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Research Article
The Mind Matters: How Stress and Mental Disruption Open the Door for COVID-19
1.2Quantabia Pearson*, MPH, 1Sindhu Thevuthasan, 1,3Rupalakshmi Vijayan, MBBS, 4Simmy Lahori, MBBS, 5Sai
Pranavi Varri, MBBS, 6Juan Pablo Sosa, MD, 7Maria Mercedes Ferreira, MD, 8Uroosa Arif, MBBS, 3Chhaya Kam-
wal, MBBS, 1Rorita Sadhu, 1Adarsh Shetty, MBBS, 1Wilson Cueva, MD, 1Eric Cabrera, MD
1 Division of Clinical & Translational Research, Larkin Health System, South Miami, FL, USA
2 The Chicago School of Professional Psychology, Chicago, IL, USA
3 Kasturba Medical College, Mangalore, India
4 Pramukhswami Medical College, Karamsad, India
5 Mamata Medical College, Khammam, India
6 Universidad Nacional deTucuman, San Miguel de Tucuman, Argentina
7 Universidad Autonoma de Bucaramanga, Bucaramanga, Colombia
8 Khyber Medical College, Pakistan
Corresponding Author
Article Citations
Quantabia Pearson, MPH, Larkin Community Hospital, 7031
The Mind Matters: How Stress and Mental Disruption Open the
SW 62nd Avenue, South Miami, FL, 33143, USA
Door for COVID-19; sjnsn.06.2021.2.1.06
Email: qmaner4@gmail.com
Approved: 18 May 2021 Published: 05 June 2021
Abstract
Aim: Mental health silently affects everyone and could be a deciding factor in recovery and remission of many health con-
ditions and disorders. Emerging issues from the cumulative effects of this pandemic’s stressors could become chronic health
issues.
Methods: We conducted a literature review on 36 articles from databases such as PubMed, Google Scholar, and ScienceDi-
rect, using search words like “mental health”, “COVID-19”, “psychological effects”, “toxic stress”, “stress response system”
and “SARS-CoV-2”, including reviews, case reports, and cohort studies.
Results: Stress disrupts body homeostasis, prompting a cascade of hormones and factors (such as increased cortisol and
dehydroepiandrosterone (DHEA) that mount a bodily response. Stress has been shown to cause structural changes in the
brain, including in the hippocampus and amygdala, which can lead to memory disorders as well as changes in cognition
and learning. Long-term activation of the stress response system causes overexposure of cortisol and subsequent deleterious
effects throughout the body. Stress can leave a body more susceptible to illnesses of all kinds.
Conclusion: As the world continues to seek answers to curtail the pandemic and bring life back to normal, attention must be
given to how mental health is handled during this crisis. It is time to push for integration of mental health with primary care,
to treat both mind and body regularly to optimize health improvement. It is vital that we understand the effects of stress to
mitigate the consequences and address mental health properly moving forward.

