Physicians' mental health and coping during the COVID-19 pandemic: One year exploration.

Numerous cross-sectional studies have examined physicians' health and coping during the COVID-19 pandemic, while longitudinal studies are lacking. This study explores the progression over one year of physicians' physical and mental health symptoms, their strategies used to cope and discusses coping strategies in relation to physical and mental health symptoms. Two surveys, one year apart, exploring physicians' physical, mental health symptoms and employed coping strategies were sent to all physicians practicing in the province of Saskatchewan, Canada. A total of 117 physicians participated in Round I (RI) (November 2020-January 2021) and 158 participated in Round II (RII) (October 2021-February 2022). Physicians' physical and mental health symptoms remained high, irrespective of their specialty or COVID-19 exposure. COVID-related Post-Traumatic Stress Disorder increased by five times at RII (p = 0.02). In RI anxiety was most prevalent in middle-aged females. In RII depression was most prevalent in physicians with no children. Most coping was adaptive (90%) and included Behavioural, Relational, Cognitive, Spiritual, and Interventional strategies. After one-year, Spiritual coping decreased, while Interventional coping increased by eight times (p = 0.01). Despite efforts to employ adaptive coping, physicians' rates of psychological and physical health difficulties remained high or worsened over one year, offering insight into the protracted health care crisis, and the need for solutions. Our observation of physicians' needs for additional supports, camaraderie and appreciation as well as the shift in coping strategies as the pandemic progressed, offer targets for interventions meant to promote recovery.

Doctors' Professional and Personal Reflections: A Qualitative Exploration of Physicians' Views and Coping during the COVID-19 Pandemic.

Numerous studies have examined the risks for anxiety and depression experienced by physicians during the COVID-19 pandemic. Still, qualitative studies investigating physicians' views, and their discovered strengths, are lacking. Our research fills this gap by exploring professional and personal reflections developed by physicians from various specialties during the pandemic. Semi-structured interviews were conducted with physicians practicing in the province of Saskatchewan, Canada, during November 2020-July 2021. Thematic analysis identified core themes and subthemes. Seventeen physicians, including nine males and eight females, from eleven specialties completed the interviews. The pandemic brought to the forefront life's temporality and a new appreciation for life, work, and each other. Most physicians found strength in values, such as gratitude, solidarity, and faith in human potential, to anchor them professionally and personally. A new need for personal fulfilment and hybrid care emerged. Negative feelings of anger, fear, uncertainty, and frustration were due to overwhelming pressures, while feelings of injustice and betrayal were caused by human or system failures. The physicians' appreciation for life and family and their faith in humanity and science were the primary coping strategies used to build adaptation and overcome negative emotions. These reflections are summarized, and implications for prevention and resilience are discussed.

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.

Factors influencing the E-learning system usage during the COVID-19 pandemic in Vietnam.

The outbreak of the COVID-19 pandemic has brought forward an unprecedented situation, which has forced the educational institutes worldwide to use a propriety "online only" model for teaching and learning. Teachers have been compelled to deliver lectures online using some form of an online delivery platform. In this dilemma situation with the closure of the educational institutes, one of the very basic necessities is to ensure quality features of e-learning systems that are being used for the purpose of education delivery, particularly from the students' perspective. The objective of this study was to identify factors affecting pharmacy students' satisfaction in Vietnam during the COVID 19 pandemic. A cross-sectional survey of a consecutive sample of 1612 valid responses from students who have been in distance learning at Hanoi University of Pharmacy has been conducted. An integrated model with three main dimensions had been developed: learner's characteristics; instructor's characteristics; system, and technology. Data were collected in the field on both online and offline platforms using the questionnaire of 39 items to investigate the critical factors affecting learners' satisfaction in e-learning. The reliability of the questionnaire was measured using Cronbach's alpha on this data. Descriptive statistics, factor analysis, and multiple regression analysis were employed for data analysis. Out of 2491 questionnaires distributed, 1612 questionnaires were completed (respond rate 64.7%). The results revealed that perceived usefulness, perceived ease of use, system and technical dimension and instructors' characteristics are the critical factors affecting learners' perceived satisfaction. The perceived usefulness of the students was the most important factor affecting overall satisfaction (beta coefficient = 0.610). Multiple regression analysis yielded the four main factors explaining 59.9% of total satisfaction. The findings revealed how to improve learners' satisfaction and further strengthen their e-learning implementation. The interventional solutions on students' characteristics, instructors' characteristics and system & technical dimension should be considered and implemented to improve the quality of e-learning and students' satisfaction at Hanoi University of Pharmacy.

