Something Really Strange Is Happening At Hospitals All Over America

Authors: Authored by Michael Snyder via TheMostImportantNews.com, TURSDAY, NOV 04, 2021 – 05:11

In a year that has been filled with so many mysteries already, I have another very odd one to share with you.  Emergency rooms are filled to overflowing all over America, and nobody can seem to explain why this is happening.  Right now, the number of new COVID cases in the United States each day is less than half of what it was just a couple of months ago.  That is really good news, and many believe that this is a sign that the pandemic is fading.  Let us hope that is true.  With less people catching the virus, you would think that would mean that our emergency rooms should be emptying out, but the opposite is actually happening.  All across the country, emergency rooms are absolutely packed, and in many cases we are seeing seriously ill patients being cared for in the hallways because all of the ER rooms are already full.

Let me give you an example of what I am talking about.  The following comes from an article entitled “ERs Are Swamped With Seriously Ill Patients, Although Many Don’t Have Covid”

Inside the emergency department at Sparrow Hospital in Lansing, Michigan, staff members are struggling to care for patients showing up much sicker than they’ve ever seen.

Tiffani Dusang, the ER’s nursing director, practically vibrates with pent-up anxiety, looking at patients lying on a long line of stretchers pushed up against the beige walls of the hospital hallways. “It’s hard to watch,” she said in a warm Texas twang.

But there’s nothing she can do. The ER’s 72 rooms are already filled.

Can anyone explain why this is happening?

If the number of COVID cases was starting to spike again, it would make sense for emergency rooms to be overflowing.

But at this particular hospital in Michigan, we are being told that some of the main things that are being treated include “abdominal pain”, “respiratory problems”, “blood clots” and “heart conditions”

Months of treatment delays have exacerbated chronic conditions and worsened symptoms. Doctors and nurses say the severity of illness ranges widely and includes abdominal pain, respiratory problems, blood clots, heart conditions and suicide attempts, among other conditions.

That mention of “heart conditions” immediately got my attention, because I have been seeing this so much in the news recently.

For instance, a high school senior in Pennsylvania just dropped dead from “a sudden cardiac incident”

The high school soccer manager ‘greatly enjoyed’ his team’s championship victory Saturday. Later that evening, he was dead.

Now, late student Blake Barklage’s high school is mourning his untimely death. As 6ABC in Philly reports, the tragedy occurred at La Salle College High School in Montgomery County, Pa.

In a letter to parents, the school announced that the senior died after ‘a sudden cardiac incident’ Saturday night.

Elsewhere in the same state, an otherwise healthy 12-year-old boy just suddenly died because of an issue with his coronary artery…

As family and friends grieve, the cause of death is in for a 12-year-old taken way too soon while warming up for school basketball practice.

As TribLive in Pittsburgh reports, Jayson Kidd, 12, of Bridgeville, Pa., died of natural causes involving his coronary artery, according to the Allegheny County Medical Examiner’s Office.

Heart problems kill elderly people all the time, but it is odd that so many healthy young people have been having these problems.

Over the weekend, Barcelona striker Sergio Aguero suddenly collapsed on the pitch during a match.

He was later diagnosed with “a cardiac arrhythmia”

Sergio “Kun” Aguero, a striker for the Barcelona soccer team, has been diagnosed with a cardiac arrhythmia after collapsing during Saturday’s match against Alaves.

The 33-year-old Argentinian was examined by medical staff at the stadium before being taken to a nearby hospital where he is still waiting to undergo further examination.

Just two days later, a match in Norway was brought to a screeching halt after a player experienced “cardiac arrest” right in the middle of a match…

A football match in Norway’s second division was halted on Monday after Icelandic midfielder Emil Pálsson suffered a cardiac arrest during play.

The 28-year-old Sogndal player suffered the attack as the game against Stjordals-Blink entered the 12th minute, his club said in a statement.

I have been seeing so many stories like this.

So why are so many young people suddenly having such serious problems with their hearts?

Can anyone out there explain this to me?

Pathological findings in organs and tissues of patients with COVID-19: A systematic review

Authors: Sasha Peiris 1 2Hector Mesa 3Agnes Aysola 4Juan Manivel 5Joao Toledo 1 2Marcio Borges-Sa 6Sylvain Aldighieri 1 2Ludovic Reveiz 2 7

Abstract

Background: Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs.

Methods and findings: A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings.

Conclusions: The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.

