Susceptibility of clinically depressed patients to COVID-19: Is there a link?

Sir,

The novel coronavirus disease (COVID-19, previously known as 2019-nCoV), first reported in Wuhan, China, in December 2019, has affected 216 countries/territories worldwide. The total number of cases amount to 12.96 million across the globe, and 0.9 million in India as of mid-July 2020.[1] It is an acute respiratory disease, and the case fatality has been reported as 3%. Severe infection causes alveolar damage and progressive respiratory failure, leading to death. Furthermore, the severity or fatality is more in older population, who have comorbidities and weaker immune functions.[2] It is plausible to correlate further that clinical depression and the subsequent low immunity can act as risk factors for prognosis, predicting the severity of COVID-19 cases.

Patients with clinical depression have lower immunity than those of healthy controls.[3] An association between declining immunologic responses and fewer circulating CD4+ T-cells in the elderly with depression has been suggested. There is also reduction in natural killer cell cytotoxic responses of lymphocyte proliferation, which is a result of mitogen activation and suppression of delayed hypersensitivity reaction in individuals with clinical depression. Patients with COVID-19 also displayed a rise in the production of pro-inflammatory cytokines with low lymphocyte proliferation. There is an abnormal regulation of the hypothalamus–pituitary–adrenal axis, sympathetic–adrenal–medullary axis, and hypothalamopituitary ovarian axis in patients with clinical depression.[4]

Patients with COVID-19 present with the symptoms of lymphopenia, particularly the reduction of peripheral blood T-cell number, and increased plasma concentrations of pro-inflammatory cytokines, including interleukin (IL)-6, IL-10, granulocyte monocyte-colony stimulating factor (GM-CSF), monocyte chemoattractant protein 1, macrophage inflammatory protein 1α, and tumor necrosis factor-α. Presence of checkpoint receptors, Tm3+PD-1+ subsets in CD4+ and CD8+ T-cells, indicated their exhaustion. GM-CSF has been reported to be produced in response to viral infections in CD8+ T-lymphocytes. Severe acute respiratory syndrome-coronavirus-2 infects epithelial cells of the lungs and produces IL-8 in addition to IL-6 in severely affected patients. IL-8 is a chemoattractant for neutrophils and T-cells. Infiltration of many inflammatory cells has been observed in the lungs of severely affected patients, comprising both innate and adaptive cells. Patients with COVID-19 who were severely affected showed CD8+ cytotoxic T-cells derived from CD4+ T-cells, which not only neutralize the virus but also cause lung injury. Circulating monocytes are induced by GM-CSF released by these T-cells. Surface markers of inflammatory monocyte subsets such as CD14+ and CD16+ which rarely exist in healthy people have also been reported in significantly higher concentrations in severe COVID-19 cases. These monocyte subsets also show high expression of IL-6, which is likely to accelerate the systemic inflammatory response. Overactivation of T-cells, manifested Th17 rise, and high cytotoxicity of CD8+ T-cells are also known to account for severe immune injury in these patients.[5]

Following the outbreak of COVID-19, there have been multiple reports on how COVID-19 can lead to depression in patients and people of other classes of society. However, the fact that patients with clinical depression have a compromised immune system and this can act as a comorbidity which helps in accelerating COVID-19 infection and hence its progression remains to be elucidated.[6] It is, therefore, plausible to conduct studies on the pathophysiology of patients with COVID-19 with a history of depression.

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Conflicts of interest

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