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1.
Psychiatric Services ; : appips20220083, 2022.
Article in English | MEDLINE | ID: covidwho-2029592

ABSTRACT

OBJECTIVE: Many health care workers avoid seeking mental health care, despite COVID-19-related increases in risk of psychopathology. This study assessed the effects of two versions (distinguished by the race of the protagonist) of a brief social contact-based video on treatment-seeking intention and stigma toward mental health services among U.S. health care workers. METHODS: Participants (N=1,402) were randomly assigned to view a 3-minute video in which a Black or White female nurse described struggles with COVID-19-related anxiety and depression, barriers to care, and how therapy helped, or to view a control video unrelated to mental health. Half of the participants receiving the intervention watched the same video (i.e., booster) again 14 days later. Treatment-seeking intention and treatment-related stigma were assessed at baseline, postintervention, and 14- and 30-day follow-ups. RESULTS: Both intervention videos elicited an immediate increase in treatment-seeking intention in the intervention groups (p<0.001, effect size [ES]=21%), with similar effects among those who watched the booster video (p=0.016, ES=13%) and larger effects among those who had never sought treatment (p<0.001, ES=34%). The increased effects were not sustained 14 days after the initial video or at 30-day follow-up. The results showed an immediate reduction in stigma, but with no booster effect. The race of the protagonist did not influence outcomes. CONCLUSIONS: This easily administered intervention could increase the likelihood of care seeking by proactively encouraging health care workers with mental health challenges to pursue treatment. Future studies should examine whether the inclusion of linkable referrals to mental health services helps to increase treatment-seeking behavior.

2.
Trials ; 23, 2022.
Article in English | PMC | ID: covidwho-2009449

ABSTRACT

Background: Substantial data from high-income countries support early interventions in the form of evidence-based Coordinated Specialty Care (CSC) for people experiencing First Episode Psychosis (FEP) to ameliorate symptoms and minimize disability. Chile is unique among Latin American countries in providing universal access to FEP services through a national FEP policy that mandates the identification of FEP individuals in primary care and guarantees delivery of community-based FEP treatments within a public health care system. Nonetheless, previous research has documented that FEP services currently provided at mental health clinics do not provide evidence-based approaches. This proposal aims to address this shortfall by first adapting OnTrackNY (OTNY), a CSC program currently being implemented across the USA, into OnTrackChile (OTCH), and then examine its effectiveness and implementation in Chile. Methods: The Dynamic Adaptation Process will be used first to inform the adaptation and implementation of OTCH to the Chilean context. Then, a Hybrid Type 1 trial design will test its effectiveness and cost and evaluate its implementation using a cluster-randomized controlled trial (RCT) (N = 300 from 21 outpatient clinics). The OTCH program will be offered in half of these outpatient clinics to individuals ages 15-35. Usual care services will continue to be offered at the other clinics. Given the current COVID-19 pandemic, most research and intervention procedures will be conducted remotely. The study will engage participants over the course of 2 years, with assessments administered at enrollment, 12 months, and 24 months. Primary outcomes include implementation (fidelity, acceptability, and uptake) and service outcomes (person-centeredness, adherence, and retention). Secondary outcomes comprise participant-level outcomes such as symptoms, functioning, and recovery orientation. Over the course of the study, interviews and focus groups with stakeholders will be conducted to better understand the implementation of OTCH. Discussion: Findings from this study will help determine the feasibility, effectiveness, and cost for delivering CSC services in Chile. Lessons learned about facilitators and barriers related to the implementation of the model could help inform the approach needed for these services to be further expanded throughout Latin America. Trial registration: www.ClinicalTrials.govNCT04247711. Registered 30 January 2020. Trial status: The OTCH trial is currently recruiting participants. Recruitment started on March 1, 2021, and is expected to be completed by December 1, 2022. This is the first version of this protocol (5/12/2021).

