Coronavirus disease 2019 (COVID-19) has shown high infection and mortality rates all over the world, and despite the global efforts, there is so far no specific therapy available for COVID-19. Interestingly, while the severity and mortality of COVID-19 are higher in males than in females, the underlying molecular mechanisms are unclear. In this review, we explore sex-related differences that may be contributing factors to the observed male-biased mortality from COVID-19. Males are considered the weaker sex in aspects related to endurance and infection control. Studies show that viral RNA clearance is delayed in males with COVID-19. A recent study has indicated that the testis can harbor coronavirus, and consequently, males show delayed viral clearance. However, the role of testis involvement in COVID-19 severity and mortality needs further research. Males and females show a distinct difference in immune system responses with females eliciting stronger immune responses to pathogens. This difference in immune system responses may be a major contributing factor to viral load, disease severity, and mortality. In addition, differences in sex hormone milieus could also be a determinant of viral infections as estrogen has immunoenhancing effects while testosterone has immunosuppressive effects. The sex-specific severity of COVID-19 infections indicates that further research on understanding the sex differences is needed. Inclusion of both males and females in basic research and clinical trials is required to provide critical information on sex-related differences that may help to better understand disease outcome and therapy.

中文翻译：

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COVID-19 严重程度和死亡率的性别差异：男性是否更容易受到伤害？

2019 冠状病毒病 (COVID-19) 在世界各地表现出较高的感染率和死亡率，尽管全球做出了努力，但迄今为止尚无针对 COVID-19 的特效疗法。有趣的是，虽然男性中 COVID-19 的严重程度和死亡率高于女性，但其潜在的分子机制尚不清楚。在这篇综述中，我们探讨了与性别相关的差异，这些差异可能是导致观察到的 COVID-19 死亡率偏向男性的因素。在耐力和感染控制方面，男性被认为是较弱的性别。研究表明，患有 COVID-19 的男性的病毒 RNA 清除延迟。最近的一项研究表明，睾丸可以藏有冠状病毒，因此男性的病毒清除速度延迟。然而，睾丸参与对 COVID-19 严重程度和死亡率的影响需要进一步研究。男性和女性的免疫系统反应存在明显差异，女性对病原体的免疫反应更强。免疫系统反应的这种差异可能是病毒载量、疾病严重程度和死亡率的主要影响因素。此外，性激素环境的差异也可能是病毒感染的决定因素，因为雌激素具有免疫增强作用，而睾酮具有免疫抑制作用。COVID-19 感染的性别特异性严重程度表明，需要进一步研究来了解性别差异。需要将男性和女性纳入基础研究和临床试验，以提供有关性别相关差异的关键信息，这可能有助于更好地了解疾病结果和治疗。