Changing Severity and Epidemiology of Adults Hospitalized With Coronavirus Disease 2019 (COVID-19) in the United States After Introduction of COVID-19 Vaccines, March 2021-August 2022.

INTRODUCTION: Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies. METHODS: Among adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed. RESULTS: Among 9825 patients, median (interquartile range [IQR]) age was 60 years (47-72), 47% were women, and 21% non-Hispanic Black. From the Alpha-predominant period (Mar-Jul 2021; N = 1312) to the Omicron BA.4/BA.5 sublineage-predominant period (Jun-Aug 2022; N = 1307): the percentage of patients who had ≥4 categories of underlying medical conditions increased from 11% to 21%; those vaccinated with at least a primary COVID-19 vaccine series increased from 7% to 67%; those ≥75 years old increased from 11% to 33%; those who did not receive any supplemental oxygen increased from 18% to 42%. Median (IQR) highest C-reactive protein and D-dimer concentration decreased from 42.0 mg/L (9.9-122.0) to 11.5 mg/L (2.7-42.8) and 3.1 mcg/mL (0.8-640.0) to 1.0 mcg/mL (0.5-2.2), respectively. In-hospital death peaked at 12% in the Delta-predominant period and declined to 4% during the BA.4/BA.5-predominant period. CONCLUSIONS: Compared to adults hospitalized during early COVID-19 variant periods, those hospitalized during Omicron-variant COVID-19 were older, had multiple co-morbidities, were more likely to be vaccinated, and less likely to experience severe respiratory disease, systemic inflammation, coagulopathy, and death.

Expression and purification of MERS-CoV envelope protein, an essential viroporin, using the baculovirus expression system.

Background and Objectives: The causative agent of Middle East Respiratory Syndrome (MERS) is a zoonotic Coronavirus (MERS-CoV) identified in Saudi Arabia in 2012. The envelope (E) protein of MERS-CoV is a small viral protein which plays several essential roles during virus replication. To facilitate study of the structure and function of the E protein, recombinant MERS-CoV E protein was expressed using the baculovirus expression system. Materials and Methods: A recombinant E open reading frame including an 8-histidine tag at the amino terminus was designed and cloned into a baculovirus transfer vector. Following construction of a recombinant virus insect cells were infected and the expression of the E protein assessed by SDS-PAGE and Western blotting. Results: Recombinant E protein, tagged at the N-terminus with a polyhistidine sequence, with a molecular mass of 10.18 kD was identified by Western blotting with an anti-His antibody. Following large scale infection E protein was released by detergent mediated lysis of infected cells and purified by Immobilized Metal Ion Affinity Chromatography (IMAC). Conclusion: Purified full length recombinant MERS-CoV E protein can be isolated by IMAC and is suitable for further functional, biophysical or immunological studies.

Protection of mRNA vaccines against hospitalized COVID-19 in adults over the first year following authorization in the United States.

BACKGROUND: COVID-19 mRNA vaccines were authorized in the United States in December 2020. Although vaccine effectiveness (VE) against mild infection declines markedly after several months, limited understanding exists on the long-term durability of protection against COVID-19-associated hospitalization. METHODS: Case control analysis of adults (≥18 years) hospitalized at 21 hospitals in 18 states March 11 - December 15, 2021, including COVID-19 case patients and RT-PCR-negative controls. We included adults who were unvaccinated or vaccinated with two doses of a mRNA vaccine before the date of illness onset. VE over time was assessed using logistic regression comparing odds of vaccination in cases versus controls, adjusting for confounders. Models included dichotomous time (<180 vs ≥180 days since dose two) and continuous time modeled using restricted cubic splines. RESULTS: 10,078 patients were included, 4906 cases (23% vaccinated) and 5172 controls (62% vaccinated). Median age was 60 years (IQR 46-70), 56% were non-Hispanic White, and 81% had ≥1 medical condition. Among immunocompetent adults, VE <180 days was 90% (95%CI: 88-91) vs 82% (95%CI: 79-85) at ≥180 days (p < 0.001). VE declined for Pfizer-BioNTech (88% to 79%, p < 0.001) and Moderna (93% to 87%, p < 0.001) products, for younger adults (18-64 years) [91% to 87%, p = 0.005], and for adults ≥65 years of age (87% to 78%, p < 0.001). In models using restricted cubic splines, similar changes were observed. CONCLUSION: In a period largely pre-dating Omicron variant circulation, effectiveness of two mRNA doses against COVID-19-associated hospitalization was largely sustained through 9 months.

