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. 2020 Jun 1:1–7. doi: 10.1080/07391102.2020.1767211

The expression level of angiotensin-converting enzyme 2 determines the severity of COVID-19: lung and heart tissue as targets

Mohammad Mahdi Nejadi Babadaei a, Anwarul Hasan b,c,✉, Samir Haj Bloukh d, Zehra Edis e, Majid Sharifi f, Ehsan Kachooei g, Mojtaba Falahati f,✉
PMCID: PMC7284141  PMID: 32397951

Abstract

Researchers have reported some useful information about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to CoV disease 2019 (COVID-19). Several studies have been performed in order to develop antiviral drugs, from which a few have been prescribed to patients. Also, several diagnostic tests have been designed to accelerate the process of identifying and treating COVID-19. It has been well-documented that the surface of host cells is covered by some receptors, known as angiotensin-converting enzyme 2 (ACE2), which mediates the binding and entry of CoV. After entering, the viral RNA interrupts the cell proliferation system to activate self-proliferation. However, having all the information about the outbreakof the SARS-COV-2, it is not still clear which factors determine the severity of lung and heart function impairment induced by COVID-19. A major step in exploring SARS-COV-2 pathogenesis is to determine the distribution of ACE2 in different tissues . In this review, the structure and origin of CoV, the role of ACE2 as a receptor of SARS-COV-2 on the surface of host cells, and the ACE2 distribution in different tissues with a focus on lung and cardiovascular system have been discussed. It was also revealed that acute and chronic cardiovascular diseases (CVDs) may result in the clinical severity of COVID-19. In conclusion, this review may provide useful information in developing some promising strategies to end up with a worldwide COVID-19 pandemic.

Communicated by Ramaswamy H. Sarma

Keywords: Coronavirus, COVID-19, SARS, MERS, SARS-CoV-2, ACE2, lung, heart

1. Introduction

Severe acute respiratory syndrome (SARS)-CoV, as well as middle east respiratory syndrome (MERS) and SARS CoV 2 (SARS-CoV-2) belong to coronaviridae family (Payne, 2017; Schwartz & Graham, 2020). All these three viruses are pathogenic and cause of respiratory problems in humans (Kwok et al., 2019; Peeri et al., 2020). In the December 2019, a series of unexpected cases of pneumonia were observed in China (He, Deng, et al., 2020; Zu et al., 2020). The government and health researchers in this country proceeded strategies to control the outbreak of the virus and programmed an etiological study (Kucharski et al., 2020; Prem et al. 2020). Finlay, World Health Organization (WHO) announced that the SARS-CoV-2 causes the CoV disease 2019 (COVID-19) (Lai et al., 2020).

The COVID-19 incubation period is estimated from 1 to 14 days (Lauer et al., 2020; Linton et al., 2020). The lungs are the main organs that are affected by COVID-19 (Aigner et al., 2020; Cheng, Wang, et al., 2020), but in serious cases other parts of the body such as central nervous system (CNS) (Baig et al., 2020), kidney (Cheng, Luo, et al., 2020; He, Mok, et al., 2020), liver (Feng et al., 2020; Zhang, Shi, et al., 2020), heart (Akhmerov & Marban, 2020; Shi et al., 2020), stomach (Poggiali et al., 2020), intestine (Cao, 2020; Monteleone & Ardizzone, 2020; Turner et al., 2020) can also be affected.

Like many other respiratory diseases, the severity of the infection caused by the SARS-CoV-2 can vary from patient to patient. According to the latest findings, some cases of SARS-CoV-2 infection were associated with pneumonia and shortness of breath (Cao et al., 2020; Wu, Zhao, et al., 2020).On the other hand, some patients diagnosed with the SARS-CoV-2 showed developed respiratory failure, septic shock, or multiple organ failure (Landi et al. 2020; Liu et al., 2020). Notably, the fatality rate of infection was reported to be approximately 2% (Banerjee et al., 2020).

Scientists are trying to figure out the reasons for increasing rate of infection and death in infected population with the SARS-CoV-2 (Pedersen & Ho, 2020). The latest data from China are based on an analysis of confirmed cases, and generally show that elderly people and those who have already suffered from serious disease are significantly at higher risk of COVID-19 (Le Couteur et al., 2020; Lipsitch et al., 2020). The fatality rate of healthy people who die from COVID-19 is less than 1%, whereas the fatality rate for people with cardiovascular disease (CVDs) is more than 10% (Matsushita et al., 2020), for diabetics 7.3% (Hill et al., 2020), and for those with chronic respiratory disease is about 6% (Halpin et al., 2020).

Overall, less than 3% of COVID-19 cases showed fatal, and statistical analysis shows that 14.8% of these patients were older than 80 years (Le Couteur et al., 2020; Rothan & Byrareddy, 2020). These statistical analysis shows that older people are more prone to severe forms of COVID-19 (Le Couteur et al., 2020). The death had occurred in all age groups except in children and there were proportionally few cases among children in general. This pattern of increasing severity of the COVID-19 with age is totally different with the outbreak of some other CoVs. It is postulated that the severity of COVID-19 depends on a person’s immune response and the type of infected organ (Rothan & Byrareddy, 2020).