Background The World Health Organization (WHO) reported that

The coronavirus pandemic (COVID-19) originated in the
Hubei province of China in December of 2019. COVID-19
is caused by an enveloped RNA virus named SARS-CoV-2,
which gains entry through receptor proteins on the surface
known as angiotensin converting enzyme II (ACE2) (Zheng,
2020). The spike-like protein uses the natural physiology
of the human body to infect. ACE2 receptors are found all
throughout the body, in the skin, liver, intestines, colons,
stomach, nasopharynx, kidneys, lymph nodes, bone mar-
row and more, although it is especially highly expressed in
the alveolar tissue of the lungs and vascular system. SARS-
CoV-2 forms a bond with the renin-aldosterone angiotensin
system that controls many of the physiological responses in-
cluding homeostasis and blood pressure (Behl et al., 2020).
The structure of this virus that has plagued the globe has
equipped the invasive organism to have a great affinity for
the anatomy of the human species. The COVID-19 virus can
suppress the immune system by discreetly penetrating the
body without activating the first responders: the macrophag-
es (Zheng, 2020). The ways in which the virus has taken a
toll on the human body is more than just transduction, trans-
mission, and infection.
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the global number of confirmed cases of COVID-19 is
33,034,598, with 996,342 deaths, as of September 28, 2020
(WHO, 2020). The impact of the pandemic has affected myr-
iad cultures, people, places, and systems, leading to a mass
panic around the world. The effects of COVID-19 on mental
health are alarming and its impact on humans is multifac-
torial (Singh et al., 2020). Pandemic events cause not only
momentarily negative impact; they also result in long-last-
ing health problems. People are facing isolation, prevention
measures, quarantine, social distancing, mortality, racial
injustice, racism, societal dysfunction, and the absence of
definitive treatment; all these factors generate intense trau-
ma and contribute to creating an atmosphere of toxic stress
across the globe (Farrell et al., 2017; Raphael, 2006).
Introduction
The emergence of the global (COVID-19) pandemic, as re-
viewed by Panchal et al., (2021) brought with it unforeseen
and unprecedented conditions for millions. Conspicuous dis-
orders of the respiratory, gastrointestinal, and neurological
systems have taken center stage, but an important category
must be brought to the forefront, the psychological and emo-
tional effects of this pandemic. Mandatory nationwide lock
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downs, self-quarantining, mask wearing, social distancing, isolation, and anxiety about the unpredictable future have been
significant stressors and have revealed both detectable and undetectable impacts on mental and physical wellbeing. Negative
affectivity including depression, loneliness, boredom, self-harm, and domestic violence doubled in the past months, as well
as financial burden and unemployment. Mental health silently affects everyone and could be a deciding factor in recovery and
remission of many health conditions and disorders including COVID-19 (Panchal et al., 2021).

Stress on the Mind Effecting the Body

Stress, or general adaptation syndrome, is a physiological and cognitive natural response to any potential harm the body
perceives. It triggers the activation of the hypothalamic-pituitary-adrenal axis (HPA axis) which leads to the production of a
vital hormone called cortisol; cortisol induces behavioral, as well as physiological changes in the body (Stephens & Wand,
2012). Stressful incidents cause a sudden rise in cortisol level followed by a rapid decrease with the termination of the stress-
ful event. While this elevation in blood cortisol is a protective mechanism, a continuous and significant rise in cortisol due to
persistent stress can turn this protective mechanism into a powerful force that can cause a wide range of physical, behavioral,
emotional, and cognitive problems (Stephens & Wand, 2012).
Figure 1. Hypothalamic-Pituitary Axis Activation to Stress

Toxic stress, which is a prolonged experience of negative stress, can lead to an immune dysregulation and a persistent in-
flammatory state that increases the risk and frequency of infections as shown in Figure 2 (BioRender, 2021) (Raphael, 2006).
Chronic elevation of inflammatory marker proteins can also damage tissues and increase the risk of diseases such as cardio-
vascular disease, autoimmune disorders, chronic obstructive pulmonary disease, viral hepatitis, and cancer (Murray, 2018).
Furthermore, its known that toxic stress is involved in the pathophysiology of depressive disorders, behavioral dysregulation,
post-traumatic stress disorder (PTSD), and psychosis (Raphael, 2006).
Figure 2. Effects of Prolonged Stress

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A study about toxic stress history and assessment of HPA axis function reported that toxic social stress during development
was related to altered acute HPA response to social stress in adulthood, and that high levels of childhood adversity had
a blunted salivary cortisol response (Lapp et al., 2019). Trauma exposure during childhood has long-lasting effects into
adulthood and potentially affect the development of the brain, the neuroendocrine and immune systems, as well potentially
impacting life opportunities, resulting in poor outcome of health and well-being (Crouch et al., 2019). This is an important
consideration in tackling the impacts of the COVID-19 pandemic on the mental health of children. There is a significant
need to prevent negative outcomes on childhood development, and policies and programs must be implemented to promote
awareness and address the short- and long-term effects.

