Study Finds Teenage Boys Six Times More Likely To Suffer Heart Problems From Vaccine Than Be Hospitalized by COVID

Authors; Paul Joseph Watson via Summit News,

Research conducted by the University of California has found that teenage boys are six times more likely to suffer from heart problems caused by the COVID-19 vaccine than to be hospitalized as a result of COVID-19 itself.

“A team led by Dr Tracy Hoeg at the University of California investigated the rate of cardiac myocarditis – heart inflammation – and chest pain in children aged 12-17 following their second dose of the vaccine,” reports the Telegraph.

“They then compared this with the likelihood of children needing hospital treatment owing to Covid-19, at times of low, moderate and high rates of hospitalisation.”

Researchers found that the risk of heart complications for boys aged 12-15 following the vaccine was 162.2 per million, which was the highest out of all the groups they looked at.

This compares to the risk of a healthy boy being hospitalized as a result of a COVID infection, which is around 26.7 per million, meaning the risk they face from the vaccine is 6.1 times higher.

Even during high risk rates of COVID, such as in January this year, the threat posed by the vaccine is 4.3 times higher, while during low risk rates, the risk of teenage boys suffering a “cardiac adverse event” from the vaccine is a whopping 22.8 times higher.

The research data was based on a study of adverse reactions suffered by teens between January and June this year.

In a sane world, such data should represent the nail in the coffin for the argument that teenagers and children should be mandated to take the coronavirus vaccine, but it obviously won’t.

In the UK, the government is pushing to vaccinate 12-15-year-olds, even without parental consent, despite the Joint Committee on Vaccination and Immunisation (JCVI) advising against it.

Meanwhile, in America, Los Angeles County school officials voted unanimously to mandate COVID shots for all

Blood molecular markers associated with COVID-19 immunopathology and multi-organ damage

Authors: Yan-Mei ChenYuanting ZhengYing YuYunzhi WangQingxia HuangFeng QianLei SunZhi-Gang SongZiyin ChenJinwen FengYanpeng AnJingcheng YangZhenqiang SuShanyue SunFahui DaiQinsheng ChenQinwei LuPengcheng LiYun LingZhong YangHuiru TangLeming ShiLi JinEdward C HolmesChen DingTong-Yu ZhuYong-Zhen Zhang

Abstract

COVID-19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID-19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID-19-infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN-I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID-19-infected patients experiencing milder disease symptoms showed robust T-cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19.

Proteomics, metabolomics and RNAseq data map immune responses in COVID-19 patients with different disease severity, revealing molecular makers associated with disease progression and alterations of tissue-specific proteins.

  • A multi-omics profiling of the host response to SARS-CoV2 infection in 66 clinically diagnosed and laboratory confirmed COVID-19 patients and 17 uninfected controls.
  • Significant correlations between multi-omics data and key clinical parameters.
  • Alteration of tissue-specific proteins and exRNAs.
  • Enhanced activation of immune responses is associated with COVID-19 pathogenesis.
  • Biomarkers to predict COVID-19 clinical outcomes pending clinical validation as prospective marker.

Introduction

Coronaviruses (family Coronaviridae) are a diverse group of positive-sense single-stranded RNA viruses with enveloped virions (Masters & Perlman, 2013; Cui et al2019). Coronaviruses are well known due to the emergence of Severe Acute Respiratory Syndrome (SARS) in 2002–2003 and Middle East Respiratory Syndrome (MERS) in 2012, both of which caused thousands of cases in multiple countries (Ksiazek et al2003; Bermingham et al2012; Cui et al2019). Coronaviruses naturally infect a broad range of vertebrate hosts including mammals and birds (Cui et al2019). As coronavirus primarily target epithelial cells, they are generally associated with gastrointestinal and respiratory infections (Masters & Perlman, 2013; Cui et al2019). In addition, they cause hepatic and neurological diseases of varying severity (Masters & Perlman, 2013).

The world is currently experiencing a disease pandemic (COVID-19) caused by a newly identified coronavirus called SARS-CoV-2 (Wu et al2020a). At the time of writing, there have been more than ~25 million cases of SARS-CoV-2 and ~830,000 deaths globally (WHO, 2020). The disease leads to both mild and severe respiratory manifestations, with the latter prominent in the elderly and those with underlying medical conditions such as cardiovascular and chronic respiratory disease, diabetes, and cancer (Guan et al., 2020). In addition to respiratory syndrome, mild gastrointestinal and/or cardiovascular symptoms and neurological manifestations have been documented in hospitalized COVID-19-infected patients (Gupta et al2020; Mao et al2020). These data point to the complexity of COVID-19 pathogenesis, especially in patients experiencing severe disease.

