Systematic Review and Meta-Analysis of Sex-Specific COVID-19 Clinical Outcomes

Abstract

To successfully mitigate the extraordinary devastation caused by the Coronavirus disease 2019 (COVID-19) pandemic, it is crucial to identify important risk factors for this disease. One such neglected health determinant is the sex of the patient. This is an essential clinical characteristic, as it can factor into a patient's clinical management and preventative measures. Some clinical studies have shown disparities in the proportion between males and females that have more severe clinical outcomes or, subsequently, die from this disease. However, this association has not been unequivocally established. Thus, the purpose of this investigation was to examine the association between male sex and COVID-19 severity. We systematically reviewed the literature, identified studies that matched predetermined selection criteria, and performed a meta-analysis to evaluate the proportion of males among four disease severity categories. Appropriate assessment strategies were implemented to assess and minimize potential biases. The results of this meta-analysis indicated that males constituted a significantly higher proportion of those who had adverse clinical outcomes and died from COVID-19. As the coronavirus spread from the East to the West, male sex remained a consistent risk factor. Our results support the establishment of the male sex as an important risk factor for this disease. Early identification and appropriate medical care for males with lab-confirmed COVID-19 may substantially change the course of clinical prognosis, resulting in greater numbers of lives saved.

Activation of the SARS-CoV-2 Receptor Ace2 through JAK/STAT-Dependent Enhancers during Pregnancy

“…Based on our study and previous data ( Ziegler et al., 2020 ) it is likely that IFNs and prolactin can activate Ace2 expression through STAT1 and STAT5. By including steroid hormones and males and females of different ages in future studies, insight into the sex differences seen in COVID-19 morbidity and mortality ( Galbadage et al., 2020 ) might emerge.…”

Early COVID-19 Interventions Failed to Replicate 1918 St. Louis vs. Philadelphia Outcomes in the United States

“…Besides, numerous risk factors have been identified for COVID-19 and its clinical outcomes. These include advanced age, sex, immune-compromised status, and comorbidities, including chronic respiratory diseases, diabetes, and hypertension ( 36 – 38 ). American Indians, African Americans, and Hispanic individuals have been reported to be four to five times more likely to be hospitalized for COVID-19 when compared to non-Hispanic whites ( 39 ).…”

Diabetes and Covid-19 among hospitalized patients in Saudi Arabia: a single-centre retrospective study

“…Men also had a higher prevalence of fever and diarrhea, as well as an over-all worse metabolic profile than women, despite having no differences in clinical outcomes. In contrast, most sexual differences among Covid-19 patients conducted elsewhere highlight similar prevalence in men and women, but with a consistently overwhelming worse outcomes in men in terms of morbidity and mortality, establishing male sex as an independent risk factor for Covid-19 [37][38][39]. The stronger innate and adaptive immune response in females can be attributed to many factors, but mostly to estrogen being immune boosting as opposed to testosterone, being immune suppressing [40].…”