Monoclonal Antibodies Specific for SARS-CoV-2 Spike Protein Suitable for Multiple Applications for Current Variants of Concern.

The global coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spawned an ongoing demand for new research reagents and interventions. Herein we describe a panel of monoclonal antibodies raised against SARS-CoV-2. One antibody showed excellent utility for immunohistochemistry, clearly staining infected cells in formalin-fixed and paraffin embedded lungs and brains of mice infected with the original and the omicron variants of SARS-CoV-2. We demonstrate the reactivity to multiple variants of concern using ELISAs and describe the use of the antibodies in indirect immunofluorescence assays, Western blots, and rapid antigen tests. Finally, we illustrate the ability of two antibodies to reduce significantly viral tissue titers in K18-hACE2 transgenic mice infected with the original and an omicron isolate of SARS-CoV-2.

Warmer ambient air temperatures reduce nasal turbinate and brain infection, but increase lung inflammation in the K18-hACE2 mouse model of COVID-19.

Warmer climatic conditions have been associated with fewer COVID-19 cases. Herein we infected K18-hACE2 mice housed at the standard animal house temperature of ∼22 °C, or at ∼31 °C, which is considered to be thermoneutral for mice. On day 2 post infection, RNA-Seq analyses showed no significant differential gene expression lung in lungs of mice housed at the two temperatures, with almost identical viral loads and type I interferon responses. There was also no significant difference in viral loads in lungs on day 5, but RNA-Seq and histology analyses showed clearly elevated inflammatory signatures and infiltrates. Thermoneutrality thus promoted lung inflammation. On day 2 post infection mice housed at 31 °C showed reduced viral loads in nasal turbinates, consistent with increased mucociliary clearance at the warmer ambient temperature. These mice also had reduced virus levels in the brain, and an ensuing amelioration of weight loss and a delay in mortality. Warmer air temperatures may thus reduce infection of the upper respiratory track and the olfactory epithelium, resulting in reduced brain infection. Potential relevance for anosmia and neurological sequelae in COVID-19 patients is discussed.

Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression.

How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified in various settings. Herein we use RNA-Seq data and bioinformatics approaches to analyze the transcriptional responses in SARS-CoV-2 infected lungs, comparing 4 human studies with the widely used K18-hACE2 mouse model, a model where hACE2 is expressed from the mouse ACE2 promoter, and a model that uses a mouse adapted virus and wild-type mice. Overlap of single copy orthologue differentially expressed genes (scoDEGs) between human and mouse studies was generally poor (≈15-35%). Rather than being associated with batch, sample treatment, viral load, lung damage or mouse model, the poor overlaps were primarily due to scoDEG expression differences between species. Importantly, analyses of immune signatures and inflammatory pathways illustrated highly significant concordances between species. As immunity and immunopathology are the focus of most studies, these mouse models can thus be viewed as representative and relevant models of COVID-19.

Evolution of ACE2-independent SARS-CoV-2 infection and mouse adaption after passage in cells expressing human and mouse ACE2.

Human ACE2 Human angiotensin converting enzyme 2 (hACE2) is the key cell attachment and entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the original SARS-CoV-2 isolates unable to use mouse ACE2 (mACE2). Herein we describe the emergence of a SARS-CoV-2 strain capable of ACE2-independent infection and the evolution of mouse-adapted (MA) SARS-CoV-2 by in vitro serial passaging of virus in co-cultures of cell lines expressing hACE2 and mACE2. MA viruses evolved with up to five amino acid changes in the spike protein, all of which have been seen in human isolates. MA viruses replicated to high titers in C57BL/6J mouse lungs and nasal turbinates and caused characteristic lung histopathology. One MA virus also evolved to replicate efficiently in several ACE2-negative cell lines across several species, including clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) ACE2 knockout cells. An E484D substitution is likely involved in ACE2-independent entry and has appeared in only ≈0.003 per cent of human isolates globally, suggesting that it provided no significant selection advantage in humans. ACE2-independent entry reveals a SARS-CoV-2 infection mechanism that has potential implications for disease pathogenesis, evolution, tropism, and perhaps also intervention development.

Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike–ACE2 Interaction

Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein receptor binding domain and directly inhibits its binding to ACE2, consistent with molecular modeling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of SARS-CoV-2 virus show that pixatimod potently inhibits the infection of monkey Vero E6 cells and physiologically relevant human bronchial epithelial cells at safe therapeutic concentrations. Pixatimod also retained broad potency against variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, in a K18-hACE2 mouse model, pixatimod significantly reduced SARS-CoV-2 viral titers in the upper respiratory tract and virus-induced weight loss. This demonstration of potent anti-SARS-CoV-2 activity tolerant to emerging mutations establishes proof-of-concept for targeting the HS–Spike protein–ACE2 axis with synthetic HS mimetics and provides a strong rationale for clinical investigation of pixatimod as a potential multimodal therapeutic for COVID-19. Heparan sulfate (HS) has emerged as a SARS-CoV-2 coreceptor. Pixatimod (PG545), an HS mimetic, inhibits infectivity of multiple variants offering a novel therapeutic approach against COVID-19.

Assessing the Impact of Traffic Emissions on Fine Particulate Matter and Carbon Monoxide Levels in Hanoi through COVID-19 Social Distancing Periods

Hanoi, Vietnam, is usually ranked as one of the most polluted capital cities in terms of air quality, particularly PM2.5. However, there has not been enough data to determine the main source of this pollution. In this study, we utilized the rare opportunity of the COVID-19 social distancing to assess the contribution of traffic emission to PM2.5 and CO levels when traffic volume was reduced significantly in Hanoi. Hourly PM2.5 and CO concentrations were measured from nine urban and traffic monitoring stations during pre-, soft, hard, and post-social distancing periods. As a result, we observed large reductions in both PM2.5 and CO levels during social distancing periods. PM2.5 concentrations were 14–18% lower during the social distancing than before this period, while CO concentrations had a more considerable drop by 28–41%. It is known that meteorological conditions can have significant effects on the ambient levels of air pollutants. To overcome this challenge, weather normalized concentrations of those pollutants were estimated using the random forest model, a machine learning technique. The normalized weather concentrations showed smaller reductions by 7–10% for PM2.5 and 5–11% for CO, indicating the presence of favorable weather conditions for better air quality during the social distancing period. In further analysis, the apparent improvement of air quality in Hanoi during the social distancing period was in line with reducing traffic emissions while emissions from coal-fired power plants remained relatively stable.

Predictors of eHealth Literacy and Its Associations with Preventive Behaviors, Fear of COVID-19, Anxiety, and Depression among Undergraduate Nursing Students: A Cross-Sectional Survey.

BACKGROUND: The infodemic has been co-existing with the COVID-19 pandemic with an influx of misinformation and conspiracy theories. These affect people's psychological health and adherence to preventive measures. eHealth literacy (eHEALS) may help with alleviating the negative effects of the infodemic. As nursing students are future healthcare professionals, having adequate eHEALS skills is critically important in their clinical practice, safety, and health. This study aimed to (1) explore the eHEALS level and its associated factors, and (2) examine the associations of eHEALS with preventive behaviors, fear of COVID-19 (FCV-19S), anxiety, and depression among nursing students. METHODS: We surveyed 1851 nursing students from 7 April to 31 May 2020 from eight universities across Vietnam. Data were collected, including demographic characteristics, eHEALS, adherence to preventive behaviors (handwashing, mask-wearing, physical distancing), FCV-19S, anxiety, and depression. Linear and logistic regression analyses were performed appropriately to examine associations. RESULTS: The mean score of eHEALS was 31.4 ± 4.4. The eHEALS score was significantly higher in males (unstandardized regression coefficient, B, 0.94; 95% confidence interval, 95% CI, 0.15 to 1.73; p = 0.019), and students with a better ability to pay for medication (B, 0.79; 95% CI, 0.39 to 1.19; p < 0.001), as compared to their counterparts. Nursing students with a higher eHEALS score had a higher likelihood of adhering to hand-washing (odds ratio, OR, 1.18; 95% CI, 1.15 to 1.22; p < 0.001), mask-wearing (OR, 1.15; 95% CI, 1.12 to 1.19; p < 0.001), keeping a safe physical distance (OR, 1.20; 95% CI, 1.15 to 1.25; p < 0.001), and had a lower anxiety likelihood (OR, 0.95; 95% CI, 0.92 to 0.99; p = 0.011). CONCLUSIONS: Nursing students who were men and with better ability to pay for medication had higher eHEALS scores. Those with higher eHEALS scores had better adherence to preventive measures, and better psychological health. The development of strategies to improve eHEALS of nursing students may contribute to COVID-19 containment and improve their psychological health.

