Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

Qi, Furong; Shen, Qian; Zhang, Shuye; Zhang, Zheng

doi:10.1101/2020.02.16.951913

Cited by 150 publications

(179 citation statements)

References 39 publications

(49 reference statements)

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“…Mechanistically, infection of gastrointestinal cells is most likely mediated by viral interaction with angiotensin converting enzyme 2 (ACE2), which serves as a functional receptor for SARS coronavirus [13] and which is expressed on gastrointestinal mucosal cells [14]. Currently, no evidence exists whether ACE2 is expressed in the vermiform appendix.…”

Section: Discussionmentioning

confidence: 99%

No SARS-CoV-2 detected in the vermiform appendix of a COVID-19 patient with appendicitis: a case report

Wolf¹,

Pietsch²,

Radosa³

et al. 2020

Preprint

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Background:SARS-CoV-2, the virus causing corona virus disease 2019 (COVID-19), has been demonstrated to infect the gastrointestinal tract and might therefore be a source of infection for the surgical team during abdominal operations. One of the most common surgical procedures performed is appendectomy. However, reports of virologic testing of appendiceal tissue specimens in COVID-19 patients are lacking. We sought to determine whether SARS-CoV-2 is present in the appendectomy specimen of a patient with COVID-19. Case presentation:A female patient presented to the emergency department of our tertiary care academic hospital with lower abdominal pain, fever, nausea, and vomiting. She was admitted to the gynecological floor because of suspected pelvic inflammatory disease. Due to worsening symptoms, a laparoscopy was performed the next day and a severely inflamed appendix was detected. Laparoscopic appendectomy was performed without complications. A few hours postoperatively, the patient was tested positive for corona virus disease 2019 (COVID 19). Real-time reverse transcription polymerase chain reaction analysis targeting the SARS-CoV-2 E-gene was performed on the appendectomy specimen. SARS-CoV-2 could not be detected. During her hospital stay, the patient developed mild respiratory symptoms while the postoperative course was otherwise uncomplicated. Conclusions:The absence of SARS-CoV-2 in the appendectomy specimen of our case adds to the preliminary available evidence indicating that appendectomy in COVID-19 patients with mild disease carries probably a low risk of infection by aerosols generated during the procedure.

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Section: Discussionmentioning

confidence: 99%

No SARS-CoV-2 detected in the vermiform appendix of a COVID-19 patient with appendicitis: a case report

Wolf¹,

Pietsch²,

Radosa³

et al. 2020

Preprint

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“…COVID19 belongs to a family of coronaviruses (CoV) that have evolved in various species (Lam et al, 2016). Human-infecting CoV such as SARS and COVID19 have acquired ability to bind the angiotensin converting enzyme (ACE) 2 on epithelial cells as a primary mechanism of entry into the host (Qi et al, 2020). Critical cases of COVID19 infection commonly manifest as cardiopulmonary symptoms and in severe cases advance into organ failure and sepsis as a result of a "cytokine storm" over activation of the immune system (Guan et al, 2020).…”

Section: Significance Statementmentioning

confidence: 99%

Does COVID19 Infect the Brain? If So, Smokers Might Be at a Higher Risk

Kabbani¹,

Olds²

2020

Mol Pharmacol

116

114

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COVID19 is a devastating global pandemic with epicenters in China, Italy, Spain, and now the United States. While the majority of infected cases appear mild, in some cases, individuals present serious cardiorespiratory complications with possible long-term Fig. 2. Mechanisms of ACE2 entry and COVID19 infection in neural cells. (A) A role for nicotine-associated upregulation of nAChRs in ACE2 expressing astrocytes and neurons. Based on published findings, upregulation of nAChRs can also increase ACE2 cell surface expression, thereby enhancing viral entry and infection. (B) A putative clinical timeline for progression of COVID19 into the brain. Coronavirus in the Brain and the Impact of Smoking

