Safety and immunogenicity of Nanocovax, a SARS-CoV-2 recombinant spike protein vaccine: Interim results of a double-blind, randomised controlled phase 1 and 2 trial.

Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12-71·55], 49·11 [41·26-58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2-152·3], 80·0 [50·8-125.9] and 95·1 [63·1-143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.

Associations of Underlying Health Conditions With Anxiety and Depression Among Outpatients: Modification Effects of Suspected COVID-19 Symptoms, Health-Related and Preventive Behaviors.

Objectives: We explored the association of underlying health conditions (UHC) with depression and anxiety, and examined the modification effects of suspected COVID-19 symptoms (S-COVID-19-S), health-related behaviors (HB), and preventive behaviors (PB). Methods: A cross-sectional study was conducted on 8,291 outpatients aged 18-85 years, in 18 hospitals and health centers across Vietnam from 14th February to May 31, 2020. We collected the data regarding participant's characteristics, UHC, HB, PB, depression, and anxiety. Results: People with UHC had higher odds of depression (OR = 2.11; p < 0.001) and anxiety (OR = 2.86; p < 0.001) than those without UHC. The odds of depression and anxiety were significantly higher for those with UHC and S-COVID-19-S (p < 0.001); and were significantly lower for those had UHC and interacted with "unchanged/more" physical activity (p < 0.001), or "unchanged/more" drinking (p < 0.001 for only anxiety), or "unchanged/healthier" eating (p < 0.001), and high PB score (p < 0.001), as compared to those without UHC and without S-COVID-19-S, "never/stopped/less" physical activity, drinking, "less healthy" eating, and low PB score, respectively. Conclusion: S-COVID-19-S worsen psychological health in patients with UHC. Physical activity, drinking, healthier eating, and high PB score were protective factors.

Negative Impact of Fear of COVID-19 on Health-Related Quality of Life Was Modified by Health Literacy, eHealth Literacy, and Digital Healthy Diet Literacy: A Multi-Hospital Survey.

BACKGROUND: The COVID-19 pandemic has been disseminating fear in the community, which has affected people's quality of life, especially those with health problems. Health literacy (HL), eHealth literacy (eHEAL), and digital healthy diet literacy (DDL) may have potential impacts on containing the pandemic and its consequences. This study aimed to examine the association between the fear of COVID-19 scale (FCoV-19S) and the health-related quality of life (HRQoL), and to examine the effect modification by HL, eHEAL, and DDL on this association. METHODS: A cross-sectional study was conducted in 11 hospitals across Vietnam from 7 April to 31 May 2020. Data were collected on 4348 outpatients, including demographic characteristics, HL, eHEAL, DDL, FCoV-19S, and HRQoL. Multiple linear regression and interaction models were used to explore associations. RESULTS: Patients with higher FCoV-19S scores had lower HRQoL scores (unstandardized coefficient, B = -0.78, p < 0.001). HL (B = 0.20, p < 0.001), eHEAL (B = 0.24, p < 0.001), and DDL (B = 0.20, p < 0.001) were positively associated with higher HRQoL scores. The negative impact of FCoV-19S on HRQoL was significantly attenuated by higher eHEAL score groups (from one standard deviation (SD) below the mean, B = -0.93, p < 0.001; to the mean, B = -0.85, p < 0.001; and one SD above the mean, B = -0.77, p < 0.001); and by higher DDL score groups (from one SD below the mean, B = -0.92, p < 0.001; to the mean, B = -0.82, p < 0.001; and one SD above the mean, B = -0.72, p < 0.001). CONCLUSIONS: eHealth literacy and digital healthy diet literacy could help to protect patients' health-related quality of life from the negative impact of the fear of COVID-19 during the pandemic.

Determinants of Health Literacy and Its Associations With Health-Related Behaviors, Depression Among the Older People With and Without Suspected COVID-19 Symptoms: A Multi-Institutional Study.

Purpose: We examined factors associated with health literacy among elders with and without suspected COVID-19 symptoms (S-COVID-19-S). Methods: A cross-sectional study was conducted at outpatient departments of nine hospitals and health centers 14 February-2 March 2020. Self-administered questionnaires were used to assess patient characteristics, health literacy, clinical information, health-related behaviors, and depression. A sample of 928 participants aged 60-85 years were analyzed. Results: The proportion of people with S-COVID-19-S and depression were 48.3 and 13.4%, respectively. The determinants of health literacy in groups with and without S-COVID-19-S were age, gender, education, ability to pay for medication, and social status. In people with S-COVID-19-S, one-score increment of health literacy was associated with 8% higher healthy eating likelihood (odds ratio, OR, 1.08; 95% confidence interval, 95%CI, 1.04, 1.13; p < 0.001), 4% higher physical activity likelihood (OR, 1.04; 95%CI, 1.01, 1.08, p = 0.023), and 9% lower depression likelihood (OR, 0.90; 95%CI, 0.87, 0.94; p < 0.001). These associations were not found in people without S-COVID-19-S. Conclusions: The older people with higher health literacy were less likely to have depression and had healthier behaviors in the group with S-COVD-19-S. Potential health literacy interventions are suggested to promote healthy behaviors and improve mental health outcomes to lessen the pandemic's damage in this age group.

