Immunological Interfaces: The COVID-19 Pandemic and Depression

Abstract

Since the start of the spread of the coronavirus disease 2019 (COVID-19) pandemic, an international effort has sought to better characterize associated extra-pulmonary health sequelae. The acute and or chronic detrimental impact of SARS-CoV-2 infection on mental health, especially depression, is increasingly described. Simultaneously the pandemic has influenced depressive symptomatology by modifying economic, social and political structures, in addition to affecting daily routines. In both cases, associated immunological perturbations favoring a pro-inflammatory state could underlie an increased risk for depressive symptomatology. A resultant elevation in global depressive burden could further tax mental health care infrastructure and contribute to a range of worse health outcomes including diminished quality of life. This suggests a critical and time-sensitive need to better understand immune interfaces between depression and COVID-19.

Keywords: COVID-19; SARS- CoV-2; cytokine storm; cytokines; depression; immunity; microglia; pandemic.

Figure 1

Immunological pathways linking depression and COVID-19: Two convergent pathways connect the COVID-19 pandemic with altered immune function and depression. These include direct immunological implications of SARS-CoV-2 infection and indirect, non-infectious pandemic-related changes in immune function induced by poor diet, sedentary behavior and psychological stress. Both pathways may act to increase risk for depression by elevation of CNS cytokines and subsequently microglial activation, altered tryptophan metabolism and deficits in neuroplasticity and neurogenesis.

Figure 2

Summary of existing literature relating COVID-19, depression and immunity. Proposed mechanisms triggering depression related to COVID-19 include elevated inflammation (best represented in cytokine storm), pathways related to angiotensin-converting enzyme 2 (ACE2) receptors, decreased physical activity and increased psychological stress. Proposed interventions include a range of complementary therapies as well as pharmaceutical [(SSRIs (selective serotonin reuptake inhibitors) and oxytocin] in addition to increasing physical activity.

Figure 3

In the context of elevated inflammatory cytokines as a result of the COVID-19 pandemic, CNS tryptophan (TRP) may be preferentially converted into kynurenine (KYN) and its metabolites including kynurenic acid (KYNA) and quinolinic acid (QUIN). This may decrease availability of serotonin (5-HT). KYN metabolites may also contribute to depression. When anti-inflammatory cytokines are present, TRP may be preferentially converted into 5-HT.