2. Structure and origin of CoV

CoVs are single-stranded RNA viruses, sense-positive with animal origin and belong to the Coronaviridae family and the Nidovirales category (Chen et al., 2020; Pal et al., 2020). The CoVs are genotypically and serologically divided into four groups of α, β, γ, and δ. Approximately 30 species of CoV have been identified in vertebrates, whereas in human CoVs are dominantly from α and β groups (Zhou et al., 2020). CoVs belong to the group of β-CoVs and SARS-CoV-2 is the third known zoonotic CoV after SARS and MERS viruses, both of which also belong to the β-CoVs group (Boopathi et al., 2020).

Epidemiological studies of the early cases of SARS-CoV-2 pneumonia have shown that many cases have been exposed to the seafood market in Wuhan, China (Li, You, et al., 2020; Yang et al., 2020). It was also reported by WHO that SARS-CoV-2 was identified in specimens collected from the seafood market (Deng & Peng, 2020), but it was not yet fully understood what specific species of animals carry the SARS-CoV-2. SARS-CoV and MERS-CoV are known to be originated from bats as the main and natural reservoir and transmitted to humans from civet and camels, respectively (Jørgensen & das Neves, 2020).

It was recently confirmed that SARS-CoV-2 is a new CoV that is highly associated with bats’ CoV (Chan et al., 2020). Moreover, it has been shown that the SARS-CoV-2 is a chimeric virus between the bat CoV and the CoV of unknown origin (Benvenuto et al., 2020; Ji et al., 2020). Recently, the RNA sequence similarity between the SARS-CoV-2 and the SARS-CoV was found to be about 80% (Wu, Wu, et al., 2020). In addition, a strong homology between SARS-CoV-2 and the bat CoV was reported. Thus, current evidence strongly confirms that the SARS-CoV-2 was originated from bats (Wu, Wu, et al., 2020; Zhou et al., 2020). Currently, SARS-CoV-2 has been isolated from pangolins, which shows 99% similarity to the strains isolated from humans infected with the SARS-CoV-2 (Wu, Wu, et al., 2020; Zhou et al., 2020). The origin of SARS-CoV-2 and the virus that trigged the outbreak of SARS in 2003 are generally related, however, the disease caused by each of these viruses is quite different (Peeri et al., 2020). The fatality rate of SARS is higher than COVID-19, but the prevalence of COVID-19 is much higher than that of SARS. Since 2003, there has been no outbreak of SARS-CoV anywhere in the world (Peeri et al., 2020).

3. The role of ACE2

One of the many factors involved in the development of high blood pressure and atherosclerosis is the renin-angiotensin system (RAS) (Battistoni & Volpe, 2020). Activation of RAS by the production of angiotensin (II) causes functional changes in the cardiovascular system (Masi et al., 2019). These changes include left ventricular hypertrophy, increased perforation of the smooth muscle of the vascular wall, and impaired vascular endothelial function (Ageev et al., 2008). In the RAS system, the angiotensin-converting enzyme 2 (ACE2) is a zinc atom-dependent metalloprotease, which catalyzes the conversion of angiotensin II to angiotensin I (Turner et al., 2002). The level of plasma ACE2 in a person is constant but varies between individuals (Hasan et al., 2020). It has been reported that SARS-CoV-2 binds to the human ACE2 via spike (S) protein C-terminal domain (CTD) (Figure 1(a)) and the SARS-CoV-2-CTD shows stronger binding affinity for human ACE2 in comparison with SARS-receptor binding domain (RBD) (Wang, Zhang, et al., 2020). The COVID-19 patients showed the symptoms of pneumonia and alveolar damage (Wang & Xu, 2020; Xu, Shi, et al., 2020). It has been shown that most of lung cells over-expressed ACE2 and the majority of ACE2 was upregulated on type II alveolar epithelial cells (AT2)(Zhao et al., 2020). It was also revealed that other types of lung cells expressed ACE2 with a limited distribution relative to AT2 (Figure 1(b)) (Zhao et al., 2020).

Figure 1.

Figure 1.

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a The structure of human ACE2 after interaction with SARS-CoV-2 S protein (Wang, Zhang, et al., 2020). b Single-cell map of human lung cells expressing ACE-2 (Zhao et al., 2020). Reprinted with permission from Refs. (Wang, Zhang, et al., 2020; Zhao et al., 2020). Abbreviation: tSNE: t-distributed Stochastic Neighbor Embedding.

4. The CoV receptor distribution

The ACE2 has been suggested as an essential receptor for the SARS-CoV-2 entry (Hasan et al., 2020; Sarma et al., 2020). Extensive expression of ACE2 in various cells, such as AT2 (Zhao et al., 2020), the upper part of esophagus, epithelial cells, and absorptive enterocytes of the ileum and colon, may play a key role in multinodular SARS-CoV-2 infection. For example, Xu, Zhong, et al. (2020) explored the potential way of SARS-CoV-2 infection in different organs as well as the mucosa of oral cavity through bulk RNA-seq analysis. The outcomes revealed the presence of ACE2 in different organs as well as epithelial cells of tongue (Figure 2A(a–d)). Indeed, these outcomes have elucidated the principal mechanism that the oral cavity is basically in higher risk to SARS-CoV-2 infection and showed a piece of conformation for the ongoing inhibition approach in clinical implementation

Figure 2.

Figure 2.