A randomized, controlled study to assess if allopathic-osteopathic collaboration influences stereotypes, interprofessional readiness, and doctor-patient communication.

Despite the growing similarities between allopathic (MD) and osteopathic (DO) medical education, few studies have examined allopathic-osteopathic collaboration. The following study focused on stereotypes and student readiness for interprofessional learning. Patient perceptions were also evaluated. Osteopathic and allopathic students were randomly allocated 1:1:1 to work in pairs (MD/DO, MD/MD, DO/DO) at the start of each shift. A questionnaire evaluating student communication was collected from patients at the end of each encounter. Surveys assessing stereotypes and interprofessional readiness were obtained from students at the end of each workday. Data collection was stopped early due to Coronavirus-related safety measures. In the ITT analysis, there were a total of 126 participants (57 students 69 patients). A per-protocol analysis was performed to account for repeat clinic volunteers. No significant differences were detected between student pairs; however, the sensitivity analysis of the questionnaire assessing interprofessional readiness was 8 points higher in the DO/DO group compared to the MD/MD and MD/DO groups (P = 0.0503). In the content analysis of qualitative responses, the MD/DO group was more likely to respond with themes of enjoyment and less concern about stereotypes than the DO/DO group. The MD/DO group was also less likely to report concerns about differences in expectations, methods, and thinking than the MD/MD group. Early trends from this study suggest that DO students may be better positioned to engage in interprofessional learning than their MD counterparts. Additionally, the findings from our content analysis provide evidence that the collaborative experience improved feelings associated with professional legitimacy and credibility among DO students. Taken in aggregate, this study provides justification for a follow-up investigation, as well as a framework for how such studies could best be executed in the future.

Posttraumatic growth related to the COVID-19 pandemic among individuals with lived experience of psychiatric disorder.

Although the COVID-19 pandemic has been shown to be detrimental to mental health, it may hold a parallel potential for positive change. Little is known about posttraumatic growth (PTG) as a potential outcome for individuals with lived experience of psychiatric disorders following trauma exposure, especially in the context of the COVID-19 pandemic. Participants were 1,424 adults with lived experience of a psychiatric disorder who took part in a longitudinal study of mental health during the COVID-19 pandemic conducted by the National Centre for Mental Health. PTG was measured using the Posttraumatic Growth Inventory-Short Form (PTGI-SF). Factors hypothesized to be associated with PTG were investigated using linear regression. The mean participant PTGI score was 12.64 (SD = 11.01). On average, participants reported the highest scores on items related to appreciation of life and lowest on those related to spiritual change subscale. We found the strongest evidence of associations between higher levels of PTG and higher scores on assessment items related to perceived social support, B = 2.86; perceptions of the pandemic as traumatic, B = 4.89; and higher psychological well-being, B = 0.40. Taken together, we did not observe evidence of widespread PTG related to the COVID-19 pandemic among individuals with lived experiences of psychiatric disorders.

Effectiveness of the Ad26.COV2.S (Johnson & Johnson) Coronavirus Disease 2019 (COVID-19) Vaccine for Preventing COVID-19 Hospitalizations and Progression to High Disease Severity in the United States.

