >90% of participants in RQ3013 and ZR202-CoV were seropositive for the omicron variant while ZR202-CoV with adjuvants containing CpG showed a slightly better durability than RQ3013. T cell responses specific to the omicron variant were similar to that of the wild-type, with RQ3013 showing the highest boosting effect. Any solicited injection site or systemic adverse events reported within 14 days after vaccination were most commonly observed in RQ3013 (47/47, 100%), followed by ZR202-CoV (46/47, 97.9%) and ChAdTS-S (43/48, 89.6%), and then CoronaVac (37/46, 80.4%) and placebo (21/47, 44.7%). More than 90% of the adverse events were grade 1 (mild) or 2 (moderate) with a typical resolution time of 3 days. No grade 4 adverse events or serious adverse events were reported by study vaccines. Interpretation: Although all study vaccines boosted neutralising antibodies with no safety concerns, RQ3013 showed much stronger cross-neutralisation and cellular responses, adding more effective vaccine candidates against the omicron variant. Funding: Yunnan Provincial Science and Technology Department China (202102AA100051 and 202003AC100010), the Double First-class University funding to Yunnan University, National Natural Science Foundation of China (81960116, 82060368 and 82170711), Yunnan Natural Science Foundation (202001AT070085), High-level Health Technical Personnel Project of Yunnan Province (H-2018102) and Spring City Plan: The High-level Talent Promotion and Training Project of Kunming.

Dynamic monitor on psychological problems of medical aid teams in the context of corona virus disease 2019: a multi-stage and multi-factor quantitative study.

BACKGROUND: To explore the psychological status and vulnerability characteristics of medical staff with the progress of the epidemic. METHODS: This study investigated the prevalence of mental problems of 2748 medical staff in four stages. The PHQ-9 (Patient Health Questionnaire), GAD-7 (Generalized Anxiety Disorder questionnaire), SSS (Somatization Symptom Checklist), Pittsburgh sleep quality index, and PCL-C (Self-rating scale for post-traumatic stress disorder) were used for the psychological evaluation, and univariate logistic standardised analysis, and multivariate logistic regression for data analysis. RESULTS: The prevalence of mental problems showed a statistically significant difference. In Stage 1, mild anxiety and mild depression reached the highest value of 41.4 and 40.72% respectively. Between 4 and 17 March that of mild depression rose from 16.07 to 26.7%, and between 17 and 26 March the prevalence of mild anxiety increased from 17.28 to 20.02%. Female, unmarried, and working in Wuhan are the risk factors of mental health of medical staff (P < 0.05). CONCLUSION: The psychological status of the medical staff has changed dynamically. Stage 1 and the latter period of Stages 2 and 3 are the high-risk stages. Female and unmarried are the dangerous characteristics of psychological vulnerability.

Two-stage mental health survey of first-line medical staff after ending COVID-19 epidemic assistance and isolation.

Facing with COVID-19 epidemic such a catastrophic health emergency, the mental health status of medical staff deserves attention. We conducted a two-stage of psychological status monitoring after the end of the assistance and 14 days of isolation, further targeted the vulnerable groups in need of intervention. The study is a cross-sectional survey on 1156 Yunnan medical staff aid to Hubei. Used Cluster sampling method to collect data at 2 time points (at the end of returning from Wuhan and the 14th day of isolation), from March 18, 2020 to April 6, 2020. Female and nurse had higher rates of depressive symptoms than male and doctors and other occupations. The proportion of female with mild and above moderate anxiety levels (22.91%, 2.61%) was higher than male (17.35%, 1.03%) (p < 0.05). Female had a better impaired sleep quality (45.06%, 17.49%) more than male (28.57%, 7.94%). Medical staff supported in Wuhan and with junior professional titles reported a higher proportion of sleep quality impairment. At the 14th isolation day stage, the proportion of nurses changed from depression to health (9.15%) and from health to depression (6.1%) better than doctors. The front-line medical staffs had suffered greater psychological pressure in the treatment process of major public health emergency. Researches on the dynamic monitor for the change of psychological status after aiding epidemic areas were still in relatively blank stage. Targeting the vulnerable characteristics of aiding medical staff is significant for effective psychological intervention and sustainable operation of health system.