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Pathophysiology

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21/05/2020 Letter
Postmortem Examination of Patients With COVID-19

JAMA

Authors:
Tina Schaller, Klaus Hirschbühl, Katrin Burkhardt

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15/05/2020 Articles
Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

CELL

Authors:
Daniel Blanco-Melo, Benjamin E. Nilsson-Payant, Wen-Chun Liu, Jean K. Lim, Randy A. Albrecht, Benjamin R. tenOever

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14/05/2020 Articles
Complement Activation In Patients With Covid-19: A Novel Therapeutic Target

CELL

Authors:
Massimo Cugno, Pier Luigi Meroni, Roberta Gualtierotti, Samantha Griffini, Elena Grovetti, Adriana Torri, Mauro Panigada, Stefano Aliberti, Francesco Blasi, Francesco Tedesco, Flora Peyvandi

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13/05/2020 Correspondence
Multiorgan and Renal Tropism of SARS-CoV-2

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors:
Victor G. Puelles, Marc Lütgehetmann, Maja T. Lindenmeyer, Jan P. Sperhake, Milagros N. Wong, Lena Allweiss, Silvia Chilla, Axel Heinemann, Nicola Wanner, Shuya Liu, Fabian Braun, Shun Lu, Susanne Pfefferle, Ann S. Schröder, Carolin Edler M.D.,Oliver Gross, M.D.Markus Glatzel, Dominic Wichmann, Thorsten Wiech, Stefan Kluge, Klaus Pueschel, Martin Aepfelbacher, Tobias B. Huber

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11/05/2020 Review
Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an...

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

JOURNAL OF CLINICAL MEDICINE

Authors:
Celestino Sardu, Jessica Gambardella, Marco Bruno Morelli, Xujun Wang , Raffaele Marfella and Gaetano Santulli

ABSTRACT

The symptoms most commonly reported by patients affected by coronavirus disease (COVID-19) include cough, fever, and shortness of breath. However, other major events usually observed in COVID-19 patients (e.g., high blood pressure, arterial and venous thromboembolism, kidney disease, neurologic disorders, and diabetes mellitus) indicate that the virus is targeting the endothelium, one of the largest organs in the human body. Herein, we report a systematic and comprehensive evaluation of both clinical and preclinical evidence supporting the hypothesis that the endothelium is a key target organ in COVID-19, providing a mechanistic rationale behind its systemic manifestations.

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08/05/2020 Review
Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern...

Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Authors:
Andrea Picchianti Diamanti,Maria Manuela Rosado,Claudio Pioli,Giorgio Sesti, Bruno Laganà

ABSTRACT

On 7 January 2020, researchers isolated and sequenced in China from patients with seve re pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CR, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient’s clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk.

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07/05/2020 Comment
Assessment of SARS-CoV-2 replication in the context of other respiratory viruses

The Lancet

Authors:
Jessica A Belser



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07/05/2020 Correspondence
Prevention of the cytokine storm in COVID-19

The Lancet

Authors:
David J M Wright

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06/05/2020 Progress
Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages

NATURE REVIEWS

Authors:
Miriam Merad, Jerome C. Martin

ABSTRACT

The COVID-19 pandemic caused by infection with SARS-CoV-2 has led to more than 200,000 deaths worldwide. Several studies have now established that the hyperinflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. Macrophages are a population of innate immune cells that sense and respond to microbial threats by producing inflammatory molecules that eliminate pathogens and promote tissue repair. However, a dysregulated macrophage response can be damaging to the host, as is seen in the macrophage activation syndrome induced by severe infections, including in infections with the related virus SARS-CoV. Here we describe the potentially pathological roles of macrophages during SARS-CoV-2 infection and discuss ongoing and prospective therapeutic strategies to modulate macrophage activation in patients with COVID-19.

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06/05/2020 Short Communication
The role of vitamin D in the prevention of coronavirus disease 2019...

The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality

SPRINGER LINK

Authors:
Petre Cristian Ilie, Simina Stefanescu, Lee Smith



ABSTRACT WHO declared SARS-CoV-2 a global pandemic. The present aim was to propose an hypothesis that there is a potential association between mean levels of vitamin D in various countries with cases and mortality caused by COVID-19. The mean levels of vitamin D for 20 European countries and morbidity and mortality caused by COVID-19 were acquired. Negative correlations between mean levels of vitamin D (average 56 mmol/L, STDEV 10.61) in each country and the number of COVID-19 cases/1 M (mean 295.95, STDEV 298.7, and mortality/1 M (mean 5.96, STDEV 15.13) were observed. Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of the population in relation to COVID-19. It should be advisable to perform dedicated studies about vitamin D levels in COVID-19 patients with different degrees of disease severity.

