scholarly journals Do sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression explain increased severity and mortality of COVID-19 in males?

Diagnosis ◽  
2020 ◽  
Vol 7 (4) ◽  
pp. 385-386 ◽  
Author(s):  
Jens Vikse ◽  
Giuseppe Lippi ◽  
Brandon Michael Henry

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), shares similarities with the former SARS outbreak, which was caused by SARS-CoV-1. SARS was characterized by severe lung injury due to virus-induced cytopathic effects and dysregulated hyperinflammatory state. COVID-19 has a higher mortality rate in men both inside and outside China. In this opinion paper, we describe how sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression may explain the increased severity and mortality of COVID-19 in males. We highlight that immunomodulatory treatment must be tailored to the underlying immunobiology at different stages of disease. Moreover, by investigating sex-based immunobiological differences, we may enhance our understanding of COVID-19 pathophysiology and facilitate improved immunomodulatory strategies.

2020 ◽  
Vol 134 (7) ◽  
pp. 747-750 ◽  
Author(s):  
Rhian M. Touyz ◽  
Hongliang Li ◽  
Christian Delles

Abstract Angiotensin converting enzyme 2 (ACE2) is the major enzyme responsible for conversion of Ang II into Ang-(1-7). It also acts as the receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2, which causes Coronavirus Disease (COVID)-19. In recognition of the importance of ACE2 and to celebrate 20 years since its discovery, the journal will publish a focused issue on the basic science and (patho)physiological role of this multifunctional protein.


2006 ◽  
Vol 81 (3) ◽  
pp. 1162-1173 ◽  
Author(s):  
Chien-Te K. Tseng ◽  
Cheng Huang ◽  
Patrick Newman ◽  
Nan Wang ◽  
Krishna Narayanan ◽  
...  

ABSTRACT Animal models for severe acute respiratory syndrome (SARS) coronavirus infection of humans are needed to elucidate SARS pathogenesis and develop vaccines and antivirals. We developed transgenic mice expressing human angiotensin-converting enzyme 2, a functional receptor for the virus, under the regulation of a global promoter. A transgenic lineage, designated AC70, was among the best characterized against SARS coronavirus infection, showing weight loss and other clinical manifestations before reaching 100% mortality within 8 days after intranasal infection. High virus titers were detected in the lungs and brains of transgene-positive (Tg+) mice on days 1 and 3 after infection. Inflammatory mediators were also detected in these tissues, coinciding with high levels of virus replication. Lower virus titers were also detected in other tissues, including blood. In contrast, infected transgene-negative (Tg−) mice survived without showing any clinical illness. Pathologic examination suggests that the extensive involvement of the central nervous system likely contributed to the death of Tg+ mice, even though viral pneumonia was present. Preliminary studies with mice of a second lineage, AC63, in which the transgene expression was considerably less abundant than that in the AC70 line, revealed that virus replication was largely restricted to the lungs but not the brain. Importantly, despite significant weight loss, infected Tg+ AC63 mice eventually recovered from the illness without any mortality. The severity of the disease that developed in these transgenic mice—AC70 in particular—makes these mouse models valuable not only for evaluating the efficacy of antivirals and vaccines, but also for studying SARS coronavirus pathogenesis.


2005 ◽  
Vol 11 (8) ◽  
pp. 875-879 ◽  
Author(s):  
Keiji Kuba ◽  
Yumiko Imai ◽  
Shuan Rao ◽  
Hong Gao ◽  
Feng Guo ◽  
...  

2020 ◽  
Vol 8 (T1) ◽  
pp. 363-365
Author(s):  
Riska Habriel Ruslie ◽  
Darmadi Darmadi ◽  
Gontar Alamsyah Siregar

Since the end of 2019 until present, coronavirus (CoV) disease (COVID)-2019 has spread globally and caused a pandemic. The disease is caused by severe acute respiratory syndrome-2 (SARS-CoV-2). The disease is showed to be less affecting pediatric population. The proportion children suffering from COVID-19 is only around 2% of total cases with only 0.08% mortality rate. Several hypotheses have been proposed regarding this condition. Children are supposed to be less exposed to patients with COVID-19, have lesser amount of angiotensin converting enzyme 2, have different immune response compared to adults, and have faster tissue recovery ability. All of them decrease the possibility of SARS-CoV-2 infection in pediatric population.


