Safety and Effectiveness of Therapeutic Products Treating COVID-19 Related Anxiety Disorders.

Abstract: With some 2.6 billion people around the world in lockdown, this is arguably the largest psychological experiment ever.

The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19.

Discovery, evaluation, and refinement of mechanistically driven interventions to address the psychological, social, and neuroscientific aspects of the pandemic are required.

The UK Academy of Medical Sciences and the mental health research charity, MQ: Transforming Mental Health have explored the psychological, social, and neuroscientific effects of COVID-19 and set out a set immediate priorities and longer-term strategies for mental health science research. These priorities were informed by surveys of the public and an expert panel convened in the first weeks of the pandemic in the UK in March 2020. Their surveys are reported online and the findings, combined with published scientific literature, informed the development of research priorities. To that end, they have now proposed a framework for the prioritization and coordination of essential, policy-relevant psychological, social, and neuroscientific research, to ensure that any research investment is efficiently targeted to the crucial mental health science questions as the pandemic unfolds.

Bazelet Health is part of a high-level International collaboration group working to ensure that these research priorities are addressed and contribute to the new ones which will be identified over time.

Immediate research priorities include the monitor and reporting the rates of anxiety, depression, self-harm, suicide, and other mental health issues, and second to understand mechanisms and it is crucial to inform interventions.

To optimize effectiveness of psychological treatments, they need to be mechanistically informed—that is, targeting factors which are both causally associated with poor mental health and modifiable by an intervention.

We need rigorous, peer-reviewed, ethically approved codeveloped research. There is an urgent need for the discovery, evaluation, and refinement of mechanistically driven interventions to address the psychological, social, and neuroscientific aspects of this pandemic. Bazelet Health will conduct experimental medicine studies to validate clinical biomarkers and repurpose new treatments.

The Psychological and Social effects: It is already evident that the direct and indirect psychological and social effects of the coronavirus disease 2019 (COVID-19) pandemic are pervasive and are affecting mental health now and will do so in the future.

The current COVID-19 lockdown will result in a secondary epidemic of burnouts and stress-related absenteeism in the latter half of 2020.

Perhaps unsurprisingly, people who are quarantined are very likely to develop a wide range of symptoms of psychological stress and disorder, including low mood, insomnia, stress, anxiety, anger, irritability, emotional exhaustion, depression and post-traumatic stress symptoms. According to a recent study1., low mood and irritability specifically stand out as being very common.

In cases where parents were quarantined with children, the mental health toll became even steeper. In one study, no less than 28% of quarantined parents warranted a diagnosis of “trauma-related mental health disorder”.

Among quarantined hospital staff, almost 10% reported “high depressive symptoms” up to three years after being quarantined. Another study reporting on the long-term effects of SARS quarantine among healthcare workers found a long-term risk for alcohol abuse, self-medication and long-lasting “avoidance” behavior”. This means that years after being quarantined, some hospital workers still avoid being in close contact with patients by simply not showing up for work.

Reasons for stress abound in lockdown and are very present in this current pandemic. Already there is a sharp increase in absenteeism in countries in lockdown. People are afraid to catch COVID-19 on the work floor and avoid work. It is the opinion of many, a second wave of this will occur in three to six months.

“Just when we need all able bodies to repair the economy, we can expect a sharp spike in absenteeism and burnout.” 2.

In general, we know at-risk groups for long-term mental health issues will be the healthcare workers who are on the frontline, young people under 30 and children, the elderly and those in precarious situations, for example, owing to mental illness, disability and poverty.

1. The psychological impact of quarantine and how to reduce it: rapid review of the evidence. The Lancet, March14, 2020
2. Dr Elke Van Hoof, Professor, health psychology and primary care psychology, Vrije Universiteit Brussel

While the insights are not new, the sheer scale of these lockdowns is. This time, ground zero is not a quarantined village or town or region; a third of the global population is dealing with these intense stressors.

“Now is the time to mitigate the toxic effects of this lockdown. An ounce of planning today will be a pound of prevention later”

Image: When disaster strikes, B. Raphael, 1986
There is broad consensus among academics about the psychological care following disasters and major incidents.
Here are ways Bazelet is working on psychological, social, and neuroscientific research that may be both adapted for, and integrated with, research efforts in other countries.
Research self-help interventions that can address the needs of large affected populations with generalized anxiety disorders [GAD] and at-risk populations to help mitigate a secondary epidemic of burnouts and stress-related absenteeism.

Research and Identify over the counter, non-prescription legal therapeutics to treat GAD, COVID-19 related anxieties.

Launch of our multi-lingual website portal accessible to over a billion people. The Bazelet Learning is a learning management system, an online platform that will provide access to relevant education and learning opportunities. The Bazelet Learning platform will offer:

For physicians and HCP’s: accredited and non-accredited online education.

For patients and patient: non-accredited online learning opportunities and access to resources that are quarantined and have developed symptoms of psychological stress and disorder.

Reinforcing to people that a psychological reaction to trauma, including COVID-19 related is normal;

Investigating longer-term consequences of COVID-19 for the younger and older generations (and other groups at high risk, including workers, those with existing mental health conditions, and caregivers).

Research tells us that severe stresses like COVID-19, especially early in life, can cause an increased risk for mental illnesses.

We know that stressors of all kinds, including both physical and psychological stressors, trigger the activation of stress hormones and brain pathways important for the regulation of both bodily functions and cognitive processes.
For example, hormonal responses to stress enable the body to navigate threatening situations successfully and properly heal from significant injury, while brain responses enable humans and animals to learn from these stressors in order to avoid future threats. Although these pathways can be incredibly important for survival, they can also be maladaptive—especially with severe or chronic forms of stress—overwhelming both the brain and the rest of the body.

Responses to stress result from a cascade of molecular, cellular, and neural-circuit level changes that have been, and continue to be, a subject of intense research efforts supported by NIMH and others.

Stress triggers activation of molecular processes that tag genes with so-called “epigenetic marks” that result in long-lasting changes in how the molecular machinery of those neurons is expressed. These marks can last for months, years, or perhaps even lifetimes.

Changes in gene expression that result from these marks alter how neurons learn and respond to the environment, and even alter how the brain responds to future stresses.

We know, at least in animals like mice and rats, that a range of different interventions can block or reverse many of these stress-induced processes, preventing some of the adverse behavioral responses to stress that we think might be relevant to human disorders like major depression and post-traumatic stress disorder (PTSD).
Despite this incredible knowledge base, we must admit that these investments have not resulted in substantial gains in the clinical realm.

Biomarkers would enable clinical scientists to make specific hypotheses about how likely it is that a given therapeutic or preventative measure would work in a specific person at risk due to stress.

The best research considers the stressor, the biological and the psychological responses. Solutions for treatment and prevention of the mental health consequences of stress are greatly needed.