The Probable Mechanism of Hair Loss in Patients With COVID-19 : The American Journal of Dermatopathology

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The Probable Mechanism of Hair Loss in Patients With COVID-19

Khezri, Mohammad Rafi PharmD*; Ghasemnejad-Berenji, Morteza PhD*,†

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The American Journal of Dermatopathology: July 2022 - Volume 44 - Issue 7 - p 539-541
doi: 10.1097/DAD.0000000000002145
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To the Editor:

Coronavirus disease 2019 (COVID-19), which has been declared as a pandemic by the WHO, is the major challenge face health care systems all over the world.1 Although this disease causes a wide range of systemic complications that have attracted the most attention, there are other complications such as hair loss, which has been reported in some patients with SARS-CoV-2 infection. However, although the direct mechanism of this hair loss is not clear, we hypothesize that the cytokine storm and subsequent inflammation induced by SARS-CoV-2 may be involved. Hair loss has been detected in infection with different viruses, such as cytomegalovirus, Epstein–Barr virus, and swine flu virus.2–4 In these viral infections, hair loss is associated with inflammatory response induced by immune cells such as T-helper cells against the virus. Activation of these cells leads to the overproduction of interferons (IFNs), which are associated with the trigger of hair loss. IFNs alone cannot induce hair loss, and it has been demonstrated that injection of IFN- γ in a mouse model contributed to infiltration of CD4+ and CD8+ T cells and upregulation of IFN-γ–induced protein 10 leading to hair loss. In contrast, the subcutaneous injection of IFN‐γ failed to induce hair loss. In addition to IFNs, high levels of other inflammatory cytokines, such as IL-2 and IL-12, in viral infections are associated with hair loss induction.5 The high levels of mentioned proinflammatory cytokines have been detected in COVID-19 patients in different studies, and thus, it can be said that these findings could also be generalized to SARS-CoV-2–induced hair loss. In addition to the mentioned viruses, the HIV 1 can also cause hair loss. Interestingly, CD147 that acts as a receptor for HIV-1 and SARS-CoV-2 is expressed on the keratinocytes, and it can be a reason for their apoptosis in HIV-1 patients.6–8 Regarding the other SARS-CoV-2 receptors, the expression of angiotensin-converting enzyme 2 (ACE2) has been noted in basal epidermal layers, sebaceous gland cells, and hair follicle cells in normal skin.9,9 In a closer look, the high expression of ACE2 in keratinocytes has been detected.10 Keratinocytes can produce and release inflammatory cytokines, such as tumor necrosis factor-α, which has been linked to hair loss.11,12 Additionally, the effect of IFN-γ on keratinocytes leads to the induction of their apoptosis.13 The apoptosis of keratinocytes that has been detected in COVID-19 patients is a central element in the controlling of hair follicle regression.14,15 On the other hand, it has been demonstrated that TMPRSS2 is expressed in skin tissue.16 If the virus can infect skin cells through ACE2 and cause its decrease on the surface of skin cells, it can be concluded that the level of Ang II in the skin will increase. Increasing of Ang II in the skin is associated with necrosis induction.17 Also, it has been demonstrated that Ang II induces the expression of adhesion molecules leading to increasing the immune cells' infiltration into the tissue,18–20 where their upregulation has been shown in alopecia areata.21 Also, CD8+ cytotoxic T lymphocytes are associated with hair loss that way. It has been demonstrated that CD8+ cytotoxic T lymphocytes in which their increased cytotoxic potential has been shown in COVID-19 patients are required for hair loss induction.22,23Figure 1 represents the possible mechanisms of hair loss seen in COVID-19 patients.

F1
FIGURE 1.:
Possible mechanisms of hair loss seen in patients with SARS-CoV-2 infection.

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