Male predisposition to severe COVID-19: Review of evidence and potential therapeutic prospects

Acheampong, Desmond Omane; Kyei-Barffour, Isaac; Boye, Alex; Aninagyei, Enoch; Ocansey, Stephen; Morna, Martin Tangnaa

doi:10.1016/j.biopha.2020.110748

Cited by 41 publications

(46 citation statements)

References 112 publications

(126 reference statements)

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“…These data also elucidate potential placental defenses against viral infection with SARS-CoV-2, including altered TMPRSS2 expression in the presence of maternal SARS-CoV-2 infection. 33 [30][31][32][33][34][35][36] 34 [30][31][32][33][34][35][36][37][38][39][40] 30 [27][28][29][30][31][32][33][34][35][36][37] 31 [26][27][28][29][30][31][32][33][34][35][36] 0.34 Black 5 ( 7) 1 ( 7) 3 ( 16) 0 (0) 1 ( 7)…”

Section: Strengths Of Our Study Include a Relatively Large Sample Size Of Pregnancies With Sars-mentioning

confidence: 99%

“…Whether male offspring are more susceptible to vertical transmission is not wellcharacterized, as vertical transmission is relatively uncommon, and sex disaggregated data are not routinely reported [2,3]. Given available data supporting a connection between COVID-19 outcomes and sex differences in ACE2 and TMPRSS2 expression levels [32,[36][37][38], and the paucity of information on ACE2 and TMPRSS2 expression during pregnancy, we sought to investigate whether placental expression of ACE2 and TMPRSS2 varies by fetal sex in the presence and absence of maternal SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

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Placental expression of ACE2 and TMPRSS2 in maternal SARS-CoV-2 infection: are placental defenses mediated by fetal sex?

Shook

Bordt

Meinsohn

et al. 2021

Preprint

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Background: Sex differences in vulnerability to and severity of SARS-CoV-2 infection have been described in non-pregnant populations. ACE2 and TMPRSS2, host molecules required for viral entry, are regulated by sex steroids and expressed in the placenta. We sought to investigate whether placental ACE2 and TMPRSS2 expression vary by fetal sex and in the presence of maternal SARS-CoV-2 infection. Methods: Placental ACE2 and TMPRSS2 were quantified in 68 pregnant individuals (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. Maternal SARS-CoV-2 status was determined by nasopharyngeal RT-PCR. Placental SARS-CoV-2 viral load was quantified. RTqPCR was performed to quantify expression of ACE2 and TMPRSS2 relative to the reference gene YWHAZ. Western blots were performed on placental homogenates to quantify protein levels. The impact of fetal sex and SARS-CoV-2 exposure on ACE2 and TMPRSS2 expression was analyzed by 2-way ANOVA. Results: SARS-CoV-2 virus was undetectable in all placentas. Maternal SARS-CoV-2 infection impacted TMPRSS2 placental gene and protein expression in a sexually dimorphic fashion (2-way ANOVA interaction p-value: 0.002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on placental ACE2 gene or protein expression. Placental TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman's rho=0.54, p=0.02) but not females (rho=0.23, p=0.34) exposed to maternal SARS-CoV-2. Conclusions: Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection. These findings may have implications for offspring vulnerability to placental infection and vertical transmission.These findings may have implications for offspring vulnerability to placental infection and vertical transmission.

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Section: Strengths Of Our Study Include a Relatively Large Sample Size Of Pregnancies With Sars-mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Placental expression of ACE2 and TMPRSS2 in maternal SARS-CoV-2 infection: are placental defenses mediated by fetal sex?

Shook

Bordt

Meinsohn

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Of great concern is that while most of the foregoing projections on the micro impact of COVID-19 on poverty have already been empirically validated and near over-researched in some settings (Austrian et al, 2020;BRAC, 2020;Kesar et al, 2020;Mahler et al, 2020bMahler et al, , 2020aMalik et al, 2020;Le Nestour et al, 2020;Rahman & Matin, 2020;Sumner et al, 2020), such pieces of evidence within the Ghanaian context remain largely unknown and insufficiently researched. Moreover, available evidence on the micro impact of COVID-19 in Ghana is largely focused on health (Acheampong et al, 2020;Afulani et al, 2020;Dzisi & Dei, 2020;Sarfo et al, 2020) and education (Demuyakor, 2020;Owusu & Frimpong-Manso, 2020;Upoalkpajor & Upoalkpajor, 2020) with very little on poverty (Durizzo et al, 2020). This notwithstanding, Durizzo et al (2020)'s study was limited in terms of content and geographical coverage.…”