SARS-CoV-2 is able to use angiotensin-converting enzyme 2 (ACE 2) as a receptor for cell entry (Hoffmann et al2020; Zheng et al2020a; Zhou et al2020b). Aside from lungs, ACE2 is expressed in other organs including heart, liver, kidney, pancreas, and small intestines (Li et al2020; Liu et al2020; Zou et al2020; Chen et al2020a). More recently, ACE2 expression has also been found in Leydig cells in the testes (Li et al2020; Wang & Xu, 2020) and neurological tissue (Baig et al2020; Bullen et al2020; Xu & Lazartigues, 2020). As such, it is possible that these organs might also be infected by SARS-CoV-2, and recent autopsy studies have also revealed multi-organ damage including heart, liver, intestine, pancreas, brain, kidney, and spleen in fatal COVID-19-infected patients (Lax et al2020; Menter et al2020; Varga et al2020; Wichmann et al2020; Wang et al2020c). The host immune response to SARS-CoV-2 may also impact pathogenicity, resulting in severe tissue damage and, occasionally, death (Tay et al2020). Indeed, several studies have reported lymphopenia, exhausted lymphocytes, and cytokine storms in COVID-19-infected patients, especially those with severe symptoms (Blanco-Melo et al2020; Cao, 2020; Chua et al2020; Liao et al2020). Numerous clinical studies have also observed the elevation of lactate dehydrogenase (LDH), IL-6, troponin I, inflammatory markers, and D-dimer in COVID-19-infected patients (Zhou et al2020a; Wang et al2020b). However, despite the enormous burden of morbidity and mortality due to COVID-19, we know little about its pathophysiology, even though this establishes the basis for successful clinical practice, vaccine development, and drug discovery.

Using a multi-omics approach employing cutting-edge transcriptomic, proteomic, and metabolomic technologies, we identified significant molecular alterations in patients with COVID-19 compared with uninfected controls in this study. Our results refine the molecular view of COVID-19 pathophysiology associated with disease progression and clinical outcome.

For More Information: https://www.embopress.org/doi/full/10.15252/embj.2020105896

Evolution of NETosis markers and DAMPs have prognostic value in critically ill COVID-19 patients

  1. Authors: Joram HuckriedeSara Bülow AnderbergAlbert MoralesFemke de VriesMichael HultströmAnders BergqvistJosé T. Ortiz-PérezJan Willem SelsKanin WichapongMiklos LipcseyMarcel van de PollAnders LarssonTomas LutherChris ReutelingspergerPablo Garcia de FrutosRobert Frithiof & Gerry A. F. Nicolaes  Scientific Reports volume 11, Article number: 15701 (2021) Cite this article

Abstract

Coronavirus disease 19 (COVID-19) presents with disease severities of varying degree. In its most severe form, infection may lead to respiratory failure and multi-organ dysfunction. Here we study the levels and evolution of the damage associated molecular patterns (DAMPS) cell free DNA (cfDNA), extracellular histone H3 (H3) and neutrophil elastase (NE), and the immune modulators GAS6 and AXL in relation to clinical parameters, ICU scoring systems and mortality in patients (n = 100) with severe COVID-19. cfDNA, H3, NE, GAS6 and AXL were increased in COVID-19 patients compared to controls. These measures associated with occurrence of clinical events and intensive care unit acquired weakness (ICUAW). cfDNA and GAS6 decreased in time in patients surviving to 30 days post ICU admission. A decrease of 27.2 ng/mL cfDNA during ICU stay associated with patient survival, whereas levels of GAS6 decreasing more than 4.0 ng/mL associated with survival. The presence of H3 in plasma was a common feature of COVID-19 patients, detected in 38% of the patients at ICU admission. NETosis markers cfDNA, H3 and NE correlated well with parameters of tissue damage and neutrophil counts. Furthermore, cfDNA correlated with lowest p/f ratio and a lowering in cfDNA was observed in patients with ventilator-free days.

