Sandbox:SRizvi

'Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief:'Syed Ali Rizvi, M.B;B.S

Contact: syedrizvi555@gmail.com

Medical Education:

Sindh Medical College.Karachi Pakistan

Membership and Certification:

Member of Association of Physicians of Pakistani Descent of North America.2017- Present

Member of Pakistan Medical Council.2007-Present

Overview

The Coronavirus disease-2019 (COVID-19), is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 forms a distinct lineage with Bat-SARS-like coronaviruses . The virus is closely related (96.3%) to bat coronavirus RaTG13, based on phylogenetic analysis, that belong to the order Nidovirales, family Coronaviridae, genus Betacoronavirus, and subgenus Sarbecovirus . Coronaviruses are enveloped, single-stranded RNA viruses that can infect a wide range of hosts including avian, wild, domestic mammalian species, and humans. Coronaviruses are well known for their ability to mutate rapidly, alter tissue tropism, cross the species barrier, and adapt to different epidemiological situations. Six human coronaviruses have been reported since the 1960s; OC43, 229E, NL63, HKU1, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV. First case of COVID-19 was reported in Wuhan, Hubei province, China, in December 2019, associated with the Huanan Seafood Wholesale Market. On March 11, 2020 the Novel Coronavirus Disease, COVID-19, was declared a pandemic by the World Health Organization

Taxonomy

• SARS-CoV-2 belong to the order nidovirale, family coronaviridae.
• Coronaviridae is classified into two subfamilies.
  • Torovirinae
  • Coronavirinae
• Coronavirinae is further classified on the basis of phylogenetic analysis and genome structure into four genera:
  • Alpha coronavirus (αCoV).
  • Beta coronavirus (βCoV).
  • Gamma coronavirus (γCoV).
  • Delta coronavirus (δCoV), which contain 17, 12, 2, and 7 unique species, respectively (ICTV 2018).
• CoV-2 falls under beta coronavirus.

https://www.wikidoc.org/index.php/File:Taxonomy_of_CoV-2.jpg

Biology

Structure

• Coronaviruses are enveloped, icosahedral symmetric particles, approximately 80–220 nm in diameter containing a non-segmented, single-strand, positive-sense RNA genome of about 26–32 kb in size.
• Corona in Latin means crown, and this name was attributed to the virus due to the presence of spike projections from the virus envelope that give it the shape of a crown under the electron microscope.
• Nido means nest and refers to the ability of the viruses of this order to make a nested set of subgenomic mRNA

Envelope

Structural Proteins

• Spike (S) Protein
  • Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases.
  • Early studies indicate that SARS-CoV-2 uses the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2) for entry and transmembrane protease serine 2 (TMPRSS2) for S protein priming.
  • The spike (S) glycoprotein is a type I transmembrane glycoprotein that plays an important role in mediating viral infection.
  • The S proteins consist of two subunits, S1 and S2.
  • The S1 subunit binds the cellular receptor through its receptor-binding domain (RBD), followed by conformational changes in the S2 subunit, which allows the fusion peptide to insert into the host target cell membrane.

• Envelope (E) Protein
  • The CoV envelope (E) protein is a small, integral membrane protein involved in several aspects of the virus’ life cycle, such as assembly, budding, envelope formation, and pathogenesis.
  • Recent studies have expanded on its structural motifs and topology, its functions as an ion-channelling viroporin, and its interactions with both other CoV proteins and host cell proteins.
  • Recombinant CoVs lacking E exhibit significantly reduced viral titres, crippled viral maturation, or yield propagation incompetent progeny, demonstrating the importance of E in virus production and maturation.

• Membrane (M) Protein
  • The CoV membrane (M) protein is a component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins.
  • M is located among the S proteins in the virus envelope along with small amounts of E and is the primary driver of the virus budding process.
  • During assembly of the authentic virion M interacts with itself, with the nucleocapsid protein N, with E and with the S protein.
  • The M protein has dominant cellular immunogenicity and elicits a strong humoral response which suggests it could serve as a potential target in vaccine design.