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A: ACE2 expression pattern in different organs. a ACE2 expression from TCGA dataset. b ACE2 expression from FANTOM5 CAGE dataset. c ACE2 expression from TCGA in different oral cavity. d ACE2 expression in two kinds of oral sites and others (Xu, Zhong, et al., 2020). B: ACE2 expression pattern in human testes. a ACE2 expression in different cell types. b TMPRSS2 expression in different cells (Wang & Xu, 2020). C: SARS-CoV-2 infection-related susceptible organs, Red: high risk, Grey: low-risk (Zou et al., 2020). Reprinted with permission from Refs. (Wang & Xu, 2020; Xu, Zhong, et al., 2020; Zou et al., 2020). Abbreviations: TCGA: The Cancer Genome Atlas; FANTOM5 CAGE: Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression; SPG: spermatogonia; TMPRSS2: transmembrane serine protease 2.

It has been also revealed that in addition to causing fever and respiratory symptoms, COVID-19 resulted in gastrointestinal disorders including diarrhoea, vomiting and some pains in abdominal part (Gu et al., 2020). It has been indicated that SARS-CoV-2 RNA is presence in anal/rectal swabs (Xu, Li, et al., 2020; Zhang, Du, et al. 2020) and stool samples (Holshue et al., 2020; Tang et al., 2020; Young et al., 2020) of patients with COVID-19 symptoms. Moreover, the viral ACE2 was revealed to be upregulated in gastrointestinal epithelial cells (Wong et al., 2020; Xiao et al., 2020).

Wang and Xu (2020) explored the sensitivity of the reproductive system to SARS-CoV-2 infection through RNA expression assay of ACE2. They found that ACE2 was remarkably upregulated in spermatogonia, Leydig, and Sertoli cells (Figure 2B(a)). Also, it has been reported recently that SARS-CoV-2 exploits the transmembrane serine protease 2 (TMPRSS2) for viral spike (S) protein cleavage (Hasan et al., 2020; Pant et al., 2020). The plots (Figure 2B(b)) indicated the pronounced upregulation of TMPRSS2 in spermatogonia and spermatids (Wang & Xu, 2020). Figure 2C also shows the SARS-CoV-2 infection-related sensitive organs which can explain about the non-respiratory symptoms identified in COVID-19 patients (Zou et al., 2020).

4.1. Lung

The distribution of ACE2 in different organs is significantly associated with the clinical symptoms of SARS-CoV-2 infection. It seems that any associated damage to the lung via external or internal factors can be mitigated by ACE2 inhibitors (Medhora et al., 2012). It has been reported that the level of pulmonary ACE2 is related to inflammatory lung disorders (Jia, 2016). Indeed, it has been well-documented that ACE2 is widley presented in the lungs (Kuba et al., 2010). It seems, the lung is the main sensitive tissue in response to SARS-CoV-2 infection (Guan et al., 2020; Wang & Xu, 2020; Yang et al., 2020).

Being involved in hemostasis, ACE2 can be considered as an important goal in the treatment of some well know diseases as well as COVID-19. However, due to the ineffectiveness of inhibitory drugs, some side effects can be observed. Some current studies are investigating the development of more potential specific ACE2 inhibitors based on chemical or biological compounds (Joshi et al., 2020). The inhibitory effects of various phases of different compounds can be investigated to reveal their concentration which inhibits the 50% of enzyme activity (Aanouz et al., 2020; Elmezayen et al., 2020). The evaluation of Km and Vmax can be used to assess the type of inhibitory mechanism by which a developed inhibitor impedes enzyme activity (Gupta et al., 2020; Muralidharan et al., 2020). The result can provide a potential model for reducing the SARS-CoV-2 infection with the ACE inhibition mechanism.

Li, He, et al. (2020) showed that the expression level of ACE2 in healthy people and patients with related disorders was not substantially different. However, relied on the increased upregulation of ACE2 in cigarette smokers, they anticipated that smoking may be identified as a risk factor for COVID-19 progression (Li, He, et al., 2020). The meta-analysis of previous results showed that ACE2 not only serves as a receptor, but it also plays an important role in post-infection mechanism such as immune system behavior, cytokine secretion, and viral viability. This result may provide a new platform for clinicians and researchers to attain more useful information regarding the pathogenesis of SARS-CoV-2 infection and to develop therapeutic platforms against COVID-19 (Li, You, et al., 2020). Pinto et al. (2020) also declared that ACE2 expression is enhanced in the lungs of COVID-19 patients with comorbidities.

4.2. Cardiovascular system

It has been well-documented that SARS-CoV-2 mainly infects alveolar epithelial cells, leading to respiratory disorders (Zheng et al., 2020). These SARS-CoV-2-induced disorders are more serious in patients with CVDs, which might be related to enhanced expression of ACE2 in these patients in comparison with healthy people. Indeed, ACE2 can be overexpressed by the consumption of some inhibitors against renin–angiotensin system (RAS) (Zheng et al., 2020). Therefore, the side effects of different therapies which might result in overexpression of ACE2 in patients infected with SARS-CoV-2 should be heedfully taken into consideration (Zheng et al., 2020).

4.2.1. Acute and chronic cardiovascular damage

Cardiac patients should be advised to take extra precautions, because the fatality rate of COVID-19 is higher in chronic CVD (Zheng et al., 2020). Patients with chronic heart disease or undergoing heart surgery have always been advised to use flu vaccines and pneumococcal vaccines at the appropriate time to prevent serious infectious and severe respiratory illness. The CoVs bind with high affinity to ACE2 receptors which are not only in the lungs, but also in other parts of the body, including the heart and digestive tract, kidney, and bladder (Hamming et al., 2004).