3.
Pediatrics ; 149, 2022.
Article in English | EMBASE | ID: covidwho-2003154

ABSTRACT

Purpose/Objectives: Our objective was to use the necessary changes in healthcare delivery during the COVID-19 pandemic to accelerate ongoing quality improvement initiatives in growing telemedicine services in our primary care practice that serves children with medical complexities. We believe that synchronous and asynchronous telehealth care greatly benefits the patients and families of our highly complex pediatric population. However, despite our efforts, participation of families and staff members was low. Our goal was to use this COVID-19 catalyst to create an enduring and sustainable telehealth presence and practice, and to do so, we invested in meeting both patient and staff needs. Design/Methods: We used the Model for Improvement to guide PDSA cycles with the aim of increasing and sustaining telehealth usage by patients and staff. This would be achieved by increasing asynchronous patient portal contacts and finding equilibrium in virtual visits and office visits (compared to pre-COVID utilization). Success of incremental improvements was measured in feedback from staff and patients (both anecdotally and with surveys) and in tracking IT service requests for virtual visit support as compared to the number of virtual visits completed. Results: Patients reported increased comfort in using the patient portal and confidence in participating in virtual visits. Percentage of patients completing office visits active to our patient portal increased from 72% preCOVID to essentially 100% during and ongoing. Patients reported high satisfaction with virtual care and planned to use whenever possible and appropriate. Staff demonstrated high levels of comfort with using the patient portal, confidence in conducting virtual visits, and working in remote environments. Completed patient appointments have maintained an even split between inclinic and virtual visits since August 2020. IT service requests compared to virtual visit appointments peaked in April 2020 and maintained high levels over the course of the spring. They have returned to pre-COVID levels while virtual visit appointments are at a 10% increase from their pre-COVID average across our organization. Conclusion/Discussion: We were able to maintain a level of patient and staff satisfaction, develop additional care coordination methods, and increase and sustain the percentage of virtual visits conducted. We had no clinic closures related to COVID-19 and little to no interruption of patient care. The user experience is important. To successfully implement broad practice change, we must remember both patients and staff are the target audience. If both groups feel supported and championed, it elevates everyone's experience.

4.
Biomacromolecules ; 22:22, 2022.
Article in English | MEDLINE | ID: covidwho-2000842

ABSTRACT

Continued SARS-CoV-2 transmission among the human population has meant the evolution of the virus to produce variants of increased infectiousness and virulence, coined variants of concern (VOCs). The last wave of pandemic infections was driven predominantly by the delta VOC, but because of continued transmission and adaptive mutations, the more highly transmissible omicron variant emerged and is now dominant. However, due to waning immunity and emergence of new variants, vaccines alone cannot control the pandemic. The application of an antiviral coating to high-touch surfaces and physical barriers such as masks are an effective means to inactivate the virus and their spread. Here, we demonstrate an environmentally friendly water-borne polymer coating that can completely inactivate SARS-CoV-2 independent of the infectious variant. The polymer was designed to target the highly glycosylated spike protein on the virion surface and inactivate the virion by disruption of the viral membrane through a nano-mechanical process. Our findings show that, even with low amounts of coating on the surface (1 g/m2), inactivation of alpha, delta, and omicron VOCs and degradation of their viral genome were complete. Furthermore, our data shows that the polymer induces little to no skin sensitization in mice and is non-toxic upon oral ingestion in rats. We anticipate that our transparent polymer coating can be applied to face masks and many other surfaces to capture and inactivate the virus, aiding in the reduction of SARS-CoV-2 transmission and evolution of new variants of concern.

5.
Food Environ Virol ; 2022.
Article in English | PubMed | ID: covidwho-1990792

ABSTRACT

This study aimed to develop a framework for combining community wastewater surveillance with state clinical surveillance for the confirmation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants within the community and to provide recommendations on how to expand on such research and apply the findings in public health responses. Wastewater samples were collected weekly from 17 geographically resolved locations in Louisville/Jefferson County, Kentucky (USA), from February 10 to December 13, 2021. Genomic surveillance and quantitative reverse transcription PCR (RT-qPCR) platforms were used to screen for SARS-CoV-2 in wastewater, and state clinical surveillance was used for confirmation. The study results highlighted an increased epidemiological value of combining community wastewater genomic surveillance and RT-qPCR with conventional case-auditing methods. The spatial scale and temporal frequency of wastewater sampling provided promising sensitivity and specificity for gaining public health screening insights about SARS-CoV-2 emergence, seeding, and spread in communities. Improved national surveillance systems are needed against future pathogens and variants, and wastewater-based genomic surveillance exhibits great potential when coupled with clinical testing. This paper presents evidence that complementary wastewater and clinical testing are cost-effectively enhanced when used in combination, as they provide a strong tool for a joint public health framework. Future pathogens of interest may be examined in either a targeted fashion or using a more global approach where all pathogens are monitored. This study has also provided novel insights developed from evidence-based public health practices.

