Immunity, Sex Hormones, and Environmental Factors as Determinants of COVID-19 Disparity in Women

Abstract

The current coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), has resulted in a major global pandemic, causing extreme morbidity and mortality. Few studies appear to suggest a significant impact of gender in morbidity and mortality, where men are reported at a higher risk than women. The infectivity, transmissibility, and varying degree of disease manifestation (mild, modest, and severe) in population studies reinforce the importance of a number of genetic and epigenetic factors, in the context of immune response and gender. The present review dwells on several contributing factors such as a stronger innate immune response, estrogen, angiotensin-converting enzyme 2 gene, and microbiota, which impart greater resistance to the SARS-CoV-2 infection and disease progression in women. In addition, the underlying importance of associated microbiota and certain environmental factors in gender-based disparity pertaining to the mortality and morbidity due to COVID-19 in women has also been addressed.

CCR2 and DPP9 expression in the peripheral blood of COVID-19 patients: Influences of the disease severity and gender

“…However, the male patients with severe COVID-19 expressed greater levels of CCR2 and DPP9 mRNA than female with same disease form. It has been reported that COVID-19-related mortality and morbidity are greater in male patients compared to female ( Rehman et al, 2021 , Chen et al, 2020 ). Moreover, profound differences have been indicated between male and female concerning the immunologic and inflammatory responses ( Rehman et al, 2021 ).…”

“…It has been reported that COVID-19-related mortality and morbidity are greater in male patients compared to female ( Rehman et al, 2021 , Chen et al, 2020 ). Moreover, profound differences have been indicated between male and female concerning the immunologic and inflammatory responses ( Rehman et al, 2021 ). Whether these differences can influence chemokine responses (such as MCP-1/CCR2 pathway) and regulatory mechanisms (such as DPP9) need to be described in future investigations.…”

Hormones and Sex-Specific Medicine in Human Physiopathology

“…Androgens' modulation in the immunological response to COVID-19 seems to be likewise in conflict. Studies on infected male mice have claimed a higher viral load and more inflammatory monocytes and macrophages [85]. These results could potentially correspond to the so-called 'cytokine storm' image present in most severe COVID-19 cases, where the hyperactivity of the immune system results in elevated concentrations of IL-6, IL-1, TNF-α, IFN-γ, and other proinflammatory cytokines [87].…”

“…The mechanisms of regulation of ACE-2 receptors by estrogens are in fact under investigation also as adjuvant therapy for the disease [84]. Many studies on animals support the protecting role of estrogens by observing worse COVID-19 outcomes in infected female mice undergoing ovariectomy or treated with estrogen receptor inhibitors [85]. The improving or deteriorating progression of the disease but also the susceptibility to infection have been markedly ascribed to the levels of female hormones present during the lifespan even if the process is still not fully clarified.…”

The Immune-Enhancing Properties of Hwanglyeonhaedok-Tang-Mediated Biosynthesized Gold Nanoparticles in Macrophages and Splenocytes

“…2 Furthermore, immune activation has been a long-term goal for treating immunosuppressive diseases and preventing infectious diseases. 3,4 Conventional immunostimulants potentiate antitumor immune responses and induces tumor regression; however, this often results in adverse inflammatory events. 5 Recombinant human interferon alfa (IFN-α) and the cytokine interleukin-2 (IL-2) were approved for the adjuvant immunotherapy of patients with resected high-risk melanoma in 1992 and 1998, respectively.…”