It has been proposed that the MERS-CoV can lead to acute myocarditis (AM) and heart-related diseases (Alhogbani, 2016). SARS-CoV-2 and MERS-CoV are similar pathogens (Elfiky & Azzam, 2020), and the AM stimulated by CoV clearly extend the adversity and complexity of patient handling. AM related to the SARS-CoV-2 can be observed in patients suffering from COVID-19, which is mostly evidenced as an enhancement in cardiac troponin I (cTnI) level (Huang et al., 2020). It was also seen that the levels of markers of AM were remarkably higher in COVID-19 patients handled in ICU, indicating that COVID-19 patients with serious stages usually show complexity involving AM (Wang, Hu, et al., 2020). Furthermore, among the identified cases of COVID-19 announced by the National Health Commission of China (NHC), a number of patients diagnosed with SARS-CoV-2 infection were primarily suffered from CVDs instead of respiratory disorders (Shi et al., 2020). Indeed, among the patients who died from SARS-CoV-2 infection with no related CVD, 12% of them suffered from considerable heart injury due to enhanced levels of cTnI (Akhmerov & Marban, 2020). Therefore, in patients with SARS-CoV-2 infection, the prevalence of AM is higher due to the systemic inflammatory behavior and immune system responses during disorder progression (Shi et al., 2020).

A follow-up survey of patients who recovered from COVID-19 revealed that around 50% suffered from CVDs (Clerkin et al., 2020). Based on the similarity between the structures of SARS-CoV-2 and SARS-CoV, it might lead to chronic injury in the cardiovascular system, therefore serious attempts should be done to result in cardiovascular protection during handling of COVID-19 (Zheng et al., 2020).

5. Conclusion and future perspective

According to a report from China, the fatality is observed in older people as well as patients with hypertension, chronic lung disease, diabetes, and CVDs. One of the most likely mechanisms by which COVID-19 can causes lung and cardiac damage is through the SARS-CoV-2 binding to ACE2 receptors. On the other hand, diabetics, hypertensive and cardiovascular patients are the most consumers of ACE inhibitor (ACEIs) and angiotensin II receptor blockers (ARBs). ACEI drugs do not directly affect the ACE2 receptor, but inhibition of angiotensin 2 production by negative feedback increases the expression of the ACE2 mRNA. Animal studies have shown that the use of some ACE2 inhibitors as potential drugs against hypertension was associated with a several fold increase in the expression of lung and cardiac ACE2 mRNA.

There are hypotheses that some drugs trigger ACE2 overexpression and therefore enhance the severity of the COVID-19. Although the genes encoding ACE2 protein, located on the X chromosome, is more abundant in women the incidence and fatality rate of COVID-19 infection is higher in men. In addition, in spite of the decrease in the expression level of ACE2 in body, the severity and fatality rate of COVID-19 infection increases with age. The ACE2 receptor has a protective effect in acute respiratory distress syndrome (ARDS) caused by influenza. In contrast, the binding of SARS-CoV-2 S protein to the ACE2 receptor reduces the ACE2 level of lung cells and increases the associated damage. At present, with the available information, it is not possible to draw any definite conclusions about whether or not to continue taking these drugs in treating COVID-19.

Disclosure statement

The authors declare no conflict of interest.