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05/05/2020 Review
COVID-19, SARS and MERS: A neurological perspective

Journal of Clinical Neuroscience

Authors:
Koy Chong, Ng Kee Kwonga, Puja, R.Mehtab, GarimaShukla, Arpan R.Mehta

ABSTRACT

Central to COVID-19 pathophysiology is an acute respiratory infection primarily manifesting as pneumonia. Two months into the COVID-19 outbreak, however, a retrospective study in China involving more than 200 participants revealed a neurological component to COVID-19 in a subset of patients. The observed symptoms, the cause of which remains unclear, included impaired consciousness, skeletal muscle injury and acute cerebrovascular disease, and appeared more frequently in severe disease. Since then, findings from several studies have hinted at various possible neurological outcomes in COVID-19 patients. Here, we review the historical association between neurological complications and highly pathological coronaviruses including SARS-CoV, MERS-CoV and SARS-CoV-2. We draw from evidence derived from past coronavirus outbreaks, noting the similarities and differences between SARS and MERS, and the current COVID-19 pandemic. We end by briefly discussing possible mechanisms by which the coronavirus impacts on the human nervous system, as well as neurology-specific considerations that arise from the repercussions of COVID-19.

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05/05/2020 Correspondence
Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19

THE NEW ENGLAND JOURNAL OF MEDICINE

Authors:
Louise Bowles, Sean Platton, Nada Yartey, Minal Dave, Kurtis Lee, Daniel P. Hart, Vickie MacDonald, M.B., B.Chir., Laura Green, Suthesh Sivapalaratnam, K. John Pasi,Peter MacCallum



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04/05/2020 Articles
Post-mortem examination of COVID19 patients reveals diffuse alveolar damage with...

Post-mortem examination of COVID19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings of lungs and other organs suggesting vascular dysfunction

WILEY ONLINE LIBRARY

Authors:
T. Menter, J.D. Haslbauer, R. Nienhold, S. Savic, H. Hopfer, N. Deigendesch, S. Frank, D. Turek, N. Willi, H. Pargger, S. Bassetti, J.D. Leuppi, G. Cathomas, M. Tolnay, K.D. Mertz, A. Tzankov

ABSTRACT Aims Coronavirus disease 2019 (COVID‐19) caused by SARS‐CoV‐2 has rapidly evolved into a sweeping pandemic. While its major manifestation is in the respiratory tract, the general extent of organ involvement as well as microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID‐19‐associated organ alterations.

Methods This study reports autopsy findings of 21 COVID‐19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in‐corpore technique was performed to ensure optimal staff safety.

Results The primary cause of death was respiratory failure with exudative diffuse alveolar damage with massive capillary congestion often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolisms (n=4), alveolar haemorrhage (n=3) and vasculitis (n=1). Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, diabetes mellitus). Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively). All relevant histological slides are linked as open‐source scans in supplementary files.

Conclusions This study provides an overview of post‐mortem findings in COVID‐19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID‐19. This provides a pathophysiological explanation for higher mortality rates amongst these patients.

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28/04/2020 Research Highlight
COVID-19: towards understanding of pathogenesis

CELL RESEARCH

Authors:
Wei Cao, Taisheng Li

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23/04/2020 Opinion
COVID-19 Infection and Circulating ACE2 Levels: Protective Role in Women and Children

FRONTIERS IN PEDIATRICS

Authors:
Elena Ciaglia, Carmine Vecchion, Annibale Alessandro Puca

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23/04/2020 Brief Report
Association of Renin-Angiotensin System Inhibitors With Severity or Risk...

Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China

JAMA

Authors:
Juyi Li, Xiufang Wang, Jian Chen, Hongmei Zhang, Aiping Deng

ABSTRACT Importance Data are lacking whether patients with hypertension who are taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have increased severity or risk of mortality during hospitalization for coronavirus disease 2019 (COVID-19).

Objective To investigate the association between ACEIs/ARBs and severity of illness and mortality in patients with hypertension hospitalized for COVID-19 infection.

Design, Setting, and Participants Retrospective, single-center case series of the 1178 hospitalized patients with COVID-19 infections at the Central Hospital of Wuhan, China, from January 15 to March 15, 2020.

