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

Meningoencephalitis associated with COVID-19: a systematic review

Authors: Ritwick Mondal 1Upasana Ganguly 1Shramana Deb 2Gourav Shome 3Subhasish Pramanik 1Deebya Bandyopadhyay 1Durjoy Lahiri 4


With the growing number of COVID-19 cases in recent times. significant set of patients with extra pulmonary symptoms has been reported worldwide. Here we venture out to summarize the clinical profile, investigations, and radiological findings among patients with SARS-CoV-2-associated meningoencephalitis in the form of a systemic review. This review was carried out based on the existing PRISMA (Preferred Report for Systematic Review and Meta analyses) consensus statement. The data for this review was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase, and Cochrane library and Preprint servers up till 30 June 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes “SARS-COV-2,” “COVID-19,” and “meningoencephalitis.” All peer reviewed, case-control, case report, pre print articles satisfying our inclusion criteria were involved in the study. Quantitative data was expressed in mean ± SD, while the qualitative date in percentages. Paired t test was used for analyzing the data based on differences between mean and respective values with a p < 0.05 considered to be statistically significant. A total of 61 cases were included from 25 studies after screening from databases and preprint servers, out of which 54 of them had completed investigation profile and were included in the final analysis. Clinical, laboratory findings, neuroimaging abnormalities, and EEG findings were analyzed in detail. This present review summarizes the available evidences related to the occurrence of meningoencephalitis in COVID-19.

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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,∗


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).

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Hyperglycemia in Acute COVID-19 is Characterized by Adipose Tissue Dysfunction and Insulin Resistance

Authors: Reiterer MRajan MGómez-Banoy NLau JDGomez-Escobar LGGilani AAlvarez-Mulett SSholle ETChandar VBram YHoffman KRubio-Navarro AUhl SShukla APGoyal PtenOever BRAlonso LCSchwartz RESchenck EJSafford MM


COVID-19 has proven to be a metabolic disease resulting in adverse outcomes in individuals with diabetes or obesity. Patients infected with SARS-CoV-2 and hyperglycemia suffer from longer hospital stays, higher risk of developing acute respiratory distress syndrome (ARDS), and increased mortality compared to those who do not develop hyperglycemia. Nevertheless, the pathophysiological mechanism(s) of hyperglycemia in COVID-19 remains poorly characterized. Here we show that insulin resistance rather than pancreatic beta cell failure is the prevalent cause of hyperglycemia in COVID-19 patients with ARDS, independent of glucocorticoid treatment. A screen of protein hormones that regulate glucose homeostasis reveals that the insulin sensitizing adipokine adiponectin is reduced in hyperglycemic COVID-19 patients. Hamsters infected with SARS-CoV-2 also have diminished expression of adiponectin. Together these data suggest that adipose tissue dysfunction may be a driver of insulin resistance and adverse outcomes in acute COVID-19.

The deadly COVID-19 pandemic is underscored by the high morbidity and mortality rates seen in certain vulnerable populations, including patients with diabetes mellitus (DM), obesity, cardiovascular disease, and advanced age, with the latter associated with many chronic cardiometabolic diseases 14 . Hyperglycemia with or without a history of DM is a strong predictor of in-hospital adverse outcomes, portending a 7-fold higher mortality compared to patients with well-controlled blood glucose levels 5 . Hyperglycemia may be seen as a biomarker that predicts poor prognosis. A retrospective study that compared hyperglycemic patients that were treated with insulin against those who were not showed increased mortality in those receiving insulin 6 . However, it remains unclear whether insulin treatment is a surrogate for increased hyperglycemia and overall morbidity, or whether it is an actual causative factor for death. There is thus uncertainty regarding specific treatments for hyperglycemia in acute COVID-19 7 .

