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Background: The CDC recommends SARS-CoV-2 (COVID-19) vaccination for all adults, but vaccine safety for breastfeeding dyads and potential effects on lactation remain incompletely understood. Breastmilk immunological responses also have not been fully elucidated after COVID vaccination, specifically the formation of secretory IgA antibodies against viral Spike protein. Methods: ADVISE (NCT04895475) is a prospective trial evaluating breastmilk antibodies among lactating women who receive COVID vaccination. Maternal and infant demographics, breastfeeding characteristics including exclusivity, and vaccination type and side-effects were recorded. Milk samples before vaccination, and weekly after Dose 1 and Dose 2, were delivered using a convenient drop-off system. Maternal blood samples at monthly intervals, along with optional infant samples using a finger-stick Mitra® microsampler device (Neoteryx), were also collected. Breastmilk was frozen at -80C until processing, and fat-free supernatant was tested for quantitative ELISA titers against SARS-CoV-2 Spike protein and neutralizing activity using a pseudo-virus blocking assay. Results: A total of 66 women were consented, 3 of whom withdrew before data or sample collection. Of the remaining 63 (55 White, 5 Black, 3 Other), the median maternal age was 34.7 years (range 23.2-42.7 years);36 received the Moderna vaccine series and 27 received the Pfizer series. The median infant age at enrollment was 6 months;most were born full-term except 3 at <32 weeks and 5 at 33-36 weeks. Three mothers (5%) reported vaccine-related lactation sideeffects including 2 with a temporary decrease in milk supply and 1 who reported transient blue discoloration of the milk. Secretory IgA Spike antibodies (1:4 dilution, OD >0.5) were detected in the initial breastmilk samples from 14% of mothers, almost all of whom had either documented COVID infection or vaccination during pregnancy. For women who received vaccination while breastfeeding, 78% of the lactating mothers had secretory IgA antibodies in breastmilk within 2 weeks, which then dropped in titer and prevalence until the booster vaccine dose (Figure). Maximum breastmilk IgA titers were not associated with specific maternal or infant characteristics, including vaccine manufacturer. IgG breastmilk antibodies were also detected after the first vaccine, but titers were consistently high and sustained after the second dose (Figure). In preliminary analyses, most breastmilk samples had measurable neutralizing activity. Blood from mothers (1:400 dilution) had variable IgA responses but consistent IgG antibodies against Spike protein. In contrast, blood from infants only contained detectable Spike IgG and IgA antibodies if their mothers had COVID infection or vaccination during pregnancy, with no evidence that breastmilk antibodies transfer into the infant circulation. Conclusion: COVID vaccination during lactation is well tolerated with few side-effects and generates a strong immune response. Secretory IgA antibodies are routinely detected in breastmilk and have viral neutralizing activity, supporting wider immunization among breastfeeding mothers.
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Background: Clinical practice guidelines recommend universal screening for mental health (MH) in the perinatal period using a screening tool such as the Edinburgh postnatal depression scores (EPDS). Objectives: To identify whether women attending antenatal and postnatal midwifery clinics at Mater Mothers Hospital were screened as per recommended protocol and to identify if those women who were identified as high risk of perinatal depression were appropriately referred. Additionally, to identify whether the COVID-19 pandemic and subsequent widespread use of telehealth impacted screening rates and referral patterns. Methods: The MatriX/ObstetriX database was searched for all completed EPDS screens at Mater Mothers Hospital for a 12-month period up to February 2020 and screening rates were compared to gold standard practice. The same data were collected for the 6-month period after the declaration of the SARS COVID-19 pandemic. Women with an EPDS score >12 at initial booking were identified and the electronic clinical record was then searched for details of referrals to any perinatal MH services (general practitioner, Mater Perinatal Mental Health service, psychologist, psychiatrist, non-government organisation or other MH service). Findings: Preliminary findings indicate screening rates were lower in the COVID-19 group (82.7% vs 88%). Rates of women identified as high risk (score > 12) were not statistically different between the two groups (5.88% vs 6.6%). Further findings regarding referral patterns are to be presented at Congress. Conclusion: Screening rates using the EPDS were below expected clinical standard practice prior to the onset of the COVID-19 pandemic;however, screening rates further declined with the widespread use of tele health.