• Nucleocapsid (N) Protein
  • The primary function of the nucleocapsid (N) protein is to package the viral RNA genome within the viral envelope into a ribonucleoprotein (RNP) complex called the capsid.
  • Ribonucleocapsid packaging is a fundamental part of viral self-assembly and replication.
  • Additionally, the N-protein of the SARS-CoV-2 affects host cell responses and may serve regulatory roles during its viral life cycle.
    

Attachment and Entry:

• The attachment of the virion to the host cell is associated with the interactions between the S protein and its receptor.
• The sites of receptor binding domains (RBD) within the S1 region of a coronavirus (SARS-CoV-2) S protein is at the C Terminus.
• SARS-CoV use angiotensin-converting enzyme 2 (ACE2) as their receptor
• After binding to the receptor, the virus next step is to gain access to the host cell cytosol.
• This is generally done by cathepsin,TMPRRS2 or some other protease. This is followed by fusion of the viral and cellular membranes.
• S protein cleavage occurs at two sites within the S2 portion of the protein, with the first cleavage important for separating the RBD (Receptor binding domain) and fusion domains of the S protein and the second for exposing the fusion peptide (cleavage at S2′).
• Fusion occurs within acidified endosomes.
• Cleavage at S2′ exposes a fusion peptide that inserts into the membrane, which is followed by joining of two heptad repeats in S2 forming an antiparallel six-helix bundle.The formation of this bundle allows for the mixing of viral and cellular membranes, resulting in fusion and ultimately release of the viral genome into the cytoplasm.

RNA Replicase Protein Expression:

• The next step in the coronavirus lifecycle is translation and assembly of the viral replicase complexes from the virion genomic RNA.

Replication and Transcription:

• The translation and assembly of the viral replicase complexes is followed by viral RNA synthesis.
• Viral RNA synthesis produces both genomic and sub-genomic RNAs. Sub-genomic RNAs serve as mRNAs for the structural and accessory genes which reside downstream of the replicase polyproteins. All positive-sense sub-genomic RNAs are 3′ co-terminal with the full-length viral genome and thus form a set of nested RNAs, a distinctive property of the order Nidovirales. Both genomic and sub-genomic RNAs are produced through negative-strand intermediates. These negative-strand intermediates are only about 1 % as abundant as their positive-sense counterparts and contain both poly-uridylate and anti-leader sequences.

References

Post heart transplant Arrhythmia's

Historical Perspective

[Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].

The association between [important risk factor/cause] and [disease name] was made in/during [year/event].

In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].

In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].

There have been several outbreaks of [disease name], including -----.

In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].

Classification

There is no established system for the classification of [disease name].

OR

[Disease name] may be classified according to [classification method] into [number] subtypes/groups: [group1], [group2], [group3], and [group4].

OR

[Disease name] may be classified into [large number > 6] subtypes based on [classification method 1], [classification method 2], and [classification method 3]. [Disease name] may be classified into several subtypes based on [classification method 1], [classification method 2], and [classification method 3].

OR

Based on the duration of symptoms, [disease name] may be classified as either acute or chronic.

OR

If the staging system involves specific and characteristic findings and features: According to the [staging system + reference], there are [number] stages of [malignancy name] based on the [finding1], [finding2], and [finding3]. Each stage is assigned a [letter/number1] and a [letter/number2] that designate the [feature1] and [feature2].

OR

The staging of [malignancy name] is based on the [staging system].

OR

There is no established system for the staging of [malignancy name].

Pathophysiology

The exact pathogenesis of [disease name] is not fully understood.

OR

It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].

OR

[Pathogen name] is usually transmitted via the [transmission route] route to the human host.

OR

Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.

OR

[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].

OR

The progression to [disease name] usually involves the [molecular pathway].

