Novel Coronavirus Disease 2019 (COVID-19) and Mental Health Issues

Mental health concerns have risen amid the global COVID-19 pandemic due to a variety of factors, including stay-at-home orders, social distancing, fear of sickness and death, loss of employment, and loss of family and friends due to illness.1

It is anticipated that patients infected with COVID-19 may suffer from mood dysregulation, anxiety, anger, and worsening of any preexisting mental illness.2

Patients are also at risk for social stigma and xenophobia.2

A systematic review of the impact of the COVID-19 pandemic showed a 14.6% to 48.3% prevalence of depression symptoms in the general population.3

Depression and Anxiety in COVID-19 Pandemic: Psycho-socio-economic Basis

Various risk factors (red) and protective factors (green) are known to impact development of depression due to stress from COVID-19 outbreak and lockdown4





COVID-19 outbreak

Personal health status

Family responsibility


Risk factors

Protective factors Outcomes


Family responsibility

Everyday life management

Financial difficulties

History of

deliberate self-harma



Younger age

History of suicidal attempt

Clinical depression

Depressive emotions

Conspiracy theories

Clinical depression

Religiosity/ spirituality

Suicidal thoughts

Deleterious Effects of COVID-19 on Mental Health: Pathologic Basis

COVID-19 induced stress leads to HPA axis dysregulation, release of excess proinflammatory cytokines and development of hyperinflammatory state in the body5


Low-grade chronic inflammation

Glucocorticoid resistance


Abbreviations: COVID-19: Novel coronavirus disease 2019; HPA: Hypothalamic-pituitary-adrenal; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2

Depression in COVID-19: Management Principles

No specific guidelines – presently, inpatient and outpatient depression treatment in COVID-19 patients is guided by MDD treatment guideline recommendations.6

VA/DoD Clinical Practice Guideline for the Management of MDD recommends evidence-based psychotherapy and/or evidence-based pharmacotherapy as first-line treatment for mild-to-moderate MDD.7

First-line pharmacotherapy includes SSRIs, SNRIs, mirtazapine, and bupropion; other agents, e.g., trazodone and vortioxetine, may also be used as adjuncts to depression treatment, among others.7

Abbreviations: COVID-19: Novel coronavirus disease 2019; MDD: major depressive disorder; SNRIs: serotonin and norepinephrine reuptake inhibitors; SSRIs: selective serotonin reuptake inhibitors; VA/DoD: The Department of Veterans Affairs/Department of Defense

Anxiety in COVID-19: Management Principles

No specific guidelines – current treatment approach is guided by individualizing therapy for each patient based on patient’s medical comorbidities, drug interactions, and preexisting mental illness.6

A combination of pharmacotherapy (targeting acute anxiety and panic symptoms) and psychotherapy (relaxation techniques, breathing exercises, and encouragement) is recommended.8

To treat acute anxiety in hospitalized patients, short-acting benzodiazepines (alprazolam, lorazepam, clonazepam), gabapentin, hydroxyzine, olanzapine, quetiapine, and haloperidol can be used.8

Managing acute anxiety pharmacologically differs significantly from managing chronic anxiety disorders.6

Beneficial Effect of Antidepressants in COVID-19: Emerging Observational Evidence

Antidepressants significantly reduced mortality risk and reduced intubation or death in hospitalized COVID-19 patients.9

SSRIs (escitalopram, fluoxetine, paroxetine) and SNRI (venlafaxine), were significantly associated with reduced risk of intubation or death.

Intracellular sigma1 receptor activation could prevent COVID-induced inflammation (cytokine storm) and subsequent clinical worsening.10

Inhibition of viral acid sphingomyelinase could prevent the virus from damaging the host cell membrane and invading the cells.9

Antidepressants could help by reducing sickness behaviour in COVID-19 patients.10

The virus is not directly targeted; hence, viral mutation is unlikely to reduce the effectiveness of these agents.10

Clear Facts:

The ongoing COVID-19 pandemic has seriously undermined public mental health all over the globe.

Psychological and socio-economic distress resulting from COVID-19-associated fear and various restrictive measures imposed on public frequently lead to depression and anxiety.

Mild to moderate depression associated with COVID-19 is treated with pharmacotherapy and/or psychotherapy.

SSRIs, SNRIs, bupropion and mirtazapine are the first-line antidepressants used to treat MDD of COVID-19.

Individualised psychotherapy and pharmacotherapy are employed together to ameliorate anxiety associated with COVID-19.

Benzodiazepines, certain antipsychotics, hydroxyzine and gabapentin are recommended for relieving acute anxiety in hospitalized COVID-19 patients.

Emerging evidence suggests paroxetine and certain other antidepressants may reduce COVID-19 disease severity through an anti-inflammatory effect.

References: 1. Marroquin B, Vine V, Morgan R. Mental health during the COVID-19 pandemic: effects of stay-at-home policies, social distancing behavior, and social resources. Psychiatry Res. 2020;293:113419. 2. Wang C, Pan R, Wan X, et al. Immediate psychological responses and associated factors during the initial stage of the 2019 coronavirus disease (COVID-19) epidemic among the general population in China. Int J Environ Res Public Health 2020; 17(5):E1729. doi:10.3390/ijerph17051729. 3. Xiong J, Lipsitz O, Nasri F, et al. Impact of COVID-19 pandemic on mental health in the general population: a systematic review. J Affect Disord. 2020;277:55-64. 4. Fountoulakis KN, Apostolidou MK, Atsiova MB, et al. Self-reported changes in anxiety, depression and suicidality during the COVID-19 lockdown in Greece. J Affect Disord. 2021 Jan 15;279:624-629. 5. Grolli RE, Dama Mingoti ME, Bertollo AG, et al. Impact of COVID-19 in the mental health in elderly: psychological and biological updates. Molecular Neurobiol 2021;58:1905-1916. 6. LaPreze J, Robinson A. The Impact of COVID-19 on Mental Health in Patients. US Pharm. 2021:46(5):HS-7-HS-12. 7. VA/DoD clinical practice guideline for the management of major depressive disorder. Published April 2016. Accessed Aug 02, 2021. 8. Khawam E, Khouli H, Pozuelo L. Treating acute anxiety in patients with COVID-19. Clev Clin J Med. 2020 May 14. doi: 10.3949/ccjm.87a.ccc016. 9. Hoertel N, Sánchez-Rico M, Vernet R, et al. Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study. Mol Psychiatry. 2021 Feb

4. 10. Zagorski N. Psychiatry news: Antidepressants may reduce severity of COVID-19.

Accessed Aug 02, 2021.


Disclaimer: The matter published herein has been developed by clinicians & medical writers. It has also been validated by experts. Although great care has been taken in compiling & checking the information, the authors, shall not be responsible or in anyway, liable for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise however, or for any consequences arising therefrom. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields.

For the use of Registered Medical Practitioner or a Hospital or a Laboratory only

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Inflammatory cytokines


Cytokines storm

COVID-19 severity Psychiatric disorders serverity




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