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.

COVID-19 Trials: Who Participates and Who Benefits?

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has disproportionately afflicted vulnerable populations. Older adults, particularly residents of nursing facilities, represent a small percentage of the population but account for 40% of mortality from COVID-19 in the United States. Racial and ethnic minority individuals, particularly Black, Hispanic, and Indigenous Americans have experienced higher rates of infection and death than the White population. Although there has been an unprecedented explosion of clinical trials to examine potential therapies, participation by members of these vulnerable communities is crucial to obtaining data generalizable to those communities. METHODS: We undertook an open-label, factorial randomized clinical trial examining hydroxychloroquine and/or azithromycin for hospitalized patients. RESULTS: Of 53 screened patients, 11 (21%) were enrolled. Ten percent (3/31) of Black patients were enrolled, 33% (7/21) of White patients, and 50% (6/12) of Hispanic patients. Forty-seven percent (25/53) of patients declined participation despite eligibility; 58%(18/31) of Black patients declined participation. Forty percent (21/53) of screened patients were from a nursing facility and 10% (2/21) were enrolled. Enrolled patients had fewer comorbidities than nonenrolled patients: median modified Charlson comorbidity score 2.0 (interquartile range 0-2.5), versus 4.0 (interquartile range 2-6) for nonenrolled patients (P = 0.006). The limitations of the study were the low participation rate and the multiple treatment trials concurrently recruiting at our institution. CONCLUSIONS: The high rate of nonparticipation in our trial of nursing facility residents and Black people emphasizes the concern that clinical trials for therapeutics may not target key populations with high mortality rates.

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.

Impacts of International Education Shifts through Transnation Stories of Three Vietnamese Doctoral Students

In response to COVID-19 global outbreaks, Canada, and Australia, two favored destinations by international students, as the contexts of this essay, have enacted different international education policies, which will be investigated through the narratives. The authors discuss transnationality and mobility as key terms in the internationalization of higher education (HE) studies through their experiences as three Vietnamese doctoral students in Canada and Australia. Transnationality is attended through a narrative of a Vietnamese returnee struggling with bringing unfamiliar knowledge of gender and sex education from the West into a Vietnamese HE context. Mobility is unpacked through stories of a Vietnamese doctoral student in Canada stuck in Vietnam due to the COVID-19 despite inviting policies from the Canadian government to international students. This experience is connected to another Vietnamese student’s experience in Australia about a controversial act to discourage international students from staying in Australia if they cannot support themselves during the pandemic. The authors’ stories are created and retold personally for introspective and contemplative reflections on what the authors have experienced and offer considerations for how transnationality and mobility in international and comparative education could be understood through education, equity, and inclusion.

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.

Semi-nested RT-PCR enables sensitive and high-throughput detection of SARS-CoV-2 based on melting analysis.