Main Outcomes and Measures COVID-19 was confirmed by real-time reverse transcription–polymerase chain reaction and epidemiologic, clinical, radiologic, laboratory, and drug therapy data were analyzed in all patients. The percentage of patients with hypertension taking ACEIs/ARBs was compared between those with severe vs nonsevere illness and between survivors vs nonsurvivors.

Results Of the 1178 patients with COVID-19, the median age was 55.5 years (interquartile range, 38-67 years) and 545 (46.3%) were men. The overall in-hospital mortality was 11.0%. There were 362 patients with hypertension (30.7% of the total group; median age, 66.0 years [interquartile range, 59-73 years]; 189 [52.2%] were men), of whom 115 (31.8%) were taking ACEI/ARBs. The in-hospital mortality in the patients with hypertension was 21.3%. The percentage of patients with hypertension taking ACEIs/ARBs did not differ between those with severe and nonsevere infections (32.9% vs 30.7%; P = .65) nor did it differ between nonsurvivors and survivors (27.3% vs 33.0%; P = .34). Similar findings were observed when data were analyzed for patients taking ACEIs and those taking ARBs.

Conclusions and Relevance This study provides clinical data on the association between ACEIs/ARBs and outcomes in patients with hypertension hospitalized with COVID-19 infections, suggesting that ACEIs/ARBs are not associated with the severity or mortality of COVID-19 in such patients. These data support current guidelines and societal recommendations for treating hypertension during the COVID-19 pandemic

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23/04/2020 Brief Communication
SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together...

SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes

NATURE MEDICINE

Authors:
Waradon Sungnak, Ni Huang, Christophe Bécavin, Marijn Berg, Rachel Queen, Monika Litvinukova, Carlos Talavera-López, Henrike Maatz, Daniel Reichart, Fotios Sampaziotis, Kaylee B. Worlock, Masahiro Yoshida, Josephine L. Barnes, HCA Lung

ABSTRACT

We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.

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20 /04/2020 Correspondence
Endothelial cell infection and endotheliitis in COVID-19

The Lancet

Authors:
Zsuzsanna Varga, Andreas J Flammer, Peter Steiger, Martina Haberecker, Rea Andermatt, Annelies S Zinkernagel, Mandeep R Mehra, Reto A Schuepbach, Frank Ruschitzka, Holger Moch

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17/04/2020 Report
Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model

Science

Authors:
Barry Rockx,Thijs Kuiken, Sander Herfst, Theo Bestebroer, Mart M. Lamers, Bas B. Oude Munnink, Dennis de Meulder, Geert van Amerongen, Judith van den Brand, Nisreen M. A. Okba, Debby Schipper, Peter van Run, Lonneke Leijten, Reina Sikkema, Ernst Verschoor, Babs Verstrepen, Willy Bogers, Jan Langermans, Christian Drosten, Martje Fentener van Vlissingen, Ron Fouchier, Rik de Swart, Marion Koopmans, Bart L. Haagmans



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17/04/2020 Summary

SARS-CoV-2 and viral sepsis: observations and hypotheses

The Lancet

Authors:
Hui Li, Liang Liu, Dingyu Zhang, Jiuyang Xu, Huaping Dai, Nan Tang, Xiao Su, Bin Cao

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12/04/2020 Articles
Estimation of airborne viral emission: Quanta emission rate of SARS-CoV-2 for infection risk assessment

MEDRXIV

Authors:
Giorgio Buonanno, Luca Stabile, Lidia Morawska

ABSTRACT

Airborne transmission is a pathway of contagion that is still not sufficiently investigated despite the evidence in the scientific literature of the role it can play in the context of an epidemic. While the medical research area dedicates efforts to find cures and remedies to counteract the effects of a virus, the engineering area is involved in providing risk assessments in indoor environments by simulating the airborne transmission of the virus during an epidemic. To this end, virus air emission data are needed. Unfortunately, this information is usually available only after the outbreak, based on specific reverse engineering cases. In this work, a novel approach to estimate the viral load emitted by a contagious subject on the basis of the viral load in the mouth, the type of respiratory activity (e.g. breathing, speaking), respiratory physiological parameters (e.g. inhalation rate), and activity level (e.g. resting, standing, light exercise) is proposed. The estimates of the proposed approach are in good agreement with values of viral loads of well-known diseases from the literature. The quanta emission rates of an asymptomatic SARS-CoV-2 infected subject, with a viral load in the mouth of 108 copies mL-1, were 10.5 quanta h-1 and 320 quanta h-1 for breathing and speaking respiratory activities, respectively, at rest. In the case of light activity, the values would increase to 33.9 quanta h-1 and 1.03×103 quanta h-1, respectively. The findings in terms of quanta emission rates were then adopted in infection risk models to demonstrate its application by evaluating the number of people infected by an asymptomatic SARS-CoV-2 subject in Italian indoor microenvironments before and after the introduction of virus containment measures. The results obtained from the simulations clearly highlight that a key role is played by proper ventilation in containment of the virus in indoor environments.