OR

The pathophysiology of [disease/malignancy] depends on the histological subtype.

Causes

Disease name] may be caused by [cause1], [cause2], or [cause3].

OR

Common causes of [disease] include [cause1], [cause2], and [cause3].

OR

The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].

OR

The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click here.

Differentiating ((Page name)) from other Diseases

[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].

OR

[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].

Epidemiology and Demographics

The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.

OR

In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.

OR

In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.

Patients of all age groups may develop [disease name].

OR

The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.

OR

[Disease name] commonly affects individuals younger than/older than [number of years] years of age.

OR

[Chronic disease name] is usually first diagnosed among [age group].

OR

[Acute disease name] commonly affects [age group].

There is no racial predilection to [disease name].

OR

[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].

[Disease name] affects men and women equally.

OR

[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.

The majority of [disease name] cases are reported in [geographical region].

OR

[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].

Risk Factors

There are no established risk factors for [disease name].

OR

The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

OR

Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.

Screening

There is insufficient evidence to recommend routine screening for [disease/malignancy].

OR

According to the [guideline name], screening for [disease name] is not recommended.

OR

According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].

Natural History, Complications, and Prognosis

If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].

OR

Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].

OR

Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.

Diagnosis

Diagnostic Study of Choice

The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].

OR

The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].

OR

The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].

OR

There are no established criteria for the diagnosis of [disease name].

History and Symptoms

The majority of patients with [disease name] are asymptomatic.

OR

The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].

Physical Examination

Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].

OR

Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

The presence of [finding(s)] on physical examination is diagnostic of [disease name].

OR

The presence of [finding(s)] on physical examination is highly suggestive of [disease name].

Laboratory Findings

An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].

OR

Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

OR

[Test] is usually normal among patients with [disease name].

OR

Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].

OR

There are no diagnostic laboratory findings associated with [disease name].

Electrocardiogram

There are no ECG findings associated with [disease name].

OR

An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

X-ray

There are no x-ray findings associated with [disease name].

OR

An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with [disease name].

OR

Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

CT scan

There are no CT scan findings associated with [disease name].

OR

[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

MRI

There are no MRI findings associated with [disease name].

OR

[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

Other Imaging Findings

There are no other imaging findings associated with [disease name].

OR

[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

There are no other diagnostic studies associated with [disease name].

OR

[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

There is no treatment for [disease name]; the mainstay of therapy is supportive care.

OR

Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].

OR

The majority of cases of [disease name] are self-limited and require only supportive care.

OR

[Disease name] is a medical emergency and requires prompt treatment.

OR

The mainstay of treatment for [disease name] is [therapy].

OR The optimal therapy for [malignancy name] depends on the stage at diagnosis.

OR

[Therapy] is recommended among all patients who develop [disease name].

OR

Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].

OR

Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].

OR

Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].

OR

Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].

Surgery

Surgical intervention is not recommended for the management of [disease name].

OR

Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]

OR

The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].

OR

The feasibility of surgery depends on the stage of [malignancy] at diagnosis.

OR

Surgery is the mainstay of treatment for [disease or malignancy].

Primary Prevention

There are no established measures for the primary prevention of [disease name].

OR

There are no available vaccines against [disease name].

OR

Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

OR

[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].

Secondary Prevention

There are no established measures for the secondary prevention of [disease name].

OR

Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].

References

ACUTE MYOCARDIAL INJURY:

Overview

Acute myocardial injury may be defined across studies as any of the following

• Elevated troponin levels .
• The upper reference limit for the high-sensitivity troponin I (hs-TnI) test (0.04ng/mL), based on the 99th percentile of measurements reported in healthy population without the occlusion of coronary arteries..
• Elevated cardiac biomarker levels to > 99th percentile of upper reference limit.
• Electrocardiographic and echocardiographic abnormalities.