Pathophysiological Response to SARS-CoV-2 Infection Detected by Infrared Spectroscopy Enables Rapid and Robust Saliva Screening for COVID-19.

Fourier transform infrared (FTIR) spectroscopy provides a (bio)chemical snapshot of the sample, and was recently used in proof-of-concept cohort studies for COVID-19 saliva screening. However, the biological basis of the proposed technology has not been established. To investigate underlying pathophysiology, we conducted controlled infection experiments on Vero E6 cells in vitro and K18-hACE2 mice in vivo. Potentially infectious culture supernatant or mouse oral lavage samples were treated with ethanol or 75% (v/v) Trizol for attenuated total reflectance (ATR)-FTIR spectroscopy and proteomics, or RT-PCR, respectively. Controlled infection with UV-inactivated SARS-CoV-2 elicited strong biochemical changes in culture supernatant/oral lavage despite a lack of viral replication, determined by RT-PCR or a cell culture infectious dose 50% assay. Nevertheless, SARS-CoV-2 infection induced additional FTIR signals over UV-inactivated SARS-CoV-2 infection in both cell and mouse models, which correspond to aggregated proteins and RNA. Proteomics of mouse oral lavage revealed increased secretion of kallikreins and immune modulatory proteins. Next, we collected saliva from a cohort of human participants (n = 104) and developed a predictive model for COVID-19 using partial least squares discriminant analysis. While high sensitivity of 93.48% was achieved through leave-one-out cross-validation, COVID-19 patients testing negative on follow-up on the day of saliva sampling using RT-PCR was poorly predicted in this model. Importantly, COVID-19 vaccination did not lead to the misclassification of COVID-19 negatives. Finally, meta-analysis revealed that SARS-CoV-2 induced increases in the amide II band in all arms of this study and in recently published cohort studies, indicative of altered ß-sheet structures in secreted proteins. In conclusion, this study reveals a consistent secretory pathophysiological response to SARS-CoV-2, as well as a simple, robust method for COVID-19 saliva screening using ATR-FTIR.

Negative Impacts of COVID-19 Induced Lockdown on Changes in Eating Behavior, Physical Activity, and Mental Health as Modified by Digital Healthy Diet Literacy and eHealth Literacy.