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“…These antibody testing results may also serve as a useful resource to help guide future protein-based studies.We next investigated ACE2 protein expression within the epithelium of the human respiratory tract using anti-ACE2 (ab15348) given its robust and specific staining patterns. Recent studies using scRNA-seq have identified ACE2 mRNA expression within ciliated epithelial cells in the nasal cavity [20][21][22] . Sungnak et al demonstrated that ciliated nasal epithelial cells have one of the highest ACE2 mRNA expression levels among investigated cell types in the respiratory tract 21 .We therefore performed double immunofluorescence staining using anti-ACE2 and antiacetylated α-tubulin (ACTUB), a marker of the cilia organelle, and discovered that not only is ACE2 expressed in ciliated epithelial cells, but within these cell types, ACE2 is abundantly present in the cilia organelle of human nasal turbinate, ethmoid sinus, uncinate process (sinus), trachea, and bronchial epithelial cells ( Fig.…”

mentioning

confidence: 99%

“…We next investigated ACE2 protein expression within the epithelium of the human respiratory tract using anti-ACE2 (ab15348) given its robust and specific staining patterns. Recent studies using scRNA-seq have identified ACE2 mRNA expression within ciliated epithelial cells in the nasal cavity [20][21][22] . Sungnak et al demonstrated that ciliated nasal epithelial cells have one of the highest ACE2 mRNA expression levels among investigated cell types in the respiratory tract 21 .…”

mentioning

confidence: 99%

Robust ACE2 protein expression localizes to the motile cilia of the respiratory tract epithelia and is not increased by ACE inhibitors or angiotensin receptor blockers

Lee

Goltsev

et al. 2020

Preprint

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We investigated the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of healthy human donors. We detected ACE2 protein expression within the cilia organelle of ciliated airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during respiratory transmission. We further determined whether ACE2 expression in the cilia of upper respiratory cells was influenced by patient demographics, clinical characteristics, co-morbidities, or medication use, and found no evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) increases ACE2 protein expression.Coronavirus disease 2019 is an ongoing pandemic infection caused by the positivesense RNA virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1 . The high transmissibility of the virus, along with case fatality estimates ranging from 1% to above 5%, has raised concerns worldwide. Patients with comorbid conditions including hypertension, diabetes, and pulmonary disease are highly represented among hospitalized patients with COVID-19 disease, suggesting the presence of risk factors that may determine susceptibility to SARS-CoV-2 infection [2][3][4][5] .A molecular connection between SARS-CoV-2 and hypertension, in particular, is suggested by the discovery that ACE2 is the major essential receptor for SARS-CoV-2 6,7 . ACE2 plays an important role in the renin-angiotensin-aldosterone system (RAAS), which consists of a cascade of vasoactive peptides that maintain blood pressure and electrolyte homeostasis. ACE2 converts vasoconstrictor peptides, angiotensin (Ang) II and Ang I, into the vasodilator peptides, Ang (1-7) and Ang (1-9), respectively 8 . These actions counterbalance the enzymatic effect of the related ACE, which generates angiotensin II from angiotensin I. ACEI and ARBs are commonly used antihypertensive drugs that target components of the RAAS. Several recent correspondences have raised concerns that ACEI and ARBs may increase expression of ACE2 and thereby elevate the risk of infection by SARS-CoV-2, thus potentially explaining why hypertension is a common comorbidity in patients with COVID-19 9-12 . This hypothesis is also rooted in human and rodent studies showing upregulation of ACE2 mRNA in the heart, kidney, and urine after ACEI/ARB administration [13][14][15] . Notably, however, the effects of ACEI and ARBs on the expression of ACE2 in the respiratory tract are currently unknown. Given SARS-CoV-2 causes respiratory infections, whether ACE2 expression is altered in the airway of patients taking ACEI or ARBs is a critical question that needs to be addressed to support continued clinical use of these antihypertensive drugs.We first determined the expression patterns of the ACE2 protein in the upper and lower respiratory tract. Gene expression analyses have identified ACE2 expression in the nasopharynx, oral muc...

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Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

Cited by 150 publications

References 39 publications

No SARS-CoV-2 detected in the vermiform appendix of a COVID-19 patient with appendicitis: a case report

No SARS-CoV-2 detected in the vermiform appendix of a COVID-19 patient with appendicitis: a case report

Does COVID19 Infect the Brain? If So, Smokers Might Be at a Higher Risk

Robust ACE2 protein expression localizes to the motile cilia of the respiratory tract epithelia and is not increased by ACE inhibitors or angiotensin receptor blockers

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