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Pathophysiology

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02/08/2020 Articles
SARS-CoV-2 can infect the placenta and is not associated with specific...

SARS-CoV-2 can infect the placenta and is not associated with specific placental histopathology: a series of 19 placentas from COVID-19-positive mothers

NATURE

Authors
Jonathon L. Hecht, Bradley Quade, Vikram Deshpande, Mari Mino-Kenudson, David T. Ting, Niyati Desai, Beata Dygulska, Taryn Heyman, Carolyn Salafia, Dejun Shen, Sara V. Bates, Drucilla J. Roberts



ABSTRACT
Congenital infection of SARS-CoV-2 appears to be exceptionally rare despite many cases of COVID-19 during pregnancy. Robust proof of placental infection requires demonstration of viral localization within placental tissue. Only two of the few cases of possible vertical transmission have demonstrated placental infection. None have shown placental expression of the ACE2 or TMPRSS2 protein, both required for viral infection. We examined 19 COVID-19 exposed placentas for histopathologic findings, and for expression of ACE2, and TMPRSS2 by immunohistochemistry. Direct placental SARS-CoV-2 expression was studied by two methods—nucleocapsid protein expression by immunohistochemistry, and RNA expression by in situ hybridization. ACE2 membranous expression in the syncytiotrophoblast (ST) of the chorionic villi is predominantly in a polarized pattern with expression highest on the stromal side of the ST. In addition, cytotrophoblast and extravillous trophoblast express ACE2. No ACE2 expression was detected in villous stroma, Hofbauer cells, or endothelial cells. TMPRSS2 expression was only present weakly in the villous endothelium and rarely in the ST. In 2 of 19 cases, SARS-CoV-2 RNA was present in the placenta focally in the ST and cytotrophoblast. There was no characteristic histopathology present in our cases including the two placental infections. We found that the placenta is capable of being infected but that this event is rare. We propose one explanation could be the polarized expression of ACE2 away from the maternal blood and pronounced paucity of TMPRSS2 expression in trophoblast.

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25/07/2020 Communication
Nox2 activation in Covid-19

ELSEVIER

Authors
Francesco Violi, Alessandra Oliva, Roberto Cangemi, Giancarlo Ceccarelli, Pasquale Pignatelli, Roberto Carnevale, Vittoria Cammisotto, Miriam Lichtner, Francesco Alessandri, Massimiliano De Angelis, Maria Claudia Miele, Gabriella D’Ettorre Franco Ruberto, Mario Venditti, Francesco Pugliese, Claudio Maria Mastroianni



ABSTRACT
Nox2 is responsible for artery dysfunction via production of reactive oxidant species. RNA viruses may activate Nox2, but it is unknown if this occurs in coronavirus 2019(Covid-19). Nox2 activation by soluble Nox2-derived peptide(sNox2-dp) was measured in patients hospitalized for Covid-19 (n = 182) and controls (n = 91). sNox2-dp values were higher in Covid-19 patients versus controls and in severe versus non severe Covid-19. Patients with thrombotic events(n = 35,19%) had higher sNox2-dp than thrombotic event-free ones. A logistic regression analysis showed that sNox2 and coronary heart disease predicted thrombotic events. Oxidative stress by Nox2 activation is associated severe disease and thrombotic events in Covid-19 patients.

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16/07/2020 Articles
Histopathology and ultrastructural findings of fatal COVID-19 infectio...

Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series

THE LANCET

Authors
Benjamin T Bradley, Heather Maioli, Robert Johnston, Irfan Chaudhry, Susan L Fink, Haodong Xu, Behzad Najafian, Gail Deutsch, J Matthew Lacy, Timothy Williams, Nicole Yarid, Desiree A Marshall


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10/07/2020 Articles
Extrapulmonary manifestations of COVID-19

NATURE

Authors
Aakriti Gupta, Mahesh V. Madhavan, Kartik Sehgal, Nandini Nair, Shiwani Mahajan, Tejasav S. Sehrawat, Behnood Bikdeli, Neha Ahluwalia, John C. Ausiello, Elaine Y. Wan, Daniel E. Freedberg, Ajay J. Kirtane, Sahil A. Parikh, Mathew S. Maurer, Anna S. Nordvig, Domenico Accili, Joan M. Bathon, Sumit Mohan, Kenneth A. Bauer, Martin B. Leon, Harlan M. Krumholz, Nir Uriel, Mandeep R. Mehra, Mitchell S. V. Elkind, Gregg W. Stone, Allan Schwartz, David D. Ho, John P. Bilezikian, Donald W. Landry