6.
WESTERN PACIFIC SURVEILLANCE AND RESPONSE ; 13(2), 2022.
Article in English | Web of Science | ID: covidwho-1939321

ABSTRACT

Problem: Fieldwork is a vital component of public health emergency response, yet little has been published on undertaking fieldwork safely. Safety is of particular importance with emerging pandemic viruses, which can pose additional risks to public health fieldwork staff. Context: During a pandemic, surge health staff may be drawn from diverse professional backgrounds;they may have limited experience in fieldwork or be unfamiliar with the risks posed by a novel virus. Novel pathogens pose dangers to fieldwork staff, particularly when there are global or local shortages of personal protective equipment. Action: During the coronavirus disease 2019 (COVID-19) pandemic, New South Wales (NSW) Health's Public Health Emergency Operations Centre (PHEOC) deployed staff for fieldwork in a range of settings. The PHEOC developed a protocol to systematize planning, risk assessment and management for COVID-19 fieldwork. The protocol was accompanied by training, discussion exercises and debriefs to support PHEOC fieldwork staff. Lessons learned: Effective fieldwork is an essential component of outbreak investigation and management, including stakeholder management. Here, we share and discuss key elements of the NSW Health protocol to support fieldwork during outbreak responses for emerging communicable diseases across various resource contexts. Limited understanding of novel viruses, particularly in the early phases of a pandemic, must be considered in decisions to deploy fieldwork staff and implement precautionary risk mitigation approaches. Planning is essential to protect staff and ensure ethical allocation of resources. Through appropriate selection of teams and training, surge staff can be supported to effectively conduct fieldwork.

7.
Journal of Mental Health Policy and Economics ; 25(SUPPL 1):S30, 2022.
Article in English | EMBASE | ID: covidwho-1913230

ABSTRACT

Background: New York State was the epicenter of the COVID-19 pandemic's initial US surge in March 2020. The pandemic precipitated dramatic and immediate changes throughout the State's psychiatric treatment system and presented serious threats to the wellbeing of individuals with serious mental illness in 23 State-operated psychiatric hospitals. Methods: We describe how the State mental health authority rapidly restructured the public mental health system and implemented infection control and vaccination programs targeting individuals with serious mental illness. Results: Changes in the supply of and demand for psychiatric services: When the pandemic struck, general hospitals in the NYC and its suburban region immediately closed about 20% of their inpatient psychiatric beds. The NYC public hospital system, which accounts for ∼40% of the city's inpatient psychiatric beds, converted ∼30% of its adult inpatient capacity and 40% of its child/adolescent capacity to COVID-19 medical services. State-operated psychiatric hospitals responded by significantly increasing admissions. These shifts were coordinated to create a single psychiatric inpatient system of care during the height of the pandemic. We will present data showing a dramatic shift to telehealth platforms for outpatient psychiatric outpatient services in the early stages of the pandemic. Risk of infection and mortality among individuals with serious mental illness: Within 3 months of the onset of the pandemic in NYS, five of the 23 State-operated psychiatric hospitals reported 50% or more of their residential/inpatient census exposed to COVID-19. Over an 18-month period from 2020-2021 spanning 3 distinct COVID-19 surges, ∼12% of the almost 11,000 patients treated in these programs were diagnosed with COVID-19 illness and 53 died from the virus. We will review infection control practices implemented in these State-operated psychiatric hospitals to mitigate the impact of the virus. Implementing a COVID-19 vaccination program: Within 8 months of onset of the pandemic, surveillance testing and vaccination programs were implemented in all 23 State-operated psychiatric hospitals. We will present data showing marked reductions in COVID- 19 transmission in this population following this implementation, which occurred while COVID-19 cases were peaking in NYS during the 2nd surge in January-February 2021. Population level management of the economic fallout related trauma, stress, anxiety, and depression: Finally, we will review results from 2 surveys of New Yorkers who used psychiatric services during the pandemic. We will report on their experiences with access to care, telehealth, and the impact of COVDI-19 on their health and wellbeing. Discussion and Implications: Mental health authorities can rapidly implement new policy and protocols to protect the health of individuals served in psychiatric hospital systems during urgent public health crises. Assertive cross-agency coordination is necessary to ensure the safety and wellbeing of these individuals.