Introduction

In severe cases, COVID-19 disease develops into acute respiratory distress syndrome (ARDS), an acute lung injury causing patients to be dependent of ventilator support, which may be accompanied by development of multiple organ failure (MOF)1. Mortality is seen primarily in patients over the age of 652,3,4,5 and is highest for infected individuals with underlying comorbidities such as hypertension, cardiovascular disease or diabetes6,7,8. For patients who are taken into the intensive care unit (ICU), a high SOFA (sequential organ failure assessment) score and increased levels of fibrin D-dimers have been reported9 to associate with poor prognosis. Thromboembolic complications develop in 35–45% of COVID-19 patients10, including thrombotic microangiopathies and disseminated intravascular coagulation (DIC) reminiscent of bacterial sepsis. Yet, COVID-19 has distinct features11 that point at a somewhat different pathological mechanism. The involvement of immune regulatory and hemostatic pathways appears evident, and recent findings have confirmed that the innate immune system and more in particular neutrophil extracellular traps (NETs) play a role in COVID-19 disease pathogenesis. NETs, networks of DNA fibers that are decorated with proteins such as histones and elastase, are released from neutrophils to bind and neutralize viral proteins, bacteria and fungi12. While extracellular histones and NE serve a protective, antimicrobial function, they are potentially harmful to the host.

NETs are abundant in lung capillaries13 and are known to be pro-coagulant due to their intrinsic capacity to activate platelets14.

Excessive NET production, initiated by several pathways that also include complement activation13, results in collateral damage to lung tissues, a disturbed microcirculation of the lung15, loss of alveolar-capillary barrier function and further release of pro-inflammatory cytokines16.

During the preparation of this work it was reported that cellular components that are released upon cellular disruption, so-called damage associated molecular patterns (DAMPs) and NETosis are involved in COVID-19 disease1718. This is fully in line with the observation that in ARDS, NETs contribute to disease progress19. Extracellular histones are cytotoxic DAMPs irrespective of their origin. They may appear during NETosis12,14,20 or originate from damaged tissues21, while cell free DNA (cfDNA) and the protease neutrophil elastase (NE) are released concomitantly22. Cellular free deoxyribonucleic acid (cfDNA) and histones promote proinflammatory cytokine release23,24. Histones have been shown to activate and recruit leukocytes25, damage alveolar macrophages26, activate erythrocytes27, epithelial and endothelial cells, in particular pulmonary endothelial cells28,29,30. If not cleared from circulation, cfDNA as well as histones facilitate severe systemic inflammation and worsen the clinical condition31,32. Presence of NE in plasma is associated with exacerbations, lung function decline and disease severity in patients with chronic obstructive pulmonary disease (COPD), bronchiectasis and cystic fibrosis33,34,35 and decrease of NE levels in bronchiectasis patients improved lung function and airway inflammation36.

At the same time that it provides a first line of defense against infections, the innate immune system initiates self-control responses to prevent damage to the host. One mechanism involved in early immunomodulation is the growth arrest-specific 6 (GAS6)/TAM ligand/receptor system37,38. The GAS6/AXL axis regulates the immune response by modulating cytokine production, inducing a reparative cellular response and by mediating efferocytosis, removing irreversibly damaged cells. The system also provides a mechanism of regulating endothelial and platelet activation and interaction39. Plasma concentrations of GAS6 and AXL increase in a diverse spectrum of inflammatory conditions40, including sepsis and septic shock; but also systemic inflammatory response syndrome (SIRS) without infection41. In several studies, GAS6 at IC admission correlated with severity of organ damage (i.e. SOFA) or with damage of specific organs41,42,43,44,45. This is also the case in viral infections46. These studies illustrate the modulatory role of the innate response provided by GAS6 and suggest that the presence of these components in plasma could be an early event in the orchestration of the immune response to viral infections.

cfDNA, extracellular histones and GAS6 are implicated in regulation of inflammatory and hemostatic pathways in the context of severe viral infections and ARDS, all of which are implicated in COVID-19. While other studies have reported the presence of DAMPs and NETosis markers in smaller COVID-19 populations, here we study a group of 100 severely ill COVID-19 patients admitted to the intensive care unit (ICU). Our hypothesis was twofold:

First, cfDNA, NE, histones and GAS6/AXL are activated in severe COVID-19. Second, cfDNA, NE, histones and GAS6/AXL are related to the severity of illness and reflect organ dysfunction in severe COVID-19.

