Covid-19, TMPRSS2, and whether android regulation affects pandemic virus gender incidence and age distribution of disease

Brenner, Steven R.

doi:10.1016/j.mehy.2020.109773

Cited by 5 publications

(10 citation statements)

References 4 publications

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“…Its expression in the lung and sputum has been found to be higher in men than in women [ 62 , 68 ]. This is consistent with the increased susceptibility of men to COVID-19 because the increased TMPRSS2 allows for increased viral entry [ 64 ]. TMPRSS2 also has an estrogen-responsive promoter, a mechanistic step that may be of significance in the hormonal control in pediatric patients as compared to adults [ 69 ].…”

Section: Mechanistic Considerations In Diagnosis In Childrensupporting

confidence: 75%

“…TMPRSS2 is essential for entry of a variety of viruses, such as SARS-Cov-2, MERS-Cov, human coronavirus 229E (HCov-229E), influenza A virus, and influenza B virus, in the primary human type II pneumocytes and enhances the virulent effects on the host [ 46 , 62 , 63 ]. Subsequently, there is emerging therapeutic potential of TMPRSS2 inhibitors in the treatment of COVID-19 [ 46 , 64 ]. The TMPRSS2 gene, located on human chromosome 21, has several androgen receptor elements and TMPRSS2 protein is expressed in an androgen-dependent manner both in prostate and lung cancer cells [ 65 , 66 ].…”

Section: Mechanistic Considerations In Diagnosis In Childrenmentioning

confidence: 99%

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The Resilient Child: Sex-Steroid Hormones and COVID-19 Incidence in Pediatric Patients

Mihalopoulos

Levine

Marayati

et al. 2020

Journal of the Endocrine Society

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COVID-19, a disease caused by the SARS-CoV-2 infection, has become an unprecedented global health emergency, with fatal outcomes among adults of all ages in the United States, and the highest incidence and mortality in adult males. As the pandemic evolves there is limited understanding of a potential association between symptomatic viral infection and age. To date, there is no knowledge of the role children (pre-pubescent, ages 9 to 13) play as “silent” vectors of the virus, with themselves being asymptomatic. Throughout different time frames and geographic locations, the current evidence on COVID-19 suggests that children are getting infected at a significantly lower rate than other age groups - as low as 1%. Androgens upregulate the protease TMPRSS2 (Type-II Transmembrane Serine Protease-2), which facilitates efficient virus-host cell fusion with the epithelium of the lungs, thus increasing susceptibility to SARS-CoV-2 infection and development of severe COVID-19. Due to low levels of steroid hormones, pre-pubertal children may have low expression of TMPRSS2, thereby limiting the viral entry into host cells. As the world anticipates a vaccine against SARS-CoV-2, the role of pre-pubescent children as vectors transmitting the virus must be interrogated to prepare for a potential resurgence of COVID-19. This review discusses the current evidence on the low incidence of COVID-19 in children and the effect of sex steroid hormones on SARS-CoV-2 viral infection and clinical outcomes of pediatric patients. Upon reopening society at large, schools will need to implement heightened health protocols, with the knowledge that children as the “silent” viral transmitters, can significantly impact the adult populations.

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Section: Mechanistic Considerations In Diagnosis In Childrensupporting

confidence: 75%

Section: Mechanistic Considerations In Diagnosis In Childrenmentioning

confidence: 99%

The Resilient Child: Sex-Steroid Hormones and COVID-19 Incidence in Pediatric Patients

Mihalopoulos

Levine

Marayati

et al. 2020

Journal of the Endocrine Society

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“…It is reported that the male predominance phenomena of COVID-19 might be due to the androgen-driven pathogen of SARS-CoV‑2 [ 26 ]. In contrast, estrogen can increase the Interferon-gamma (IFN-γ) promoter’s activity, which participates in the responses to viral pathogens [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Influence of age and gender on the epidemic of COVID-19