For More Information: https://pubmed.ncbi.nlm.nih.gov/33909679/

Recent Randomized Trials of Antithrombotic Therapy for Patients With COVID-19

Authors: JACC State-of-the-Art ReviewAzita H. Talasaz, PharmD,a,bParham Sadeghipour, MD,cHessam Kakavand, PharmD,a,bMaryam Aghakouchakzadeh, PharmD,aElaheh Kordzadeh-Kermani, PharmD,aBenjamin W. Van Tassell, PharmD,d,eAzin Gheymati, PharmD,aHamid Ariannejad, MD,bSeyed Hossein Hosseini, PharmD,aSepehr Jamalkhani,cMichelle Sholzberg, MDCM, MSc,f,gManuel Monreal, MD, PhD,hDavid Jimenez, MD, PhD,iGregory Piazza, MD, MS,jSahil A. Parikh, MD,k,lAjay J. Kirtane, MD, SM,k,lJohn W. Eikelboom, MBBS,mJean M. Connors, MD,nBeverley J. Hunt, MD,oStavros V. Konstantinides, MD, PhD,p,qMary Cushman, MD, MSc,r,sJeffrey I. Weitz, MD,t,uGregg W. Stone, MD,k,vHarlan M. Krumholz, MD, SM,w,x,yGregory Y.H. Lip, MD,z,aaSamuel Z. Goldhaber, MD,j and Behnood Bikdeli, MD, MSj,k,w,∗

Abstract

Endothelial injury and microvascular/macrovascular thrombosis are common pathophysiological features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses, and durations of therapy are being assessed in ongoing randomized controlled trials (RCTs) that focus on outpatients, hospitalized patients in medical wards, and patients critically ill with COVID-19. This paper provides a perspective of the ongoing or completed RCTs related to antithrombotic strategies used in COVID-19, the opportunities and challenges for the clinical trial enterprise, and areas of existing knowledge, as well as data gaps that may motivate the design of future RCTs.

Thromboembolism in Patients With Coronavirus Disease-2019

Microvascular and macrovascular thrombotic complications, including arterial and especially venous thromboembolism (VTE), seem to be common clinical manifestations of coronavirus disease-2019 (COVID-19), particularly among hospitalized and critically ill patients (1234). Pooled analyses have helped in providing aggregate estimates of thrombotic events (4,5). In a recent systematic review and meta-analysis, the overall incidence of VTE among inpatients with COVID-19 was estimated at 17% (95% confidence interval [CI]: 13.4 to 20.9), with variation based on study design and method of ascertainment; there was a four-fold higher incidence rate in patients in the intensive care units (ICUs) compared with non-ICU settings (28% vs. 7%) (6). In addition, postmortem studies show frequent evidence of microvascular thrombosis in patients with COVID-19 (7,8). The influence of these events on mortality rates remains unknown (9).Go to:

Pathophysiology of Thromboembolism in COVID-19: Virchow’s Triad in Action

COVID-19 can potentiate all 3 components of Virchow’s triad and increases the risk of thrombosis (Figure 1 ). First, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection may trigger endothelial dysfunction. Using the angiotensin-converting enzyme 2, which is expressed on the surface of many cells, SARS-CoV-2 enters endothelial cells and may impair their intrinsic antithrombotic properties. It is proposed that viremia, hypoxia, the inflammatory response, increased expression of tissue factor, and elevated levels of neutrophil extracellular traps (NETs) can together disrupt the hemostasis equilibrium and promote endothelial activation (101112). This induction of a procoagulant state along with the reduction in plasminogen activators further results in increased platelet reactivity (131415). Inflammatory cytokines and endothelial activation can lead to downregulation of antithrombin and protein C expression. They can also lead to an increase in the levels of plasminogen activator inhibitor; fibrinogen; factors V, VII, VIII, and X; and von Willebrand factor (16). Increased platelet reactivity, NETosis, and alterations in the aforementioned hemostatic factors result in a hypercoagulable state (171819202122).