References

  1. Aanouz I., Belhassan A., El Khatabi K., Lakhlifi T., El Idrissi M., & Bouachrine M. (2020). Moroccan medicinal plants as inhibitors of COVID-19: Computational investigations. Journal of Biomolecular Structure and Dynamics, 1–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ageev F., Ovchinnikov A., Serbul V., & Belenkov Y. N. (2008). Left ventricular hypertrophy: Renin-angiotensin system role. Cardiovascular Therapy and Prevention, 7, 98–108. [Google Scholar]
  3. Aigner C., Dittmer U., Kamler M., Collaud S., & Taube C. (2020). COVID-19 in a lung transplant recipient. The Journal of Heart and Lung Transplantation, 1–9. 10.1016/j.healun.2020.04.004 [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Akhmerov A., & Marban E. (2020). COVID-19 and the heart. Circulation Research, 126(10), 1443–1455. 10.1161/CIRCRESAHA.120.317055 [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Alhogbani T. (2016). Acute myocarditis associated with novel Middle East respiratory syndrome coronavirus. Annals of Saudi Medicine, 36(1), 78–80. 10.5144/0256-4947.2016.78 [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Baig A. M., Khaleeq A., Ali U., & Syeda H. (2020). Evidence of the COVID-19 virus targeting the CNS: Tissue distribution, host–virus interaction, and proposed neurotropic mechanisms. ACS Chemical Neuroscience, 11(7), 995–998. 10.1021/acschemneuro.0c00122 [DOI] [PubMed] [Google Scholar]
  7. Banerjee S., Dhar S., Bhattacharjee S., & Bhattacharjee P. (2020). Decoding the lethal effect of SARS-CoV-2 (novel coronavirus) strains from global perspective: Molecular pathogenesis and evolutionary divergence. bioRxiv, 1–25. [Google Scholar]
  8. Battistoni A., & Volpe M. (2020). Might renin–angiotensin system blockers play a role in the COVID-19 pandemic? European Heart Journal-Cardiovascular Pharmacotherapy, 1–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Benvenuto D., Giovanetti M., Ciccozzi A., Spoto S., Angeletti S., & Ciccozzi M. (2020). The 2019‐new coronavirus epidemic: Evidence for virus evolution. Journal of Medical Virology, 92(4), 455–459. 10.1002/jmv.25688 [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Boopathi S., Poma A. B., & Kolandaivel P. (2020). Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. Journal of Biomolecular Structure and Dynamics, 1–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cao X. (2020). COVID-19: Immunopathology and its implications for therapy. Nature Reviews Immunology, 20(5), 269–270. 10.1038/s41577-020-0308-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cao Y., Liu X., Xiong L., & Cai K. (2020). Imaging and clinical features of patients with 2019 novel coronavirus SARS‐CoV‐2: A systematic review and meta‐analysis. Journal of Medical Virology, 1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chan J. F.-W., Kok K.-H., Zhu Z., Chu H., To K. K.-W., Yuan S., & Yuen K.-Y. (2020). Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerging Microbes & Infections, 9(1), 221–236. 10.1080/22221751.2020.1719902 [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Chen Y., Liu Q., & Guo D. (2020). Emerging coronaviruses: Genome structure, replication, and pathogenesis. Journal of Medical Virology, 92(4), 418–423. 10.1002/jmv.25681 [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cheng H., Wang Y., & Wang G. Q. (2020). Organ‐protective effect of angiotensin‐converting Enzyme 2 and its effect on the prognosis of COVID‐19. Journal of Medical Virology, 1–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cheng Y., Luo R., Wang K., Zhang M., Wang Z., Dong L., Li J., Yao Y., Ge S., & Xu G. (2020). Kidney impairment is associated with in-hospital death of COVID-19 patients. medRxiv, 1–21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Clerkin K. J., Fried J. A., Raikhelkar J., Sayer G., Griffin J. M., Masoumi A., Jain S. S., Burkhoff D., Kumaraiah D., & Rabbani L. (2020). Coronavirus disease 2019 (COVID-19) and cardiovascular disease. Circulation, 1–23. [DOI] [PubMed] [Google Scholar]
  18. Deng S.-Q., & Peng H.-J. (2020). Characteristics of and public health responses to the coronavirus disease 2019 outbreak in China. Journal of Clinical Medicine, 9(2), 575 10.3390/jcm9020575 [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Elfiky A. A., & Azzam E. B. (2020). Novel guanosine derivatives against MERS CoV polymerase: An in silico perspective. Journal of Biomolecular Structure and Dynamics, 1–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Elmezayen A. D., Al-Obaidi A., Şahin A. T., & Yelekçi K. (2020). Drug repurposing for coronavirus (COVID-19): In silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes. Journal of Biomolecular Structure and Dynamics, 1–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Feng G., Zheng K. I., Yan Q.-Q., Rios R. S., Targher G., Byrne C. D., Van Poucke S., Liu W.-Y., & Zheng M.-H. (2020). COVID-19 and liver dysfunction: Current insights and emergent therapeutic strategies. Journal of Clinical and Translational Hepatology, 8(1), 18–24. 10.14218/JCTH.2020.00018 [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gu J., Han B., & Wang J. (2020). COVID-19: Gastrointestinal manifestations and potential fecal–oral transmission. Gastroenterology, 158(6), 1518–1519. 10.1053/j.gastro.2020.02.054 [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Guan W-j., Ni Z-y., Hu Y., Liang W-h., Ou C-q., He J-x., Liu L., Shan H., Lei C-l., Hui D. S. C., Du B., Li L-j., Zeng G., Yuen K.-Y., Chen R-c., Tang C-l., Wang T., Chen P-y., Xiang J., … Zhong N-s. (2020). Clinical characteristics of coronavirus disease 2019 in China. The New England Journal of Medicine, 382(18), 1708–1720. 