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BACKGROUND: BPDCN is a rare, aggressive hematologic malignancy characterized by historically poor overall survival and limited therapeutic options. Despite the recent approval of tagraxofusp-erzs for BPDCN, outcomes remain suboptimal for many patients. Additionally, patients with BPDCN are older and often have co-morbidities at baseline, preventing them from receiving tagraxofusp-erzs. Therefore, novel therapies are needed in the frontline setting for patients with BPDCN. Overexpression of CD123 (IL-3Rα) is present in all BPDCN cases, thereby establishing this surface marker as a target for therapeutic intervention. IMGN632 is a CD123-targeting ADC, comprised of a high-affinity anti-CD123 antibody coupled to a DNA-alkylating payload of the novel IGN (indolinobenzodiazepine pseudodimer) class. IMGN632 has demonstrated favorable safety and promising clinical activity in relapsed/refractory (R/R) BPDCN [Blood (2020) 136 (Supplement 1): 11-13], leading to the FDA granting IMGN632 Breakthrough Therapy Designation (BTD) for R/R BPDCN (Oct 2020). Following BTD and alignment with FDA, a pivotal cohort in frontline (no prior systemic treatment) BPDCN patients was initiated in addition to a continuing cohort of patients with R/R disease, where we have enrolled 33 patients to date. Here we report the initial experience of three frontline patients who are not part of the pivotal cohort. METHODS: IMGN632 was administered IV at a dose of 0.045 mg/kg on day 1 of a 21-day cycle to all patients. Efficacy was assessed using modified Severity Weighted Assessment Tool (for skin lesions), PET/CT, and blast percentage in bone marrow aspirates. The response criteria were adapted from established BPDCN criteria (Pemmaraju NEJM 2019). RESULTS: Three patients with frontline BPDCN (no prior systemic therapy) received IMGN632. All three of these frontline patients achieved a clinical complete remission (CRc). Patient 1 was a 79yo woman who presented with skin, nodal, and extensive bone marrow disease (80% involvement). After one dose of IMGN632, she cleared her bone marrow (0%), and after 3 cycles, her nodal lesions and skin lesions resolved to achieve a CRc. Upon complete response, treatment was held due to patient co-morbidities. With just 3 cycles of IMGN632, this patient achieved duration of response (DOR) of 10.7 months without further therapy. Patient 2 was a 67yo man who had extensive skin disease covering >20% of the body;over several cycles, he achieved a PR then a CRc and bridged to an allogeneic stem cell transplant (SCT). The patient achieved a DOR of 13.5 months, with no evidence of disease relapse when he died from graft versus host disease. Patient 3 was a 66yo woman who presented with extensive skin and nodal lesions. After improvement over 4 cycles, she achieved a CRc with clearing of most of her skin lesions and all nodal lesions. Unfortunately, while still in CRc, the patient died of COVID-19 pneumonia, with a DOR of 3.7 months. CONCLUSION: Administration of IMGN632 to frontline BPDCN patients resulted in clinical complete remission in the initial three patients with durable responses in the two non-COVID impacted patients. None of these patients progressed while on therapy, and one patient successfully bridged to SCT. Enrollment continues in the pivotal frontline and R/R cohorts. (BPDCNtrial.com;NCT03386513).
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Introduction: COVID-19 gastrointestinal (GI) symptoms have significant heterogeneity in prevalence, duration, and severity, but limited data are available on patients who do not require hospitalization. We aimed to elucidate the characteristics of GI symptoms in the outpatient setting and define symptoms from onset to resolution compared to the recommended isolation guidelines. Methods: The study included all adults with a positive COVID-19 test in an outpatient setting over a 2-month period. Data were collected from electronic health records and included symptoms upon diagnosis that were followed to their resolution. Descriptive analyses used means and standard deviations or medians and inter-quartile ranges (depending on data distribution) for continuous variables and frequencies with proportions for categorical data. Mann-Whitney U tests, chi square tests, and Spearman Rho correlations were used for statistical analysis. Results: We screened 1165 patients and included 299 in the study. The mean age was 47.19 years old, with women showing predominance (57.7%). No correlation was found between age and time to resolutions of GI symptoms: diarrhea (r=-0.022, n = 40, p =0.892), nausea (r=0.097, n=26, p =0.636), and vomiting (r=-0.207, n=6, p =0.694). Fever was present in 65.6% (196/299) of the patients. Diarrhea was the most prevalent GI symptom (21.1%;63/299), followed by nausea (13.4%;40/299) and vomiting (4.7%;14/299). Diarrhea was significantly more prevalent in patients with fever (25.5%;50/196) compared to patients with no fever (12.6%;13/103) [p =0.009]. Median time to resolution of GI symptoms was 17.5 days (11.75-33.25) compared to 17 days (12-23.5) for non-GI symptoms [p =0.569] (Figure 1a). Median time to resolution of diarrhea was 13 days (11-20) among smokers and 24 days (13-36) among non-smokers [p =0.042] (Figure 1b). Conclusion: No demographic data led to prolonged GI symptoms in patients with COVID-19 in the outpatient setting. Diarrhea lasted longer in patients who had fever, increasing the risk of possible fecal-oral viral transmission. Despite its established negative impact on health, smoking was correlated with a shorter duration of diarrhea. The median symptom duration was higher than the CDCrecommended isolation time of 10 days. Despite vaccine availability, COVID-19 spread continues to pose a challenge. Larger scale studies are needed to corroborate these findings to guide recommendations for length of quarantine and care escalation in non-hospitalized patients..