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963001/

Anticoagulation in COVID-19: current concepts and controversies

  1. Authors: http://orcid.org/0000-0002-3809-8926Atanu Chandra16289Uddalak Chakraborty2, Shrestha Ghosh1, Sugata Dasgupta3

Abstract

Rising incidence of thromboembolism secondary to COVID-19 has become a global concern, with several surveys reporting increased mortality rates. Thrombogenic potential of the SARS-CoV-2 virus has been hypothesised to originate from its ability to produce an exaggerated inflammatory response leading to endothelial dysfunction. Anticoagulants have remained the primary modality of treatment of thromboembolism for decades. However, there is no universal consensus regarding the timing, dosage and duration of anticoagulation in COVID-19 as well as need for postdischarge prophylaxis. This article seeks to review the present guidelines and recommendations as well as the ongoing trials on use of anticoagulants in COVID-19, identify discrepancies between all these, and provide a comprehensive strategy regarding usage of these drugs in the current pandemic.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

Introduction

The novel beta-coronavirus, appropriately named SARS-CoV-2 by the International Committee of Taxonomy of Viruses, belongs to a family of single-stranded RNA viruses, members of which have been recognised as causative agents of the SARS-CoV and Middle East respiratory syndrome coronavirus outbreak in 2002 and 2012, respectively.1 2 Presently, the novel COVID-19 poses a major global health crisis, having been declared a pandemic on 11 March 2020 by the WHO.

Over the past several months, an overwhelming amount of literature suggests an increased risk of thromboembolic manifestations associated with COVID-19.2 Several hypotheses have been suggested to understand the underlying pathophysiology behind development of a prothrombotic state in COVID-19 such as exaggerated inflammatory response resulting in activation of the coagulation cascade and endothelial injury.3 4 Usage of anticoagulants in COVID-19 remains an area of conjecture with no definite guidelines published to date highlighting the timing, dosage and duration of anticoagulation as well as the drug of choice. Most internationally published guidelines, based on consensus statements and expert opinions, recommend therapeutic doses of heparin only in patients diagnosed with or highly suspected of developing macrothrombi such as pulmonary embolism (PE) or deep vein thrombosis (DVT). However, these guidelines including those by CHEST, rarely address the requirement of post discharge thromboprophylaxis.5

For More Information: https://pmj.bmj.com/content/early/2021/04/12/postgradmedj-2021-139923

Potential mechanisms of cerebrovascular diseases in COVID-19 patients

Authors: Manxue Lou 1Dezhi Yuan 2 3Shengtao Liao 4Linyan Tong 1Jinfang Li 5Affiliations expand

Abstract

Since the outbreak of coronavirus disease 2019 (COVID-19) in 2019, it is gaining worldwide attention at the moment. Apart from respiratory manifestations, neurological dysfunction in COVID-19 patients, especially the occurrence of cerebrovascular diseases (CVD), has been intensively investigated. In this review, the effects of COVID-19 infection on CVD were summarized as follows: (I) angiotensin-converting enzyme 2 (ACE2) may be involved in the attack on vascular endothelial cells by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to endothelial damage and increased subintimal inflammation, which are followed by hemorrhage or thrombosis; (II) SARS-CoV-2 could alter the expression/activity of ACE2, consequently resulting in the disruption of renin-angiotensin system which is associated with the occurrence and progression of atherosclerosis; (III) upregulation of neutrophil extracellular traps has been detected in COVID-19 patients, which is closely associated with immunothrombosis; (IV) the inflammatory cascade induced by SARS-CoV-2 often leads to hypercoagulability and promotes the formation and progress of atherosclerosis; (V) antiphospholipid antibodies are also detected in plasma of some severe cases, which aggravate the thrombosis through the formation of immune complexes; (VI) hyperglycemia in COVID-19 patients may trigger CVD by increasing oxidative stress and blood viscosity; (VII) the COVID-19 outbreak is a global emergency and causes psychological stress, which could be a potential risk factor of CVD as coagulation, and fibrinolysis may be affected. In this review, we aimed to further our understanding of CVD-associated COVID-19 infection, which could improve the therapeutic outcomes of patients. Personalized treatments should be offered to COVID-19 patients at greater risk for stroke in future clinical practice.

For More Information: https://pubmed.ncbi.nlm.nih.gov/33534131/

The Impact of the Covid 19 Pandemic on Cerebrovascular Disease: CORD-Papers-2021-06-28

Abstract:           

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a systemic disease that affects nearly all organ systems through infection and subsequent dysregulation of the vascular endothelium. One of the most striking phenomena has been a coronavirus disease 2019 (COVID-19)associated coagulopathy. Given these findings, questions naturally emerged about the prothrombotic impact of COVID-19 on cerebrovascular disease and whether ischemic stroke is a clinical feature specific to COVID-19 pathophysiology. Early reports from China and several sites in the northeastern United States seemed to confirm these suspicions. Since these initial reports, many cohort studies worldwide observed decreased rates of stroke since the start of the pandemic, raising concerns for a broader impact of the pandemic on stroke treatment. In this review, we provide a comprehensive assessment of how the pandemic has affected stroke presentation, epidemiology, treatment, and outcomes to better understand the impact of COVID-19 on cerebrovascular disease. Much evidence suggests that this decline in stroke admissions stems from the global response to the virus, which has made it more difficult for patients to get to the hospital once symptoms start. However, there does not appear to be a demonstrable impact on quality metrics once patients arrive at the hospital. Despite initial concerns, there is insufficient evidence to ascribe a causal relationship specific to the pathogenicity of SARS-CoV-2 on the cerebral vasculature. Nevertheless, when patients infected with SARS-CoV-2 present with stroke, their presentation is likely to be more severe, and they have a markedly higher rate of in-hospital mortality than patients with either acute ischemic stroke or COVID-19 alone.