For More Information: https://www.nature.com/articles/s41598-021-95209-x

Long covid: Damage to multiple organs presents in young, low risk patients

Authors: Gareth Iacobucci BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4470 (Published 17 November 2020)Cite this as: BMJ 2020;371:m4470

Young, low risk patients with ongoing symptoms of covid-19 had signs of damage to multiple organs four months after initially being infected, a preprint study has suggested.1

Initial data from 201 patients suggest that almost 70% had impairments in one or more organs four months after their initial symptoms of SARS-CoV-2 infection.

The results emerged as the NHS announced plans to establish a network of more than 40 long covid specialist clinics across England this month to help patients with long term symptoms of infection.

The prospective Coverscan study examined the impact of long covid (persistent symptoms three months post infection) across multiple organs in low risk people who are relatively young and had no major underlying health problems. Assessment was done using results from magnetic resonance image scans, blood tests, and online questionnaires.

The research has not yet been peer reviewed and could not establish a causal link between organ impairment and infection. But the authors said the results had “implications not only for [the] burden of long covid but also public health approaches which have assumed low risk in young people with no comorbidities.”

The study enrolled participants at two UK sites in Oxford and London between April and August 2020. Two hundred and one individuals (mean age 44 (standard deviation 11.0) years) completed assessments after SARS-CoV-2 infection a median of 140 days after initial symptoms.

Participants were eligible if they tested positive for SARS-CoV-2 by random polymerase chain reaction swab (n=62), a positive antibody test (n=63), or had typical symptoms and were determined to have covid-19 by two independent clinicians (n=73).

The prevalence of pre-existing conditions was low (obesity: 20%, hypertension: 6%, diabetes: 2%, heart disease: 4%), and less than a fifth (18%) of individuals had been hospitalised with covid-19.

The most commonly reported ongoing symptoms—regardless of hospitalization status—were fatigue (98%), muscle ache (88%), shortness of breath (87%), and headache (83%). There was evidence of mild organ impairment in the heart (32% of patients), lungs (33%), kidneys (12%), liver (10%), pancreas (17%), and spleen (6%).

For More Information: https://www.bmj.com/content/371/bmj.m4470

Comorbidity and its Impact on Patients with COVID-19

Authors: Adekunle Sanyaolu 1Chuku Okorie 2Aleksandra Marinkovic 3Risha Patidar 3Kokab Younis 4Priyank Desai 5Zaheeda Hosein 6Inderbir Padda 7Jasmine Mangat 6Mohsin Altaf 8

Abstract

A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in Wuhan, China, in December 2019. Since then, the virus has made its way across the globe to affect over 180 countries. SARS-CoV-2 has infected humans in all age groups, of all ethnicities, both males and females while spreading through communities at an alarming rate. Given the nature of this virus, there is much still to be learned; however, we know that the clinical manifestations range from a common cold to more severe diseases such as bronchitis, pneumonia, severe acute respiratory distress syndrome (ARDS), multi-organ failure, and even death. It is believed that COVID-19, in those with underlying health conditions or comorbidities, has an increasingly rapid and severe progression, often leading to death. This paper examined the comorbid conditions, the progression of the disease, and mortality rates in patients of all ages, infected with the ongoing COVID-19 disease. An electronic literature review search was performed, and applicable data was then collected from peer-reviewed articles published from January to April 20, 2020. From what is known at the moment, patients with COVID-19 disease who have comorbidities, such as hypertension or diabetes mellitus, are more likely to develop a more severe course and progression of the disease. Furthermore, older patients, especially those 65 years old and above who have comorbidities and are infected, have an increased admission rate into the intensive care unit (ICU) and mortality from the COVID-19 disease. Patients with comorbidities should take all necessary precautions to avoid getting infected with SARS CoV-2, as they usually have the worst prognosis.

For More Information: https://pubmed.ncbi.nlm.nih.gov/32838147/

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19) – anatomic pathology perspective on current knowledge

Authors: Sambit K. MohantyAbhishek SatapathyMachita M. NaiduSanjay MukhopadhyayShivani SharmaLisa M. BartonEdana StrobergEric J. DuvalDinesh PradhanAlexandar Tzankov & Anil V. Parwani 

Abstract

Background

The world is currently witnessing a major devastating pandemic of Coronavirus disease-2019 (COVID-19). This disease is caused by a novel coronavirus named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). It primarily affects the respiratory tract and particularly the lungs. The virus enters the cell by attaching its spike-like surface projections to the angiotensin-converting enzyme-2 (ACE-2) expressed in various tissues. Though the majority of symptomatic patients have mild flu-like symptoms, a significant minority develop severe lung injury with acute respiratory distress syndrome (ARDS), leading to considerable morbidity and mortality. Elderly patients with previous cardiovascular comorbidities are particularly susceptible to severe clinical manifestations.