Healthy Dietary Intake Behavior Potentially Modifies the Negative Effect of COVID-19 Lockdown on Depression: A Hospital and Health Center Survey.

Background: The COVID-19 pandemic causes a huge burden for affected countries. Several public health interventions were applied to contain the infection. However, the pandemic itself and the lockdown measure negatively influence people's lifestyles and psychological health. Purpose: To explore determinants of healthy dietary intake and depression, and examine the interaction between healthy dietary intake and COVID-19 lockdown on depression. Methods: A cross-sectional study was conducted at 18 hospitals and health centers from February 14 to May 31, 2020. Data of 8,291 outpatients were collected including patients' characteristics, clinical parameters, health literacy, healthy dietary intake (using the healthy eating score, HES), other health-related behaviors, and depression (using the patient health questionnaire, PHQ). Depression was defined as PHQ score ≥ 10. Results: Protective factors of healthy dietary intake and depression were higher education, better medication payment ability, higher social status, more physical activity, and higher health literacy, whereas older age, ever married, own business or other types of occupation, lockdown, suspected COVID-19 symptoms, and comorbidity were associated with lower HES scores and a higher depression likelihood. Besides, overweight/obesity and alcohol drinking were associated with lower HES scores. As compared with patients not under lockdown and with lowest HES score, those who were under lockdown and with lowest HES score had 10.6 times higher depression likelihood (odds ratio, OR, 10.60; 95% CI 6.88, 16.32; p < 0.001), whereas people with higher HES score had 15% lower depression likelihood (OR 0.85; 95% CI 0.82, 0.89; p < 0.001). Conclusions: Healthy dietary intake and depression were determined by several sociodemographic, clinical, and behavioral factors. Lockdown measure affects people's dietary intake behavior and depression. Importantly, healthy dietary intake potentially modifies the negative effect of lockdown on depression.

Impacts and interactions of COVID-19 response involvement, health-related behaviours, health literacy on anxiety, depression and health-related quality of life among healthcare workers: a cross-sectional study.

OBJECTIVES: We examined impacts and interactions of COVID-19 response involvement, health-related behaviours and health literacy (HL) on anxiety, depression, and health-related quality of life (HRQoL) among healthcare workers (HCWs). DESIGN: A cross-sectional study was conducted. Data were collected 6 April to 19 April 2020 using online-based, self-administered questionnaires. SETTING: 19 hospitals and health centres in Vietnam. PARTICIPANTS: 7 124 HCWs aged 21-60 years. RESULTS: The COVID-19 response-involved HCWs had higher anxiety likelihood (OR (95% CI)=4.41 (3.53 to 5.51)), higher depression likelihood (OR(95% CI)=3.31 (2.71 to 4.05)) and lower HRQoL score (coefficient, b(95% CI)=-2.14 (-2.89 to -1.38)), compared with uninvolved HCWs. Overall, HCWs who smoked or drank at unchanged/increased levels had higher likelihood of anxiety, depression and lower HRQoL scores; those with unchanged/healthier eating, unchanged/more physical activity and higher HL scores had lower likelihood of anxiety, depression and higher HRQoL scores. In comparison to uninvolved HCWs who smoked or drank at never/stopped/reduced levels, involved HCWs with unchanged/increased smoking or drinking had lower anxiety likelihood (OR(95% CI)=0.34 (0.14 to 0.83)) or (OR(95% CI)=0.26 (0.11 to 0.60)), and lower depression likelihood (OR(95% CI)=0.33 (0.15 to 0.74)) or (OR(95% CI)=0.24 (0.11 to 0.53)), respectively. In comparison with uninvolved HCWs who exercised at never/stopped/reduced levels, or with those in the lowest HL quartile, involved HCWs with unchanged/increased exercise or with one-quartile HL increment reported lower anxiety likelihood (OR(95% CI)=0.50 (0.31 to 0.81)) or (OR(95% CI)=0.57 (0.45 to 0.71)), lower depression likelihood (OR(95% CI)=0.40 (0.27 to 0.61)) or (OR(95% CI)=0.63 (0.52 to 0.76)), and higher HRQoL scores (b(95% CI)=2.08 (0.58 to 3.58)), or (b(95% CI)=1.10 (0.42 to 1.78)), respectively. CONCLUSIONS: Physical activity and higher HL were found to protect against anxiety and depression and were associated with higher HRQoL. Unexpectedly, smoking and drinking were also found to be coping behaviours. It is important to have strategic approaches that protect HCWs' mental health and HRQoL.

Health Literacy, eHealth Literacy, Adherence to Infection Prevention and Control Procedures, Lifestyle Changes, and Suspected COVID-19 Symptoms Among Health Care Workers During Lockdown: Online Survey.

