Evaluate, manage the stress response in susceptible individuals affected by COVID-19

Steroid therapy should be explored for quarantined mental health patients


Psychological First Aid is an innovative program launched by the American Red Cross with the goal of addressing issues of concern such as those stemming from COVID-19–related stress. According to Red Cross mental health volunteer representative Deb Butman-Perkins, the program provides “a general overview of what does stress look like, how do we feel it, how do we recognize it in our bodies ... physical, emotional, spiritual, physiological, where does all that stress occur?”1

Dr. Faisal Islam

Dr. Faisal A. Islam

The program brings a spotlight to the interdisciplinary nature of the stress response, especially with respect to the importance of developing the necessary coping skills during an ongoing crisis. However, to effectively evaluate and manage the overall stress response for psychiatric patients during quarantine conditions, as well as those who are formally diagnosed with COVID-19, clinicians also will need to revisit what we’ve learned about the hypothalamic-pituitary-adrenal (HPA) axis.

We know that the stress response – which varies somewhat across the spectrum – is necessary to ensure homeostatic regulation. A feedback loop is initiated at the receptor level, involving a myriad of hormones and chemical signals that bring forth the body’s “flight-or-fight” response. Hormones such as epinephrine/norepinephrine and cortisol are secreted by the HPA axis in reaction to the stress response, resulting in a spike in heart rate, blood pressure, and transient hyperglycemia, respectively. In particular, hyperglycemia provides immediate energy to muscles during a perceived crisis.2

In addition, prolonged exposure to living in quarantine can lead to feelings of isolation and estrangement – and excessive anxiety. Combined, those conditions may exert an indelible effect on the HPA axis – leading to a warped pattern of cortisol secretion with respect to baseline.3 (It has been noted in the literature that serum cortisol plays a protective role in thwarting off the effects of PTSD development. Consistent with this line of thinking, military personnel have been preemptively treated with high-dose cortisol during acute exposure.)

Prolonged exposure to psychosocial stressors also increases the overall risk of developing medical comorbidities. Patients who adopt maladaptive responses to traumatic events, for example, may experience dysregulation in eating behaviors and/or disordered sleep.4

In light of those realities, clinicians should explore the role of steroid therapy as a means of treating mental health patients experiencing psychological stress formation tied to ongoing quarantine conditions.

Challenges of neuroendocrine medications for COVID-19

COVID-19, caused by exposure to SARS-CoV-2, adeptly leverages the ACE2 receptor of the lungs as an entry point to evade the host’s defenses. It should be noted that the ACE2 protein is expressed on the cells of multiple organs of the body, including the adrenals, which are largely responsible for coordinating the stress response of the HPA axis.

Dr. Mohammed S. Islam

Postmortem analysis from severe acute respiratory syndrome (SARS-CoV is also from the Coronaviridae family) patients indicates the presence of necrotic adrenal cells, further solidifying the association of the HPA axis to the COVID-19 disease state and pathophysiological course.5 Molecular mimicry of the adrenocorticotropic hormone allows SARS-CoV the ability to infiltrate the host’s defenses, in particular, the ability to mount a clinically apt cortisol stress response (e.g., hypocortisolism).As for those who survived the 2003 SARS outbreak, less than half of the patients have been observed to develop symptoms of frank hypocortisolism within a few months after exposure.

The World Health Organization recently endorsed the use of steroid therapy for critically ill COVID-19 patients, and an ongoing clinical trial is evaluating the safety and efficacy parameters of corticosteroids in COVID-19–exposed patients.

In addition, there is reason to believe that application of prophylactic steroids might affect the overall clinical course of COVID-19, thereby reducing mortality and morbidity rates in patients with severe presentation, such as septic shock. The rationale for this line of thought is based on the ability of glucocorticoids to suppress an ensuing cytokine storm by the virus in question.5,6 In clinical practice, steroids have been used to treat a host of viral diseases, including influenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus.

Aside from the selective use of corticosteroids, the medication regimen may incorporate ACE inhibitors and/or angiotensin receptor blockers (ARBs) because of COVID-19’s ability to activate the renin-angiotensin-aldosterone system with respect to the physiological stress response.

The interplay of the HPA axis with the sympathoadrenal system is responsible for adaptive behaviors in the individual. Disrupted feedback loops from prolonged activation are associated with numerous stress-based conditions in mental illness, namely, PTSD, anxiety, and mood disorders. We are concerned about frontline health care workers, who are particularly prone to chronic stress and burnout because of the cumbersome patient load and equipment shortage that have characterized the coronavirus crisis.

Timely administration of corticosteroids on a case-by-case basis would keep the cytokines at bay by precluding their undue activation of the HPA axis and corresponding cascade stress response. Steroids are also known to restore disrupted feedback loops at the level of the immune cells. However, because of conflicting reports concerning viral clearance in some SARS and COVID-19 studies, treatment with steroids may be limited to select patient populations with the necessary dose adjustments. Ongoing clinical trials will further elucidate upon the applicability of steroids as well as the role of other neuroendocrine agents, such as ACE inhibitors or ARBs, in the treatment of COVID-19.


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