"Coronavirus and Heart Disease – A Latest Update"

 

Coronavirus and Heart Disease – A Latest Update

Introduction

Today, the world is facing a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), etiological agent of COVID-19 disease. The first signs of the new virus began to show up in December 2019 in Wuhan, China. In this century, two coronavirus epidemics occurred, the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. SARS-CoV-2 presents a transmissibility ten times faster than 2002 SARS-CoV. Due to its fast dissemination, COVID-19 was declared a pandemic by the World Health Organization (WHO). By the 10 September 2021, the world had already registered 22,30,22,538 individuals contaminated, with 46,02,882 deaths.


The coronaviruses are single-stranded RNA viruses, with great capacity for fast mutations and recombination, causing respiratory or intestinal infections in humans and animals. Coronavirus infection occurs through the coupling of S-protein located on the surface of the virus with angiotensin-converting enzyme 2 (ACE2), which acts as a receptor for the virus. ACE2 is mostly present in the lungs and seems to be the main gateway for the virus. It is also present in great amounts in the heart, which can lead to cardiovascular (CV) complications.

The main clinical manifestations of COVID-19 are respiratory, varying from a mild presentation to acute respiratory distress syndrome (ARDS), being potentially fatal. Moreover, as in other respiratory infections, preexisting CV diseases and risk factors can increase the severity of COVID-19, leading to the aggravation and decompensation of chronic underlying cardiac pathologies as well as acute-onset of new cardiac complications, highlighting that myocardial injury can be present in approximately 12% of hospitalized patients with SARSCoV-2 infection.

With incessant advances in science and technology, cardiology has seen the most rapid advances in the last three decades. In the midst of this, the world is now facing the worst pandemic of the century. Although the most common presenting symptoms are fever, cough and malaise, several reports have seen varied manifestations including myocardial ischemia and heart failure. Also, the prognosis of COVID-19 patients is worse when there is accompanying myocardial injury.

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Impact of preexisting cardiovascular disease — 

Symptoms and signs of heart disease in a patient with COVID-19 may result from an acute disease process, from hemodynamic demands in the setting of chronic heart disease, or may be caused by an acute exacerbation of chronic disease. As discussed separately, there is substantial evidence of association between preexisting cardiovascular disease (such as hypertension and coronary artery disease) and the risk and severity of COVID-19 infection. The causes of this association have not been determined. Proposed mechanisms include impaired physiologic reserve (cardiovascular and pulmonary), impaired immune response, augmented inflammatory response, vulnerability to SARS-CoV-2-induced endothelial dysfunction and effects mediated by the angiotensin-converting enzyme 2 receptor.

Pathophysiology


ACE2 Receptor

SARS-CoV-2 uses its S-spike to bind to ACE2 receptors as the point of entry into the cell. These ACE2 receptors are expressed in type 1 and type 2 pneumocytes and other cell types, including endothelial cells. ACE2 is an inverse regulator of the renin-angiotensin-aldosterone system. Like other coronaviruses, SARS-CoV-2 uses these ACE2 receptors to target the respiratory system primarily. 

SARS-CoV-2 and the Immune Response

There are two immune-response phases of COVID-19 disease. Phase 1 occurs during the incubation stage of the disease, during which the adaptive immune system works to eliminate the virus; if any defects occur at this stage, SARS-CoV-2 will disseminate and induce systemic organ damage, with more significant destruction of organs with higher expression of ACE2 receptors, including lung, endothelial cells, the heart, and the kidneys. This massive damage leads to phase 2 severe inflammation in the affected organs.

Diabetes, atherosclerosis, and obesity, which are risk factors for cardiovascular disease, downregulate the immune system. These have been associated with a poor prognosis in COVID-19.

Mechanisms of Cardiac Damage in COVID-19 

Multiple mechanisms have been suggested for cardiac damage, based on studies conducted during the previous SARS and MERS epidemics and the ongoing COVID-19 epidemic. Part of the systemic inflammatory response in severe COVID-19 is the release of high levels of cytokines that can injure multiple tissues, including vascular endothelium and cardiac myocytes.