10.1056/NEJMoa2002032 [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Gupta M. K., Vemula S., Donde R., Gouda G., Behera L., & Vadde R. (2020). In-silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel. Journal of Biomolecular Structure and Dynamics, 1–17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Halpin D. M., Faner R., Sibila O., Badia J. R., & Agusti A. (2020). Do chronic respiratory diseases or their treatment affect the risk of SARS-CoV-2 infection? The Lancet Respiratory Medicine, 8(5), 436–438. 10.1016/S2213-2600(20)30167-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hamming I., Timens W., Bulthuis M., Lely A., Navis G., & van Goor H. (2004). Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. The Journal of Pathology, 203(2), 631–637. 10.1002/path.1570 [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hasan A., Paray B. A., Hussain A., Qadir F. A., Attar F., Aziz F. M., Sharifi M., Derakhshankhah H., Rasti B., & Mehrabi M. (2020). A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin. Journal of Biomolecular Structure and Dynamics, 1–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. He F., Deng Y., & Li W. (2020). Coronavirus disease 2019 (COVID‐19): What we know? Journal of Medical Virology, 1–7. 10.1002/jmv.25766 [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. He Q., Mok T. N., Yun L., He C., Li J., & Pan J. H. (2020). Single cell RNA sequencing analysis of human kidney reveals the presence of ACE2 receptor: A potential pathway of COVID-19 infection. SSRN, 1–29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Hill M. A., Mantzoros C., & Sowers J. R. (2020). Commentary: COVID-19 in patients with diabetes. Metabolism: Clinical and Experimental, 107, 154217 10.1016/j.metabol.2020.154217 [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Holshue M. L., DeBolt C., Lindquist S., Lofy K. H., Wiesman J., Bruce H., Spitters C., Ericson K., Wilkerson S., Tural A., Diaz G., Cohn A., Fox L., Patel A., Gerber S. I., Kim L., Tong S., Lu X., Lindstrom S., … Pillai S. K. (2020). First case of 2019 novel coronavirus in the United States. The New England Journal of Medicine, 382(10), 929–936. 10.1056/NEJMoa2001191 [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., Cheng Z., Yu T., Xia J., Wei Y., Wu W., Xie X., Yin W., Li H., Liu M., … Cao B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan. The Lancet, 395(10223), 497–506. 10.1016/S0140-6736(20)30183-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ji W., Wang W., Zhao X., Zai J., & Li X. (2020). Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross-species transmission from snake to human. Journal of Medical Virology, 1–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Jia H. (2016). Pulmonary angiotensin-converting enzyme 2 (ACE2) and inflammatory lung disease. Shock (Augusta, Ga.), 46(3), 239–248. 10.1097/SHK.0000000000000633 [DOI] [PubMed] [Google Scholar]
  35. Jørgensen H. J., & das Neves C. (2020). COVID-19: One world, one health. Tidsskrift for Den Norske Legeforening, 1–3. 10.4045/tidsskr.20.0212 [DOI] [PubMed] [Google Scholar]
  36. Joshi R. S., Jagdale S. S., Bansode S. B., Shankar S. S., Tellis M. B., Pandya V. K., Chugh A., Giri A. P., & Kulkarni M. J. (2020). Discovery of potential multi-target-directed ligands by targeting host-specific SARS-CoV-2 structurally conserved main protease$. Journal of Biomolecular Structure and Dynamics, 1–16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kuba K., Imai Y., Ohto-Nakanishi T., & Penninger J. M. (2010). Trilogy of ACE2: A peptidase in the renin–angiotensin system, a SARS receptor, and a partner for amino acid transporters. Pharmacology & Therapeutics, 128(1), 119–128. 10.1016/j.pharmthera.2010.06.003 [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Kucharski A. J., Russell T. W., Diamond C., Liu Y., Edmunds J., Funk S., Eggo R. M., Sun F., Jit M., Munday J. D., Davies N., Gimma A., van Zandvoort K., Gibbs H., Hellewell J., Jarvis C. I., Clifford S., Quilty B. J., Bosse N. I., … Flasche S. (2020). Early dynamics of transmission and control of COVID-19: A mathematical modelling study. The Lancet Infectious Diseases, 20(5), 553–558. 10.1016/S1473-3099(20)30144-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Kwok K. O., Tang A., Wei V. W., Park W. H., Yeoh E. K., & Riley S. (2019). Epidemic models of contact tracing: Systematic review of transmission studies of severe acute respiratory syndrome and Middle East respiratory syndrome. Computational and Structural Biotechnology Journal, 17, 186–194. 10.1016/j.csbj.2019.01.003 [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Lai C.-C., Shih T.-P., Ko W.-C., Tang H.-J., & Hsueh P.-R. (2020). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): The epidemic and the challenges. International Journal of Antimicrobial Agents, 55(3), 105924 10.1016/j.ijantimicag.2020.105924 [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Landi F., Barillaro C., Bellieni A., Brandi V., Carfì A., D’Angelo M., Fusco D., Landi G., Lo Monaco R., Martone A. M., Marzetti E., Pagano F., Pais C., Russo A., Salini S., Tosato M., Tummolo A., Benvenuto F., Bramato G., Catalano L., Ciciarello F., & Bernabei R. (2020). The New challenge of geriatrics: Saving frail older people from the SARS-CoV-2 pandemic infection. The Journal of Nutrition, Health & Aging, 24(5), 466–470. 10.1007/s12603-020-1356-x [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lauer S. A., Grantz K. H., Bi Q., Jones F. K., Zheng Q., Meredith H. R., Azman A. S., Reich N. G., & Lessler J. (2020). The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: Estimation and application. Annals of Internal Medicine, 172(9), 577 10.7326/M20-0504 [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Le Couteur D. G., Anderson R. M., & Newman A. B. (2020). COVID-19 is a disease of older people. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 1–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Li G., He X., Zhang L., Ran Q., Wang J., Xiong A., Wu D., Chen F., Sun J., & Chang C. (2020). Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19. Journal of Autoimmunity, 102463 10.1016/j.jaut.2020.102463 [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Li J.