As discussed in the above sections, stress affects the body in a myriad of ways – the psychophysiology is intricate and
complex. In addition to disrupting body homeostasis and prompting a cascade of hormones and factors (Figure 3) (such as
cortisol, DHEA, catecholamines, etc.) (BioRender, 2021; Turner et al., 2020; McEwen & Stellar, 1993) that mount a bodily
response, mental stress has been shown to cause structural changes in the brain, particularly in the hippocampus and the
amygdala (Yaribeygi et al., 2017). These can lead to memory disorders and changes in cognition and learning. Long-term
activation of the stress response system causes overexposure of cortisol and subsequent deleterious effects throughout the
body, including the immune, cardiovascular, gastrointestinal, and endocrine systems (Yaribeygi et al., 2017).

Figure 3. The Myriad of Ways Stress Effects and Disrupts

Moreover, psychological stress exacts a hidden toll, and chronic stress over time can leave a body more susceptible to not
only illnesses, but other acute, stressful events as well (Turner et al., 2020), compounding the effect with potential for further
harm. Various studies in literature and reviews have shown evidence that responses of pathways such as the HPA axis to acute
stress are related to future health outcomes, in terms of both physical and mental health (Turner et al., 2020).
Moreover, psychological stress exacts a hidden toll, and and downs of physiologic responses, the elevated acuity of
chronic stress over time can leave a body more susceptible physiologic systems under challenge, the changes in metab-
to not only illnesses, but other acute, stressful events as well olism and the impact of wear and tear on a number of organs
(Turner et al., 2020), compounding the effect with potential and tissues, [which] can predispose the organism to disease”
for further harm. Various studies in literature and reviews (McEwen & Stellar, 1993). Allostatic load can be affected
have shown evidence that responses of pathways such as by the entire spectrum of stressors, ranging from daily life
the HPA axis to acute stress are related to future health out- experiences to major life changes to everything in between,
comes, in terms of both physical and mental health (Turner including habitual behaviors such as lack of sleep, poor diet,
et al., 2020). lack of social engagement, and sedentary lifestyle (Fava et
al., 2019).
The Concept of Allostatic Load and Health
Another important concept to consider in discussing the ef- COVID-19’s Invasion on Mental Health
fects of stress on mental health is allostasis, which refers to During this COVID-19 pandemic, both minor and tox-
the process of making physiological changes (through acti- ic stressors, are affecting much of the general population.
vation of neuroendocrine-immune mechanisms) in response Numbers of positive cases and the death toll continued to
to stressors to promote adaptation and maintain stability climb steadily since the declaration of the global pandemic
(McEwen & Stellar, 1993; Sterling, 1998; Fava et al., 2019). in March 2020 (Hagerty & Williams, 2020). The impact of
Adaptation or allostasis often has a cost that promotes patho- COVID-19 on mental health has been alarming and may be
physiology called allostatic load. Authors McEwen and Stel- getting overlooked due to comorbidities and lack of knowl-
lar (1993), further defined the concept of allostatic load, re- edge. The affects the pandemic on the human body and mind
ferring to the “strain on the body produced by repeated ups in a multifactorial manner, has presented as a universal

