key: cord-0923251-uxjrmduo
authors: Niazi, Sana; Niazi, Feizollah; Doroodgar, Farideh; Safi, Morteza
title: The Cardiac Effects of COVID-19 Review of articles
date: 2021-09-14
journal: Curr Probl Cardiol
DOI: 10.1016/j.cpcardiol.2021.100981
sha: df32747ccd36a51b1a078b86ce2f3dd31f7d60aa
doc_id: 923251
cord_uid: uxjrmduo

Cardiovascular wellbeing has been dramatically affected by SARS-CoV-2, the reason for the COVID-19 pandemic. There is a greater risk of morbidity and death in individuals with preexisting heart diseases. Clinical syndromes of the acute coronary syndrome, acute myocardial injury, myocarditis, arrhythmias, heart failure, and venous thromboembolism can, directly and indirectly, affect the heart. There may also be adverse heart effects of specific therapeutics under review for COVID-19. The RAAS mechanism in virus replication makes it essential to understand the consequences of the system-modulating medications. For optimum patient care, detailed knowledge of specific cardiovascular symptoms of COVID-19 and the role of RAAS in the prognosis of COVID-19 disease is necessary.

A global tumult has been produced for the coronavirus disease pandemic in 2019 . 1 According to current reports, ~20-36 percent of patients with COVID-19 infection are affected by severe myocardial injury with a higher prevalence than those without cardiac injury, commensurate with the elevation of cardiac troponin (cTn). [2] [3] [4] Furthermore, ~6-17% of patients experience cardiac arrhythmias, such as malignant ventricular arrhythmias (VAs) 5, 6 , with a higher incidence (~44%) recorded in patients admitted to the intensive care unit (ICU). 6 Notably, there can be a low prevalence of arrhythmias in clinically healthy patients 7 , but seriously ill patients are at more serious risk of cardiac arrhythmias. 8 Patients with preexisting comorbidities are at an elevated risk of SARS-CoV2 infection and appear to have poorer health outcomes. High side effects are postulated in patients with cardiovascular diseases, diabetes, and hypertension.

In cardiac patients, death rates of 10.5% and death rates of 7.3% and 6.0% for diabetes and hypertension have been recorded. 9

Men have more potentiate for hospital admission, morbidity, and mortality during the COVID-19 outbreak. Data from the COVID-19 net dataset (May 9, 2020) from the United States reported that males accounted for 52.9 percent of the hospitalized population, compared to 47.1 percent of females. A study of 5700 patients from a hospital system in New York showed that 60.3 percent of the admitted patients were males. In this research, COVID-19 mortality was higher in males than females at all ages. 10 The pathophysiology and importance of male predominance of COVID-19 disease remain unknown. In this field, further research is underway.

There is a direct relationship between age and the risk of contracting significant COVID-19 disease. CDC research in the United States indicates that patients younger than 20 years old with COVID-19 disease have a hospitalization rate of 2% to 3% relative to a hospitalization risk that is 2% to 3%. Over 31% of patients over the age of 85. 11 In comparison, no patients under the age of 20 in this cohort need. The hospitalization rate was 2% to 4% in the 20-45 age range, and the hospitalization rate rose in the 75-84-year cohort.

Increased mortality with age in the US with case fatality rates of 0.1 percent to 0.2 percent in patients younger than 44 years of age and 10.4 percent to 27.3 percent in patients 85 years old and up being estimated to be 11 percent to 31 percent. 12 There have been studies of a rare multisystem lately, COVID-19-related inflammatory syndrome resembling Kawasaki disease in children. 13 Much is uncertain as to how often this happens and what the risk factors might be.

In addition to ethnicity and race, other socio-economic influences have been found to exacerbate COVID-19 disease outcomes. With high resulting morbidity and mortality, nursing homes and assisted living facilities have shown to be places of quick spread. It has been reported that all prisoners and corrections personnel in US jails are at risk. Homeless shelters were also shown to be at risk of COVID-19 illness. 11

Encounter from the United States and the UK have proposed that race/ ethnicity may play a part in the severity of COVID-19 disease. Information from the CDC found that in patients hospitalized for COVID-19 illness, dark patients have spoken to 33% of the COVID-19 inpatient populace whereas speaking to 18% of the community in common, individually. 14 This indicates that the African American community has a disproportionate influence. It has also been mentioned that aboriginal groups are at elevated risk of COVID-19 disease. In the US, as opposed to the world as a whole, the COVID-19 occurs four times as high on reservations. 15