-Y., You Z., Wang Q., Zhou Z.-J., Qiu Y., Luo R., & Ge X.-Y. (2020). The epidemic of 2019-novel-coronavirus (2019-nCoV) pneumonia and insights for emerging infectious diseases in the future. Microbes and Infection, 22(2), 80–85. 10.1016/j.micinf.2020.02.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Linton N. M., Kobayashi T., Yang Y., Hayashi K., Akhmetzhanov A. R., Jung S-m., Yuan B., Kinoshita R., & Nishiura H. (2020). Incubation period and other epidemiological characteristics of 2019 novel coronavirus infections with right truncation: A statistical analysis of publicly available case data. Journal of Clinical Medicine, 9(2), 538 10.3390/jcm9020538 [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Lipsitch M., Swerdlow D. L., & Finelli L. (2020). Defining the epidemiology of Covid-19—studies needed. The New England Journal of Medicine, 382(13), 1194–1196. 10.1056/NEJMp2002125 [DOI] [PubMed] [Google Scholar]
  48. Liu Y., Chen H., Tang K., & Guo Y. (2020). Clinical manifestations and outcome of SARS-CoV-2 infection during pregnancy. Journal of Infection, 1–8. 10.1016/j.jinf.2020.02.028 [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Masi S., Uliana M., & Virdis A. (2019). Angiotensin II and vascular damage in hypertension: Role of oxidative stress and sympathetic activation. Vascular Pharmacology, 115, 13–17. 10.1016/j.vph.2019.01.004 [DOI] [PubMed] [Google Scholar]
  50. Matsushita K., Ding N., Kou M., Hu X., Chen M., Gao Y., Honda Y., Dowdy D., Mok Y., & Ishigami J. (2020). The relationship of COVID-19 severity with cardiovascular disease and its traditional risk factors: A systematic review and meta-analysis. medRxiv, 1–29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Medhora M., Gao F., Jacobs E. R., & Moulder J. E. (2012). Radiation damage to the lung: Mitigation by angiotensin-converting enzyme (ACE) inhibitors. Respirology (Carlton, Vic.), 17(1), 66–71. 10.1111/j.1440-1843.2011.02092.x [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Monteleone G., & Ardizzone S. (2020). Are patients with inflammatory bowel disease at increased risk for Covid-19 infection? Journal of Crohn’s and Colitis, 1–3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Muralidharan N., Sakthivel R., Velmurugan D., & Gromiha M. M. (2020). Computational studies of drug repurposing and synergism of lopinavir, oseltamivir and ritonavir binding with SARS-CoV-2 Protease against COVID-19. Journal of Biomolecular Structure and Dynamics, 1–7. [DOI] [PubMed] [Google Scholar]
  54. Pal M., Berhanu G., Desalegn C., & Kandi V. (2020). Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2): An update. Cureus, 12, 1–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Pant S., Singh M., Ravichandiran V., Murty U., & Srivastava H. K. (2020). Peptide-like and small-molecule inhibitors against Covid-19. Journal of Biomolecular Structure and Dynamics, 1–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Payne S. (2017). Family Coronaviridae. Viruses, 149–158. [Google Scholar]
  57. Pedersen S. F., & Ho Y.-C. (2020). SARS-CoV-2: A storm is raging. The Journal of Clinical Investigation, 130(5), 2202–2205. 10.1172/JCI137647 [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Peeri N. C., Shrestha N., Rahman M. S., Zaki R., Tan Z., Bibi S., Baghbanzadeh M., Aghamohammadi N., Zhang W., & Haque U. (2020). The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: What lessons have we learned? International Journal of Epidemiology, 1–10. 10.1093/ije/dyaa033 [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Pinto B. G., Oliveira A. E., Singh Y., Jimenez L., Goncalves A. N., Ogava R. L., Creighton R., Peron J. P., & Nakaya H. I. (2020). ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19. medRxiv, 1–16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Poggiali E., Bastoni D., Ioannilli E., Vercelli A., & Magnacavallo A. (2020). Abdominal pain: A real challenge in novel COVID-19 infection. European Journal of Case Reports in Internal Medicine, 7(5), 1 10.12890/2020_001646 [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Prem K., Liu Y., Russell T. W., Kucharski A. J., Eggo R. M., Davies N., Jit M., Klepac P., Flasche S., Clifford S., Pearson C. A. B., Munday J. D., Abbott S., Gibbs H., Rosello A., Quilty B. J., Jombart T., Sun F., Diamond C., … Hellewell J. (2020). The effect of control strategies to reduce social mixing on outcomes of the COVID-19 epidemic in Wuhan, China: A modelling study. The Lancet Public Health, 5(5), e261–e270. 10.1016/S2468-2667(20)30073-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Rothan H. A., & Byrareddy S. N. (2020). The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of Autoimmunity, 109, 102433 10.1016/j.jaut.2020.102433 [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Sarma P., Sekhar N., Prajapat M., Avti P., Kaur H., Kumar S., Singh S., Kumar H., Prakash A., & Dhibar D. P. (2020). In-silico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain). Journal of Biomolecular Structure and Dynamics, 1–11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Schwartz D. A., & Graham A. L. (2020). Potential maternal and infant outcomes from (Wuhan) coronavirus 2019-nCoV infecting pregnant women: Lessons from SARS, MERS, and other human coronavirus infections. Viruses, 12(2), 194 10.3390/v12020194 [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Shi S., Qin M., Shen B., Cai Y., Liu T., Yang F., Gong W., Liu X., Liang J., & Zhao Q. (2020). Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiology, 1–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Tang A., Tong Z-d., Wang H-l., Dai Y-x., Li K-f., Liu J-n., Wu W-j., Yuan C., Yu M-l., Li P., & Yan J-b. (2020). Detection of novel Coronavirus by RT-PCR in stool specimen from asymptomatic child. Emerging Infectious Diseases, 26(6), 1 10.3201/eid2606.20.0301 [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Turner A. J., Tipnis S. R., Guy J. L., Rice G. I., & Hooper N. M. (2002). ACEH/ACE2 is a novel mammalian metallocarboxypeptidase and a homologue of angiotensin-converting enzyme insensitive to ACE inhibitors. Canadian Journal of Physiology and Pharmacology, 80(4), 346–353. 10.1139/y02-021 [DOI] [PubMed] [Google Scholar]
