Exploring the Utility of Recombinant Snake Venom Serine Protease Toxins as Immunogens for Generating Experimental Snakebite Antivenoms

Snakebite is a neglected tropical disease that causes high rates of global mortality and morbidity. Although snakebite can cause a variety of pathologies in victims, haemotoxic effects are particularly common and are typically characterised by haemorrhage and/or venom-induced consumption coagulopathy. Despite polyclonal antibody-based antivenoms being the mainstay life-saving therapy for snakebite, they are associated with limited cross-snake species efficacy, as there is often extensive toxin variation between snake venoms, including those used as immunogens for antivenom production. This restricts the therapeutic utility of any antivenom to certain geographical regions. In this study, we explored the feasibility of using recombinantly expressed toxins as immunogens to stimulate focused, pathology-specific, antibodies in order to broadly counteract specific toxins associated with snakebite envenoming. Three snake venom serine proteases (SVSP) toxins, sourced from geographically diverse and medically important viper snake venoms, were successfully expressed in HEK293F mammalian cells and used for murine immunisation. Analyses of the resulting antibody responses revealed that ancrod and RVV-V stimulated the strongest immune responses, and that experimental antivenoms directed against these recombinant SVSP toxins, and a mixture of the three different immunogens, extensively recognised and exhibited immunological binding towards a variety of native snake venoms. While the experimental antivenoms showed some reduction in abnormal clotting parameters stimulated by the toxin immunogens and crude venom, specifically reducing the depletion of fibrinogen levels and prolongation of prothrombin times, fibrinogen degradation experiments revealed that they broadly protected against venom- and toxin-induced fibrinogenolytic functional activities. Overall, our findings further strengthen the case for the use of recombinant venom toxins as supplemental immunogens to stimulate focused and desirable antibody responses capable of neutralising venom-induced pathological effects, and therefore potentially circumventing some of the limitations associated with current snakebite therapies.     

Early SARS-CoV-2 Reinfections within 60 Days and Implications for Retesting Policies

Illustrated by a clinical case supplemented by epidemiologic data, early reinfections with SARS-CoV-2 Omicron BA.1 after infection with Delta variant, and reinfection with Omicron BA.2 after Omicron BA.1 infection, can occur within 60 days, especially in young, unvaccinated persons. The case definition of reinfection, which influences retesting policies, should be reconsidered.     

Behavioral Health Risk Factors and Motivation to Change among Cardiovascular General Hospital Patients Aged 50 to 79 Years

Little is known about the (co-)occurrence of smoking, alcohol at-risk drinking, physical inactivity and overweight, and the motivation to change these behavioral health risk factors (HRFs) in older general hospital patients with cardiovascular disease. Between October and December 2016, all consecutively admitted patients aged 50 to 79 years were proactively recruited on 3 cardiology wards and asked to participate in a survey on HRFs and behavior change motivation. Of the eligible patients, 80.4% participated in the survey (n = 328). The mean age was 66.5 years (standard deviation 9.0), and 65.5% were male. At least 1 HRF was present in 91.8% (n = 280), at least 2 HRFs in 54.4% (n = 166), and 3 or 4 HRFs in 12.1% (n = 37) of participants. The proportion of older adults who contemplated or were changing or planning to change their behavior to meet health behavior recommendations ranged between 66.0% (smoking) and 93.2% (alcohol consumption). The results indicate a notable co-occurrence of behavioral HRFs in older patients with cardiovascular disease. The majority of older adults were at least considering changing the respective behavior. To prevent and treat diseases efficiently, hospitalization may be a suitable moment for systematic multiple HRF screening and intervention.     

Emergency Use of Convalescent Plasma: Perception of the Regulatory Framework from a Clinical Perspective

The pandemic spread of an infectious disease poses a plethora of challenges to society, clinicians, health care providers and regulating authorities. In order to mount a rapid response and to provide hope in a potentially catastrophic situation as the current COVID-19 pandemic, emergency plans, regulations and funding strategies have to be developed on regional, national and international levels. The speed needed to establish rapid response programs is challenged by the dynamics of the spread of the disease, the concurrent and competing development of different and potentially more effective treatment options, and not the least by regulatory uncertainty. Convalescent plasma, that is plasma collected from patients who have recovered from COVID-19 infections, has emerged as one of the first potential treatment options in the absence of drugs or vaccines with proven efficacy against SARS-CoV-2. The societal aspects of convalescent plasma and the public awareness gave an additional boost to the rapid employment of convalescent plasma donation platforms immediately after the SARS-CoV-2 outbreak. At the same time, uncertainty remains as to the efficacy of convalescent plasma. With evidence mostly limited to empirical reports, convalescent plasma has been used for decades for the prophylaxis and treatment of various infectious diseases. Clinical trials have addressed different infectious agents, stages of disease, target groups of patients and yielded sometimes inconclusive results. The aim of this short review is to delineate the regulatory background for the emergency use of convalescent plasma in the USA, in the European Union and in Germany, and the transition to the setting of clinical trials. In addition, we describe observations made in the process of collecting COVID-19 convalescent plasma (herein referred to as CCP), and formulate proposals to further improve the framework for rapid responses in future emergency situations.     

Exploring the intergenerational persistence of mental health: Evidence from three generations

This paper uses data from the 1970 British Cohort Study to quantify the intergenerational persistence of mental health, and the long-run economic costs associated with poor parental mental health. We find a strong and significant intergenerational correlation that is robust to different covariate sets, sample restrictions, model specifications and potential endogeneity. Importantly, the intergenerational persistence is economically relevant, with maternal mental health associated with lasting effects on the child's educational attainment, future household income and the probability of having criminal convictions. These results do not disappear after controlling for children's own childhood and adulthood mental health.