8.
Petroleum Economist ; - (February):6-7, 2021.
Article in English | Scopus | ID: covidwho-1905336

ABSTRACT

Oversupply of refining capacity worldwide is seen even before the Covid-19 pandemic, with projections of capacity growth exceeding increases in refined product demand by a factor of 2:1. Refinery throughput reductions have been significant globally in 2020 but have varied by region. In the US, refinery utilization rates dropped ≤ 68 pc in April before recovering to 80 pc in August and decreasing back to 76 pc in November. For OECD Europe, production for October stabilized at 10.6 million bpd. In China, refinery throughput averaged at 80 pc in November, in line with October levels, while the smaller independent refineries in the Shandong region maintained slighter lower run rates of 72 pc. Over 550,000 bpd of capacity shutdowns have already been announced to take effect between 2021 and 2023, with the potential for further closures on the horizon.

9.
Diseases of the Colon and Rectum ; 65(5):216, 2022.
Article in English | EMBASE | ID: covidwho-1893956

ABSTRACT

Purpose/Background: The lack of screening and healthcare access during COVID-19 has delayed diagnosis of rectal cancer. Purpose: To determine whether the COVID-19 pandemic influenced sphincter preserving surgery rates. Hypothesis/Aim: The COVID-19 pandemic influenced sphincter preserving surgery rates in rectal cancer. Methods/Interventions: Methods: In this retrospective cross-sectional study patients undergoing surgery for rectal cancer between 2016 and 2021 were divided into two groups. Patients operated during the COVID-19 pandemic (2020 - 2021) and patients operated before the pandemic (2016-2020). Intervention(s): Sphincter preserving surgical interventions included transanal local excision and low anterior resection with restorative proctectomy or coloanal anastomosis. Radical surgery included abdominoperineal resection with a permanent colostomy. Results/Outcome(s): 234 patients were included, 180 patients (76.9 %) in the pre-COVID-19 group, and 54 patients (23.1%) in the COVID-19 era group. There were no differences between the groups in mean patient age (60.0 ± 12.7 vs 60.6 ± 12.7;p = 0.7648), gender (33.3% vs 40.7% females;p = 0.31) and BMI (26.6 ± 4.8 vs. 27.4 ± 4.6;p = 0.2580). The COVID-19 era group had a significantly lower rates of sphincter preserving surgery (73.1% vs. 86%;p=0.028). Patients in the COVID-19 era also presented with a significantly higher rate of locally advanced disease (stage T3/T4 78.8% vs 57.9%;p=0.02) and metastatic disease (9.4% vs. 2.8%;p = 0.05) compared to the pre COVID-19 group. Time from diagnosis to surgery in this group was also significantly longer (median 272 vs. 146 days, p<0.0001). Limitations: Retrospective single center study Conclusions/Discussion: Patients diagnosed with rectal cancer during the COVID-19 era presented at a more advanced oncological stage and underwent sphincter preserving surgery at lower rates.