ABSTRACT
The CAlthough COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

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01/07/2020 Archivies
Adrenal Vascular Changes in COVID-19 Autopsies

COLLEGE OF AMERICAN PATHOLOGISTS

Authors
Alina C Iuga, Charles C Marboe, Mine M Yilmaz, Jay H Lefkowitch, Cosmin Gauran, Stephen M Lagana


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29/06/2020 Editorial
COVID-19 as a Vascular Disease: Lesson Learned from Imaging and Blood ...

COVID-19 as a Vascular Disease: Lesson Learned from Imaging and Blood Biomarkers

MDPI

Authors
PAOLO ZAMBONI



ABSTRACT
COVID-19, a disease initially thought to be prominently an interstitial pneumonia with varying degrees of severity, can be considered a vascular disease with regards to serious complications and causes of mortality. Quite recently, blood clots have emerged as the common factor unifying many of the symptoms initially attributed without an explanation to COVID-19. Cardiovascular biomarkers and particularly, D-dimer and troponin appear to be very powerful prognostic markers, signaling the need for earlier and more aggressive interventions and treatments in order to avoid and/or minimize arterial/venous thromboembolism and myocardial infarct. The ultrasound imaging patterns at both the lung and peripheral vascular level can also be very useful weapons that have the advantage of being able to monitor longitudinally the clinical picture, something that real-time PCR/nasopharyngeal swab is not able to do and that CT can only pursue with significant radiation exposure. A lesson learned in the early phase of the COVID-19 pandemic suggests quitting and starting again with targeted imaging and blood vascular biomarkers.

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24/06/2020
SARS-CoV-2-induced Acute Respiratory Distress Syndrome: Pulmonary Mech...

SARS-CoV-2-induced Acute Respiratory Distress Syndrome: Pulmonary Mechanics and Gas Exchange Abnormalities

ORCID

Authors
Enric Barbeta, Ana Motos, Antoni Torres, Adrian Ceccato, Miquel Ferrer, Catia Cilloniz, Leticia Bueno, Joan Ramon Badia, Pedro Castro, Carlos Ferrando, Rut Andrea, Manuel Castellà, Javier Fernández, Alex Soriano, Ricard Mellado, Rubén López-Aladid, Hua Yang, Minlan Yang, Laia Fernandez-Barat, Andrea Catalina Palomeque, Ivan Vollmer; José María Nicolás


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24/06/2020 Articles
ACE2 is on the X chromosome: could this explain COVID-19 gender differ...

ACE2 is on the X chromosome: could this explain COVID-19 gender differences?

EUROPEAN HEART JOURNAL

Authors
Esther Culebras, Félix Hernández


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22/06/2020 Articles
A systematic review of pathological findings in COVID-19: a pathophysi...

A systematic review of pathological findings in COVID-19: a pathophysiological timeline and possible mechanisms of disease progression

NATURE

Authors
Samuel B. Polak, Inge C. Van Gool, Danielle Cohen, Jan H. von der Thüsen, Judith van Paassen



ABSTRACT
Since the outbreak of the COVID-19 pandemic, much has been learned regarding its clinical course, prognostic inflammatory markers, disease complications, and mechanical ventilation strategy. Clinically, three stages have been identified based on viral infection, pulmonary involvement with inflammation, and fibrosis. Moreover, low and high elastance phenotypes can be distinguished in mechanically ventilated patients, based on lung mechanics, ventilation-to-perfusion ratio, and CT scans; these two phenotypes have presumed differences in their underlying pathophysiology. Although essential for therapeutic guidance, the pathophysiology of COVID-19 is poorly understood. Here, we systematically reviewed published case reports and case series in order to increase our understanding of COVID-19 pathophysiology by constructing a timeline and correlating histopathological findings with clinical stages of COVID-19. Using PRISMA-IPD guidelines, 42 articles reporting 198 individual cases were included in our analysis. In lung samples (n = 131 cases), we identified three main histological patterns: epithelial (n = 110, 85%), with reactive epithelial changes and DAD; vascular (n = 76, 59%) with microvascular damage, (micro)thrombi, and acute fibrinous and organizing pneumonia; and fibrotic (n = 28, 22%) with interstitial fibrosis. The epithelial and vascular patterns can present in all stages of symptomatic COVID-19, whereas the fibrotic pattern presents starting at ~3 weeks. Moreover, patients can present with more than one pattern, either simultaneously or consecutively. These findings are consistent with knowledge regarding clinical patterns of viral infection, development of hyperinflammation and hypercoagulability, and fibrosis. Close collaboration among medical staff is necessary in order to translate this knowledge and classification of pathophysiological mechanisms into clinical stages of disease in individual patients. Moreover, further research, including histopathological studies, is warranted in order to develop reliable, clinically relevant biomarkers by correlating these pathological findings with laboratory results and radiological findings, thus, increasing our understanding of COVID-19 and facilitating the move to precision medicine for treating patients.

