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\begin{document}

\title{COVID-19 pandemic: the potential effects of quarantine-induced stress on
arrhythmias}



\author[1]{Anna Vittoria Mattioli}%
\author[1]{Andrea Cossarizza}%
\author[2]{Giuseppe Boriani}%
\affil[1]{University of Modena and Reggio Emilia Faculty of Medicine and Surgery}%
\affil[2]{Azienda Ospedaliera Universitaria Policlinico di Modena}%


\vspace{-1em}



  
  \date{June 14, 2024}


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\selectlanguage{english}
\begin{abstract}
Since the WHO defined the diffusion of novel coronavirus, Severe Acute
Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) as pandemic, the global
effort has been on finding a cure and preventing transmission. As a
consequence, people are going through many psychological problems in
adjusting to the current lifestyles and fear of the disease. The link
between the psychological effects of quarantine and arrhythmias has been
poorly explored. However it is known that sudden catastrophic events
i.e. earthquake are associated with an increase in sudden cardiac
deaths. Acute stress and anxiety could act as a trigger for ventricular
arrhythmias, which are found to have increased significantly after an
earthquake. Quarantine induced a chronic stress enforced by alarming
news reports in the media. Closure of businesses increased the stress
due the expected crisis after the lockdown. Stress activates both the
sympathetic nervous system and the axis of the
renin-angiotensin-aldosterone system, leading to an increased risk of
cardiac events. The aim of the present editorial is to analyze the
potential impact of quarantine --induced stress on the development of
arrhythmias.%
\end{abstract}%



\sloppy


\textbf{COVID-19 outbreak, stress, atherosclerosis and immune function}

Stress is a major factor that can alter the immune system. During the
lockdown due to the pandemic, a huge number of persons have developed
relevant signs of psychological suffering, that can significantly affect
the capacity of the organism to react to external stimuli like those
represented by microorganisms. It has been known for a long time that
the immune response is regulated by soluble factors which include not
only numerous cytokines and chemokines, but also a large number of
hormones and neurotransmitters, whose receptors are found both on cells
of innate and acquired immunity. Among these molecules, glucocorticoids
play a fundamental role, and are responsible for a variety of
immunological effects. Psychological stress, as well as several
proinflammatory cytokines, acts at the hypothalamus level, provoking the
production and release of corticotropin-releasing hormone (CRH) and
arginine vasopressin (AVP) that, in turn, induce the anterior pituitary
gland to synthesize adrenocorticotropin hormone (ACTH), which is able to
stimulate steroidogenesis in adrenocortical cells.
\textsuperscript{5,6}This is crucial to give origin to cortisol, the
main corticosteroid. In turn, glucocorticoids trigger a negative
feedback, according to which the hypothalamic--pituitary--adrenal axis
is inhibited. In general, it can be well stated that the main
physiological effects of glucocorticoids go in the direction to suppress
immune responses. However, these are not the only important effects
described for these molecules. Atherosclerosis is a process in which
ACTH and cortisol may play an important role. Acting on proinflammatory
or anti-inflammatory cytokines, they can regulate vascular endothelial
functionality and recruit monocytes, that can enter the wall and
differentiate first into macrophages, second into foam cells. Their
capability to modulate the capacity of macrophages to remove the excess
free cholesterol from the atherosclerotic plaque is also crucial for
maintaining an efficient endothelial functionality. \textsuperscript{6}
The pathogenesis of COVID-19 is associated with elevation of several
immune plays as well as inflammatory factors which contributes to
cytokine storms.

\textbf{Covid-19 outbreak and arrhythmias}

Currently, little is known about the psychological impact and mental
health of the general public during the peak of the COVID-19
epidemic.\textsuperscript{1,2,3} This is especially pertinent with the
uncertainty surrounding an outbreak of such unparalleled magnitude.

Wang and coworkers analyzed the psychological impact of COVID 19
epidemic in China and suggest that with respect to the initial
psychological responses of the general public between 31 January and 2
February 2020, just two weeks into the country's outbreak of COVID-19
and one day after the WHO declared a public health emergency of
international concern, 53.8\% of respondents rated the psychological
impact of the outbreak as moderate or severe; 16.5\% of respondents
reported moderate to severe depressive symptoms; 28.8\% of respondents
reported moderate to severe anxiety symptoms; and 8.1\% reported
moderate to severe stress levels. \textsuperscript{7}

Varshney M and coworkers reported a lower psychological impact of
COVID-19. They found that 33.2\% of respondents to the questionnaire
showed significant (mild / moderate /severe) psychological impact
regarding COVID-19. However, as these results were registered during the
initial phase of the COVID-19 epidemic in the country, it is likely that
they may have changed over time and should therefore be interpreted
accordingly. \textsuperscript{8}

Depression, anxiety and post-traumatic stress symptoms are known risk
factors for adverse events in patients with chronic heart disease.
Interestingly, much less is known about the effect of stress on the
incidence and course of arrhythmias.