For More Information: https://covid19-data.nist.gov/pid/rest/local/paper/the_impact_of_the_covid_19_pandemic_on_cerebrovascular_disease

Pathological findings in organs and tissues of patients with COVID-19: A systematic review

  1. Authors: Sasha Peiris, Hector Mesa, Agnes Aysola, Juan Manivel, Joao Toledo, Marcio Borges-Sa, Sylvain Aldighieri, Ludovic Reveiz

Abstract

Background

Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs.

Methods and findings

A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings.

Conclusions

The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.

For More Information: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250708

COVID-19 – A vascular disease

Authors: Hasan K. Siddiqi,a,bPeter Libby,a,⁎ and Paul M Ridkera,b

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to multi-system dysfunction with emerging evidence suggesting that SARS-CoV-2-mediated endothelial injury is an important effector of the virus. Potential therapies that address vascular system dysfunction and its sequelae may have an important role in treating SARS-CoV-2 infection and its long-lasting effects.

SARS-CoV-2 infection and vascular dysfunction

In health, the vascular endothelium maintains homeostasis through regulation of immune competence, inflammatory equilibrium, tight junctional barriers, hemodynamic stability as well as optimally balanced thrombotic and fibrinolytic pathways. In the novel coronavirus disease of 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), dysregulation of many of these pathways has emerged as a mediator of severe disease. The constellation of clinical and biomarker derangements seen in COVID-19 can be classified into disruption of the immune, renin-angiotensin-aldosterone (RAA), and thrombotic balance, all of which converge on the vascular endothelium as a common pathway. Accumulating evidence from basic science, imaging and clinical observations, has clarified the picture of COVID-19 as a vascular disease. Understanding the disease in this context may provide novel avenues of understanding COVID-19 and lead to critically needed improvements in therapeutic strategies.

SARS-CoV-2 uses the angiotensin converting enzyme 2 (ACE2) to facilitate entry into target cells and initiate infection. This viral entry into the cell is further mediated by transmembrane serine protease 2 (TMPRSS2) and cathepsin L which cleave the S protein on the viral particle to permit engagement with ACE2 [1]. Endothelial cells (ECs) in general and cardiac pericytes in particular express abundant ACE2, making them a direct target of SARS-CoV-2 infection (Fig. 1 ) [2]. Examination of the pulmonary vascular bed shows severe derangements in COVID-19, compared to control and influenza patients, particularly with widespread thrombosis and microangiopathy, endothelial activation and extensive angiogenesis [3]. These studies and pervasive findings establish the role of viral injury to the vascular system with resulting vascular dysfunction in COVID-19 patients [4].

Fig. 1

Open in a separate windowFig. 1

SARS-CoV-2 Induced Endothelial Injury

Legend: A schematic of SARS-CoV-2 infection and proposed resulting endothelial injury, involving immune activation, pro-thrombotic milieu, and RAAS dysregulation. These insults interact with each other to cause end-organ dysfunction that is manifest in many COVID-19 patients.

TMPRSS2 = Transmembrane protease serine 2; ADAM17 = A disintegrin and metalloproteinase 17; TNF = Tumor necrosis factor; TNFr = Tumor necrosis factor receptor; TLR = toll-like receptor; DAMPs = Damage-associated molecular patterns; PAMPs = Pathogen-associated molecular patterns; PAI-1 = plasminogen activator inhibitor-1; vWF = von Willebrand factor; eNOS = endothelial nitric oxide; tPA = tissue plasminogen activator; AT1R = angiotensin 1 receptor; ARDS = acute respiratory distress syndrome.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556303/

How COVID-19 Affects the Brain

Authors: Maura Boldrini, MD, PhD1,2Peter D. Canoll, MD, PhD3Robyn S. Klein, MD, PhD4,5,6

COVID-19 has resulted in more than 120 million cases and 2.6 million deaths to date. Respiratory and gastrointestinal symptoms are accompanied by short- and long-term neuropsychiatric symptoms (NPs) and long-term brain sequelae.