Despite our early recognition of the association between hyperglycemia and perilous outcomes, the pathophysiological mechanisms that underlie hyperglycemia in COVID-19 remain undefined 8,9 . Hypotheses have included a broad range of pathologies from direct infection of islets leading to beta cell failure (BCF) and to inflammation and glucocorticoids leading to insulin resistance (IR). Although COVID-19 is primarily a respiratory tract infection, SARS-CoV-2 is known to infect other cell types and often leads to extrapulmonary consequences 10,11 ACE2 and other entry receptors for SARS-CoV-2 can be expressed on pancreatic islet cells and endocrine cells differentiated from human pluripotent stem cells are permissive to infection 12 . Early reports of unexpected diabetic ketoacidosis (DKA) in COVID-19 patients fuelled concerns for a novel form of acute onset beta cell failure. For example, one case described a patient with new onset diabetic ketoacidosis (DKA) who was found to be autoantibody negative for type 1 DM (T1DM) but showed evidence of prior SARS-CoV-2 infection based on serology results, suggesting the possibility of pancreatic beta cell dysfunction or destruction as a result of COVID-19 13 . However, given the high rates of COVID-19 during this pandemic coupled with low background rates of new onset T1DM, the connection between these two events in this case could be “true, true, and unrelated.” Recent studies disagree on whether ACE2 is expressed on pancreatic beta cells or whether the SARS-CoV-2 virus is found in pancreatic beta cells of deceased individuals with COVID-19 1416 . Conversely, the well-known connection between obesity and insulin resistance might lead to impaired immunity and more severe SARS-CoV-2 infection 17 . In fact, population level studies have reported higher risk of complications in obese patients with COVID-19 1820 . Viral infection may lead to systemic insulin resistance and worsened hyperglycemia. In sum, despite much attention, the pathophysiology of hyperglycemia in COVID-19 remains unknown.

Dexamethasone substantially reduces mortality in patients with severe COVID-19 infection requiring oxygen or invasive mechanical ventilation 21 . Glucocorticoids can also provoke hyperglycemia by inducing insulin resistance and beta cell dysfunction. The widespread usage of dexamethasone in severe SARS-CoV-2 infection is sure to exacerbate both the incidence and severity of hyperglycemia in COVID-19.

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Severe COVID-19: what have we learned with the immunopathogenesis?


The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a theoretical model on immunopathogenesis associated with severe COVID-19, based on the current literature of SARS-CoV-2 and other epidemic pathogenic coronaviruses, such as SARS and MERS. Several studies have suggested that immune dysregulation and hyperinflammatory response induced by SARS-CoV-2 are more involved in disease severity than the virus itself.

Immune dysregulation due to COVID-19 is characterized by delayed and impaired interferon response, lymphocyte exhaustion and cytokine storm that ultimately lead to diffuse lung tissue damage and posterior thrombotic phenomena.

Considering there is a lack of clinical evidence provided by randomized clinical trials, the knowledge about SARS-CoV-2 disease pathogenesis and immune response is a cornerstone to develop rationale-based clinical therapeutic strategies. In this narrative review, the authors aimed to describe the immunopathogenesis of severe forms of COVID-19.


The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense single-stranded RNA-enveloped virus, is the causative agent of coronavirus disease 2019 (COVID-19), being first identified in Wuhan, China, in December 2019. Previously, other epidemic coronavirus such as severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and the middle-east respiratory syndrome coronavirus (MERS-CoV) in 2012, had serious impact on human health and warned the world about the possible reemergence of new pathogenic strains [1]. Despite being a new virus, several common morpho-functional characteristics have been reported between SARS-CoV and the SARS-CoV-2, including the interaction of the viral spike (S) glycoprotein with the human angiotensin converting enzyme 2 (ACE2). These similarities may help understanding some pathophysiological mechanisms and pointing out possible therapeutic targets.