Baldi and coworkers found an increased number of out of hospital cardiac
arrests in northern Italy that matched the same geographical areas most
harshly affected by the pandemia. {[}9{]} A significant increase in SCD
events (58\%) was reported in this region and these investigators
attribute this spike to late complications of myocardial infract or
ischemia, as patients were more likely to remain at home and avoid
hospitalization for fear of COVID-19 infection. \textsuperscript{9}

Similarly, a significant reductions in the overall number of hospital
admissions in patients presenting with acute coronary syndromes has been
reported. \textsuperscript{10,11}

The responses to chronic stress also include a number of modifying
lifestyle behaviors such as increased alcohol consumption, heavier
smoking, and diet high in sugar and fat. \textsuperscript{2,12} Together
with sedentary lifestyle these unhealthy changes in diet contribute to
excess energy intakes and weight gain. Unhealthy lifestyle increases
oxidative stress and inflammation. \textsuperscript{2,12} When subjects
respond to stress by eating more, substantial anecdotal evidence
suggests the foods selected are typically high in sugar and fat. This
phenomenon has been described as ``Food craving''. Food craving has been
defined as a multidimensional experience since it includes cognitive
(e.g., thinking about food), emotional (e.g., desire to eat), behavioral
(e.g., seeking and consuming food), and physiological (e.g., salivation)
aspects. \textsuperscript{12,13} Food craving can be associated with a
reduced intake of fruit and vegetables. However, a plant-based diet,
rich in anti-inflammatory and anti-oxidative components, has been shown
to significantly affect the most common cardiovascular risk factors in a
positive way.

Sedentary life also contributes to an increase in cardiovascular risk.

While the positive effects of exercise are well studied also in the
elderly less attention was dedicated to the impact of detraining in the
elderly, although the worsening of dynamic balance found in patients
aged 75 as a consequence of a 3-month period of detraining may have an
impact not only on quality of life but also on exercise-induced
cardiovascular adaptations and probably stress-induced
arrhythmogenesis.\textsuperscript{2,14}

We expect an increase in arrhythmic phenomena following quarantine due
to higher stress levels and an unhealthy lifestyle that heightens the
overall cardiovascular risk factor. In addition, stress related to
quarantine induces a change in lifestyle and nutritional habits:, which
is mainly due to reduced availability of goods, limited access to food,
and reduction of outdoor physical activity. (figure 1)

\textbf{Conclusions}

We need to be prepared to confront the likely increase in arrhythmias
risk burden following the pandemic.\textsuperscript{15} Following
quarantine period we must promote going back to a healthy lifestyle that
includes a healthy diet and physical activity. Selected patients may
benefit from psychological support and evaluation for persisting anxiety
disorders. Moreover, it will be necessary to re-evaluate the
arrhythmogenic risk of patients to prevent the sudden development of
arrhythmias.

\textbf{Acknowledgements}

We would like to thank Mrs Janet Ann Carter for editing the paper.

We thank everyone who is working to resolve the SARS-CoV-2 pandemic.