Background: The COVID-19-induced lockdown has been implemented in many countries, which may cause unfavorable changes in lifestyles and psychological health. People's health literacy, healthy diet, and lifestyles play important roles in mitigating the negative impacts of the pandemic. Therefore, we aimed to examine associations of COVID-19 lockdown with changes in eating behavior, physical activity, and mental health; and the modification effects by digital healthy diet literacy (DDL) and eHealth literacy (eHEALS) on the associations. Methods: We conducted an observational study on 4,348 outpatients from 7th April to 31st May 2020. Data from 11 hospitals in Vietnam included demographic characteristics, DDL, eHEALS, eating behavior, physical activity, and mental health changes. Multiple logistic regression and interaction models were performed to examine associations. Results: Patients under lockdown had a lower likelihood of having "unchanged or healthier" eating behavior (odds ratio, OR, 0.38; 95% confidence interval, 95%CI, 0.29 to 0.51; p < 0.001), "unchanged or more" physical activity (OR, 0.79; 95% CI, 0.69 to 0.90; p < 0.001), and "stable or better" mental health (OR, 0.77; 95% CI, 0.67 to 0.89; p < 0.001), as compared to those after lockdown. In interaction models, as compared to patients after lockdown and with the lowest DDL score, those under lockdown and with a one-score increment of DDL had a higher likelihood of having "unchanged or healthier" eating behavior (OR, 1.05; 95% CI, 1.02 to 1.07; p < 0.001), and "stable or better" mental health (OR, 1.02; 95% CI, 1.01 to 1.04; p < 0.001). Similarly, as compared to patients after lockdown and with the lowest eHEALS score, those under lockdown and with a one-score increment of eHEALS had a higher likelihood of having an "unchanged or more" physical activity (OR, 1.03; 95% CI, 1.01 to 1.05; p < 0.001). Conclusion: The COVID-19 lockdown measure could negatively affect eating behavior, physical activity, and mental health among outpatients. Better DDL and eHEALS were found to mitigate the negative impacts of the lockdown, which may empower outpatients to maintain healthy lifestyles and protect mental health. However, this study holds several limitations that may undermine the certainty of reported findings.

Two-Component Nanoparticle Vaccine Displaying Glycosylated Spike S1 Domain Induces Neutralizing Antibody Response against SARS-CoV-2 Variants.

Vaccines pave the way out of the SARS-CoV-2 pandemic. Besides mRNA and adenoviral vector vaccines, effective protein-based vaccines are needed for immunization against current and emerging variants. We have developed a virus-like particle (VLP)-based vaccine using the baculovirus-insect cell expression system, a robust production platform known for its scalability, low cost, and safety. Baculoviruses were constructed encoding SARS-CoV-2 spike proteins: full-length S, stabilized secreted S, or the S1 domain. Since subunit S only partially protected mice from SARS-CoV-2 challenge, we produced S1 for conjugation to bacteriophage AP205 VLP nanoparticles using tag/catcher technology. The S1 yield in an insect-cell bioreactor was ∼11 mg/liter, and authentic protein folding, efficient glycosylation, partial trimerization, and ACE2 receptor binding was confirmed. Prime-boost immunization of mice with 0.5 µg S1-VLPs showed potent neutralizing antibody responses against Wuhan and UK/B.1.1.7 SARS-CoV-2 variants. This two-component nanoparticle vaccine can now be further developed to help alleviate the burden of COVID-19. IMPORTANCE Vaccination is essential to reduce disease severity and limit the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Protein-based vaccines are useful to vaccinate the world population and to boost immunity against emerging variants. Their safety profiles, production costs, and vaccine storage temperatures are advantageous compared to mRNA and adenovirus vector vaccines. Here, we use the versatile and scalable baculovirus expression vector system to generate a two-component nanoparticle vaccine to induce potent neutralizing antibody responses against SARS-CoV-2 variants. These nanoparticle vaccines can be quickly adapted as boosters by simply updating the antigen component.

Impacts of Digital Healthy Diet Literacy and Healthy Eating Behavior on Fear of COVID-19, Changes in Mental Health, and Health-Related Quality of Life among Front-Line Health Care Workers.

BACKGROUND: We aimed to examine the impacts of digital healthy diet literacy (DDL) and healthy eating behaviors (HES) on fear of COVID-19, changes in mental health, and health-related quality of life (HRQoL) among front-line healthcare workers (HCWs). METHODS: An online survey was conducted at 15 hospitals and health centers from 6-19 April 2020. Data of 2299 front-line HCWs were analyzed-including socio-demographics, symptoms like COVID-19, health literacy, eHealth literacy, DDL, HES, fear of COVID-19, changes in mental health, and HRQoL. Regression models were used to examine the associations. RESULTS: HCWs with higher scores of DDL and HES had lower scores of FCoV-19S (regression coefficient, B, -0.04; 95% confidence interval, 95% CI, -0.07, -0.02; p = 0.001; and B, -0.10; 95% CI, -0.15, -0.06; p < 0.001); had a higher likelihood of stable or better mental health status (odds ratio, OR, 1.02; 95% CI, 1.00, 1.05; p = 0.029; and OR, 1.04; 95% CI, 1.00, 1.07; p = 0.043); and HRQoL (OR, 1.02; 95% CI, 1.01, 1.03; p = 0.006; and OR, 1.04; 95% CI, 1.02, 1.06; p = 0.001), respectively. CONCLUSIONS: DDL and HES were found as independent predictors of fear of COVID-19, changes in mental health status, and HRQoL in front-line HCWs. Improving DDL and HES should be considered as a strategic approach for hospitals and healthcare systems.