Cytokine Release Syndrome

Cytokine release syndrome occurs in patients with severe COVID-19 infection. Many proinflammatory cytokines are significantly elevated in severe cases, including interleukin (IL)-2, IL-10, IL-6, IL-8 and tumor necrosis factor (TNF)-α. Cytokines play an important role during infection with the virus (phase 1) and during ongoing severe inflammation (phase 2), resulting in acute respiratory distress syndrome (ARDS) and other end-organ damage.

Direct Myocardial Cell Injury

The interaction of SARS-CoV-2 with ACE2 can cause changes to the ACE2 pathways, leading to acute injury of the lung, heart and endothelial cells. A small number of case reports have indicated that SARS-CoV2 might directly infect the myocardium, causing viral myocarditis. However, in most cases, myocardial damage appeared to be caused by increased cardiometabolic demand associated with the systemic infection and ongoing hypoxia caused by severe pneumonia or ARDS.

Acute Coronary Syndrome

Plaque rupture leading to acute coronary syndrome can result from the systemic inflammation and catecholamine surge inherent in this disease. Coronary thrombosis also has been identified as a possible cause of acute coronary syndrome in COVID-19 patients.

Other Possible Mechanisms

Certain medications such as corticosteroids, antiviral medications sand immunological agents may have cardiotoxic side effects. Electrolyte disturbances can occur in any critical systemic illness and trigger arrhythmias, for which patients with underlying cardiac disease are at higher risk. There is particular concern about hypokalemia in patients with COVID-19, given the interaction of SARS-CoV-2 with the renin-angiotensin-aldosterone system. Hypokalemia is well known to increase vulnerability to various kinds of arrhythmia. 

Spectrum of Clinical Presentations

Patients with COVID-19 present with a broad spectrum of clinical cardiac presentations: some patients manifest no clinical evidence of heart disease, some have no symptoms of heart disease but have cardiac test abnormalities and some have symptomatic heart disease. Cardiac complications include myocardial injury, heart failure, cardiogenic shock, and cardiac arrhythmias including sudden cardiac arrest. The following sections review the spectrum of cardiac manifestations in patients with COVID-19.

Most patients with COVID-19 with abnormalities on cardiac testing have typical symptoms of COVID-19, including cough, fever, myalgia, headache, and dyspnea, as described separately. A minority of patients with COVID-19 present with symptoms that may suggest heart disease (such as palpitations or chest pain). These symptoms may or may not be accompanied by prior or concurrent symptoms typical of COVID-19 infection. Symptoms such as dyspnea and chest pain may be caused by noncardiac and cardiac causes.

Asymptomatic heart disease — Most patients with COVID-19 with cardiac test abnormalities (such as cardiac troponin elevation, electrocardiographic [ECG] abnormalities or cardiac imaging findings) lack symptoms of heart disease.

As noted above, some symptoms, such as dyspnea, are nonspecific and are evaluated in the context of concurrent symptoms, signs, and test findings to determine if they are more likely caused by a noncardiac condition (eg, pneumonia) or cardiac disease. 

Myocardial injury — Myocardial injury as detected by troponin elevation is commonly identified in patients hospitalized with COVID-19, but the causes of myocardial injury have not been fully elucidated. Cardiac troponin elevation does not distinguish among the causes of injury. As discussed above, there are many putative causes of myocardial injury in patients with COVID-19, but the cause in individual patients is frequently not identified. Clinical conditions associated with myocardial injury include myocarditis, stress cardiomyopathy, and myocardial infarction (MI).

The term "myocardial injury" encompasses all conditions causing cardiomyocyte death. Cardiac troponin elevation is the generally accepted marker for identifying myocardial injury. Myocardial injury is commonly clinically identified by the presence of at least one cardiac troponin value above the 99th percentile upper reference limit, in accordance with the definition of myocardial injury in the Fourth Universal Definition of Myocardial Infarction. While high-sensitivity cardiac troponin levels are sensitive markers of myocardial injury, some patients with disease processes causing cardiomyocyte death may have troponin levels below the 99th percentile URL.