Coronavirus disease 2019 (COVID-19) is a rapidly expanding global pandemic which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) , resulting in significant morbidity and mortality. Some hospitalized patients can develop an acute COVID-19 myocardial injury, which can manifest with a variety of clinical presentations but often presents as an acute cardiac injury with cardiomyopathy, ventricular arrhythmias, and hemodynamic instability, acute coronary syndrome, cardiogenic shock. patents with preexisting cardiovascular disease have higher morbidity and mortality.

Historical Perspective

• One of the first reports of myocardial injury associated with SARS-CoV-2 was a study of 41 patients diagnosed with COVID-19 in Wuhan, China, wherein 5 patients (12%) had a high-sensitivity troponin I above the threshold of 28 pg/mL

Classification

There is no established system for the classification of Acute myocardial injury.

Pathophysiology

• The pathophysiology of myocardial injury include,
  • Hyperinflammation and cytokine storm mediated through pathologic T-cells and monocytes leading to myocarditis
  • Respiratory failure and hypoxemia resulting in damage to cardiac myocytes
  • Down regulation of ACE2 expression and subsequent protective signaling pathways in cardiac myocytes
  • Hypercoagulability and development of coronary microvascular thrombosis
  • Diffuse endothelial injury and ‘endotheliitis’ in several organs, including the heart as a direct consequence of SARS-CoV-2 viral involvement and/or resulting from host inflammatory response.
  • inflammation and/or stress causing coronary plaque rupture or supply-demand mismatch leading to myocardial ischemia/infarction.
  • Electrolyte imbalances and adverse medication effects may disproportionately challenge a diseased heart, with special consideration for the regimen of hydroxychloroquine and azithromycin treatment due to the potential for QTc prolongation
  • Direct invasion of the cardiac tissue by COVID-19.

Hyperinflammation and cytokine storm:

• Immune dysregulation, including T cell and immune signaling dysfunction, recognized as an important factor in the pathogenesis of vascular disease, may also adversely affect the body's response to SARS-CoV-2 infection
• The role of CD4(+)CD25(+)FOXP3(+) regulatory T (TREG) cells in the modulation of inflammation and immunity has received increasing attention. Given the important role of TREG cells in the induction and maintenance of immune homeostasis and tolerance, dysregulation in the generation or function of TREG cells can trigger abnormal immune responses and lead to pathology.
• Evidence from experimental and clinical studies has indicated that TREG cells might have an important role in protecting against cardiovascular disease, in particular atherosclerosis and abdominal aortic aneurysm.
• The role of TREG cells is evident in the pathogenesis of a number of cardiovascular diseases, including atherosclerosis, hypertension, ischaemic stroke, abdominal aortic aneurysm, Kawasaki disease, pulmonary arterial hypertension, myocardial infarction and remodelling, postischaemic neovascularization, myocarditis and dilated cardiomyopathy, and heart failure.

Role of ACE Receptor :

• ACE-2 is a membrane-bound aminopeptidate receptor expressed on the epithelial cells of the lungs, intestines, kidneys and blood vessels. It has important immune and cardiovascular roles. Angiotensin-converting enzyme (ACE) cleaves angiotensin I to generate angiotensin II (Ang II), which binds to and activates AT₁R, thus promoting vasoconstriction.
• ACE-2 cleaves angiotensin II and generates angiotensin 1–7, a powerful vasodilator acting through Mas receptors.
• SARS-CoV-2 has a spike protein receptor-binding domain, similar to SARS-CoV-1, which interacts with the ACE-2 receptor and acts as the primary functional receptor for pathogenicity and human-to-human transmission. Furthermore, SARS-CoV-2 binding to ACE-2 leads to its down regulation and increases angiotensin II,a pro-inflammatory factor in the lung.
• This subsequently leads to lower amount of angiotensin 1–7. Thus loss of protective signaling pathway in cardiac myocytes. The detrimental effect of ACE-2 downregulation would impede cardioprotective effects of angiotensin 1–7 leading to increased TNFα production, other cytokines release that can result in acute respiratory syndrome, acute cardiac injury and multiorgan dysfunction.