Body

Currently, our limited knowledge of the pathologic findings is based on post-mortem biopsies, a few limited autopsies, and very few complete autopsies. From these reports, we know that the virus can be found in various organs but the most striking tissue damage involves the lungs resulting almost always in diffuse alveolar damage with interstitial edema, capillary congestion, and occasional interstitial lymphocytosis, causing hypoxia, multiorgan failure, and death. A few pathology studies have also reported intravascular microthrombi and pulmonary thromboembolism. Although the clinical presentation of this disease is fairly well characterized, knowledge of the pathologic aspects remains comparatively limited.

Conclusion

In this review, we discuss clinical, pathologic, and genomic features of COVID-19, review current hypotheses regarding the pathogenesis, and briefly discuss the clinical characteristics. We also compare the salient features of COVID-19 with other coronavirus-related illnesses that have posed significant public health issues in the past, including SARS and the Middle East Respiratory Syndrome (MERS).

For More Information: https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-020-01017-8

Acute Respiratory Distress Syndrome and COVID-19: A Scoping Review and Meta-analysis

Authors: Mehdi Jafari-Oori 1Fatemeh Ghasemifard 2Abbas Ebadi 3Leila Karimi 3Farshid Rahimi-Bashar 4Tannaz Jamialahmadi 5 6Paul C Guest 7Amir Vahedian-Azimi 8Amirhossein Sahebkar 9 10 11 12

Abstract

Acute respiratory distress syndrome (ARDS) is a fatal complication of the new severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes COVID-19 disease. This scoping review was carried out with international, peer-reviewed research studies and gray literature published up to July 2020 in Persian and English languages. Using keywords derived from MESH, databases including Magiran, IranMedex, SID, Web of Sciences, PubMed, Embase via Ovid, Science Direct, and Google Scholar were searched. After screening titles and abstracts, the full texts of selected articles were evaluated, and those which passed the criteria were analyzed and synthesized with inductive thematic analysis. Study quality was also evaluated using a standard tool. The overall prevalence of ARDS was estimated using a random-effects model. This led to identification of 23 primary studies involving 2880 COVID-19 patients. All articles were observational with a cross-sectional, retrospective, case report, and cohort design with moderate to strong quality. The main findings showed that COVID-19-related ARDS has a high prevalence and is different to ARDS due to other etiologies. Elderly and patients with comorbidities and organ failure should be closely surveyed for respiratory organ indications for several weeks after the onset of respiratory symptoms. There is currently no definitive treatment for ARDS in COVID-19 disease, and supportive therapies and their effects are somewhat controversial.

For More Information: https://pubmed.ncbi.nlm.nih.gov/33656726/

Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition

Authors: Jia YuXuan YuanHang ChenShruti ChaturvediEvan M. BraunsteinRobert A. Brodsky

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious respiratory virus that can lead to venous/arterial thrombosis, stroke, renal failure, myocardial infarction, thrombocytopenia, and other end-organ damage. Animal models demonstrating end-organ protection in C3-deficient mice and evidence of complement activation in humans have led to the hypothesis that SARS-CoV-2 triggers complement-mediated endothelial damage, but the mechanism is unclear. Here, we demonstrate that the SARS-CoV-2 spike protein (subunit 1 and 2), but not the N protein, directly activates the alternative pathway of complement (APC). Complement-dependent killing using the modified Ham test is blocked by either C5 or factor D inhibition. C3 fragments and C5b-9 are deposited on TF1PIGAnull target cells, and complement factor Bb is increased in the supernatant from spike protein–treated cells. C5 inhibition prevents the accumulation of C5b-9 on cells, but not C3c; however, factor D inhibition prevents both C3c and C5b-9 accumulation. Addition of factor H mitigates the complement attack. In conclusion, SARS-CoV-2 spike proteins convert nonactivator surfaces to activator surfaces by preventing the inactivation of the cell-surface APC convertase. APC activation may explain many of the clinical manifestations (microangiopathy, thrombocytopenia, renal injury, and thrombophilia) of COVID-19 that are also observed in other complement-driven diseases such as atypical hemolytic uremic syndrome and catastrophic antiphospholipid antibody syndrome. C5 inhibition prevents accumulation of C5b-9 in vitro but does not prevent upstream complement activation in response to SARS-CoV-2 spike proteins.