Myocarditis — The exact pathophysiology of severe COVID-19 disease is still elusive. However, a consistent observation is the presence of a proinflammatory surge, the so-called “cytokine storm.” This is thought to be central to the pathogenesis of the acute lung injury-acute respiratory distress syndrome spectrum that amplifies the immune response of alveolar tissue. This phenomenon is thought to be a contributory factor to myocardial injury, observed in other forms of viral infections, such as H1N1. Huang et al. showed this among a cluster of 41 patients with COVID-19. Patients who required intensive care (n = 13) showed higher plasma concentrations of cytokines and chemokines, including GCSF, IP10, MCP1, MIP1A, and tumour necrosis factor α. However, it is unknown if myocarditis is the actual cause of the troponin increase in this case series, because the authors did not report data showing correlative cardiac outcomes or demonstration of left ventricular dysfunction. 

Chen and colleagues also had a similar observation, with elevation of interleukin (IL)-2R, IL-6, IL-10, and tumour necrosis factor α among the cohort of severe COVID-19 patients in a single-centre retrospective study. Cytokine storm is not unique to severe COVID-19, because MERS-CoV and SARS-CoV have shown cytokine surge syndrome among the spectrum of coronavirus disease. Whether this phenomenon is the main cause of fulminant myocarditis still uncertain.

Another potential cause of myocarditis is direct viral involvement. SARS-CoV-2 uses the angiotensin-converting enzyme 2 via its S-spike to bind and anchor to the receptors, hence an entry point to the cell. Hence, it is reasonable to consider viral inclusion or associated myocardial inflammation as the pathogenesis of myocarditis. This direct myocardial involvement was seen in MERS, with one report showing evidence of subepicardial late gadolinium enhancement, consistent with myocarditis. In this case, the distribution of late gadolinium enhancement in the subepicardial region is consistent with myocarditis.

Stress cardiomyopathy — Stress cardiomyopathy has been reported in patients with COVID-19. In addition, some case reports of clinically suspected myocarditis complicating COVID-19 have described marked recovery of left ventricular systolic function within days, suggestive of stress cardiomyopathy or fulminant myocarditis.

In a review of 12 cases of stress cardiomyopathy associated with COVID-19, the mean age was 70.8 and the majority of patients were female. An elevated troponin level was identified in 11 of the cases. There was no significant coronary artery disease on invasive coronary angiography in two patients, coronary artery disease in arteries supplying a different territory in one case, negative computed tomography coronary angiography in five cases, and no coronary artery disease on autopsy in one case; the coronary arteries were not examined in three cases. Complications included HF, cardiogenic shock, cardiac tamponade, and hypertensive crisis.

Myocardial infarction — Studies suggest that COVID-19 increases the risk of acute MI. In one study, there was an increased risk of acute MI in patients with a new diagnosis of COVID-19 compared to noninfected controls. With COVID-19 infection, the majority of MIs are type 2 and related to the primary infection, hemodynamic, and respiratory derangement. As such, the primary disorders should be treated, and in most cases the patient can be treated conservatively with regard to coronary disease. If a type 1 infarction is thought to be the primary etiology of the MI, standard therapies can be considered. 

Heart failure

General prevalence — HF in patients with COVID-19 may be precipitated by acute illness in patients with preexisting known or undiagnosed heart disease (eg, coronary artery disease or hypertensive heart disease), acute hemodynamic stress or acute myocardial injury. Cardiovascular risk factors and cardiovascular disease are highly prevalent in hospitalized patients with COVID-19. Patients with a known history of HF may suffer an acute decompensation due to the development of COVID-19 disease.