Section: Introductionmentioning

confidence: 99%

Impact of COVID-19 on poverty and living standards in Ghana: A micro-perspective

Bukari

Essilfie

Aning-Agyei

et al. 2021

Cogent Economics & Finance

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The novel Coronavirus disease 2019 (COVID-19), which has become a global epidemic, hit Ghana on 12 March 2020 and, in less than a week, increased by over 300% with two deaths. As of 11 August 2020, Ghana had recorded over 41,000 cases with over 215 deaths. This study seeks to provide a micro-level evidence on how COVID-19 is posing a threat to some of the Sustainable Development Goals, particularly poverty in Ghana. Specifically, the study examined the effect of COVID-19 on poverty and living standards of Ghanaian households. The study further analysed which class of persons within the income distributions has been mostly hit by the pandemic. Data on 3,905 households were obtained via concurrent online survey and telephone interviews. Multiple analytical approaches were employed-Ordinary least squares, probit model and simultaneous quantile regressions. Results showed that COVID-19 had significantly increased the poverty levels of households while deteriorating living standards. The study also discovered that gender and locational heterogeneities exist regarding the impact of COVID-19 with females and rural dwellers mostly disadvantaged. However, simultaneous quantile regression result shows that in terms of overall household consumption, those in the middle and upper classes are profoundly affected compared to those in the lowest class. A ABOUT THE AUTHOR Chei Bukari is a Course Demonstrator and researcher in the School of Economics at the University of Cape Coast, Ghana. He has over five years of teaching and extensive research experience. His area of research includes poverty, inequality, finance and corruption. He has several research papers in refereed journals in these fields of interest. He has worked with several reputable organization including Ghana Statistical Service. The major contribution of this study is that COVID-19 is undermining Ghana's efforts to achieve the Sustainable Development Goals (SDGs) particularly poverty and hunger. By implication, while governments must not be complacent in their fight against COVID-19, post-COVID-19 policies will require extra-efforts if agenda 2030 (i.e., SDGs) is to be achieved.

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“…The co-expression of these two proteins varies between cells but has been shown to be present at the highest level in nasal cavity type 2 pneumocyte cells [ 33 , 34 ], which is in agreement with the clinical symptoms of this infection. Abnormalities in ACE2 expression in patients with hypertension and obesity [ 35 , 36 ] and abnormalities in TMPRSS2 expression in individuals exposed to high levels of androgens [ 37 , 38 ] have been shown to be risk factors for COVID-19 [ 6 ].…”

Section: Potential Pharmacological Actions Of Spironolactone In Comentioning

confidence: 99%

COVID-19—The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection

et al. 2021

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In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO). The clinical course of the disease is unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to acute respiratory distress syndrome (ARDS). It has been shown that pulmonary fibrosis may be one of the major long-term complications of COVID-19. In animal models, the use of spironolactone was proven to be an important drug in the prevention of pulmonary fibrosis. Through its dual action as a mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor, spironolactone can provide significant benefits concerning COVID-19 infection. The primary effect of spironolactone in reducing pulmonary edema may also be beneficial in COVID-19 ARDS. Spironolactone is a well-known, widely used and safe anti-hypertensive and antiandrogenic medication. It has potassium-sparing diuretic action by antagonizing mineralocorticoid receptors (MRs). Spironolactone and potassium canrenoate, exerting combined pleiotropic action, may provide a therapeutic benefit to patients with COVID-19 pneumonia through antiandrogen, MR blocking, antifibrotic and anti-hyperinflammatory action. It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin–angiotensin–aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia. Future prospective clinical trials are warranted to evaluate its therapeutic potential.

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Male predisposition to severe COVID-19: Review of evidence and potential therapeutic prospects

Abstract: Graphical abstract

Cited by 41 publications

References 112 publications

Placental expression of ACE2 and TMPRSS2 in maternal SARS-CoV-2 infection: are placental defenses mediated by fetal sex?

Placental expression of ACE2 and TMPRSS2 in maternal SARS-CoV-2 infection: are placental defenses mediated by fetal sex?

Impact of COVID-19 on poverty and living standards in Ghana: A micro-perspective

COVID-19—The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection

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