scholarly journals SARS-CoV-2 infection of circulating immune cells is not responsible for virus dissemination in severe COVID-19 patients

2021 ◽  
Author(s):  
Nicole L. Rosin ◽  
Arzina Jaffer ◽  
Sarthak Sinha ◽  
Rory P. Mulloy ◽  
Carolyn Robinson ◽  
...  

SummaryIn late 2019 a novel coronavirus (SARS-CoV-2) emerged, and has since caused a global pandemic. Understanding the pathogenesis of COVID-19 disease is necessary to inform development of therapeutics, and management of infected patients. Using scRNAseq of blood drawn from SARS-CoV-2 patients, we asked whether SARS-CoV-2 may exploit immune cells as a ‘Trojan Horse’ to disseminate and access multiple organ systems. Our data suggests that circulating cells are not actively infected with SARS-CoV-2, and do not appear to be a source of viral dissemination.

Author(s):  
Usman M Ashraf ◽  
Ahmed A Abokor ◽  
Jonnelle M. Edwards ◽  
Emily W. Waigi ◽  
Rachel S. Royfman ◽  
...  

A novel coronavirus disease, COVID-19, has created a global pandemic in 2020, posing an enormous challenge to healthcare systems and affected communities. COVID-19 is caused by Severe Acute Respiratory Syndrome (SARS)-CoronaVirus-2 (CoV-2) that manifests as bronchitis, pneumonia, or a severe respiratory illness. SARS-CoV-2 infects human cells via binding a "spike" protein on its surface to angiotensin-converting enzyme 2 (ACE2) within the host. ACE2 is crucial for maintaining tissue homeostasis and negatively regulates the renin-angiotensin-aldosterone system (RAAS) in the humans. The RAAS is paramount for normal function in multiple organ systems including the lungs, heart, kidney, and vasculature. Given that SARS-CoV-2 internalizes via ACE2, the resultant disruption in ACE2 expression can lead to altered tissue function and exacerbate chronic diseases. The widespread distribution and expression of ACE2 across multiple organs is critical to our understanding of the varied clinical outcomes of COVID-19. This perspective review based on the current literature was prompted to show how disruption of ACE2 by SARS-CoV-2 can affect different organ systems.


Author(s):  
Balraj Singh ◽  
Sarah Ayad ◽  
Parminder Kaur ◽  
Ro-Jay Reid ◽  
Sachin Gupta ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for the current global pandemic, coronavirus disease 2019 (COVID-19). COVID-19 usually presents with respiratory symptoms but can affect multiple organ systems. A wide spectrum of complications can occur depending upon the comorbidities of patients. There is limited literature available regarding the presentation and outcome of COVID-19 in chronic lymphocytic leukaemia (CLL) patients. We report 2 cases of COVID-19-induced hyperleucocytosis (WBC count >100,000/?l) in CLL patients.


2020 ◽  
pp. 000486742096147
Author(s):  
Christos Pantelis ◽  
Mahesh Jayaram ◽  
Anthony J Hannan ◽  
Robb Wesselingh ◽  
Jess Nithianantharajah ◽  
...  

Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood–brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health.


2020 ◽  
Vol 7 ◽  
Author(s):  
Georgina M. Ellison-Hughes ◽  
Liam Colley ◽  
Katie A. O'Brien ◽  
Kirsty A. Roberts ◽  
Thomas A. Agbaedeng ◽  
...  