The first step for SARS-CoV-2 entry into the host cell is the interaction between the S glycoprotein and ACE2 on cell surface. Since the latter acts as a viral receptor, the virus will only infect ACE2 expressing cells, notably type II pneumocytes. These cells represent 83% of the ACE2-expressing cells in humans, but cells from other tissues and organs, such as heart, kidney, intestine and endothelium, can also express this receptor [2]. A host type 2 transmembrane serine protease, TMPRSS2, facilitates virus entry by priming S glycoprotein. TMPRSS2 entails S protein in subunits S1/S2 and S2´, allowing viral and cellular membrane fusion driven by S2 subunit [3]. Once inside the cell viral positive sense single strand RNA is translated into polyproteins that will form the replicase-transcriptase complex. This complex function as a viral factory producing new viral RNA and viral proteins for viral function and assembly [4]. Considering these particularities, the infection first begins on upper respiratory tract mucosa and then reaches the lungs. The primary tissue damage is related to the direct viral cytopathic effects. At this stage, the virus has the potential to evade the immune system, where an inadequate innate immune response can occur, depending on the viral load and other unknown genetic factors. Subsequently, tissue damage is induced by additional mechanisms derived from a dysregulated adaptive immune response [5].

Although most of COVID-19 cases have a mild clinical course, up to 14% can evolve to a severe form, with respiratory rate ≥ 30/min, hypoxemia with pulse oxygen saturation ≤ 93%, partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300 and/or pulmonary infiltrates involving more than 50% of lung parenchyma within 24 to 48 h. Up to 5% of the cases can be critical, evolving with respiratory failure, septic shock and/or multiple organ dysfunction, presumably driven by a cytokine storm [6]. Host characteristics, including aging (immunosenescence) and comorbidities (hypertension, diabetes mellitus, lung and heart diseases) may influence the course of the disease [7]. The false paradox between inflammation and immunodeficiency is highlighted by the severe form of COVID-19. Thus, severe pneumonia caused by SARS-CoV-2 is marked by immune system dysfunction and hyperinflammation leading to acute respiratory distress syndrome (ARDS), macrophage activation, hypercytokinemia and coagulopathy [8].

Herein, we aim to review the factors related to the dysregulated immune response against the SARS-CoV-2, along with its relation with severe forms of COVID-19, namely ARDS and cytokine storm (CS).

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Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19

Authors: Davide Scozzi,1Marlene Cano,2Lina Ma,2Dequan Zhou,1Ji Hong Zhu,1Jane A. O’Halloran,3Charles Goss,4Adriana M. Rauseo,3Zhiyi Liu,1Sanjaya K. Sahu,2Valentina Peritore,5Monica Rocco,6Alberto Ricci,7Rachele Amodeo,8Laura Aimati,8Mohsen Ibrahim,1,5Ramsey Hachem,2Daniel Kreisel,1Philip A. Mudd,9Hrishikesh S. Kulkarni,2,10 and Andrew E. Gelman1,11



Mitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating cell-free MT-DNA quantitation could be used to predict the risk of poor COVID-19 outcomes remains undetermined.


We measured circulating MT-DNA levels in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at hospital presentation. Our primary outcome was mortality. Intensive care unit (ICU) admission, intubation, vasopressor, and renal replacement therapy requirements were secondary outcomes. Multivariate regression analysis determined whether MT-DNA levels were independent of other reported COVID-19 risk factors. Receiver operating characteristic and area under the curve assessments were used to compare MT-DNA levels with established and emerging inflammatory markers of COVID-19.


Circulating MT-DNA levels were highly elevated in patients who eventually died or required ICU admission, intubation, vasopressor use, or renal replacement therapy. Multivariate regression revealed that high circulating MT-DNA was an independent risk factor for these outcomes after adjusting for age, sex, and comorbidities. We also found that circulating MT-DNA levels had a similar or superior area under the curve when compared against clinically established measures of inflammation and emerging markers currently of interest as investigational targets for COVID-19 therapy.


These results show that high circulating MT-DNA levels are a potential early indicator for poor COVID-19 outcomes.

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Use of DAMPs and SAMPs as Therapeutic Targets or Therapeutics: A Note of Caution

  • 2020 Jun;24(3):251-262. doi: 10.1007/s40291-020-00460-z.