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18/06/2020 Editorial
Inhibitors of the Renin–Angiotensin–Aldosterone System and Covid-19

THE NEW ENGLISH JOURNAL OF MEDICINE

Authors
John A. Jarcho, Julie R. Ingelfinger, Mary Beth Hamel, Ralph B. D’Agostino, David P. Harrington


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16/06/2020 Viewpoint
Therapeutic blockade of granulocyte macrophage colony-stimulating fact...

Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities

THE LANCET

Authors
Puja Mehta, Joanna C Porter, Jessica J Manson, John D Isaacs, Peter J M Openshaw, Iain B McInnes, Charlotte Summers, Rachel C Chambers


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16/06/2020 Articles
The thromboembolism in COVID-19: the unsolved problem

EDIZIONE MINERVA MEDICA

Authors
Matteo CASALE, Giuseppe DATTILO, Egidio IMBALZANO, Marianna GIGLIOTTI DE FAZIO, Claudia MORABITO, Maurizio MAZZETTI, Paolo BUSACCA, Salvatore Santo SIGNORELLI, Natale Daniele BRUNETTI, michele CORREALE



ABSTRACT
INTRODUCTIONː The recent Sars-Cov-2 pandemic (COVID-19) has led to growing research to explain the poor clinical prognosis in some patients.
EVIDENCE ACQUISITIONː While early observational studies highlighted the role of the virus in lung failure, in a second moment thrombosis emerged as a possible explanation of the worse clinical course in some patients. Despite initial difficulties in management of such patients, the constant increase of literature in the field is to date clarifying some questions from clinicians. However, several other questions need answer.
EVIDENCE SYNTHESISː A novel disease (Covid-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was responsible for thousands of hospitalizations for severe acute respiratory syndrome, with several cases of thrombotic complications due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. Covid-19 and hospitalizations for Covid-19 may carry several potential risk factors for thrombosis. Severe coagulation abnormalities may occur in almost all of the severe and critical ill COVID-19 cases.
CONCLUSIONSː Despite a strong pathophysiological rationale, the evidences in literature are not enough to recommend an aggressive antithrombotic therapy in COVID- 19. However, it is our opinion that an early use, even at home at the beginning of the disease, could improve the clinical course.

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16/06/2020 Articles
The thromboembolism in COVID-19: the unsolved problem

EDIZIONE MINERVA MEDICA

Authors
Matteo CASALE, Giuseppe DATTILO, Egidio IMBALZANO, Marianna GIGLIOTTI DE FAZIO, Claudia MORABITO, Maurizio MAZZETTI, Paolo BUSACCA, Salvatore Santo SIGNORELLI, Natale Daniele BRUNETTI, michele CORREALE



ABSTRACT
INTRODUCTIONː The recent Sars-Cov-2 pandemic (COVID-19) has led to growing research to explain the poor clinical prognosis in some patients.
EVIDENCE ACQUISITIONː While early observational studies highlighted the role of the virus in lung failure, in a second moment thrombosis emerged as a possible explanation of the worse clinical course in some patients. Despite initial difficulties in management of such patients, the constant increase of literature in the field is to date clarifying some questions from clinicians. However, several other questions need answer.
EVIDENCE SYNTHESISː A novel disease (Covid-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was responsible for thousands of hospitalizations for severe acute respiratory syndrome, with several cases of thrombotic complications due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. Covid-19 and hospitalizations for Covid-19 may carry several potential risk factors for thrombosis. Severe coagulation abnormalities may occur in almost all of the severe and critical ill COVID-19 cases.
CONCLUSIONSː Despite a strong pathophysiological rationale, the evidences in literature are not enough to recommend an aggressive antithrombotic therapy in COVID- 19. However, it is our opinion that an early use, even at home at the beginning of the disease, could improve the clinical course.

