Sex differences in immunological responses to COVID-19: a cross-sectional analysis of a single-centre cohort

Abstract

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Biological sex is associated with heterogeneous responses to IL-6 receptor inhibitor treatment in COVID-19—A retrospective cohort study

“…Dissimilarities in immune responses to COVID-19 may underpin sex- specific outcome differences. We have previously shown higher cytokine levels among males compared to females, despite similar age, viral load, degree of hypoxaemia at presentation, and requirement for organ support, consistent with an exaggerated host immune response in males 6 .…”

“…Biological mechanisms underpinning these observations have been investigated in an attempt to better understand the pathophysiology of COVID-19 15 . Several differences in the immune response between males and females have been described including higher pro-inflammatory innate immunity chemokines and cytokines in male patients 6 , 16 . Greater expression of virus entry factors (Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) in airway secretory cells and alveolar type 2 cells in males may explain the greater cytokine levels in male patients 17 .…”

The unique interplay of mitochondrial oxidative phosphorylation (OXPHOS) and immunity and its potential implication for the sex‐ and age‐related morbidity of severe COVID‐19 patients

“…Male patients are more vulnerable to severe or critical symptoms and are at a higher risk of death than females 8–14 . Elevated inflammation and cytokine storms have been proposed as contributors to the sex dimorphism in immune responses; in particular, the elevated innate immune reactions seen with some COVID‐19 patients are increasingly attracting attention 15–17 …”

“…[8][9][10][11][12][13][14] Elevated inflammation and cytokine storms have been proposed as contributors to the sex dimorphism in immune responses; in particular, the elevated innate immune reactions seen with some COVID-19 patients are increasingly attracting attention. [15][16][17] Sex steroid hormones have been proven to regulate immunity, and androgens especially are able to suppress immune responses. 18 Low baseline levels of androgens predict a poor prognosis and mortality in COVID-19 patients.…”

“… 8 , 9 , 10 , 11 , 12 , 13 , 14 Elevated inflammation and cytokine storms have been proposed as contributors to the sex dimorphism in immune responses; in particular, the elevated innate immune reactions seen with some COVID‐19 patients are increasingly attracting attention. 15 , 16 , 17 …”