Background . Adults in the United States (US) began receiving the adenovirus vector coronavirus disease 2019 (COVID-19) vaccine, Ad26.COV2.S (Johnson & Johnson [Janssen]), in February 2021. We evaluated Ad26.COV2.S vaccine effectiveness (VE) against COVID-19 hospitalization and high disease severity during the first 10 months of its use. Methods . In a multicenter case-control analysis of US adults (≥18 years) hospitalized 11 March to 15 December 2021, we estimated VE against susceptibility to COVID-19 hospitalization (VEs), comparing odds of prior vaccination with a single dose Ad26.COV2.S vaccine between hospitalized cases with COVID-19 and controls without COVID-19. Among hospitalized patients with COVID-19, we estimated VE against disease progression (VEp) to death or invasive mechanical ventilation (IMV), comparing odds of prior vaccination between patients with and without progression. Results . After excluding patients receiving mRNA vaccines, among 3979 COVID-19 case-patients (5% vaccinated with Ad26.COV2.S) and 2229 controls (13% vaccinated with Ad26.COV2.S), VEs of Ad26.COV2.S against COVID-19 hospitalization was 70% (95% confidence interval [CI]: 63-75%) overall, including 55% (29-72%) among immunocompromised patients, and 72% (64-77%) among immunocompetent patients, for whom VEs was similar at 14-90 days (73% [59-82%]), 91-180 days (71% [60-80%]), and 181-274 days (70% [54-81%]) postvaccination. Among hospitalized COVID-19 case-patients, VEp was 46% (18-65%) among immunocompetent patients. Conclusions . The Ad26.COV2.S COVID-19 vaccine reduced the risk of COVID-19 hospitalization by 72% among immunocompetent adults without waning through 6 months postvaccination. After hospitalization for COVID-19, vaccinated immunocompetent patients were less likely to require IMV or die compared to unvaccinated immunocompetent patients.

Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States.

BACKGROUND: As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes. METHODS: In a multicenter case-control analysis of US adults hospitalized March 11 - May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2. RESULTS: Among 1210 participants, median age was 58 years, 22.8% were Black, 13.8% were Hispanic, and 20.6% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 was most common variant (59.7% of sequenced viruses). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 45/590 (7.6%) cases and 215/620 (34.7%) controls. Overall vaccine effectiveness was 86.9% (95% CI: 80.4 to 91.2%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.3%; 95% CI: 78.9 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (59.2%; 95% CI: 11.9 to 81.1%) than without immunosuppression (91.3%; 95% CI: 85.5 to 94.7%). CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.

COVID-19-related posttraumatic stress disorder in adults with lived experience of psychiatric disorder.

BACKGROUND: Prevalence estimates of COVID-19-related posttraumatic stress disorder (PTSD) have ranged from 1% to over 60% in the general population. Individuals with lived experience of a psychiatric disorder may be particularly vulnerable to COVID-19-related PTSD but this has received inadequate attention. METHODS: Participants were 1571 adults with lived experience of psychiatric disorder who took part in a longitudinal study of mental health during the COVID-19 pandemic. PTSD was assessed by the International Trauma Questionnaire (ITQ) anchored to the participant's most troubling COVID-19-related experiencevent. Factors hypothesised to be associated with traumatic stress symptoms were investigated by linear regression. RESULTS: 40.10% of participants perceived some aspect of the pandemic as traumatic. 5.28% reported an ICD-11 PTSD qualifying COVID-19 related traumatic exposure and 0.83% met criteria for probable ICD-11 COVID-19-related PTSD. Traumatic stress symptoms were associated with younger age, lower income, lower social support, and financial worries, and lived experience of PTSD/complex PTSD. Depression and anxiety measured in June 2020 predicted traumatic stress symptoms at follow-up approximately 20 weeks later in November 2020. CONCLUSIONS: We did not find evidence of widespread COVID-19-related PTSD among individuals with lived experience of a psychiatric disorder. There is a need for future research to derive valid prevalence estimates of COVID-19-related PTSD.

SARS-CoV-2 Virus-like Particles Produced by a Single Recombinant Baculovirus Generate Anti-S Antibody and Protect against Variant Challenge.