BACKGROUND: The COVID-19 pandemic has imposed a heavy burden on health care systems and governments. Health literacy (HL) and eHealth literacy (as measured by the eHealth Literacy Scale [eHEALS]) are recognized as strategic public health elements but they have been underestimated during the pandemic. HL, eHEALS score, practices, lifestyles, and the health status of health care workers (HCWs) play crucial roles in containing the COVID-19 pandemic. OBJECTIVE: The aim of this study is to evaluate the psychometric properties of the eHEALS and examine associations of HL and eHEALS scores with adherence to infection prevention and control (IPC) procedures, lifestyle changes, and suspected COVID-19 symptoms among HCWs during lockdown. METHODS: We conducted an online survey of 5209 HCWs from 15 hospitals and health centers across Vietnam from April 6 to April 19, 2020. Participants answered questions related to sociodemographics, HL, eHEALS, adherence to IPC procedures, behavior changes in eating, smoking, drinking, and physical activity, and suspected COVID-19 symptoms. Principal component analysis, correlation analysis, and bivariate and multivariate linear and logistic regression models were used to validate the eHEALS and examine associations. RESULTS: The eHEALS had a satisfactory construct validity with 8 items highly loaded on one component, with factor loadings ranked from 0.78 to 0.92 explaining 76.34% of variance; satisfactory criterion validity as correlated with HL (ρ=0.42); satisfactory convergent validity with high item-scale correlations (ρ=0.80-0.84); and high internal consistency (Cronbach α=.95). HL and eHEALS scores were significantly higher in men (unstandardized coefficient [B]=1.01, 95% CI 0.57-1.45, P<.001; B=0.72, 95% CI 0.43-1.00, P<.001), those with a better ability to pay for medication (B=1.65, 95% CI 1.25-2.05, P<.001; B=0.60, 95% CI 0.34-0.86, P<.001), doctors (B=1.29, 95% CI 0.73-1.84, P<.001; B 0.56, 95% CI 0.20-0.93, P=.003), and those with epidemic containment experience (B=1.96, 95% CI 1.56-2.37, P<.001; B=0.64, 95% CI 0.38-0.91, P<.001), as compared to their counterparts, respectively. HCWs with higher HL or eHEALS scores had better adherence to IPC procedures (B=0.13, 95% CI 0.10-0.15, P<.001; B=0.22, 95% CI 0.19-0.26, P<.001), had a higher likelihood of healthy eating (odds ratio [OR] 1.04, 95% CI 1.01-1.06, P=.001; OR 1.04, 95% CI 1.02-1.07, P=.002), were more physically active (OR 1.03, 95% CI 1.02-1.03, P<.001; OR 1.04, 95% CI 1.03-1.05, P<.001), and had a lower likelihood of suspected COVID-19 symptoms (OR 0.97, 95% CI 0.96-0.98, P<.001; OR 0.96, 95% CI 0.95-0.98, P<.001), respectively. CONCLUSIONS: The eHEALS is a valid and reliable survey tool. Gender, ability to pay for medication, profession, and epidemic containment experience were independent predictors of HL and eHEALS scores. HCWs with higher HL or eHEALS scores had better adherence to IPC procedures, healthier lifestyles, and a lower likelihood of suspected COVID-19 symptoms. Efforts to improve HCWs' HL and eHEALS scores can help to contain the COVID-19 pandemic and minimize its consequences.

People with Suspected COVID-19 Symptoms Were More Likely Depressed and Had Lower Health-Related Quality of Life: The Potential Benefit of Health Literacy.

The coronavirus disease 2019 (COVID-19) epidemic affects people's health and health-related quality of life (HRQoL), especially in those who have suspected COVID-19 symptoms (S-COVID-19-S). We examined the effect of modifications of health literacy (HL) on depression and HRQoL. A cross-sectional study was conducted from 14 February to 2 March 2020. 3947 participants were recruited from outpatient departments of nine hospitals and health centers across Vietnam. The interviews were conducted using printed questionnaires including participants' characteristics, clinical parameters, health behaviors, HL, depression, and HRQoL. People with S-COVID-19-S had a higher depression likelihood (OR, 2.88; p < 0.001), lower HRQoL-score (B, -7.92; p < 0.001). In comparison to people without S-COVID-19-S and low HL, those with S-COVID-19-S and low HL had 9.70 times higher depression likelihood (p < 0.001), 20.62 lower HRQoL-score (p < 0.001), for the people without S-COVID-19-S, 1 score increment of HL resulted in 5% lower depression likelihood (p < 0.001) and 0.45 higher HRQoL-score (p < 0.001), while for those people with S-COVID-19-S, 1 score increment of HL resulted in a 4% lower depression likelihood (p = 0.004) and 0.43 higher HRQoL-score (p < 0.001). People with S-COVID-19-S had a higher depression likelihood and lower HRQoL than those without. HL shows a protective effect on depression and HRQoL during the epidemic.