Although acute HF incidence was not documented in some series of hospitalized patients with COVID-19, elevated natriuretic peptides and N-terminal pro-BNP are common, particularly in patients with evidence of cardiac injury, as described below. 


Right heart failure — Acute cor pulmonale (right HF due to acute pulmonary hypertension) precipitated by acute pulmonary embolism or adult respiratory distress syndrome (ARDS) has been described in patients with COVID-19. Patients with COVID-19 are at risk for development of ARDS. Venous thromboembolism (including extensive deep vein thrombosis and pulmonary embolism) is common in acutely ill patients with COVID-19.

Cardiogenic shock — The first confirmed instance of Cardiogenic Shock due to COVID-19 infection through myocardial infiltration by viral particles was in a 69-year-old patient from Italy. This was confirmed via biopsy. Since then, the two most probable mechanisms of cardiogenic shock related to COVID-19 are direct invasion and cytokine storm. According to a recent study out of an ICU in Washington state, one-third of critically ill patients with COVID-19 had clinical signs of cardiogenic shock and cardiomyopathy. According to another observational study in China, COVID-19 associated cardiogenic shock has a poor prognosis.

The two most likely mechanisms that contribute to COVID-19 cardiogenic shock are:

·Direct invasion of the virus into the cardiomyocytes

· Cytokine storm activated by T helper cells that triggers a systemic hyperinflammatory response

The causes of cardiogenic shock related to COVID-19 may include: 

·  Newly emerging COVID-19 associated myocarditiscardiac arrhythmiascardiomyopathy, or an acute coronary syndrome deteriorated into cardiogenic shock

·        Worsening of previous left ventricular failure due to COVID-19

·        COVID-19-associated multisystem inflammatory syndrome in children (MIS-C)

Cardiogenic Shock: A Critical Care Crisis in the Age of COVID-19

Multisystem inflammatory syndrome in adults (MIS-A) — Multisystem inflammatory syndrome (MIS) was initially described in children (MIS-C) with recent COVID-19 infection as a Kawasaki-like illness associated with fever, gastrointestinal symptoms, shock, LV systolic dysfunction and elevated inflammatory markers.

Similar cases of MIS have been described in young to middle-aged adults (MIS-A) also presenting with fever, gastrointestinal symptoms, and shock with vasoplegia, LV systolic dysfunction and elevated inflammatory markers. Many of these patients had history of recent COVID-19 and had positive SARS-CoV-2 antibody tests, with fewer having positive SARS-CoV-2 reverse transcription polymerase chain reaction tests. This diagnosis should be considered in young adults presenting in inflammatory shock. This syndrome appears to be highly responsive to parenteral steroids.

Multisystem inflammatory syndrome in adults

Cardiac arrhythmias — The prevalence of arrhythmias and conduction system disease (and cardiovascular disease in general) in patients with COVID-19 varies from population to population. The vast majority of patients presenting with a systemic illness consistent with COVID-19 will not have symptoms or signs of arrhythmias or conduction system disease. Patients may be tachycardic (with or without palpitations) in the setting of other illness-related symptoms (eg, fever, shortness of breath, pain, etc). In most available reports, the specific cause of palpitations or type of arrhythmia have not been specified. Hypoxia and electrolyte abnormalities, both known to contribute to the development of acute arrhythmias, have been frequently reported in the acute phase of severe COVID-19 illness; therefore, the exact contribution of COVID-19 infection to the development of arrhythmias in asymptomatic, mildly ill, critically ill, and recovered patients is not known.

  •  The most common arrhythmia overall in patients with COVID-19 is sinus tachycardia, but the most likely pathologic arrhythmias include atrial fibrillation, atrial flutter, and monomorphic or polymorphic VT.
  •  The differentiation between various tachycardias based on regularity (ie, regular or irregular) and QRS width (ie, narrow or wide QRS complex) requires only a surface ECG.
  •  Bradyarrhythmias, including sinus pauses or high-grade heart block with slow escape rhythms, have not typically been seen but can be identified using a surface ECG if present.