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threat to human holistic health posed by the virus. Worries
over transmission of the disease and disruption of daily life,
coupled with social distancing and isolation in many parts
have taken a toll on all people regardless of age, race or
background (Hagerty & Williams, 2020).
Isolation, prevention measures, quarantine, social distanc-
ing, mortality, and the absence of a definitive treatment gen-
erates fear, frustration, stress, and anxiety of the population.
Quarantine, self-isolation, and social distancing cause a
negative impact on mental health (Javed et al., 2020). So-
cial isolation and loneliness can instigate many psychiat-
ric disorders, trigger suicidal behavior, promote unhealthy
lifestyle choices such as smoking, substance abuse, alcohol
consumption, and poor dietary and physical activity choic-
es; loneliness can also cause physiological changes in the
body, including increased HPA axis activation which leads
to an avenue of endocrine responses as shown in Figure 4
(BioRender, 2021; Hwang et al., 2020; Holt-Lunstad et al.,
2015; Hu et al., 2020). Community anxiety rises during out-
breaks (Rubin & Wesseley, 2020; Vindegaard & Benros,
2020) and it increases even more with increased reporting in
the media and misinformation as the media struggles to keep
up with the ever-changing guidelines and scientific research.
Previous studies conducted after the MERS and SARS out-
breaks have shown that incidences of depression, anxiety,
and PTSD increased during and after the outbreaks (Shah et
al., 2020; Silva et al., 2020), and the severity of emotional
distress faced by both the general population and healthcare
providers increased (Shah et al., 2020; Talevi et al., 2020). A
nationwide survey of psychological distress in China during
this pandemic showed that 53.8% of respondents rated the
psychological impact as moderate or severe, while 16.5% re-
ported moderate to severe depressive symptoms, and 28.8%
reported moderate to severe anxiety symptoms (Qiu et al.,
2020).
Another important consideration is how those who are af-
fected by the disease or have family members affected by
the disease are viewed by those who manage to avoid it.
Those in affected areas sometimes face social ostracizing
and discrimination (Rubin & Wessely, 2020). This increase
in stigmatization can have broad impact on mental health
and feelings of safety, as well as implications for social dis-
ruption that can last for years (Torales et al., 2020). With
social distancing and mask wearing being enforced legally in
many areas, those who are grieving sudden losses of a loved
ones due to COVID-19 or other reasons may not have the
chance to properly grieve or find closure, and this can lead
to long-lasting emotions of resentment or anger (Ho et al.,
2020). Those with pre-existing conditions who must receive
treatment in isolation or those with mental health disorders
who suddenly do not have access to their support systems
all face increased susceptibilities and could be at higher risk
for COVID-19 or infections (Silva et al., 2020; Barber et
al., 2020). Suicide numbers have been potentially linked to
the psychological implications of COVID-19 in some coun-
tries, such as South Korea and India (Talevi et al., 2020). An
increased risk of suicide has been linked to economic insta-
bility; the pandemic resulted in tens of thousands of people
losing their jobs, linking unemployment and increased prev-
alence of depression, alcohol, or substance use disorders
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(Sher, 2020).
Figure 4. Neurophysiology: Avenues Vulnerable to Disruption
The health outcomes of this virus not only affect the general
population, but they also affect health professionals working
on the front line; it has been shown that they present with
medium to high levels of anxiety, depression, nervousness,
insomnia, and stress (Serafini et al., 2020). Furthermore,
high-risk populations such as the homeless, elderly, children,
people with disabilities, and people with mental health dis-
orders can be further affected or have increased deterioration
of their mental and physical health due to the COVID-19
pandemic (Javed et al., 2020).
According to Zhang et al. (2020) emerging mental health is-
sues from the cumulative effects of this pandemic’s psycho-
social stressors could become chronic health issues for many,
or these issues could encourage and increase the stigma that
already surrounds mental health. Disregarding the mental
effects of the pandemic on the body has potential to lead to
more vulnerable states and worsening of mental health in the
general population. Studies from previous pandemics have
shown that the impact of such stressors extends beyond the
period immediately surrounding the pandemic or quarantine
situation (Zhang et al., 2020).
Future Scope
This unprecedented pandemic and its far-reaching psycho-
logical effects paint a picture of an increasing number of peo-
ple in more vulnerable states and worsening of mental health
in the general population (Serafini et al., 2020). As the world
continues to seek answers to curtail the pandemic and bring
life back to normal, attention must be given to how mental
health is handled during this crisis and long after. It is time to
push for immediate and purposeful integrating mental health
with primary care specific to concerns related to but not lim-
ited to the COVID-19 pandemic to treat the mind for the
physiological reactions to daily and long-term stress. Mental
health is the gateway into the physical well-being or the bod-
ies’ ability to heal itself from further illness. The high impact
of COVID-19 on mental health is a public health priority and
demonstrates a need for developing and implementing com-
munity-based strategies and policies to support psychologi-
cally vulnerable individuals and reduce the burden of disease
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(Serafini et al., 2020). The traumatic experience of the pan-
demic has changed the lives of everyone, but the burden of
disease has always been an issue and continues to increase
with chronic disease on the rise. Although the pandemic did
not help the global prevalence of disease it has provided the
platform to educate and restructure communities for preven-
tion of future attacks on health. This article seeks to state the
importance of mental care for the improvement of health and
healing.
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