2020 ◽  
Vol 8 (2) ◽  
pp. 168-175
Author(s):  
Rudi Saputra

Introduction: COVID-19 (Coronavirus Disease 2019) is a new disease due to SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) which can be transmitted through droplets. One effort to prevent transmission of COVID-19 is to use a mask. Medical masks are effective in preventing transmission of COVID-19, but their numbers are very limited and are very much needed by medical personnel when treating COVID-19 patients. Therefore, to prevent the spread of COVID-19 more broadly, alternative medical masks are needed, namely by using cloth masks which have not been discussed much about the purpose of their use to the public. Discussion: SARS-CoV-2 is a cause of COVID-19 and infects the respiratory tract, especially in the lungs (pulmo) through the ACE2 receptor (Angiotensin-Converting Enzyme 2). SARS-CoV-2 has a diameter of around 120 nm. Cloth masks as an alternative to the scarcity of medical masks are recommended for public use. The recommended cloth masks are made of cotton or a cloth towel. A cloth mask is able to hold large droplets (> 5 μm), but not small droplets. Conclusion: Cloth masks can be used by the community in an effort to minimize transmission of COVID-19 by holding large droplets, but it is not effective in preventing transmission of COVID-19 because it can still be passed by SARS-CoV-2. Suggestion: Cloth masks can be optimized using nanoparticles to resist SARS-CoV-2.


Author(s):  
Huihui Mou ◽  
Brian D. Quinlan ◽  
Haiyong Peng ◽  
Yan Guo ◽  
Shoujiao Peng ◽  
...  

SUMMARYThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme 2 (ACE2). ACE2 is also the viral receptor of SARS-CoV (SARS-CoV-1), a related coronavirus that emerged in 2002-2003. Horseshoe bats (genus Rhinolophus) are presumed to be the original reservoir of both viruses, and a SARS-like coronavirus, RaTG13, closely related SARS-CoV-2, has been isolated from one horseshoe-bat species. Here we characterize the ability of S-protein receptor-binding domains (RBDs) of SARS-CoV-1, SARS-CoV-2, and RaTG13 to bind a range of ACE2 orthologs. We observed that the SARS-CoV-2 RBD bound human, pangolin, and horseshoe bat (R. macrotis) ACE2 more efficiently than the SARS-CoV-1 or RaTG13 RBD. Only the RaTG13 RBD bound rodent ACE2 orthologs efficiently. Five mutations drawn from ACE2 orthologs of nine Rhinolophus species enhanced human ACE2 binding to the SARS-CoV-2 RBD and neutralization of SARS-CoV-2 by an immunoadhesin form of human ACE2 (ACE2-Fc). Two of these mutations impaired neutralization of SARS-CoV-1. An ACE2-Fc variant bearing all five mutations neutralized SARS-CoV-2 five-fold more efficiently than human ACE2-Fc. These data narrow the potential SARS-CoV-2 reservoir, suggest that SARS-CoV-1 and -2 originate from distinct bat species, and identify a more potently neutralizing form of ACE2-Fc.


2020 ◽  
Vol 26 (10) ◽  
pp. 1166-1172
Author(s):  
Jinghong Li ◽  
Qi Wei ◽  
Willis X. Li ◽  
Karen C. McCowen ◽  
Wei Xiong ◽  
...  

Objective: Although type 2 diabetes mellitus (T2DM) has been reported as a risk factor for coronavirus disease 2019 (COVID-19), the effect of pharmacologic agents used to treat T2DM, such as metformin, on COVID-19 outcomes remains unclear. Metformin increases the expression of angiotensin converting enzyme 2, a known receptor for severe acute respiratory syndrome coronavirus 2. Data from people with T2DM hospitalized for COVID-19 were used to test the hypothesis that metformin use is associated with improved survival in this population. Methods: Retrospective analyses were performed on de-identified clinical data from a major hospital in Wuhan, China, that included patients with T2DM hospitalized for COVID-19 during the recent epidemic. One hundred and thirty-one patients diagnosed with COVID-19 and T2DM were used in this study. The primary outcome was mortality. Demographic, clinical characteristics, laboratory data, diabetes medications, and respiratory therapy data were also included in the analysis. Results: Of these 131 patients, 37 used metformin with or without other antidiabetes medications. Among the 37 metformin-taking patients, 35 (94.6%) survived and 2 (5.4%) did not survive. The mortality rates in the metformin-taking group versus the non-metformin group were 5.4% (2/37) versus 22.3% (21/94). Using multivariate analysis, metformin was found to be an independent predictor of survival in this cohort ( P = .02). Conclusion: This study reveals a significant association between metformin use and survival in people with T2DM diagnosed with COVID-19. These clinical data are consistent with potential benefits of the use of metformin for COVID-19 patients with T2DM. Abbreviations: ACE2 = angiotensin-converting enzyme 2; AMPK = AMP-activated protein kinase; BMI = body mass index; COVID-19 = coronavirus disease 2019; SARSCoV-2 = severe acute respiratory syndrome coronavirus 2; T2DM = type 2 diabetes mellitus


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