CARDIAC TEST FINDINGS

A variety of cardiac test abnormalities have been described in patients with COVID-19, as described in the following sections.

Biomarkers — Cardiac troponin and natriuretic peptide (B-type natriuretic peptide [BNP] and N-terminal pro-BNP [NT-proBNP]) biomarkers are commonly elevated among hospitalized patients with COVID-19 and are associated with increased risk of mortality. 

Troponin — Cardiac troponin elevation is a marker of myocardial injury and is commonly identified in patients hospitalized with COVID-19, but the causes of troponin elevation have not been fully elucidated. 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 36 percent. The frequency of troponin elevation appears to be lower among patients with mildly symptomatic COVID-19.

Natriuretic peptides — Natriuretic peptides (BNP and NT-proBNP) are commonly elevated in hospitalized patients with COVID-19 and natriuretic peptide elevation is associated with mortality risk, as described above.

Electrocardiogram — The various ECG findings observed in patients with COVID-19 likely reflect the combined effects of acute illness and chronic heart disease. The range of ECG findings was illustrated in a study of 756 patients (mean age 63 years) hospitalized with COVID-19 in New York. The mortality rate was 11.9 percent during the follow-up period of two to seven weeks. Cardiovascular risk factors and conditions were common, including obesity (37 percent), diabetes mellitus (29 percent), hypertension (57 percent), coronary artery disease (CAD, 14 percent) and HF (7 percent). This study did not include data on troponin levels or comparison with prior ECGs.

●Atrial fibrillation or flutter was observed in 5.6 percent. Atrial premature beats were observed in 7.7 percent and premature ventricular contractions in 3.4 percent.

●Right bundle branch block was identified in 7.8 percent, left bundle branch block in 1.5 percent and nonspecific intraventricular conduction delay in 2.5 percent.

●Repolarization abnormalities included localized ST elevation in 0.7 percent, localized T-wave inversion in 10.5 percent and nonspecific repolarization abnormalities in 29 percent.

●In a multivariable model including age, clinical characteristics, and ECG findings, the variables associated with risk of death were presence of CAD, an immunosuppressed state, hypoxemia, and the following ECG findings: APBs (OR 2.57, 95% CI 1.23-5.36), RBBB or IVCD (OR 2.61, 95% CI 1.32-5.18), localized T-wave inversion (OR 3.49, 95% CI 1.56-7.80), and nonspecific repolarization abnormality (OR 2.31, 95% CI 1.27-4.21).

Cardiac imaging

Echocardiogram — A variety of echocardiographic findings have been identified in patients with COVID-19, as illustrated by a study of an unselected population of 100 patients hospitalized with COVID-19.

●Transthoracic echocardiography findings included right ventricular dilation and dysfunction (39 percent), LV diastolic dysfunction (16 percent) and LV systolic dysfunction (10 percent). Patients with an elevated troponin level or worse clinical condition had worse RV function.

●Among the 20 percent of patients with subsequent clinical deterioration, the most common echocardiographic findings were worsened RV function (12 patients) and worsened LV systolic and diastolic function (5 patients). Femoral deep vein thrombosis was identified in 5 of 12 patients with RV failure.


Cardiovascular magnetic resonance — Cardiovascular magnetic resonance abnormalities have been identified in patients with COVID-19 as well as in patients who have recently recovered from COVID-19, though most reported abnormalities have been nonspecific. CMR findings identified in some of these patients include elevations in native T1 (a nonspecific finding seen with acute myocardial injury, fibrosis, or infiltration), T2 (a marker of edema), and, less commonly, late gadolinium enhancement (a marker of acute myocardial injury, fibrosis, or infarction). Since limited endomyocardial biopsy data and no follow-up data have been reported, the clinical significance of these findings is uncertain. Moreover, since no patients had a CMR examination before COVID-19, it remains undetermined whether the abnormal findings might have already been present and therefore be unrelated to COVID-19.