13.
Rheumatology (United Kingdom) ; 61(SUPPL 1):i63, 2022.
Article in English | EMBASE | ID: covidwho-1868393

ABSTRACT

Background/Aims The impact of dealing with COVID-19 for rheumatology higher specialist trainees has been profound. Sacrifices were made to their training to support the UK's pandemic response. Virtual Reality (VR) has long been used as a solution for specific surgical skills;providing a hands-on experience to enable specific delivery of outcomes. We utilised existing technology alongside a specialist VR and haptics team to review ways at delivering a valid and reliable training tool to administer joint injections, beginning with the review of this procedure specific to the knee. We aimed to describe this process. Methods A qualitative study using focus groups was undertaken, one medical student, four higher specialty trainees and two consultants were convened in a focus group to review existing mannequin-based training with the purpose of identifying a skill to develop in virtual reality. A story board was developed through collaboration with a graphic designer. The scenario was imbedded into a virtual reality environment in collaboration with a virtual reality partner. Results The focus group identified intra-articular knee injection as the most appropriate rheumatology skill to develop. Storyboarding built a series of scenarios around clinical situations which would require injection or aspiration. Working with the engineering team we successfully mapped knee joint anatomy and rendered an authentic clinical environment for the storyboards to run inside. Conclusion Virtual reality training scenarios are complex to develop but have enormous potential to create immersive training and assessment experiences which are not boundaried by the challenges of social distancing and COVID-19 risks.

14.
Journal of Mental Health Policy and Economics ; 25:S30-S30, 2022.
Article in English | Web of Science | ID: covidwho-1866122
15.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333747

ABSTRACT

Development of effective vaccines against Coronavirus Disease 2019 (COVID-19) is a global imperative. Rapid immunization of the world human population against a widespread, continually evolving, and highly pathogenic virus is an unprecedented challenge, and many different vaccine approaches are being pursued to meet this task. Engineered filamentous bacteriophage (phage) have unique potential in vaccine development due to their inherent immunogenicity, genetic plasticity, stability, cost-effectiveness for large-scale production, and proven safety profile in humans. Herein we report the design, development, and initial evaluation of targeted phage-based vaccination approaches against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) by using dual ligand peptide-targeted phage and adeno-associated virus/phage (AAVP) particles. Towards a unique phage- and AAVP-based dual-display candidate approach, we first performed structure-guided antigen design to select six solvent-exposed epitopes of the SARS-CoV-2 spike (S) protein for display on the recombinant major capsid coat protein pVIII. Targeted phage particles carrying one of these epitopes induced a strong and specific humoral response. In an initial experimental approach, when these targeted phage particles were further genetically engineered to simultaneously display a ligand peptide (CAKSMGDIVC) on the minor capsid protein pIII, which enables receptor-mediated transport of phage particles from the lung epithelium into the systemic circulation (termed "dual-display"), they enhanced a systemic and specific spike (S) protein-specific antibody response upon aerosolization into the lungs of mice. In a second line of investigation, we engineered targeted AAVP particles to deliver the entire S protein gene under the control of a constitutive cytomegalovirus (CMV) promoter, which induced tissue-specific transgene expression stimulating a systemic S protein-specific antibody response. As proof-of-concept preclinical experiments, we show that targeted phage- and AAVP-based particles serve as robust yet versatile enabling platforms for ligand-directed immunization and promptly yield COVID-19 vaccine prototypes for further translational development. SIGNIFICANCE: The ongoing COVID-19 global pandemic has accounted for over 2.5 million deaths and an unprecedented impact on the health of mankind worldwide. Over the past several months, while a few COVID-19 vaccines have received Emergency Use Authorization and are currently being administered to the entire human population, the demand for prompt global immunization has created enormous logistical challenges--including but not limited to supply, access, and distribution--that justify and reinforce the research for additional strategic alternatives. Phage are viruses that only infect bacteria and have been safely administered to humans as antibiotics for decades. As experimental proof-of-concept, we demonstrated that aerosol pulmonary vaccination with lung-targeted phage particles that display short epitopes of the S protein on the capsid as well as preclinical vaccination with targeted AAVP particles carrying the S protein gene elicit a systemic and specific immune response against SARS-CoV-2 in immunocompetent mice. Given that targeted phage- and AAVP-based viral particles are sturdy yet simple to genetically engineer, cost-effective for rapid large-scale production in clinical grade, and relatively stable at room temperature, such unique attributes might perhaps become additional tools towards COVID-19 vaccine design and development for immediate and future unmet needs.