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Coronavirus with intact infectivity attached to PPE surfaces pose significant threat to the spread of COVID-19. We tested the hypothesis that an electroceutical fabric, generating weak potential difference of 0.5 V, disrupts the infectivity of coronavirus upon contact by destabilizing the electrokinetic properties of the virion. Porcine respiratory coronavirus AR310 particles (105) were placed in direct contact with the fabric for 1 or 5 min. Following one minute of contact, zeta potential of the porcine coronavirus was significantly lowered indicating destabilization of its electrokinetic properties. Size-distribution plot showed appearance of aggregation of the virus. Testing of the cytopathic effects of the virus showed eradication of infectivity as quantitatively assessed by PI-calcein and MTT cell viability tests. This work provides the rationale to consider the studied electroceutical fabric, or other materials with comparable property, as material of choice for the development of PPE in the fight against COVID-19.
Subject(s)
COVID-19/prevention & control , COVID-19/transmission , Electrochemistry/methods , Textiles , Animals , Anti-Infective Agents , Body Fluids , Cell Line , Cell Survival , Fluoresceins , Humans , Hydrogen Peroxide , Kinetics , Nanoparticles , Propidium , SARS-CoV-2 , Swine , Temperature , Tetrazolium Salts , Thiazoles , Virion , Wound HealingABSTRACT
School closures due to COVID-19 left students in Michigan without physical access to school mental health professionals (SMHPs) and other supports typically available in schools. This report examines the needs of SMHPs across Michigan during the early months of the COVID-19 pandemic and how those needs informed programming and resources provided by a University of Michigan school mental health training and implementation program. In April 2020, a web-based survey asking about student and SMHP mental health was sent to 263 SMHPs who had previously participated in this program. 155 SMHPs (58.9%) responded. Nearly half of SMHPs reported their students' most pressing needs were support for self-care, anxiety, depression, and traumatic stress. Some SMHPs also met screening criteria themselves for depression and/or anxiety. This survey provided an overview of SMHPs' concerns early in the COVID-19 pandemic and drove development of new COVID-19-related resources designed to support SMHPs.
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The spring 2020 campus closures due to the COVID-19 pandemic may have posed particular challenges related to the mentorship of science graduate students. In this study, science faculty mentors from one U.S. university report on potential delays to degree completion and their expectations of their mentees during this time. Nearly half of the faculty advisors surveyed expected their graduate student mentees to experience delayed time to graduation. Respondents also described making an effort to support their mentees through providing encouragement and identifying research-related goals students could complete remotely. One-fourth of respondents stated that they were not altering their expectations for their mentees. The respondents who did report having altered expectations varied between altering their immediate expectations and changing their overall expectations for degree completion. These findings relate not only to the immediate impact on graduate mentees, but also to the long-term impacts of COVID-19 on graduate education in the United States.
ABSTRACT
In this time of Covid-19, life in healthcare has changed immeasurably. It has rapidly been injected with an 'all hands-on deck' approach, to facilitate the necessary adaptations required to reduce the spread of the virus and deliver frontline clinical care. Inevitably aspects of these changes have disrupted the delivery of medical education, notably clinical placements have been cancelled and social distancing guidelines prohibit face-to-face teaching. The training of future doctors is an essential part of this effort. Indeed, the emergence of a global health threat has underlined its continued importance. For medical educators and students alike, we have been presented with a challenge. Concurrently, this presents us with an impetus and opportunity for innovation. For some time now, a transformation in medical education has been called for, with an increasing recognition of the need to prepare students for the changing landscape of healthcare systems. This has included a focus on the use of technology-enhanced and self-directed learning. As a team of educators and clinicians in psychiatry, working in the School of Medicine and Medical Sciences (SMMS) in University College Dublin (UCD), we will share how we have responded. We outline the adaptations made to our 'Psychiatry' module and consider the influence this may have on its future delivery. These changes were informed by direct student input.