Walter Gottlieb Land 1 2 PMID: 32248387

PMCID: PMC7127836

DOI: 10.1007/s40291-020-00460-z

Free PMC article


This opinion article discusses the increasing attention paid to the role of activating damage-associated molecular patterns (DAMPs) in initiation of inflammatory diseases and suppressing/inhibiting DAMPs (SAMPs) in resolution of inflammatory diseases and, consequently, to the future roles of these novel biomarkers as therapeutic targets and therapeutics. Since controlled production of DAMPs and SAMPs is needed to achieve full homeostatic restoration and repair from tissue injury, only their pathological, not their homeostatic, concentrations should be therapeutically tackled. Therefore, distinct caveats are proposed regarding choosing DAMPs and SAMPs for therapeutic purposes. For example, we discuss the need to a priori identify and define a context-dependent “homeostatic DAMP:SAMP ratio” in each case and a “homeostatic window” of DAMP and SAMP concentrations to guarantee a safe treatment modality to patients. Finally, a few clinical examples of how DAMPs and SAMPs might be used as therapeutic targets or therapeutics in the future are discussed, including inhibition of DAMPs in hyperinflammatory processes (e.g., systemic inflammatory response syndrome, as currently observed in Covid-19), administration of SAMPs in chronic inflammatory diseases, inhibition of SAMPs in hyper-resolving processes (e.g., compensatory anti-inflammatory response syndrome), and administration/induction of DAMPs in vaccination procedures and anti-cancer therapy.

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Role of DAMPs in respiratory virus-induced acute respiratory distress syndrome—with a preliminary reference to SARS-CoV-2 pneumonia

Authors: Walter Gottlieb Land Genes & Immunity volume 22, pages141–160 (2021 )Cite this article


When surveying the current literature on COVID-19, the “cytokine storm” is considered to be pathogenetically involved in its severe outcomes such as acute respiratory distress syndrome, systemic inflammatory response syndrome, and eventually multiple organ failure. In this review, the similar role of DAMPs is addressed, that is, of those molecules, which operate upstream of the inflammatory pathway by activating those cells, which ultimately release the cytokines. Given the still limited reports on their role in COVID-19, the emerging topic is extended to respiratory viral infections with focus on influenza. At first, a brief introduction is given on the function of various classes of activating DAMPs and counterbalancing suppressing DAMPs (SAMPs) in initiating controlled inflammation-promoting and inflammation-resolving defense responses upon infectious and sterile insults. It is stressed that the excessive emission of DAMPs upon severe injury uncovers their fateful property in triggering dysregulated life-threatening hyperinflammatory responses. Such a scenario may happen when the viral load is too high, for example, in the respiratory tract, “forcing” many virus-infected host cells to decide to commit “suicidal” regulated cell death (e.g., necroptosis, pyroptosis) associated with release of large amounts of DAMPs: an important topic of this review. Ironically, although the aim of this “suicidal” cell death is to save and restore organismal homeostasis, the intrinsic release of excessive amounts of DAMPs leads to those dysregulated hyperinflammatory responses—as typically involved in the pathogenesis of acute respiratory distress syndrome and systemic inflammatory response syndrome in respiratory viral infections. Consequently, as briefly outlined in this review, these molecules can be considered valuable diagnostic and prognostic biomarkers to monitor and evaluate the course of the viral disorder, in particular, to grasp the eventual transition precociously from a controlled defense response as observed in mild/moderate cases to a dysregulated life-threatening hyperinflammatory response as seen, for example, in severe/fatal COVID-19. Moreover, the pathogenetic involvement of these molecules qualifies them as relevant future therapeutic targets to prevent severe/ fatal outcomes. Finally, a theory is presented proposing that the superimposition of coronavirus-induced DAMPs with non-virus-induced DAMPs from other origins such as air pollution or high age may contribute to severe and fatal courses of coronavirus pneumonia.


When the first articles on severe and fatal outcomes of COVID-19 were published, researchers worldwide working in the field of damage-associated molecular patterns (DAMPs) thought spontaneously: this is the work of DAMPs! And the researchers were surprised that most authors focused on the pathogenetic role of the “cytokine storm” observed in patients developing viral pneumonia-induced acute respiratory distress syndrome (ARDS) without discussing the fundamental part of DAMPs in initiating cytokine production. However, quite admittedly, the dataset on the pathogenetic role of DAMPs in COVID-19 is still too poor to prove their vital pathogenetic role in this challenging disease. On the other hand, there is accumulating evidence indicating that DAMPs are involved in respiratory viral disorders (as in all infectious diseases), culminating in three recent reports on their detection in COVID-19 patients [1,2,3]. This should be reason enough for a short review.