Myocardial histology and viral genome analysis — Myocarditis is commonly suspected in patients with COVID-19 and elevated cardiac troponin levels. However, there have been few reported cases of histologically confirmed myocarditis and viral myocarditis caused by SARS-CoV-2 has not been definitively confirmed by histologic and viral genome analysis.

Proof that SARS-CoV-2 is a cause of viral myocarditis requires identification of histologic findings of active myocarditis plus myocyte necrosis not typical of ischemic injury, identification of the SARS-CoV-2 genome or viral particles in cardiomyocytes and exclusion of known cardiotropic viruses. Cardiotropic viruses that are known to be associated with myocarditis (eg, enterovirus, which is associated with diarrhea and parvovirus B19, which is associated with a pseudoinfarct presentation) were not searched for in most of the reported cases and might be involved.

Treatment

Comprehensive Cardiovascular Care for COVID-19 Patients

Cardiac care needs to be optimized for COVID-19 patients with an aim for early detection and management of cardiac ailments with the simultaneous aim at triaging cases and proper protection to prevent or minimize COVID-19 exposure. As Bonow et al. have rightly put, the message to the patients should be clear that prompt emergency care to be sought in case of warning cardiac symptoms. Mask-wearing, physical distancing remains as essential as ever. Simultaneously, doctors and researchers are finding the best practices for COVID-19 related cardiovascular disease. 

ACE inhibitors (ACEI)/ Angiotensin Receptor Blockers (ARB)

Early in 2020, a controversy grew regarding the safe usage of these drugs in COVID-19 patients. The current consensus agrees to the continued use of these medications. BRACE CORONA trial was presented in ESC Congress 2020, which found no significant difference in the number of days alive and out of hospital through 30 days among subjects receiving continuous ACEI/ARB and hospitalized for COVID-19 compared to those in whom these medicines were temporarily suspended. Five common classes of antihypertensive medications are safe in patients of COVID-19 and do not increase the likelihood of infection. 

Remdesivir 

Remdesivir is an antiviral (RNA polymerase inhibitor) drug used to treat COVID-19. A multicenter, double-blind RCT from China studied Remdesivir for adult patients hospitalized for severe COVID-19. The study showed a reduction in clinical improvement in the treatment group compared with controls, but the difference was not significant. A subsequent trial, sponsored by the US National Institute of Allergy and Infectious Disease, assessed 1063 hospitalized COVID-19 patients in a remdesivir treatment trial. Results published in the New England Journal of Medicine indicated a faster time to recovery for patients who received remdesivir vs. placebo. 

The US Food and Drug Administration (FDA) has issued an emergency use authorization for remdesivir in all patients hospitalized with COVID-19. Thus far, no prominent cardiovascular side effects have been reported with Remdesivir, although these may become apparent with future use during the COVID-19 pandemic.

Hydroxychloroquine and Chloroquine

Hydroxychloroquine was introduced as a potential treatment for COVID-19 patients based on an open-label, single-group study from France. However, an observational study of hospitalized COVID-19 patients conducted at a large medical center in New York City found no apparent benefit from hydroxychloroquine. The use of hydroxychloroquine alone or hydroxychloroquine plus azithromycin did not improve a composite endpoint of intubation or death.

Chloroquine has been noted to cause atrioventricular blocks and prolonged QTc, especially when combined with azithromycin. The lack of benefit seen in clinical trials and the potential for cardiovascular side effects has led the FDA to revoke its emergency use authorization of hydroxychloroquine and chloroquine for patients in COVID-19.

Azithromycin

Azithromycin was commonly used in combination with hydroxychloroquine as a treatment early in the pandemic. However, several studies of this combination have not shown any clinical benefit.  Azithromycin is a macrolide and is known to prolong the QTc interval. Combining azithromycin with chloroquine or hydroxychloroquine increases QTc prolongation and potentially the risk for torsade de points. The lack of clinical benefit and the potential for cardiac arrhythmias has discouraged physicians from using azithromycin in COVID-19.