Coronavirus Disease 2019 (COVID-19), caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has highlighted the need for the rapid generation of efficient vaccines for emerging disease. Virus-like particles, VLPs, are an established vaccine technology that produces virus-like mimics, based on expression of the structural proteins of a target virus. SARS-CoV-2 is a coronavirus where the basis of VLP formation has been shown to be the co-expression of the spike, membrane and envelope structural proteins. Here we describe the generation of SARS-CoV-2 VLPs by the co-expression of the salient structural proteins in insect cells using the established baculovirus expression system. VLPs were heterologous ~100 nm diameter enveloped particles with a distinct fringe that reacted strongly with SARS-CoV-2 convalescent sera. In a Syrian hamster challenge model, non-adjuvanted VLPs induced neutralizing antibodies to the VLP-associated Wuhan S protein and reduced virus shedding and protected against disease associated weight loss following a virulent challenge with SARS-CoV-2 (B.1.1.7 variant). Immunized animals showed reduced lung pathology and lower challenge virus replication than the non-immunized controls. Our data suggest SARS-CoV-2 VLPs offer an efficient vaccine that mitigates against virus load and prevents severe disease.

COVID-19 Vaccination Gap in Admitted Trauma Patients: A Critical Opportunity.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination is the core strategy for pandemic management. We hypothesized that a vaccination gap might exist between emergency department (ED) patients admitted for trauma and other ED patients. STUDY DESIGN: This was an observational quality improvement study using electronic health record data at an academic level-1 trauma center. Participants were all patients presenting to the adult ED with a Tennessee home address between January 1 and June 1, 2021. We measured the proportional difference in vaccination between admitted trauma patients and other ED patients over time (by week) and association via Spearman's rank correlation coefficient. Binary logistic regression facilitated covariate analysis to account for age, sex, race, home county, and ethnicity without and then with interaction between trauma admission and time. Geographic visual analysis compared county-level vaccination rates with odds of trauma admission by home county using a bivariate chloropleth map. RESULTS: The proportional difference in vaccination between trauma-admitted and other ED patients increased over time (Spearman's = 0.699). Adjusting for age, sex, race, home county, and ethnicity, there was a statistically significant vaccination difference between trauma-admitted and other ED patients (odds ratio = 0.53, 95% CI 0.43-0.65, p < 0.0001). Geographic analysis revealed increased trauma admission odds and lower vaccination rates in surrounding counties compared with Davidson County. CONCLUSIONS: We observed a widening COVID-19 vaccination gap between trauma-admitted and other ED patients. Vaccine outreach during trauma admission may provide a valuable point of contact for unvaccinated patients.

COVID-19 severity from Omicron and Delta SARS-CoV-2 variants.

The Omicron variant of SARS-CoV-2 achieved worldwide dominance in late 2021. Early work suggests that infections caused by the Omicron variant may be less severe than those caused by the Delta variant. We sought to compare clinical outcomes of infections caused by these two strains, confirmed by whole genome sequencing, over a short period of time, from respiratory samples collected from SARS-CoV-2 positive patients at a large medical center. We found that infections caused by the Omicron variant caused significantly less morbidity, including admission to the hospital and requirement for oxygen supplementation, and significantly less mortality than those caused by the Delta variant.

Informal Education Pedagogy Transcendence from the 'Academy' to Society in the Current and Post COVID Environment

The purpose of this paper is to consider the following two notions;(1) that the use of 'informal education pedagogies' within teaching and learning in the 'academy' can both support the learning process within the 'classroom' but also transcend to society via students;and (2) that synergies exist between informal education and social pedagogical concepts. The discussions are situated from the perspective of an experienced practitioner and academic who is currently teaching youth related degree courses within a Higher Education Institution. This experiential learning has informed knowledge acquisition, understanding and skills application from professional practice to the teaching environment. An experiential learning perspective will be the primary method adopted;the value of this paper lies in its potential to re-affirm that degree courses which embed a 'practice the practice' approach in their teaching methodology support the embedding of core values of the said discipline. The paper argues that the ethically value-based principles and practice of informal education pedagogy, and social pedagogy, are relevant for the current and post COVID-19 pandemic environment.

Effectiveness of mRNA Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death - United States, March 2021-January 2022.

COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) are effective at preventing COVID-19-associated hospitalization (1-3). However, how well mRNA vaccines protect against the most severe outcomes of these hospitalizations, including invasive mechanical ventilation (IMV) or death is uncertain. Using a case-control design, mRNA vaccine effectiveness (VE) against COVID-19-associated IMV and in-hospital death was evaluated among adults aged ≥18 years hospitalized at 21 U.S. medical centers during March 11, 2021-January 24, 2022. During this period, the most commonly circulating variants of SARS-CoV-2, the virus that causes COVID-19, were B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Previous vaccination (2 or 3 versus 0 vaccine doses before illness onset) in prospectively enrolled COVID-19 case-patients who received IMV or died within 28 days of hospitalization was compared with that among hospitalized control patients without COVID-19. Among 1,440 COVID-19 case-patients who received IMV or died, 307 (21%) had received 2 or 3 vaccine doses before illness onset. Among 6,104 control-patients, 4,020 (66%) had received 2 or 3 vaccine doses. Among the 1,440 case-patients who received IMV or died, those who were vaccinated were older (median age = 69 years), more likely to be immunocompromised* (40%), and had more chronic medical conditions compared with unvaccinated case-patients (median age = 55 years; immunocompromised = 10%; p<0.001 for both). VE against IMV or in-hospital death was 90% (95% CI = 88%-91%) overall, including 88% (95% CI = 86%-90%) for 2 doses and 94% (95% CI = 91%-96%) for 3 doses, and 94% (95% CI = 88%-97%) for 3 doses during the Omicron-predominant period. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated death and respiratory failure treated with IMV. CDC recommends that all persons eligible for vaccination get vaccinated and stay up to date with COVID-19 vaccination (4).

Mental health prior to and during the COVID-19 pandemic in individuals with bipolar disorder: Insights from prospective longitudinal data.

OBJECTIVES: Many studies have examined the impact of COVID-19 on the mental health of the public, but few have focused on individuals with existing severe mental illness with longitudinal data before and during the pandemic. AIMS: To investigate the impact of the COVID-19 pandemic on the mental health of people with bipolar disorder (BD). METHODS: In an ongoing study of people with BD who used an online mood monitoring tool, True Colours, 356 participants provided weekly data on their mental health. Symptoms of depression, mania, insomnia, and suicidal thoughts were compared in 2019 and 2020. From May 2020, participants also provided weekly data on the effect of the COVID-19 pandemic on anxiety, coping strategies, access to care, and medications. RESULTS: On average, symptoms of depression, mania, insomnia, and suicidal thoughts did not significantly differ in 2020 compared to 2019, but there was evidence of heterogeneity. There were high rates of anxiety about the pandemic and its impact on coping strategies, which increased to over 70% of responders in January 2021. A significant proportion of participants reported difficulty accessing routine care (27%) and medications (21%). CONCLUSIONS: Although mood symptoms did not significantly increase during the pandemic overall, we observed heterogeneity among our BD sample and other impacted areas. Individuals' unique histories and psychosocial circumstances are key and should be explored in future qualitative studies. The significant impacts of the pandemic may take time to manifest, particularly among those who are socioeconomically disadvantaged, highlighting the need for further long-term prospective studies.

The effect of the COVID-19 pandemic on mental health in individuals with pre-existing mental illness.

BACKGROUND: There is evidence that the COVID-19 pandemic has negatively affected mental health, but most studies have been conducted in the general population. AIMS: To identify factors associated with mental health during the COVID-19 pandemic in individuals with pre-existing mental illness. METHOD: Participants (N = 2869, 78% women, ages 18-94 years) from a UK cohort (the National Centre for Mental Health) with a history of mental illness completed a cross-sectional online survey in June to August 2020. Mental health assessments were the GAD-7 (anxiety), PHQ-9 (depression) and WHO-5 (well-being) questionnaires, and a self-report question on whether their mental health had changed during the pandemic. Regressions examined associations between mental health outcomes and hypothesised risk factors. Secondary analyses examined associations between specific mental health diagnoses and mental health. RESULTS: A total of 60% of participants reported that mental health had worsened during the pandemic. Younger age, difficulty accessing mental health services, low income, income affected by COVID-19, worry about COVID-19, reduced sleep and increased alcohol/drug use were associated with increased depression and anxiety symptoms and reduced well-being. Feeling socially supported by friends/family/services was associated with better mental health and well-being. Participants with a history of anxiety, depression, post-traumatic stress disorder or eating disorder were more likely to report that mental health had worsened during the pandemic than individuals without a history of these diagnoses. CONCLUSIONS: We identified factors associated with worse mental health during the COVID-19 pandemic in individuals with pre-existing mental illness, in addition to specific groups potentially at elevated risk of poor mental health during the pandemic.