Causes

• Acute respiratory distress syndrome. (ARDS)
• Pneumonia.
• Hypercoagulability and plaque rupture.
• Hyperinflammation and cytokine storm.
• Electrolyte imbalances and adverse medication effects
• Direct invasion of the cardiac tissue by COVID-19.
• Myocarditis and myocyte necrosis.

Epidemiology and Demographics

• A summary of 44,672 COVID-19 cases documented by the Chinese Center for Disease Control and Prevention demonstrated a case fatality rate of 10.5% with comorbid CVD ( cardiovascular disease) compared to a 2.4% overall case fatality rate
• The frequency of myocardial injury (as reflected by elevation in cardiac troponin levels) is variable among hospitalized patients with COVID-19, with reported frequencies of 7 to 28 percent . Some studies have identified greater frequency and magnitude of troponin elevations in hospitalized patients with more severe disease and worse outcomes
• In a series of 416 patients with COVID-19 who were hospitalized in Wuhan, China, 19.7 percent had high-sensitivity troponin I (hs-TnI) above the 99th percentile upper reference limit on admission . Patients with this marker of myocardial injury were older and had more comorbidities (including chronic heart failure in 14.6 versus 1.5 percent), greater laboratory abnormalities (including higher levels of C-reactive protein, procalcitonin, and aspartate aminotransferase), more lung radiographic abnormalities, and more complications compared with those without myocardial injury. The mortality rate was also higher in those with myocardial injury (51.2 versus 4.5 percent). The risk of death starting from the time of symptom onset was more than four times higher in patients with evidence of myocardial injury on admission.

Risk Factors

A meta-analysis of 6 studies inclusive of 1,527 patients with COVID-19 examined the prevalence of cardio vascular disease (CVD) and reported the prevalence of hypertension, cardiac and cerebrovascular disease, and diabetes to be 17.1%, 16.4%, and 9.7%, respectively

Screening

• There is insufficient evidence to recommend routine screening for acute myocardial injury in COVID-19 patients.

Natural History, Complications, and Prognosis

• The disease also contributes to cardiovascular complications, including
  • Acute coronary syndromes
  • Arrhythmias
  • Myocarditis
  • Pericarditis
  • Heart failure
  • Cardiogenic shock
  • Death.

• Older patients with preexisting cardiovascular comorbidities and diabetes are prone to develop a higher acuity of illness after contracting SARS-CoV-2 associated with higher risk of myocardial injury and a markedly higher short-term mortality rate.

Diagnosis

Diagnostic Study of Choice

• Cardiac Biomarkers and Acute Cardiac Injury
  • he upper reference limit for the high-sensitivity troponin I (hs-TnI) test (0.04ng/mL), based on the 99th percentile of measurements reported in healthy population without the occlusion of coronary arteries.
  • In the recently published retrospective study of 191 COVID-19 patients from two separate hospitals in China, the incidence of elevation in high-sensitivity cardiac troponin I (cTnI) (>28 pg/ml) was 17%, and it was significantly higher among non-survivors (46% versus 1%, p<0.001).¹⁰ Furthermore, elevation of this biomarker was noted to be a predictor of in-hospital death (univariable OR 80.07, 95% CI [10.34–620.36], p<0.0001). The most abrupt increase in cTnI in non-survivors was noted beyond day 16 after the onset of disease. In the same study, the incidence of acute cardiac injury was 17% among all-comers, but significantly higher among non-survivors (59% versus 1%, p<0.0001).
  • CK-MB >2.2 ng/mL
  • Guo et al¹¹ provide additional novel insights that TnT levels are significantly associated with levels of C-reactive protein and N-terminal pro-B-type natriuretic peptide (NT-proBNP), thus linking myocardial injury to severity of inflammation and ventricular dysfunction