Lou

Meng

et al. 2021

Wien Klin Wochenschr

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Background The pandemic of coronavirus disease 2019 (COVID-19) is spreading worldwide with an uncertain ultimate impact on every aspect of human society. Recognizing the groups with higher susceptibility and fatality are in urgent need. Methods We retrieved the total number of confirmed incident and death cases of COVID-19 in 177 countries/territories from the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Data of age and gender composition were collected from the United Nations Department of Economic and Social Affairs. Spearman's correlation analysis was used to explore the association between the composition of age and gender and the incidence rate (IRC), case fatality rate (CFRC), and mortality rate of COVID-19 (MRC). Multiple comparisons were adjusted by the Bonferroni method, and the threshold p-value was set as p < 0.01. Software SPSS 23.0, ArcGIS Dingtao Hu and Xiaoqi Lou contributed equally to this work and should be considered as co-first authors. Data availability statement Data is available to authorized users.

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“…This loop results in a rapidly progressive and widespread alveolar damage [ 11 ]. Transmembrane Protease, Serine 2 (TMPRSS2) by contrast, is a transmembrane serine protease receptor (required for S protein priming, which may prevent cell entry of SARS-CoV-2 [ 59 ]. A TMPRSS2 inhibitor blocking entry might constitute a treatment option of SARS-CoV-2 [ 60 ].…”

Section: The Mechanism Of Sars-cov-2 Entrymentioning

confidence: 99%

COVID-19 Is a Multifaceted Challenging Pandemic Which Needs Urgent Public Health Interventions

et al. 2020

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Until less than two decades ago, all known human coronaviruses (CoV) caused diseases so mild that they did not stimulate further advanced CoV research. In 2002 and following years, the scenario changed dramatically with the advent of the new more pathogenic CoVs, including Severe Acute Respiratory Syndome (SARS-CoV-1), Middle Eastern respiratory syndrome (MERS)-CoV, and the new zoonotic SARS-CoV-2, likely originated from bat species and responsible for the present coronavirus disease (COVID-19), which to date has caused 15,581,007 confirmed cases and 635,173 deaths in 208 countries, including Italy. SARS-CoV-2 transmission is mainly airborne via droplets generated by symptomatic patients, and possibly asymptomatic individuals during incubation of the disease, although for the latter, there are no certain data yet. However, research on asymptomatic viral infection is currently ongoing worldwide to elucidate the real prevalence and mortality of the disease. From a clinical point of view, COVID-19 would be defined as “COVID Planet “ because it presents as a multifaceted disease, due to the large number of organs and tissues infected by the virus. Overall, based on the available published data, 80.9% of patients infected by SARS-CoV-2 develop a mild disease/infection, 13.8% severe pneumonia, 4.7% respiratory failure, septic shock, or multi-organ failure, and 3% of these cases are fatal, but mortality parameter is highly variable in different countries. Clinically, SARS-CoV-2 causes severe primary interstitial viral pneumonia and a “cytokine storm syndrome”, characterized by a severe and fatal uncontrolled systemic inflammatory response triggered by the activation of interleukin 6 (IL-6) with development of endothelitis and generalized thrombosis that can lead to organ failure and death. Risk factors include advanced age and comorbidities including hypertension, diabetes, and cardiovascular disease. Virus entry occurs via binding the angiotensin-converting enzyme 2 (ACE2) receptor present in almost all tissues and organs through the Spike (S) protein. Currently, SARS-CoV-2 infection is prevented by the use of masks, social distancing, and improved hand hygiene measures. This review summarizes the current knowledge on the main biological and clinical features of the SARS-CoV-2 pandemic, also focusing on the principal measures taken in some Italian regions to face the emergency and on the most important treatments used to manage the COVID-19 pandemic.

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Covid-19, TMPRSS2, and whether android regulation affects pandemic virus gender incidence and age distribution of disease

Cited by 5 publications

References 4 publications

The Resilient Child: Sex-Steroid Hormones and COVID-19 Incidence in Pediatric Patients

The Resilient Child: Sex-Steroid Hormones and COVID-19 Incidence in Pediatric Patients

Influence of age and gender on the epidemic of COVID-19

COVID-19 Is a Multifaceted Challenging Pandemic Which Needs Urgent Public Health Interventions

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