16.
Diseases of the Colon & Rectum ; 65(5):216-216, 2022.
Article in English | Web of Science | ID: covidwho-1798260
17.
34th Australasian Joint Conference on Artificial Intelligence, AI 2021 ; 13151 LNAI:332-343, 2022.
Article in English | Scopus | ID: covidwho-1782718

ABSTRACT

There are many ways machine learning and big data analytics are used in the fight against the COVID-19 pandemic, including predictions, risk management, diagnostics, and prevention. This study focuses on predicting COVID-19 patient shielding—identifying and protecting patients who are clinically extremely vulnerable from coronavirus. This study focuses on techniques used for the multi-label classification of medical text. Using the information published by the United Kingdom NHS and the World Health Organisation, we present a novel approach to predicting COVID-19 patient shielding as a multi-label classification problem. We use publicly available, de-identified ICU medical text data for our experiments. The labels are derived from the published COVID-19 patient shielding data. We present an extensive comparison across 12 multi-label classifiers from the simple binary relevance to neural networks and the most recent transformers. To the best of our knowledge this is the first comprehensive study, where such a range of multi-label classifiers for medical text are considered. We highlight the benefits of various approaches, and argue that, for the task at hand, both predictive accuracy and processing time are essential. © 2022, Springer Nature Switzerland AG.

18.
Journal of the American College of Cardiology ; 79(9):663, 2022.
Article in English | EMBASE | ID: covidwho-1768624

ABSTRACT

Background: Left Atrial Appendage Occlusion (LAAO) with the Watchman device is considered an elective procedure, and thus often deferred during outbreak peaks associated with the COVID-19 pandemic. Patients with bleeding issues on anticoagulation may require additional hospitalization for bleeding episodes or suffering increased risk of stroke by postponing occlusion while anticoagulation is discontinued. We chose to develop a protocol for screening, same day discharge, and follow up of selected LAAO patients and continuing to provide quality clinical outcomes while accounting for decreased bed and staff capacity due to the pandemic. Methods: Utilizing Knowledge to Action (KTA) nursing framework, a protocol was developed and reviewed with key stakeholders. Criteria for Same Day Discharge (SDD) includes: support at home, stable vitals and access site hemostasis prior to DC, agreeable to SDD, tolerant of oral intake, ability to urinate and safely ambulate prior to DC. Exclusion for SDD includes: Liver disease, Plt count <70,000, ESRD or CKD IV or any site or procedure complications. With Perclose usage patients must have 3 hours of bedrest, with manual pressure closure must have bedrest for 6 hours and purse string suture removed. This is followed by a next day phone call to ensure the patient is taking appropriate medicines and have no medical issues. Results: 38 out of 113 patients were screened as SDD candidates from January 2021-October 2021. Average patient age was 76, 31% female, with average CHA2DS2-VASc of 5. One patient required overnight hospitalization due to underlying asthma and need for nebulizer. One patient presented to an outpatient ED on a weekend with chest pain and underwent heart catheterization due to elevated troponin and did not require intervention. There were no access site complications. No patients contracted SARS-Cov-2 within 6 weeks post procedurally, compared with 2 of the overnight stays during the same period (75 patients). Conclusion: SDD in a carefully selected patient population is a feasible and safe strategy for LAAO patients. These patients had a clinically significant, though underpowered decrease in incidence of COVID-19 diagnosis within 6 weeks post implant.