  68. Turner D., Huang Y., Martín-de-Carpi J., Aloi M., Focht G., Kang B., Zhou Y., Sanchez C., Kappelman M. D., Uhlig H. H., Pujol-Muncunill G., Ledder O., Lionetti P., Dias J. A., Ruemmele F. M., & Russell R. K. (2020). COVID-19 and paediatric inflammatory bowel diseases: Global experience and provisional guidance (March 2020) from the paediatric IBD porto group of ESPGHAN. Journal of Pediatric Gastroenterology and Nutrition, 1 10.1097/MPG.0000000000002729 [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., Wang B., Xiang H., Cheng Z., Xiong Y., Zhao Y., Li Y., Wang X., & Peng Z. (2020). Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA, 323(11), 1061–1069. 10.1001/jama.2020.1585 [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Wang Q., Zhang Y., Wu L., Niu S., Song C., Zhang Z., Lu G., Qiao C., Hu Y., Yuen K.-Y., Wang Q., Zhou H., Yan J., & Qi J. (2020). Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell, 1–21. 10.1016/j.cell.2020.03.045 [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Wang Z., & Xu X. (2020). scRNA-seq profiling of human testes reveals the presence of the ACE2 receptor, a target for SARS-CoV-2 infection in spermatogonia, leydig and sertoli cells. Cells, 9(4), 920 10.3390/cells9040920 [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Wong S. H., Lui R. N., & Sung J. J. (2020). Covid‐19 and the digestive system. Journal of Gastroenterology and Hepatology, 35(5), 744–748. 10.1111/jgh.15047 [DOI] [PubMed] [Google Scholar]
  73. Wu D., Wu T., Liu Q., & Yang Z. (2020). The SARS-CoV-2 outbreak: What we know. International Journal of Infectious Diseases: IJID: Official Publication of the International Society for Infectious Diseases, 94, 44–48. 10.1016/j.ijid.2020.03.004 [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W., Tian J.-H., Pei Y.-Y., Yuan M.-L., Zhang Y.-L., Dai F.-H., Liu Y., Wang Q.-M., Zheng J.-J., Xu L., Holmes E. C., & Zhang Y.-Z. (2020). A new coronavirus associated with human respiratory disease in China. Nature, 579(7798), 265–269. 10.1038/s41586-020-2008-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Xiao F., Tang M., Zheng X., Liu Y., Li X., & Shan H. (2020). Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology, 158(6), 1831–1833.e3. 10.1053/j.gastro.2020.02.055 [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Xu H., Zhong L., Deng J., Peng J., Dan H., Zeng X., Li T., & Chen Q. (2020). High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. International Journal of Oral Science, 12(1), 8 10.1038/s41368-020-0074-x [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Xu Y., Li X., Zhu B., Liang H., Fang C., Gong Y., Guo Q., Sun X., Zhao D., Shen J., Zhang H., Liu H., Xia H., Tang J., Zhang K., & Gong S. (2020). Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nature Medicine, 26(4), 502–504. 10.1038/s41591-020-0817-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., Liu S., Zhao P., Liu H., Zhu L., Tai Y., Bai C., Gao T., Song J., Xia P., Dong J., Zhao J., & Wang F.-S. (2020). Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine, 8(4), 420–422. 10.1016/S2213-2600(20)30076-X [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Yang X., Yu Y., Xu J., Shu H., Xia J., Liu H., Wu Y., Zhang L., Yu Z., Fang M., Yu T., Wang Y., Pan S., Zou X., Yuan S., & Shang Y. (2020). Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. The Lancet Respiratory Medicine, 8(5), 475–481. 10.1016/S2213-2600(20)30079-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Young B. E., Ong S. W. X., Kalimuddin S., Low J. G., Tan S. Y., Loh J., Ng O.-T., Marimuthu K., Ang L. W., Mak T. M., Lau S. K., Anderson D. E., Chan K. S., Tan T. Y., Ng T. Y., Cui L., Said Z., Kurupatham L., Chen M. I.-C., Chan M., Vasoo S., & Lye D. C. (2020). Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA, 323(15), 1488 10.1001/jama.2020.3204 [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Zhang C., Shi L., & Wang F.-S. (2020). Liver injury in COVID-19: Management and challenges. The Lancet Gastroenterology & Hepatology, 5(5), 428–430. 10.1016/S2468-1253(20)30057-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Zhang W., Du R.-H., Li B., Zheng X.-S., Yang X.-L., Hu B., Wang Y.-Y., Xiao G.-F., Yan B., Shi Z.-L., & Zhou P. (2020). Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerging Microbes & Infections, 9(1), 386–389. 10.1080/22221751.2020.1729071 [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Zhao Y., Zhao Z., Wang Y., Zhou Y., Ma Y., & Zuo W. (2020). Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRxiv, 1–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Zheng Y.-Y., Ma Y.-T., Zhang J.-Y., & Xie X. (2020). COVID-19 and the cardiovascular system. Nature Reviews Cardiology, 17(5), 259–260. 10.1038/s41569-020-0360-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Zhou P., Yang X.-L., Wang X.-G., Hu B., Zhang L., Zhang W., Si H.-R., Zhu Y., Li B., Huang C.-L., Chen H.-D., Chen J., Luo Y., Guo H., Jiang R.-D., Liu M.-Q., Chen Y., Shen X.-R., Wang X., … Shi Z.-L. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798), 270–273. 10.1038/s41586-020-2012-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Zou X., Chen K., Zou J., Han P., Hao J., & Han Z. (2020). Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Frontiers of Medicine, 1–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Zu Z. Y., Jiang M. D., Xu P. P., Chen W., Ni Q. Q., Lu G. M., & Zhang L. J. (2020). Coronavirus disease 2019 (COVID-19): a perspective from China. Radiology, 1–29. [DOI] [PMC free article] [PubMed] [Google Scholar]

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