Lopinavir-ritonavir

Lopinavir and ritonavir are protease inhibitors approved by the FDA for HIV-1 infection. In a recent study published in the New England Journal of Medicine, researchers observed no survival benefit after treatment with lopinavir-ritonavir in hospitalized adults with severe COVID-19. Lopinavir-ritonavir can interact with cardiovascular drugs such as antiarrhythmic agents, antiplatelet drugs and anticoagulants that are metabolized by cytochrome P-450 3A4; therefore, it should be used with caution, especially in patients with underlying cardiovascular disease.

Steroids

The World Health Organization has recommended using systemic steroids to treat COVID-19 infection. Corticosteroids are known to possess potent anti-inflammatory effects and they have been studied extensively in the treatment of sepsis and ARDS. However, they are also known to cause fluid retention, electrolyte derangement, hyperglycemia, and hypertension. At the onset of the COVID-19 pandemic, concerns about potential harm from steroids in COVID-19 were based on data collected and extrapolated during the previous SARS-CoV outbreak. Nonetheless, the recent RECOVERY trial compared dexamethasone 6 mg once daily for up to 10 days versus usual care alone in hospitalized patients with COVID-19 receiving invasive mechanical ventilation or oxygen. Dexamethasone reduced 28-day mortality by one-third in patients on a mechanical ventilator and by one-fifth in patients requiring oxygen therapy.

Aspirin

In a retrospective study, the use of low-dose Aspirin in patients hospitalized with COVID-19 was associated with better outcomes. 

Tocilizumab

Tocilizumab, an anti–IL-6 receptor antibody, has been investigated to treat hospitalized COVID-19 patients. IL-6 levels are elevated in COVID-19 patients and significantly elevated in patients with severe disease. Tocilizumab’s potential efficacy lies in its ability to reduce the inflammatory response, including the cytokine storm that contributes to ARDS and death. As for cardiac side effects, tocilizumab is known to increase cholesterol levels, but there are conflicting reports on its effect on long-term cardiac morbidity and mortality.

Convalescent Plasma 

Convalescent plasma for the treatment of COVID-19 patients is obtained from individuals who have recovered from COVID-19 and have generated an immune response. Small randomized trials and case studies have shown some benefit from convalescent plasma in hospitalized patients with severe COVID-19, especially if given early in the disease course. The FDA has granted emergency use authorization for convalescent plasma in hospitalized patients with COVID-19. 

Ivermectin

Ivermectin was introduced as a potential treatment for COVID-19 patients. Ivermectin is an antiparasitic drug used to treat Strongyloides and onchocerciasis infection. A Meta-analysis by Dr. Andrew Hill investigated Ivermectin in 18 randomized clinical trials. There was a 75% reduction in mortality found in moderate or severe infection in six randomized trials. In another randomized trial of 476 patients, Ivermectin did not shorten the duration of the infection. Multiorgan failure was reported in four patients. The FDA has issued a warning against using Ivermectin to prevent or treat COVID-19 infection. 

Vaccination

The SARS-CoV-2 genetic sequence was published in January 2020 and since then, researcher teams worldwide have been working actively to develop a vaccine against SARS-CoV-2. More than 90 vaccines are being developed at this time. Vaccination has already started in various countries. The mRNA- based vaccines developed by Pfizer and Moderna have been granted emergency use authorization (EUA) by the US Food and Drug Administration (FDA). Many healthcare workers have already received these vaccines. Two vaccines were granted emergency use authorization by the Central Drugs Standard Control Organization (CDSCO) in India, Covishield® (AstraZeneca's vaccine manufactured by Serum Institute of India) and Covaxin® (manufactured by Bharat Biotech Limited). Sputnik - V has been granted EUA in the month of April 2021 in India.