19.
Open Forum Infectious Diseases ; 8(SUPPL 1):S387-S388, 2021.
Article in English | EMBASE | ID: covidwho-1746427

ABSTRACT

Background. DNA vaccines are safe, tolerable, elicit humoral and cellular responses, allow for repeated dosing over time, are thermostable at room temperature, and are easy to manufacture. We present a compilation of Phase 1 and Phase 2 data of Inovio's US COVID-19 DNA Vaccine (INO-4800) targeting the full-length Spike antigen of SARS-CoV-2. A South Korean Phase 2 study is ongoing. Methods. Participants in the open-label Phase 1 trial received 0.5 mg, 1.0 mg or 2.0 mg intradermally (ID) followed by electroporation (EP) at Days 0 and 28. An optional booster dose was administered >6 months post-dose 2. The Phase 2 further compared the 1.0 mg and 2.0 mg doses against placebo in a total of 401 participants randomized at a 3:3:1:1 ratio. ClinicalTrials.gov identifiers: NCT04336410 and NCT04642638 Results. The majority of adverse events (AEs) related to INO-4800 across both trials were mild in severity and did not increase in frequency with age and subsequent doses. In Phase 1, 78% (14/18) and 84% (16/19) of subjects generated neutralizing antibody responses with geometric mean titers (GMTs) of 17.4 (95%CI 8.3, 36.5) and 62.3 (95% CI 36.4, 106.7) in the 1.0 and 2.0 groups, respectively (Figure 1). By week 8, 74% (14/19) and 100% (19/19) subjects generated T cell responses by Th1- associated IFNγ ELISPOT assay . Following a booster dose, neutralizing GMTs rose to 82.2 (95% CI 38.2, 176.9) and 124.7 (95% CI 62.8, 247.7) in the 1.0 mg and 2.0 mg groups, respectively, demonstrating the ability of INO-4800 to boost (Figure 2). In Phase 2, neutralizing antibody responses demonstrated GMTs of 93.6 (95%CI 77.3, 113.4) in the 1.0 mg dose group and 150.6 (95%CI 123.8, 183.1) in the 2.0 mg dose group (Figure 3). Conclusion. INO-4800 appears safe and tolerable as a primary series and as a booster with the induction of both humoral and cellular immune responses. In addition to eliciting neutralizing antibodies, INO-4800 also induced T cell immune responses as demonstrated by IFNγ ELISpot. Finally, as a homologous booster, INO-4800, when administered 6-10.5 months following the primary series, resulted in an increased immune response without increase in reactogenicity. The 2.0 mg dose was selected for Phase 3 evaluation.

20.
Open Forum Infectious Diseases ; 8(SUPPL 1):S390-S391, 2021.
Article in English | EMBASE | ID: covidwho-1746420

ABSTRACT

Background. Global surveillance has identified emerging SARS-CoV-2 variants of concern (VOC) associated with increased transmissibility, disease severity, and resistance to neutralization by current vaccines under emergency use authorization (EUA). Here we assessed cross-immune responses of INO-4800 vaccinated subjects against SARS-CoV-2 VOCs. Methods. We used a SARS-CoV-2 IgG ELISA and a pseudo neutralization assay to assess humoral responses, and an IFNγ ELISpot to measure cellular responses against SARS-CoV-2 VOC in subjects immunized with the DNA vaccine, INO-4800. Results. IgG binding titers were not impacted between wild-type (WT) and B.1.1.7 or B.1.351 variants. An average 1.9-fold reduction was observed for the P.1 variant in subjects tested at week 8 after receiving two doses of INO-4800 (Figure 1a). We performed a SARS-CoV-2 pseudovirus neutralization assay using sera collected from 13 subjects two weeks after administration of a third dose of either 0.5 mg, 1 mg, or 2 mg of INO-4800. Neutralization was detected against WT and the emerging variants in all samples tested. The mean ID50 titers for the WT, B.1.1.7, B.1.351 and P.1. were 643 (range: 70-729), 295 (range: 46-886), 105 (range: 25-309), and 664 (range: 25-2087), respectively. Compared to WT, there was a 2.1 and 6.9-fold reduction for B.1.1.7 and B.1.351, respectively, while there was no difference between WT and the P.1 variant (Figure 1b). Next, we compared cellular immune responses to WT and SARS-CoV-2 Spike variants elicited by INO-4800 vaccination. We observed similar cellular responses to WT (median = 82.2 IQR = 58.9-205.3), B.1.1.7 (79.4, IQR = 38.9- 179.7), B.1.351 (80, IQR = 40.0-208.6) and P.1 (78.3, IQR = 53.1-177.8) Spike peptides (Figure 2). Conclusion. INO-4800 vaccination induced neutralizing antibodies against all variants tested, with reduced levels detected against B.1.351. IFNγ T cell responses were fully maintained against all variants tested.

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