ACE2-lentiviral transduction enables mouse SARS-CoV-2 infection and mapping of receptor interactions.

SARS-CoV-2 uses the human ACE2 (hACE2) receptor for cell attachment and entry, with mouse ACE2 (mACE2) unable to support infection. Herein we describe an ACE2-lentivirus system and illustrate its utility for in vitro and in vivo SARS-CoV-2 infection models. Transduction of non-permissive cell lines with hACE2 imparted replication competence, and transduction with mACE2 containing N30D, N31K, F83Y and H353K substitutions, to match hACE2, rescued SARS-CoV-2 replication. Intrapulmonary hACE2-lentivirus transduction of C57BL/6J mice permitted significant virus replication in lung epithelium. RNA-Seq and histological analyses illustrated that this model involved an acute inflammatory disease followed by resolution and tissue repair, with a transcriptomic profile similar to that seen in COVID-19 patients. hACE2-lentivirus transduction of IFNAR-/- and IL-28RA-/- mouse lungs was used to illustrate that loss of type I or III interferon responses have no significant effect on virus replication. However, their importance in driving inflammatory responses was illustrated by RNA-Seq analyses. We also demonstrate the utility of the hACE2-lentivirus transduction system for vaccine evaluation in C57BL/6J mice. The ACE2-lentivirus system thus has broad application in SARS-CoV-2 research, providing a tool for both mutagenesis studies and mouse model development.

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.

Simple rapid in vitro screening method for SARS-CoV-2 anti-virals that identifies potential cytomorbidity-associated false positives.

BACKGROUND: The international SARS-CoV-2 pandemic has resulted in an urgent need to identify new anti-viral drugs for treatment of COVID-19. The initial step to identifying potential candidates usually involves in vitro screening that includes standard cytotoxicity controls. Under-appreciated is that viable, but stressed or otherwise compromised cells, can also have a reduced capacity to replicate virus. A refinement proposed herein for in vitro drug screening thus includes a simple growth assay to identify drug concentrations that cause cellular stress or "cytomorbidity", as distinct from cytotoxicity or loss of viability. METHODS: A simple rapid bioassay is presented for antiviral drug screening using Vero E6 cells and inhibition of SARS-CoV-2 induced cytopathic effects (CPE) measured using crystal violet staining. We use high cell density for cytotoxicity assays, and low cell density for cytomorbidity assays. RESULTS: The assay clearly illustrated the anti-viral activity of remdesivir, a drug known to inhibit SARS-CoV-2 replication. In contrast, nitazoxanide, oleuropein, cyclosporine A and ribavirin all showed no ability to inhibit SARS-CoV-2 CPE. Hydroxychloroquine, cyclohexamide, didemnin B, γ-mangostin and linoleic acid were all able to inhibit viral CPE at concentrations that did not induce cytotoxicity. However, these drugs inhibited CPE at concentrations that induced cytomorbidity, indicating non-specific anti-viral activity. CONCLUSIONS: We describe the methodology for a simple in vitro drug screening assay that identifies potential anti-viral drugs via their ability to inhibit SARS-CoV-2-induced CPE. The additional growth assay illustrated how several drugs display anti-viral activity at concentrations that induce cytomorbidity. For instance, hydroxychloroquine showed anti-viral activity at concentrations that slow cell growth, arguing that its purported in vitro anti-viral activity arises from non-specific impairment of cellular activities. The cytomorbidity assay can therefore rapidly exclude potential false positives.

A versatile reverse genetics platform for SARS-CoV-2 and other positive-strand RNA viruses.