Effectiveness of Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccines for Preventing Coronavirus Disease 2019 Hospitalizations in the United States.

BACKGROUND: As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination coverage increases in the United States, there is a need to understand the real-world effectiveness against severe coronavirus disease 2019 (COVID-19) and among people at increased risk for poor outcomes. METHODS: In a multicenter case-control analysis of US adults hospitalized March 11-May 5, 2021, we evaluated vaccine effectiveness to prevent COVID-19 hospitalizations by comparing odds of prior vaccination with a messenger RNA (mRNA) vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with COVID-19 and hospital-based controls who tested negative for SARS-CoV-2. RESULTS: Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B0.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of 2 vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% confidence interval [CI], 80.7-91.3). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.4%; 95% CI, 79.3-9.7). Among 45 patients with vaccine-breakthrough COVID hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI,20.8-82.6) than without immunosuppression (91.3%; 95% CI, 85.6-94.8). CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing COVID-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.

Impact of COVID-19 on mental health research: is this the breaking point?

There are many structural problems facing the UK at present, from a weakened National Health Service to deeply ingrained inequality. These challenges extend through society to clinical practice and have an impact on current mental health research, which was in a perilous state even before the coronavirus pandemic hit. In this editorial, a group of psychiatric researchers who currently sit on the Academic Faculty of the Royal College of Psychiatrists and represent the breadth of research in mental health from across the UK discuss the challenges faced in academic mental health research. They reflect on the need for additional investment in the specialty and ask whether this is a turning point for the future of mental health research.

Gravity-Driven Microfluidic Siphons: Fluidic Characterization and Application to Quantitative Immunoassays.

A range of biosensing techniques including immunoassays are routinely used for quantitation of analytes in biological samples and available in a range of formats, from centralized lab testing (e.g., microplate enzyme-linked immunosorbent assay (ELISA)) to automated point-of-care (POC) and lateral flow immunochromatographic tests. High analytical performance is intrinsically linked to the use of a sequence of reagent and washing steps, yet this is extremely challenging to deliver at the POC without a high level of fluidic control involving, e.g., automation, fluidic pumping, or manual fluid handling/pipetting. Here we introduce a microfluidic siphon concept that conceptualizes a multistep ″dipstick″ for quantitative, enzymatically amplified immunoassays using a strip of microporous or microbored material. We demonstrated that gravity-driven siphon flow can be realized in single-bore glass capillaries, a multibored microcapillary film, and a glass fiber porous membrane. In contrast to other POC devices proposed to date, the operation of the siphon is only dependent on the hydrostatic liquid pressure (gravity) and not capillary forces, and the unique stepwise approach to the delivery of the sample and immunoassay reagents results in zero dead volume in the device, no reagent overlap or carryover, and full start/stop fluid control. We demonstrated applications of a 10-bore microfluidic siphon as a portable ELISA system without compromised quantitative capabilities in two global diagnostic applications: (1) a four-plex sandwich ELISA for rapid smartphone dengue serotype identification by serotype-specific dengue virus NS1 antigen detection, relevant for acute dengue fever diagnosis, and (2) quantitation of anti-SARS-CoV-2 IgG and IgM titers in spiked serum samples. Diagnostic siphons provide the opportunity for high-performance immunoassay testing outside sophisticated laboratories, meeting the rapidly changing global clinical and public health needs.