History and Symptoms

• Patients with COVID-19 can present with the typical symptoms and signs of SARS-CoV-2 nfection such as fever, cough, dyspnea, and bilateral infiltrates on chest imaging can present with chest pain, dyspnea, dysarrhythmia, and acute left ventricular dysfunction

Electrocardiogram

• The electrocardiogram (ECG) can demonstrate a range of findings
  • In some cases mimicking acute coronary syndrome (ACS).
  • The ECG abnormalities result from myocardial inflammation and include non-specific ST segment-T wave abnormalities.
  • T wave inversion.
  • PR segment and ST segment deviations (depression and elevation)

Treatment

Treatment of Acute myocardial injury depends upon the complication the

References

COVID 19

For the main page on coronavirus infection, please click here

The novel coronavirus (SARS-CoV-2), also known as the Wuhan coronavirus, is a contagious virus that causes respiratory infection and has shown evidence of human-to-human transmission, first identified by authorities in Wuhan, Hubei, China, as the cause of the ongoing 2019–20 Wuhan coronavirus outbreak. Genomic sequencing has shown that it is a positive-sense, single-stranded RNA coronavirus.

Due to reports that the initial cases had epidemiological links to a large seafood and animal market, the virus is thought to have a zoonotic origin, though this has not been confirmed. Comparisons of genetic sequences between this virus and other existing virus samples have shown similarities to SARS-CoV (79.5%) and bat coronaviruses (96%), with a likely origin in bats being theorized.

Epidemiology

Main article: 2019–20 Wuhan coronavirus outbreak

The first known human infection occurred in early December 2019. Molecular clock approaches suggest a similar, or slightly earlier, date of origin.

An outbreak of SARS-CoV-2 was first detected in Wuhan, China, in mid-December 2019. The virus subsequently spread to other provinces of Mainland China and other countries, including Thailand, Japan, Taiwan, South Korea, Australia, France, and the United States.

As of 29 January 2020 (04:00 UTC), there were 6,057 confirmed cases of infection, of which 5,970 were within mainland China. Cases outside China, to date, were people who have either travelled from Wuhan, or were in direct contact with someone who travelled from the area. The number of deaths was 132 as of 29 January 2020 (04:00 UTC). Human-to-human spread was first confirmed in Guangdong, China, on 20 January 2020.

Treatment

No specific treatment is currently available, so treatment is focused on alleviation of symptoms, which include fever, fatigue, dry cough, and shortness of breath, or pneumonia and kidney failure in severe cases. The Chinese Center for Disease Control and Prevention (CCDC) is testing existing pneumonia treatments for efficacy in treating coronavirus-related pneumonia.

Existing anti-virals are being studied, including protease inhibitors like indinavir, saquinavir, remdesivir, lopinavir/ritonavir and interferon beta. The effectiveness of previously identified monoclonal antibodies (mAbs) is also under investigation.

Virology

Infection

Human-to-human transmission of the virus has been confirmed. Reports have emerged that the virus is infectious even during the incubation period, although as of 27 January 2020 officials at the Centers for Disease Control and Prevention (CDC) in the United States stated they "don't have any evidence of patients being infectious prior to symptom onset."

Research groups have estimated the basic reproduction number (<math>R_0</math>, pronounced R-nought) of the virus to be between 1.4 and 5, with most estimates below 3.8. This means that, when unchecked, the virus typically results in 1.4 to 3.8 new cases per established infection. It has been established that the virus is able to transmit along a chain of at least four people.

Reservoir

Animals sold for food are suspected to be the reservoir or the intermediary because many of the first identified infected individuals were workers at the Huanan Seafood Market. Consequently, they were exposed to greater contact with animals. A market selling live animals for food was also blamed in the SARS epidemic in 2003; such markets are considered to be incubators for novel pathogens. The outbreak has prompted a temporary ban on the trade and consumption of wild animals in China.