The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We demonstrate that despite the large size of the viral RNA genome (~30 kb), infectious full-length cDNA is readily assembled in vitro by a circular polymerase extension reaction (CPER) methodology without the need for technically demanding intermediate steps. Overlapping cDNA fragments are generated from viral RNA and assembled together with a linker fragment containing CMV promoter into a circular full-length viral cDNA in a single reaction. Transfection of the circular cDNA into mammalian cells results in the recovery of infectious SARS-CoV-2 virus that exhibits properties comparable to the parental virus in vitro and in vivo. CPER is also used to generate insect-specific Casuarina virus with ~20 kb genome and the human pathogens Ross River virus (Alphavirus) and Norovirus (Calicivirus), with the latter from a clinical sample. Additionally, reporter and mutant viruses are generated and employed to study virus replication and virus-receptor interactions.

Targeting novel LSD1-dependent ACE2 demethylation domains inhibits SARS-CoV-2 replication.

Treatment options for COVID-19 remain limited, especially during the early or asymptomatic phase. Here, we report a novel SARS-CoV-2 viral replication mechanism mediated by interactions between ACE2 and the epigenetic eraser enzyme LSD1, and its interplay with the nuclear shuttling importin pathway. Recent studies have shown a critical role for the importin pathway in SARS-CoV-2 infection, and many RNA viruses hijack this axis to re-direct host cell transcription. LSD1 colocalized with ACE2 at the cell surface to maintain demethylated SARS-CoV-2 spike receptor-binding domain lysine 31 to promote virus-ACE2 interactions. Two newly developed peptide inhibitors competitively inhibited virus-ACE2 interactions, and demethylase access to significantly inhibit viral replication. Similar to some other predominantly plasma membrane proteins, ACE2 had a novel nuclear function: its cytoplasmic domain harbors a nuclear shuttling domain, which when demethylated by LSD1 promoted importin-α-dependent nuclear ACE2 entry following infection to regulate active transcription. A novel, cell permeable ACE2 peptide inhibitor prevented ACE2 nuclear entry, significantly inhibiting viral replication in SARS-CoV-2-infected cell lines, outperforming other LSD1 inhibitors. These data raise the prospect of post-exposure prophylaxis for SARS-CoV-2, either through repurposed LSD1 inhibitors or new, nuclear-specific ACE2 inhibitors.

Digital Healthy Diet Literacy and Self-Perceived Eating Behavior Change during COVID-19 Pandemic among Undergraduate Nursing and Medical Students: A Rapid Online Survey.

Assessing healthy diet literacy and eating behaviors is critical for identifying appropriate public health responses to the COVID-19 pandemic. We examined the psychometric properties of digital healthy diet literacy (DDL) and its association with eating behavior changes during the COVID-19 pandemic among nursing and medical students. We conducted a cross-sectional study from 7 April to 31 May 2020 at 10 public universities in Vietnam, in which 7616 undergraduate students aged 19-27 completed an online survey to assess socio-demographics, clinical parameters, health literacy (HL), DDL, and health-related behaviors. Four items of the DDL scale loaded on one component explained 71.32%, 67.12%, and 72.47% of the scale variances for the overall sample, nursing, and medical students, respectively. The DDL scale was found to have satisfactory item-scale convergent validity and criterion validity, high internal consistency reliability, and no floor or ceiling effect. Of all, 42.8% of students reported healthier eating behavior during the pandemic. A 10-index score increment of DDL was associated with 18%, 23%, and 17% increased likelihood of healthier eating behavior during the pandemic for the overall sample (OR, 1.18; 95%CI, 1.13, 1.24; p < 0.001), nursing students (OR, 1.23; 95%CI, 1.10, 1.35; p < 0.001), and medical students (OR, 1.17; 95%CI, 1.11, 1.24; p < 0.001), respectively. The DDL scale is a valid and reliable tool for the quick assessment of digital healthy diet literacy. Students with higher DDL scores had a higher likelihood of healthier eating behavior during the pandemic.

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.