Egg-derived anti-SARS-CoV-2 immunoglobulin Y (IgY) with broad variant activity as intranasal prophylaxis against COVID-19: preclinical studies and randomized controlled phase 1 clinical trial

COVID-19 emergency use authorizations and approvals for vaccines were achieved in record time. However, there remains a need to develop additional safe, effective, easy-to-produce, and inexpensive prevention to reduce the risk of acquiring SARS-CoV-2 infection. This need is due to difficulties in vaccine manufacturing and distribution, vaccine hesitancy, and, critically, the increased prevalence of SARS-CoV-2 variants with greater contagiousness or reduced sensitivity to immunity. Antibodies from eggs of hens (immunoglobulin Y; IgY) that were administered receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were developed as nasal drops to capture the virus on the nasal mucosa. Although initially raised against the 2019 novel coronavirus index strain (2019- nCoV), these anti-SARS-CoV-2 RBD IgY surprisingly had indistinguishable enzyme-linked immunosorbent assay binding against variants of concern that have emerged, including Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529). This is distinct for sera from immunized or convalescent patients. Culture neutralization titers against available Alpha, Beta, and Delta were also indistinguishable from the index SARS-CoV-2 strain. Efforts to develop these IgY for clinical use demonstrated that the intranasal anti-SARS-CoV-2 RBD IgY preparation showed no binding (cross-reactivity) to a variety of human tissues and had an excellent safety profile in rats following 28-day intranasal delivery of the formulated IgY. A double-blind, randomized, placebo- controlled phase 1 study evaluating single-ascending and multiple doses of anti-SARS-CoV-2 RBD IgY administered intranasally for 14 days in 48 healthy adults also demonstrated an excellent safety and tolerability profile, and no evidence of systemic absorption. As these antiviral IgY have broad selectivity against many variants of concern, are fast to produce, and are a low-cost product, their use as prophylaxis to reduce SARS-CoV-2 viral transmission warrants further evaluation. (ClinicalTrials.gov: NCT04567810, https://www.clinicaltrials.gov/ct2/show/NCT04567810)

Primary care clinical management following self-harm during the first wave of COVID-19 in the UK

BackgroundA substantial reduction in GP-recorded self-harm occurred during the first wave of COVID-19 but effects on primary care management of self-harm are unknown. AimTo examine the impact of COVID-19 on clinical management within three months of an episode of self-harm. Design and settingProspective cohort study using data from the UK Clinical Practice Research Datalink. MethodWe compared cohorts of patients with an index self-harm episode recorded during a pre-pandemic period (10th March-10th June, 2010-2019) versus the COVID-19 first-wave period (10th March-10th June 2020). Patients were followed up for three months to capture psychotropic medication prescribing, GP/practice nurse consultation and referral to mental health services. Results48,739 episodes of self-harm were recorded during the pre-pandemic period and 4,238 during the first-wave COVID-19 period. Similar proportions were prescribed psychotropic medication within 3 months in the pre-pandemic (54.0%) and COVID-19 first-wave (54.9%) cohorts. Likelihood of having at least one GP/practice nurse consultation was broadly similar (83.2% vs. 80.3% in the COVID-19 cohort). The proportion of patients referred to mental health services in the COVID-19 cohort (3.4%) was around half of that in the pre-pandemic cohort (6.5%). ConclusionDespite the challenges experienced by primary healthcare teams during the initial COVID-19 wave, prescribing and consultation patterns following self-harm were broadly similar to pre-pandemic levels. However, the reduced likelihood of referral to mental health services warrants attention. Accessible outpatient and community services for people who have self-harmed are required as the COVID-19 crisis recedes and the population faces new challenges to mental health.

Tetryl exposure: forgotten hazards of antique munitions

BACKGROUND: Older yet still abundant munitions such as tetryl present easily forgotten health hazards and associated needs for worker protection. CASE PRESENTATION: Symptoms and findings from 22 workers who were exposed to tetryl are summarized. CONCLUSIONS: This study highlights the health hazards from exposure to tetryl. Occupational health professionals need to maintain vigilance to protect workers from the risks of handling older munitions.