DAMPs in infectious diseases at a glance

The danger/injury model in Immunology, proposed in 1994 [45] and after that several times modified, argues that immune responses are driven by cell stress and tissue injury, including pathogen-caused stress and injury, rather than by the recognition of non-self molecules derived, for example, from pathogenic invaders. The core of this model refers to the generation and emission of DAMPs, that is, molecules that are generated, exposed, or emitted upon any stress, damage, or death of cells.

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Potential mechanisms of cerebrovascular diseases in COVID-19 patients

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


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.

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Elevated level of C‐reactive protein may be an early marker to predict risk for severity of COVID‐19

Authors: Nurshad Ali 1

The outbreak of coronavirus disease‐2019 (COVID‐19) is an emerging global health threat. The healthcare workers are facing challenges in reducing the severity and mortality of COVID‐19 across the world. Severe patients with COVID‐19 are generally treated in the intensive care unit, while mild or non‐severe patients treated in the usual isolation ward of the hospital. However, there is an emerging challenge that a small subset of mild or non‐severe COVID‐19 patients develops into a severe disease course. Therefore, it is important to early identify and give the treatment of this subset of patients to reduce the disease severity and improve the outcomes of COVID‐19. Clinical studies demonstrated that altered levels of some blood markers might be linked with the degree of severity and mortality of patients with COVID‐19. 1 Of these clinical parameter, serum C‐reactive protein (CRP) has been found as an important marker that changes significantly in severe patients with COVID‐19. 3 CRP is a type of protein produced by the liver that serves as an early marker of infection and inflammation. 6 In blood, the normal concentration of CRP is less than 10 mg/L; however, it rises rapidly within 6 to 8 hours and gives the highest peak in 48 hours from the disease onset. 7 Its half‐life is about 19 hours 8 and its concentration decreases when the inflammatory stages end and the patient is healing. CRP preferably binds to phosphocholine expressed highly on the surface of damaged cells. 9 This binding makes active the classical complement pathway of the immune system and modulates the phagocytic activity to clear microbes and damaged cells from the organism. 7 When the inflammation or tissue damage is resolved, CRP concentration falls, making it a useful marker for monitoring disease severity. 7

The available studies that have determined serum concentration of CRP in patients with COVID‐19 are presented in Table 1. A significant increase of CRP was found with levels on average 20 to 50 mg/L in patients with COVID‐19. 10 12 21 Elevated levels of CRP were observed up to 86% in severe COVID‐19 patients. 10 11 13 Patients with severe disease courses had a far elevated level of CRP than mild or non‐severe patients. For example, a study reported that patients with more severe symptoms had on average CRP concentration of 39.4 mg/L and patients with mild symptoms CRP concentration of 18.8 mg/L. 12 CRP was found at increased levels in the severe group at the initial stage than those in the mild group. 1 In another study, the mean concentration of CRP was significantly higher in severe patients (46 mg/L) than non‐severe patients (23 mg/L). 21 The patients who died from COVID‐19 had about 10 fold higher levels of CRP than the recovered patients (median 100 vs 9.6 mg/L). 16 A recent study showed that about 7.7% of non‐severe COVID‐19 patients were progressed to severe disease courses after hospitalization, 3 and compared to non‐severe cases, the aggravated patients had significantly higher concentrations of CRP (median 43.8 vs 12.1 mg/L). A significant association was observed between CRP concentrations and the aggravation of non‐severe patients with COVID‐19 [1], and the authors proposed CRP as a suitable marker for anticipating the aggravation probability of non‐severe COVID‐19 patients, with an optimal threshold value of 26.9 mg/L. 3 The authors also noted that the risk of developing severe events is increased by 5% for every one‐unit increase in CRP concentration in patients with COVID‐19.

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