BACKGROUND: Asymptomatic transmission was found to be the Achilles' heel of the symptom-based screening strategy, necessitating the implementation of mass testing to efficiently contain the transmission of COVID-19 pandemic. However, the global shortage of molecular reagents and the low throughput of available realtime PCR facilities were major limiting factors. METHODS: A novel semi-nested and heptaplex (7-plex) RT-PCR assay with melting analysis for detection of SARS-CoV-2 RNA has been established for either individual testing or 96-sample pooled testing. The complex melting spectrum collected from the heptaplex RT-PCR amplicons was interpreted with the support of an artificial intelligence algorithm for the detection of SARS-CoV-2 RNA. The analytical and clinical performance of the semi-nested RT-PCR assay was evaluated using RNAs synthesized in-vitro and those isolated from nasopharyngeal samples. RESULTS: The LOD of the assay for individual testing was estimated to be 7.2 copies/reaction. Clinical performance evaluation indicated a sensitivity of 100% (95% CI: 97.83-100) and a specificity of 99.87% (95% CI: 99.55-99.98). More importantly, the assay supports a breakthrough sample pooling method, which makes possible parallel screening of up to 96 samples in one real-time PCR well without loss of sensitivity. As a result, up to 8,820 individual pre-amplified samples could be screened for SARS-CoV-2 within each 96-well plate of realtime PCR using the pooled testing procedure. CONCLUSION: The novel semi-nested RT-PCR assay provides a solution for highly multiplex (7-plex) detection of SARS-CoV-2 and enables 96-sample pooled detection for increase of testing capacity. .

Acceptance and Willingness to Pay for Vaccine Against Human Papilloma Virus (HPV) Among Parents of Boys in Central Vietnam.

Human papilloma virus (HPV) vaccine for adolescents was recommended as an effective prevention strategy of HPV-related cancers. In Vietnam, HPV vaccination has not been introduced to male adolescent. This study was conducted to examine the acceptance of having boys vaccinated against HPV and its underlying reasoning, and to identify their parent's willingness to pay (WTP) for HPV vaccination in central Vietnam. 785 parents of boys were directly interviewed based on a structured questionnaire. Parent's acceptability of HPV vaccine for their sons was identified by one question with response on 3-point scale (agree, don't know, and disagree). Multivariate logistic regression model was used to determine contributing factors to participant's acceptance. Bidding game method was applied to elicit WTP values for HPV vaccination with initial bid of 161.2 USD. The results showed that 49.2% of parents agreed to have their sons vaccinated against HPV. Factors that influenced parent's acceptance including son's age older than 12 years (OR = 1.5; 95% CI: 1.08-1.98); being eldest son (OR = 1.6; 95% CI: 1.13-2.19), being mother (OR = 1.4; 95% CI: 1.01-1.91), parents with high educational level (OR = 1.7; 95% CI: 1.11-2.47) and their knowledge of HPV and HPV vaccine (OR = 1.8; 95% CI: 1.23-2.65). Average WTP value for full doses of HPV vaccine was 137.5 USD, ranging between 9 USD and 188.3 USD. Parents' knowledge of HPV and HPV vaccine was the only factor affecting WTP value (Rho: 0.11; p-value: 0.030). The findings suggest a strategy be introduced for HPV vaccination to male adolescents in Vietnam.

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.

The Care of the Leukemic Patients in Times of SARS-CoV-2.

PURPOSE OF REVIEW: The spread of the novel coronavirus SARS-CoV-2 and its associated disease, coronavirus disease of 2019 (COVID-19), has significantly derailed cancer care. Patients with leukemia are more likely to have severe infection and increased rates of mortality. There is paucity of information on how to modify care of leukemia patients in view of the COVID-19 risks and imposed restrictions. We review the available literature on the impact of COVID-19 on different types of leukemia patients and suggest general as well as disease-specific recommendations on care based on available evidence. RECENT FINDINGS: The COVID-19 infection impacts leukemia subtypes in variable ways and the standard treatments for leukemia have similarly, varying effects on the course of COVID-19 infection. Useful treatment strategies include deferring treatment when possible, use of less intensive regimens, outpatient targeted oral agents requiring minimal monitoring, and prioritization of curative or life-prolonging strategies. Reducing health care encounters, rational transfusion standards, just resource allocation, and pre-emptive advance care planning will serve the interests of leukemia patients. Ad hoc modifications based on expert opinions and extrapolations of previous well-designed studies are the way forward to navigate the crisis. This should be supplanted with more rigorous prospective evidence.