Read More »

11/06/2020 PERSPECTIVE
Considering how biological sex impacts immune responses and COVID-19 o...

Considering how biological sex impacts immune responses and COVID-19 outcomes

NATURE

Authors
Eileen P. Scully, Jenna Haverfield, Rebecca L. Ursin, Cara Tannenbaum, Sabra L. Klein



ABSTRACT
A male bias in mortality has emerged in the COVID-19 pandemic, which is consistent with the pathogenesis of other viral infections. Biological sex differences may manifest themselves in susceptibility to infection, early pathogenesis, innate viral control, adaptive immune responses or the balance of inflammation and tissue repair in the resolution of infection. We discuss available sex-disaggregated epidemiological data from the COVID-19 pandemic, introduce sex-differential features of immunity and highlight potential sex differences underlying COVID-19 severity. We propose that sex differences in immunopathogenesis will inform mechanisms of COVID-19, identify points for therapeutic intervention and improve vaccine design and increase vaccine efficacy.

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08/06/2020 Articles
Pulmonary post-mortem findings in a series of COVID-19 cases from nort...

Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study

THE LANCET

Authors
Luca Carsana, Aurelio Sonzogni, Ahmed Nasr, Roberta Simona Rossi, Alessandro Pellegrinelli, Pietro Zerbi, Roberto Rech, Riccardo Colombo, Spinello Antinori, Mario Corbellino, Massimo Galli, Emanuele Catena, Antonella Tosoni, Andrea Gianatti, Manuela Nebuloni


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01/06/2020 Editorial
COVID-19 coagulopathy: an evolving story

The Lancet

Authors
The Lancet Haematology

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29/05/2020 Images
Magnetic Resonance Imaging Alteration of the Brain in a Patient With C...

Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia

JAMA

Authors
Letterio S. Politi, Ettore Salsano, Marco Grimaldi

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28/05/2020 Report
COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrati...

COVID-19: hemoglobin, iron, and hypoxia beyond inflammation. A narrative review

CLINICS AND PRACTICE

Authors
Attilio Cavezzi, Emidio Troiani, Salvatore Corrao



ABSTRACT
Coronavirus disease-19 (COVID-19) has been regarded as an infective-inflammatory disease, which affects mainly lungs. More recently, a multi-organ involvement has been highlighted, with different pathways of injury. A hemoglobinopathy, hypoxia and cell iron overload might have a possible additional role. Scientific literature has pointed out two potential pathophysiological mechanisms: i) severe acute respiratory syndrome-coronavirus-2 (SARS-CoV- 2) interaction with hemoglobin molecule, through CD147, CD26 and other receptors located on erythrocyte and/or blood cell precursors; ii) hepcidin-mimetic action of a viral spike protein, inducing ferroportin blockage. In this translational medicine-based narrative review, the following pathologic metabolic pathways, deriving from hemoglobin denaturation and iron metabolism dysregulation, are highlighted: i) decrease of functioning hemoglobin quote; ii) iron overload in cell/tissue (hyperferritinemia); iii) release of free toxic circulating heme; iv) hypoxemia and systemic hypoxia; v) reduction of nitric oxide; vi) coagulation activation; vii) ferroptosis with oxidative stress and lipoperoxidation; viii) mitochondrial degeneration and apoptosis. A few clinical syndromes may follow, such as pulmonary edema based on arterial vasoconstriction and altered alveolo-capillary barrier, sideroblastic-like anemia, endotheliitis, vasospastic acrosyndrome, and arterio- venous thromboembolism. We speculated that in COVID-19, beyond the classical pulmonary immune-inflammation view, the occurrence of an oxygen-deprived blood disease, with iron metabolism dysregulation, should be taken in consideration. A more comprehensive diagnostic/therapeutic approach to COVID-19 is proposed, including potential adjuvant interventions aimed at improving hemoglobin dysfunction, iron over-deposit and generalized hypoxic state.

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27/05/2020 Articles
SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in t...

SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract

SCIENCE DIRECT

Authors
Yixuan J. Hou, Kenichi Okuda, Caitlin E. Edwards, David R. Martinez, Takanori Asakura, Kenneth H. Dinnon, III, Takafumi Kato, Rhianna E. Lee, Boyd L. Yount, Teresa M. Mascenik, Gang Chen, Kenneth N. Olivier, Andrew Ghio, Longping V. Tse, Sarah R. Leist, Lisa E. Gralinski, Alexandra Schäfer, Hong Dang, Rodney Gilmore, Satoko Nakano, Ling Sun, M. Leslie Fulcher, Alessandra Livraghi-Butrico, Nathan I. Nicely, Mark Cameron, Cheryl Cameron, David J. Kelvin, Aravinda de Silva, David M. Margolis, Alena Markmann, Luther Bartelt, Ross Zumwalt, Fernando J. Martinez, Steven P. Salvatore, Alain Borczuk, Purushothama R. Tata, Vishwaraj Sontake, Adam Kimple, Ilona

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22/05/2020 Articles
Microvascular COVID-19 lung vessels obstructive thromboinflammatory sy...

Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS)...

Publmed.gov

Authors
Fabio Ciceri, Luigi Beretta, Anna Mara Scandroglio, Sergio Colombo, Giovanni Landoni, Annalisa Ruggeri, Jacopo Peccatori, Armando D’Angelo, Francesco De Cobelli, Patrizia Rovere-Querini, Moreno Tresoldi, Lorenzo Dagna and Alberto Zangrillo

ABSTRACT

We suggest the use of MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) as a new name for severe pulmonary coronavirus disease 2019 (COVID-19). We hypothesise that, in predisposed individuals, alveolar viral damage is followed by an inflammatory reaction and by microvascular pulmonary thrombosis. This progressive endothelial thromboinflammatory syndrome may also involve the microvascular bed of the brain and other vital organs, leading to multiple organ failure and death. Future steps in the understanding of the disease and in the identification of treatments may benefit from this definition and hypothesised sequence of events.

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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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16/05/2020 Articles
Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expr...

Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expression of the SARS-CoV- 2 Receptor ACE2 in the Respiratory Tract

DEVELOPMENTAL CELL

Authors
Joan C. Smith, Erin L. Sausville, Vishruth Girish, Monet Lou Yuan, Anand Vasudevan, Kristen M. John, Jason M. Sheltzer

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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 T...

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...

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 ...

Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern...

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 Correspondence
Prevention of the cytokine storm in COVID-19

The Lancet

Authors
David J M Wright

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

Assessment of SARS-CoV-2 replication in the context of other respiratory viruses

The Lancet

Authors
Jessica A Belser

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

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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06/05/2020 Progress
Pathological inflammation in patients with COVID-19: a key role for mo...

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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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 Co...

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 d...

Post-mortem examination of COVID19 patients reveals diffuse alveolar damage with...

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 Brief Communication
SARS-CoV-2 entry factors are highly expressed in nasal epithelial cell...

SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together...

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

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 Ri...

Association of Renin-Angiotensin System Inhibitors With Severity or Risk...

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

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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12/04/2020 Articles
Estimation of airborne viral emission: Quanta emission rate of SARS-Co...

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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09/04/2020 Articles
Coagulation disorders in coronavirus infected patients: COVID-19, SARS...

Coagulation disorders in coronavirus infected patients: COVID-19, SARS- CoV-1, MERS-CoV and lessons from the past

ELSEVIER

Authors
Dimitrios Giannis , Ioannis A.Ziogas, Panagiota Gianni



ABSTRACT
Coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus strain disease, has recently emerged in China and rapidly spread worldwide. This novel strain is highly transmittable and severe disease has been reported in up to 16% of hospitalized cases. More than 600,000 cases have been confirmed and the number of deaths is constantly increasing. COVID-19 hospitalized patients, especially those suffering from severe respiratory or systemic manifestations, fall under the spectrum of the acutely ill medical population, which is at increased venous thromboembolism risk. Thrombotic complications seem to emerge as an important issue in patients infected with COVID-19. Preliminary reports on COVID-19 patients’ clinical and laboratory findings include thrombocytopenia, elevated D-dimer, prolonged prothrombin time, and disseminated intravascular coagulation. As the pandemic is spreading and the whole picture is yet unknown, we highlight the importance of coagulation disorders in COVID-19 infected patients and review relevant data of previous coronavirus epidemics caused by the severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and the Middle East Respiratory Syndrome coronavirus (MERS-CoV).

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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 Dis...

The Dilemma of Coronavirus Disease 2019, Aging, and Cardiovascular Disease..

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 ...

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 ...

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 Chal...

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

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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 respir...

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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