With a sufficient number of sequenced genomes, it is possible to reconstruct a phylogenetic tree of the mutation history of a family of viruses. During 17 years of research on the origin of the SARS 2003 epidemic, many SARS-like bat coronaviruses were isolated and sequenced, most of them originating from the Rhinolophus genus of bats. SARS-CoV-2 has been found to fall into this category of SARS-related coronaviruses. Two genome sequences from Rhinolophus sinicus published in 2015 and 2017 show a resemblance of 80% to SARS-CoV-2. A third unpublished virus genome from Rhinolophus affinis, "RaTG13", is said to have a 96% resemblance to SARS-CoV-2. For comparison, this amount of variation among viruses is similar to the amount of mutation observed over ten years in the H3N2 human flu virus strain.

Phylogenetics and taxonomy

Genomic information

File:2019-nCoV genome.svg Genome organisation (click to enlarge)
NCBI genome ID	MN908947
Genome size	29,903 bases
Year of completion	2020

SARS-CoV-2 belongs to the broad family of viruses known as coronaviruses. Other coronaviruses are capable of causing illnesses ranging from the common cold to more severe diseases such as the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). It is the seventh known coronavirus to infect people, after 229E, NL63, OC43, HKU1, MERS-CoV, and SARS-CoV.

Though genetically distinct from other coronaviruses that infect humans, it is, like SARS-CoV, a member of the subgenus Sarbecovirus (Beta-CoV lineage B). Its RNA sequence is approximately 30 kb in length.

By 12 January, five genomes of the novel coronavirus had been isolated from Wuhan and reported by the Chinese Center for Disease Control and Prevention and other institutions; the number of genomes increased to 28 by 26 January. Except for the earliest GenBank genome, the genomes are under an embargo at GISAID. A phylogenic analysis for the samples is available through Nextstrain.

Structural biology

File:Coronavirus 2019-nCoV.3.png

Innophore Phyre2 ribbon diagram of the SARS-CoV-2 M(pro) protease, a prospective target for antiviral drugs

The publications of the genome led to several protein modeling experiments on the receptor binding protein (RBD) of the nCoV spike (S) protein suggesting that the S protein retained sufficient affinity to the Angiotensin converting enzyme 2 (ACE2) receptor to use it as a mechanism of cell entry. On 22 January, a group in China working with the full virus and a group in the U.S. working with reverse genetics independently and experimentally demonstrated ACE2 as the receptor for SARS-CoV-2.

To look for potential protease inhibitors, the viral 3C-like protease M(pro) from the Orf1a polyprotein was also modeled for drug docking experiments. Innophore has produced two computational models based on SARS protease, and the Chinese Academy of Sciences has produced an unpublished experimental structure of a recombinant SARS-CoV-2 protease.

Vaccine research

In January 2020, several organizations and institutions began work on creating vaccines for 2019 n-CoV based on the published genome.

In China, the Chinese Center for Disease Control and Prevention is developing a vaccine against the novel coronavirus. The team of Yuen Kwok-yung at the University of Hong Kong, which previously participated in work on the SARS coronavirus during its 2003 outbreak, has also announced that a vaccine is under development there but has yet to proceed to animal testing.

Elsewhere, three vaccine projects are being supported by the Coalition for Epidemic Preparedness Innovations (CEPI), including one project by the biotechnology company Moderna and another by the University of Queensland. The United States National Institutes of Health (NIH) is cooperating with Moderna to create an RNA vaccine matching a spike of the coronavirus surface, and is hoping to start production by May 2020. In Australia, the University of Queensland is investigating the potential of a molecular clamp vaccine that would genetically modify viral proteins to make them mimic the coronavirus and stimulate an immune reaction.

In an independent project, the Public Health Agency of Canada has granted permission to the International Vaccine Centre (VIDO-InterVac) at the University of Saskatchewan to begin work on a vaccine. VIDO-InterVac aims to start production and animal testing in March 2020, and human testing in 2021.