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06/04/2020 Review
Dysregulation of lung myeloid cells in COVID-19

Springer

Authors:
Bérengère Salomé, Assaf Magen

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06/04/2020 Review
Fighting COVID-19 exhausts T cells

Springer

Authors:
Chang Moon

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03/04/2020 Viewpoint
The Dilemma of Coronavirus Disease 2019, Aging, and Cardiovascular Disease..

The Dilemma of Coronavirus Disease 2019, Aging, and Cardiovascular Disease Insights From Cardiovascular Aging Science

JAMA

Authors:
Majd AlGhatrif, Oscar Cingolani, Edward G. Lakatta

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27/03/2020 Report
A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV

Science

Authors:
Meng Yuan, Nicholas C. Wu, Xueyong Zhu, Chang-Chun D. Lee, Ray T. Y. So, Huibin Lv, Chris K. P. Mok, Ian A. Wilson

Abstract

The outbreak of COVID-19 caused by SARS-CoV-2 virus has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein to 3.1 Å. CR3022 targets a highly conserved epitope, distal from the receptor-binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBD on the trimeric S protein are in the “up” conformation and slightly rotated. Overall, this study provides molecular insights into antibody recognition of SARS-CoV-2.

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27/03/2020 Articles
Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2

Science

Authors:
Renhong Yan, Yuanyuan Zhang, Yaning Li, Lu Xia, Yingying Guo, Qiang Zhou

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious epidemic COVID-19. Here we present cryo-EM structures of full-length human ACE2, in the presence of a neutral amino acid transporter B0AT1, with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 Å, with a local resolution of 3.5 Å at the ACE2-RBD interface. The ACE2- B0AT1 complex is assembled as a dimer of heterodimers, with the Collectrin-like domain (CLD) of ACE2 mediating homo-dimerization. The RBD is recognized by the extracellular peptidase domain (PD) of ACE2 mainly through polar residues. These findings provide important insights to the molecular basis for coronavirus recognition and infection.

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18/03/2020 PERSPECTIVE
SARS-CoV-2, the Virus that Causes COVID-19: Cytometry and the New Challenge for Global Health

Wiley Online Library

Authors:
Andrea Cossarizza, Sara De Biasi,Giovanni Guaraldi, Massimo Girardis, Cristina Mussini

SARS-CoV-2; Covid-19, coronavirus, cytometry, CD4, CD8, T cells

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01/03/2020 Articles
Molecular immune pathogenesis and diagnosis of COVID-19

ELSEVIER Journal of Pharmaceutical Analysis

Authors:
Xiaowei Li, Manman Geng, Yizhao Peng, Liesu Meng, Shemin Lu

Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus (SARS- CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) in the twenty-first century. In this minireview, we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis, diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections, which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection. © 2020 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license"

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27/02/2020 Review
The neuroinvasive potential of SARS‐CoV2 may play a role in the respiratory failure of COVID‐19 patients

Wiley Online Library

Authors:
Yan‐Chao Li, Wan‐Zhu Bai, Tsutomu Hashikawa

Following the severe acute respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV), another highly pathogenic coronavirus named SARS‐CoV‐2 (previously known as 2019‐nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with SARS‐CoV, and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID‐19) with clinical symptoms similar to those reported for SARS‐CoV and MERS‐CoV. The most characteristic symptom of patients with COVID‐19 is respiratory distress, and most of the patients admitted to the intensive care could not breathe spontaneously. Additionally, some patients with COVID‐19 also showed neurologic signs, such as headache, nausea, and vomiting. Increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases. The infection of SARS‐CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Furthermore, some coronaviruses have been demonstrated able to spread via a synapse‐connected route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. Considering the high similarity between SARS‐CoV and SARS‐CoV2, it remains to make clear whether the potential invasion of SARS‐CoV2 is partially responsible for the acute respiratory failure of patients with COVID‐19. Awareness of this may have a guiding significance for the prevention and treatment of the SARS‐CoV‐2‐induced respiratory failure.

cell susceptibility, coronavirus, dissemination, nervous system

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