For More Information: https://ashpublications.org/blood/article/136/18/2080/463611/Direct-activation-of-the-alternative-complement

Complement control for COVID-19

Authors: Markus Bosmann1,2,3,4,*

The complement system is an integral part of innate immune defense. It consists of about 50 proteins in plasma, on cell surfaces, and inside host cells. The traditional view is that complement proteins guard the local extracellular spaces and systemic bloodstream against invading pathogens. Loss-of-function mutations resulting in terminal complement pathway deficiencies are associated with a 10,000-fold higher risk for life-threatening meningococcal infections in humans. Surprisingly, the complement system is redundant for defense against most pathogens except encapsulated bacteria. Recent concepts embrace the view that complement factors mediate functions inside cells either directly or through surface receptors. Complement activity fine-tunes homeostasis, metabolism, and biogenesis. On the other hand, uncontrolled complement activation causes disease and can even worsen the outcome of infections. Toxic complement effectors mediate tissue destruction and organ injury during inflammatory diseases. Acute respiratory distress syndrome (ARDS) and sepsis are frequent and severe complications of acute infections and notorious for excessive complement consumption. The three pathways of complement activation are designed for immune sensing of nonself surfaces and foreign antigens. The mannose-binding lectin (MBL)/ficolin pathway starts with soluble pathogen pattern recognition receptors as sensors for foreign carbohydrate motifs (Fig. 1). The alternative pathway is fueled by a spontaneous “smoldering” hydrolysis of C3 targeting all surfaces, unless these surfaces present complement inhibitory proteins (CD46, CD55, and CD59) as a protective self-signal. This C3 “tick-over” is sustained by the high concentrations of C3 in plasma (1 to 2 g/liter), the highest level of all complement factors. The classical pathway is initiated by antigen-antibody complexes that are recognized by the multimeric C1 complex. As a safeguard, IgG antibodies bound in clusters or pentameric IgM are required to surpass the activation threshold. All complement pathways converge on C3 convertase complexes leading to C3 cleavage into the larger C3b and the smaller anaphylactic C3a peptides. C3b is essential for the formation of C5 convertase for cleavage of C5 into C5b and the anaphylatoxin C5a. C5b is the starting point of the pore-forming membrane attack complex (MAC) consisting of C5b-C9 with a channel diameter of ~100 Å. The C3/C5 hub represents a gigantic amplification loop. The alternative C3bBb convertase (half-life of ~3 min) cleaves additional C3, resulting in more C3bBb and so on and so forth. This enzymatic chain reaction can deposit millions of C3b molecules on target surfaces in a few seconds. It is no surprise that such explosive events need to be tightly regulated to maintain the delicate balance of effective and justified pathogen attack, while avoiding damage of innocent bystander cells.

For More Information: https://immunology.sciencemag.org/content/6/59/eabj1014.full

Evidence Shows that COVID-19 Attacks Blood Vessels

Authors: Carolyn Crist

As researchers learn more about COVID-19, they’ve seen reports from patients about unusual rashes, blood clots, and strokes, which could all be linked to damaged blood vessels.

Scientists are now looking at the vascular system, which includes arteries, veins, and capillaries, to monitor the various ways that the coronavirus attacks the body, according to NPR.

In particular, they’ve found that the virus seems to attack the endothelium, or the single layer of cells that line the inside of blood vessels. These cells prevent clotting, control blood pressure, and protect the body from invading pathogens.

“When the virus damages the inside of the blood vessel and shreds the lining, that’s like the ice after a hockey game,” William Li, a vascular biologist at the Angiogenesis Foundation, told NPR.

Li and a group of international researchers published a study this July that found lung tissue damage in COVID-19 patients. As compared with patients who died from the flu, the lung tissue of coronavirus patients had nine times as many small blood clots. They also saw what’s classified as “severe endothelial injury.”

“The surprise was that this respiratory virus makes a beeline for the cells lining blood vessels, filling them up like a gumball machine and shredding the cell from the inside out,” Li says. “We found blood vessels are blocked and blood clots are forming because of that lining damage.”

For More Information: https://www.webmd.com/lung/news/20201109/evidence-shows-that-covid-19-attacks-blood-vessels