Some patients present with anosmia, cognitive and attention deficits (ie, brain fog), new-onset anxiety, depression, psychosis, seizures, and even suicidal behavior.1,2 These present before, during, and after respiratory symptoms and are unrelated to respiratory insufficiency,1 suggesting independent brain damage. Follow-ups conducted in Germany and the United Kingdom found post–COVID-19 NPs in 20% to 70% of patients, even in young adults, and lasting months after respiratory symptoms resolved,1 suggesting brain involvement persists.

Entering through angiotensin-converting enzyme 2 receptors,2 SARS-CoV-2 can damage endothelial cells leading to inflammation, thrombi, and brain damage. Moreover, systemic inflammation leads to decreased monoamines and trophic factors and activation of microglia, resulting in increased glutamate and N-methyl-d-aspartate (NMDA)3 and excitotoxicity (Figure). These insults induce new-onset or re-exacerbation of preexisting NPs.

Brain Vascular Injury, Neurotransmitter System Dysfunction, Thrombotic Events, Neuronal Damage, and Neuropsychiatric Symptoms

A, SARS-CoV-2 invades endothelial cells via transmembrane angiotensin-converting enzyme 2 (ACE2) receptor, enabled by transmembrane protease, serine 2 (TMPRSS2). B, Cytokine elevation and microglia activation result in increased kynurenine, quinolinic acid, and glutamate, and neurotransmitter depletion. C, Coagulation cascade and elevation of von Willebrand factor (vWF) lead to thrombotic events. D, Altered neurotransmission, excitotoxicity by increased glutamate, and hypoxic injury contribute to neuronal dysfunction and loss. E, Neuropsychiatric symptoms differ depending on the Brodmann area involved. IL indicates interleukin; NMDA, N-methyl-d-aspartate; TNF, tumor necrosis factor.

Does the Virus Invade the Brain?

SARS-CoV-2 is known to penetrate the olfactory mucosa, causing loss of smell, and may enter the brain, migrating from the cribriform plate along the olfactory tract2 or through vagal or trigeminal pathways; however, definitive evidence for this is lacking. SARS-CoV-2 could pass the blood-brain barrier (BBB) because inflammatory cytokines induce BBB instability or via monocytes.4 It could reach brain tissue via circumventricular organs (CVOs), midline structures around the third and fourth ventricles, that monitor blood and cerebral spinal fluid content via fenestrated capillaries lacking the junctional proteins expressed in the BBB. Viral RNA was detected by reverse transcription–quantitative real-time polymerase chain reaction but not by in situ hybridization in medulla and cerebellum,2 located next to the area postrema, a CVO that controls emetic responses to toxins. SARS-CoV-2 protein has been found in brain vascular endothelium but not in neurons or glia.2 Thus, detected viral RNA may represent contamination by vasculature in leptomeninges and Virchow-Robin spaces. Histopathologic analysis of whole human brain showed microglial nodules and phagocytosis of neurons (neuronophagia) in brain stem and less frequently in cortex and limbic structures, associated with sparse lymphocytic infiltration, and no correlations between histopathologic findings and levels of viral messenger RNA in the same brain.5 While ageusia, nausea, and vomiting may be related to CVO and brain stem viral invasion, other short-term and long-lasting NPs are more likely due to neuroinflammation and hypoxic injury. Brain stem involvement may explain persistent autonomic abnormalities and anxiety.

For More Information: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2778090

The complement system in COVID-19: friend and foe?

Authors: Anuja Java,1 Anthony J. Apicelli,2 M. Kathryn Liszewski,3 Ariella Coler-Reilly,3 John P. Atkinson,3 Alfred H.J. Kim,3 and Hrishikesh S. Kulkarni4

Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic and a disruptive health crisis. COVID-19–related morbidity and mortality have been attributed to an exaggerated immune response. The role of complement activation and its contribution to illness severity is being increasingly recognized. Here, we summarize current knowledge about the interaction of coronaviruses with the complement system. We posit that (a) coronaviruses activate multiple complement pathways; (b) severe COVID-19 clinical features often resemble complementopathies; (c) the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19; (d) a subset of patients with COVID-19 may have a genetic predisposition associated with complement dysregulation; and (e) these observations create a basis for clinical trials of complement inhibitors in life-threatening illness.

For More Information: https://insight.jci.org/articles/view/140711