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has led to 47 m infected cases and 1. 2 m (2.6%) deaths. A hallmark of more severe cases of SARS-CoV-2 in patients with acute respiratory distress syndrome (ARDS) appears to be a virally-induced over-activation or unregulated response of the immune system, termed a “cytokine storm,” featuring elevated levels of pro-inflammatory cytokines such as IL-2, IL-6, IL-7, IL-22, CXCL10, and TNFα. Whilst the lungs are the primary site of infection for SARS-CoV-2, in more severe cases its effects can be detected in multiple organ systems. Indeed, many COVID-19 positive patients develop cardiovascular complications, such as myocardial injury, myocarditis, cardiac arrhythmia, and thromboembolism, which are associated with higher mortality. Drug and cell therapies targeting immunosuppression have been suggested to help combat the cytokine storm. In particular, mesenchymal stromal cells (MSCs), owing to their powerful immunomodulatory ability, have shown promise in early clinical studies to avoid, prevent or attenuate the cytokine storm. In this review, we will discuss the mechanistic underpinnings of the cytokine storm on the cardiovascular system, and how MSCs potentially attenuate the damage caused by the cytokine storm induced by COVID-19. We will also address how MSC transplantation could alleviate the long-term complications seen in some COVID-19 patients, such as improving tissue repair and regeneration.


2021 ◽  
Author(s):  
Rachel R Deer ◽  
Madeline A Rock ◽  
Nicole Vasilevsky ◽  
Leigh C Carmody ◽  
Halie M Rando ◽  
...  

Importance: Since late 2019, the novel coronavirus SARS-CoV-2 has given rise to a global pandemic and introduced many health challenges with economic, social, and political consequences. In addition to a complex acute presentation that can affect multiple organ systems, there is mounting evidence of various persistent long-term sequelae. The worldwide scientific community is characterizing a diverse range of seemingly common long-term outcomes associated with SARS-CoV-2 infection, but the underlying assumptions in these studies vary widely making comparisons difficult. Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations of long COVID. Observations: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts of individuals three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to Human Phenotype Ontology (HPO) terms. Conclusions and Relevance: Patients and clinicians often use different terms to describe the same symptom or condition. Addressing the heterogeneous and inconsistent language used to describe the clinical manifestations of long COVID combined with the lack of standardized terminologies for long COVID will provide a necessary foundation for comparison and meta-analysis of different studies. Translating long COVID manifestations into computable HPO terms will improve the analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared or pooled more effectively. Furthermore, mapping lay terminology to HPO for long COVID manifestations will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, which may improve the stratification and thereby diagnosis and treatment of long COVID.


2021 ◽  
Author(s):  
Halie M. Rando ◽  
Tellen D. Bennett ◽  
James Brian Byrd ◽  
Carolyn Bramante ◽  
Tiffany J. Callahan ◽  
...  

Since late 2019, the novel coronavirus SARS-CoV-2 has introduced a wide array of health challenges globally. In addition to a complex acute presentation that can affect multiple organ systems, increasing evidence points to long-term sequelae being common and impactful. As the worldwide scientific community forges ahead with efforts to characterize a wide range of outcomes associated with SARS-CoV-2 infection, the proliferation of available data has made it clear that formal definitions are needed in order to design robust and consistent studies of Long COVID that consistently capture variation in long-term outcomes. In the present study, we investigate the definitions used in the literature published to date and compare them against data available from electronic health records and patient-reported information collected via surveys. Long COVID holds the potential to produce a second public health crisis on the heels of the pandemic. Proactive efforts to identify the characteristics of this heterogeneous condition are imperative for a rigorous scientific effort to investigate and mitigate this threat.


2021 ◽  
Vol 32 (2) ◽  
pp. 551-555
Author(s):  
Ayşegül Bilge ◽  
İsmail Karasoy ◽  
Elif Neziroğlu ◽  
Yeşim Güner

Although novel coronavirus-2019 (COVID-19) primarily affects the respiratory system, it can affect multiple organ systems, leading to serious complications, such as acute respiratory distress syndrome (ARDS) and multiple organ failure. Nearly 20 to 55% of patients with COVID-19 experience coagulation disorders that cause high mortality in line with the severity of the clinical picture. Thromboembolism can be observed in both venous and arterial systems. The vast majority of thromboembolic events are associated with the venous system and are often observed as pulmonary embolism. Arterial thromboembolisms often involve the arteries in the lower extremities, followed by those in the upper extremities. Herein, we report a rare case of COVID-19 pneumonia whose left arm was amputated at the forearm level after arterial thromboembolism in the left upper extremity. This case report is valuable, as it is the first reported case of upper extremity arterial thromboembolism in Turkey, as well as the only case in the literature in which the patient underwent four surgical interventions and is still alive.