\textbf{REFERENCES}

\begin{enumerate}
\tightlist
\item
  Brooks SK, Webster RK, Smith LE, Woodland L, Wessely S, Greenberg N,
  Rubin GJ. The psychological impact of quarantine and how to reduce it:
  rapid review of the evidence \emph{Lancet} 2020; 395:
  912--20.\emph{https://doi.org/10.1016/}S0140-6736(20)30460-8
\item
  Mattioli AV, Ballerini Puviani M, Nasi M, Farinetti A. COVID-19
  pandemic: the effects of quarantine on cardiovascular risk. \emph{Eur
  J Clin Nutr} 2020 74 :852 - 855; May 05, 2020;
  10.1038/s41430-020-0646-7
\item
  Louvardi, M., Pelekasis, P., Chrousos, G., \& Darviri, C. Mental
  Health in Chronic Disease Patients during the COVID-19 Quarantine in
  Greece.~\emph{Palliative and Supportive Care,} ~ 2020 1-17.
  doi:10.1017/S1478951520000528
\item
  Zhang XQ, Chen M, Yang Q, Yan SD, Huang de J. Effect of the Wenchuan
  earthquake in China on hemodynamically unstable ventricular
  tachyarrhythmia in hospitalized patients. \emph{Am J Cardiol} .
  2009;103:994e997
\item
  Elovainio M, Hakulinen C, Pulkki-R\selectlanguage{ngerman}åback L, Virtanen M, Josefsson K,
  Jokela M, Vahtera J, Kivimäki M. Contribution of risk factors to
  excess mortality in isolated and lonely individuals: an analysis of
  data from the UK biobank cohort study. \emph{Lancet Public Health} .
  2017;2:e260--6.
\item
  Stopper M, Joska T, Burg MM, Batsford WP, McPherson CA, Jain D,
  Lampert R. Electrophysiologic characteristics of anger-triggered
  arrhythmias. \emph{Heart Rhythm} . 2007 Mar;4(3):268-73.
\item
  Wang C, Pan R, Wan X, Tan Y, Xu L, Ho CS, Ho RC. Immediate
  Psychological Responses and Associated Factors during the Initial
  Stage of the 2019 Coronavirus Disease (COVID-19) Epidemic among the
  General Population in China. \emph{Int J Environ Res Public Health} .
  2020 Mar; 17(5): 1729. Published online 2020 Mar 6. doi:
  10.3390/ijerph17051729
\item
  Varshney M, Parel JT, Raizada N, Sarin SK. Initial psychological
  impact of COVID-19 and its correlates in Indian Community: An online
  (FEEL-COVID) survey. \emph{PLoS ONE} 2020 15(5): e0233874.
  https://doi.org/10.1371/journal.pone.0233874
\item
  Baldi E, Sechi GM, Mare C, Canevari F, Brancaglione A, Primi R, Klersy
  C, Palo A, Contri E, Ronchi V, Beretta G, Reali F, Parogni P, Facchin
  F, Bua D, Rizzi U, Bussi D, Ruggeri S, Oltrona Visconti L, Savastano
  S; Lombardia CARe Researchers.. Out-of-hospital cardiac arrest during
  the COVID-19 outbreak in Italy. \emph{N Engl J Med} . April 29, 2020.
  DOI: 10.1056/NEJMc2010418
\item
  De Filippo O, D'Ascenzo F, Angelini F, Bocchino PP, Conrotto F,
  Saglietto A, Secco GG, Campo G, Gallone G, Verardi R, Gaido L,
  Iannaccone M, Galvani M, Ugo F, Barbero U, Infantino V, Olivotti L,
  Mennuni M, Gili S, Infusino F, Vercellino M, Zucchetti O, Casella G,
  Giammaria M, Boccuzzi G, Tolomeo P, Doronzo B, Senatore G, Grosso
  Marra W, Rognoni A, Trabattoni D, Franchin L, Borin A, Bruno F,
  Galluzzo A, Gambino A, Nicolino A, Truffa Giachet A, Sardella G,
  Fedele F, Monticone S, Montefusco A, Omedè P, Pennone M, Patti G,
  Mancone M, De Ferrari GM.. Reduced rate of hospital admissions for ACS
  during Covid-19 outbreak in Northern Italy. \emph{N Eng J Med} . 2020
  Jul 2;383(1):88-89. doi: 10.1056/NEJMc2009166. Epub 2020 Apr 28..
\item
  Metzler B, Siostrzonek P, Binder RK, Bauer A, Reinstadler SJ. Decline
  of acute coronary syndrome admissions in Austria since the outbreak of
  COVID-19: The pandemic response causes cardiac collateral
  damage.\emph{Eur Heart J} . 2020 Apr 16. doi:
  10.1093/eurheartj/ehaa314.
\item
  Mattioli AV, Sciomer S, Cocchi C, Maffei S, Gallina S. ``Quarantine
  during COVID-19 outbreak: changes in Diet and physical activity
  increase the risk of cardiovascular disease''. \emph{Nutr Metab
  Cardiovasc Dis} . 2020 May 30:S0939-4753(20)30213-1. doi:
  10.1016/j.numecd.2020.05.020.
\item
  Mattioli AV, Pinti M, Farinetti A, Nasi M. Obesity risk during
  collective quarantine for the COVID-19 epidemic, Obesity Medicine,
  2020\emph{https://doi.org/10.1016/j.obmed.2020.100263}
\item
  Pedersen BK, Saltin B. Evidence for prescribing exercise as therapy in
  chronic disease. \emph{Scand J Med Sci Sports} . 2006 Feb;16 Suppl
  1:3-63
\item
  Hall J. The impact of COVID-19 on critical cardiac care and what is~to
  come postpandemic {[}published online ahead of print, 2020 Jul
  10{]}.~\emph{Future Cardiol} . 2020;10.2217/fca-2020-0093.
  doi:10.2217/fca-2020-0093
\end{enumerate}

Figure 1

Mechanisms involved in the relationship between quarantine-induced
stress and COVID-19\selectlanguage{english}
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