Johnson & Johnson The Johnson & Johnson vaccine is a viral vector vaccine like the one developed by Oxford-AstraZeneca. The vaccine uses a modified adenovirus to deploy the SARS-CoV-2 virus's "spike protein" to human cells, which triggers an immune response. The three-dose ZyCoV-D vaccine prevented symptomatic disease in 66% of those vaccinated, according to an interim study quoted by the vaccine maker Cadila Healthcare. The ZyCoV-D vaccine is also the world's first DNA vaccine against Covid-19. Like other vaccines, a DNA vaccine, once administered, teaches the body's immune system to fight the real virus.

No significant cardiac complication has been reported with any of the vaccines thus far.


Prognosis

Most of the patients (80%) will get a mild form of the disease. The severe form of the disease occurs in about 15% of patients requiring hospitalization and the critical form occurs in about 5% of patients requiring intensive care. The current mortality rate ranges between 2% to 5% of all patients with COVID-19 but is much higher in patients requiring invasive mechanical ventilation. The major cause of death in COVID-19 is acute respiratory distress (ARDS); however, there is also significant other vital organ involvement, including the cardiovascular system and shock. The presence of chronic cardiac diseases or cardiac involvement leads to a higher mortality rate in comparison to patients without cardiovascular disease.

In this COVID-19 pandemic, fewer cardiac patients have attended clinics or hospitals due to the fear of contracting the infection. On the contrary, cardiac patients irrespective of SARS-CoV-2 infection need prompt evaluation and management, more so during this pandemic as the resources and workforce are often compromised.

The prognostic significance of cardiovascular disease was amply illustrated in a cohort of 191 patients in which 30% had hypertension and constituted 48% of nonsurvivors, whereas 8% had cardiovascular disease and constituted 13% of nonsurvivors. In a report of 44672 confirmed cases of COVID-19 from the Chinese Center for Disease Control and Prevention, the overall case-fatality rate was 2.3% for the entire cohort but significantly higher for patients with hypertension (6%), diabetes (7%), or cardiovascular disease (11%).

Conclusion

COVID-19 is mainly a lung disease. However, a hyperergic immune reaction, or “cytokine storm”, with a dramatic systemic impact can be also observed in a later stage of the disease. In addition, COVID-19 prognosis can be deteriorated by pre-existing cardiovascular diseases, or acute cardiovascular events can be induced by COVID-19 even in the absence of a related history. They include the possibility of thrombotic manifestations in the form of local (i.e. pulmonary) or systemic (DIC) events, as well as QT interval prolongation. Finally, in the lack of evidence regarding the postulated harmful effect of ACE inhibitors and sartans in terms of SARS-CoV-2 virulence, these drugs should not be discontinued. Indeed, whether infection by coronaviruses might affect ACE2 function adversely, thus potentially contributing to infectious disease burden in selected patients, is a possibility that deserves investigation.

There is an interaction between COVID-19 and CVD. SARS-CoV-2 can cause CVD, including acute myocardial injury, arrhythmia, and heart failure, through a variety of pathways. COVID-19 patients with underlying CVD have a higher mortality rate. Therefore, close attention should be paid to cardiovascular complications during the diagnosis and treatment of COVID-19 to reduce the mortality of patients. At present, there is insufficient evidence that the use of ACEIs/ARBs aggravates the condition of COVID-19 patients. Therefore, it is not necessary to stop treatment with ACEIs/ARBs in CVD patients after SARS-CoV-2 infection.

Dr. Mayank Chandrakar is a writer also. My first book "Ayurveda Self Healing: How to Achieve Health and Happiness" is available on Kobo and InstamojoYou can buy and read. 

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https://www.kobo.com/search?query=Ayurveda+Self+Healing

The second Book "Think Positive Live Positive: How Optimism and Gratitude can change your life" is available on Kobo and Instamojo.


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The Third Book "Vision for a Healthy Bharat: A Doctor’s Dream for India’s Future" is recently launch in India and Globally in Kobo and Instamojo.

https://www.kobo.com/ebook/vision-for-a-healthy-bharat-a-doctor-s-dream-for-india-s-future


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