2021 ◽  
pp. 72-79
Author(s):  
Riana Shamilievna Tinaeva ◽  
Vsevolod Vladimirovich Skvortsov Vsevolod

The World Health Organization (WHO) as a pandemic recognized the outbreak of the novel coronavirus COVID-19, which was first reported on December 8, 2019 in Hubei Province in China, on March 11, 2020. This disease was recognized as an infection with a new beta-coronavirus. Today, the current problem is COVID-19 and its effect on blood vessels and blood. Although COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects other organ systems. COVID-19 is manifested by hypercoagulation, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Clinically, the vascular dysfunction associated with COVID-19 manifests itself outside the lungs in various ways, including deep vein thrombosis, pulmonary embolism, large artery thrombosis, and multiple organ venous and arterial thrombosis, and these manifestations are attributed to factors such as hypoxemia, viral sepsis, immobility, and sometimes vasculitis. In some cases, DIC syndrome (which is a simulator of vasculitis) can occur with the lightning-fast lung disease COVID-19, and is also characterized by diffuse thrombosis and bleeding. If you exclude DIC and large vessel thrombosis, it is clear that patients with severe COVID-19 pneumonia may also have severe changes such as skin vasculitis, suspected cerebral vasculitis, and multiple organ failure, resulting in suspected viral endothelitis, direct viral infection, or vasculitis. Understanding the vascular effects of COVID-19 is essential for comprehensive medical care.


Author(s):  
T. L. Benning ◽  
P. Ingram ◽  
J. D. Shelburne

Two benzofuran derivatives, chlorpromazine and amiodarone, are known to produce inclusion bodies in human tissues. Prolonged high dose chlorpromazine therapy causes hyperpigmentation of the skin with electron-dense inclusion bodies present in dermal histiocytes and endothelial cells ultrastructurally. The nature of the deposits is not known although a drug-melanin complex has been hypothesized. Amiodarone may also cause cutaneous hyperpigmentation and lamellar lysosomal inclusion bodies have been demonstrated within the cells of multiple organ systems. These lamellar bodies are believed to be the product of an amiodarone-induced phospholipid storage disorder. We performed transmission electron microscopy (TEM) and energy dispersive x-ray microanalysis (EDXA) on tissue samples from patients treated with these drugs, attempting to detect the sulfur atom of chlorpromazine and the iodine atom of amiodarone within their respective inclusion bodies.A skin biopsy from a patient with hyperpigmentation due to prolonged chlorpromazine therapy was fixed in 4% glutaraldehyde and processed without osmium tetroxide or en bloc uranyl acetate for Epon embedding.


2010 ◽  
Vol 15 (3) ◽  
pp. 1-7
Author(s):  
Richard T. Katz

Abstract This article addresses some criticisms of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) by comparing previously published outcome data from a group of complete spinal cord injury (SCI) persons with impairment ratings for a corresponding level of injury calculated using the AMA Guides, Sixth Edition. Results of the comparison show that impairment ratings using the sixth edition scale poorly with the level of impairments of activities of daily living (ADL) in SCI patients as assessed by the Functional Independence Measure (FIM) motor scale and the extended FIM motor scale. Because of the combinations of multiple impairments, the AMA Guides potentially overrates the impairment of paraplegics compared with that of quadriplegics. The use and applicability of the Combined Values formula should be further investigated, and complete loss of function of two upper extremities seems consistent with levels of quadriplegia using the SCI model. Some aspects of the AMA Guides contain inconsistencies. The concept of diminishing impairment values is not easily translated between specific losses of function per organ system and “overall” loss of ADLs involving multiple organ systems, and the notion of “catastrophic thresholds” involving multiple organ systems may support the understanding that variations in rating may exist in higher rating cases such as those that involve an SCI.


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