As far as previous reports,7% of COVID-19-related deaths are presumably associated with myocardial infection with COVID-19; however, its actual occurrence is still indeterminate. The range of symptoms can differ from minor symptoms like minor chest pain, weakness, and dyspnea to the more extreme left and right ventricular failure, arrhythmias, cardiogenic shock, and abrupt cardiac death with fulminant myocarditis. 16 Figure 1 illustrated the most critical cardiac manifestations and mechanisms. [17] [18] [19] [20] [21] [22] [23] [24] While there is no clear current evidence promoting direct COVID-19 viral myocarditis, MERS-CoV and SARS-CoV viral RNAs, which are closely linked to SARS-CoV-2, have been identified in the cardiac tissue of infected animals. COVID-19 myocarditis is possibly usually a combination of direct cell damage and cytotoxicity mediated by T lymphocytes that can be enhanced by cytokine storm syndrome. 16 Myocarditis caused by COVID-19 can mimic a coronary artery disease with an elevation of the ST segment and cardiac enzymes due to injury. 25

Symptomatic/asymptomatic tachycardia is the most often diagnosed arrhythmia in COVID-19

disease. Bradycardia has also been noted. Arrhythmia may happen within the setting of myocarditis, myocardial ischemia, and in basically sick patients with shock and hypoxia. 26 Different types of arrhythmias have been accounted for due to the COVID-19 disease. A few instruments might trigger or disturb arrhythmias in patients with COVID-19. Potential causes incorporate unsettling electrolyte influence (for the most part hypokalemia), antagonistic impacts of treatments (e.g., chloroquine, Azithromycin, and Hydroxychloroquine) that draw out QT span with expected advancement of polymorphic ventricular tachycardia (VT) 27 and fever, which may expose instances of heart channelopathies, for example, Brugada disorder and long QT condition. 9

In the case of COVID 19 disease, there are no precise data on ST-segment elevation myocardial infarction (STEMI) from intracoronary plaque rupture or obstruction is possibly flawed. Plaque collapse and coronary thrombosis may cause acute coronary events due to inflammation/increased shear stress in high-risk patients. Tam et al. detailed a considerable decrease in the number of patients with STEMI looking for clinical consideration at their institute. 28 They ascribed this to the hesitance of patients to go to an emergency clinic during the COVID-19 episode, delays in assessing patients with STEMI after medical clinic appearance because of preventive measures, for example, definite travel and contact history, symptomatology, and chest X-ray. The transfer of patients to the catheterization center consequently postpone. Further preventive measures taken in the catheterization laboratory, like the time necessary to wear protective clothing, can further prolong the operation . 28

Data on the occurrence of left ventricular systolic malfunction, acute left ventricular collapse, and cardiogenic shock are inadequate. Fifty-two percent of dead patients and 12 percent of discharged patients reported heart disease in one report. 29 Many critically ill patients may develop reversible sepsis-related cardiomyopathy with left ventricular dilatation, impaired systolic function, and recovery within 7 to 10 days. 16 COVID-19 infections can cause decompensation of underlying heart failure and may lead to mixed shock syndrome. If possible, intrusive hemodynamic monitoring can help to control the cardiac portion of shock in such circumstances. 30

It is too early to estimate long-term cardiovascular sequels in patients emerging from COVID-19 infection (Table 1) . 6, 25, 29, 31, 32 Nevertheless, the likely results could be close to that observed in SARS-CoV virus-induced severe acute respiratory syndrome (SARS). Outcomes of patients suffering from SARS for 12 years found that 40% had cardiovascular problems, 60% had impaired glucose metabolism, and 68% had irregular lipid metabolism. 28

A prothrombotic condition that induces venous and arterial thrombosis and elevated D-dimer is consistent with COVID-19 infection. 33 The documented occurrence of cerebrovascular disorder in drastic patients with COVID-19 ranged from 2.3% to 22%. 34 As a potential cause of ischaemic stroke, increased production of antiphospholipid antibodies has been indicated. The correlation of stroke with COVID-19 illustrated with a 2.5-fold rise in disease incidence. 34

The laboratory and autopsy reports detected a hypercoagulable condition with severe COVID-19 disease. Coagulation factors and platelets are implicated in host immune response regulation, demonstrating proinflammatory roles separate from their immune response. Hemostatic effects and higher D-dimer correlates with bad outcomes. 35 

The renin-angiotensin-aldosterone system (RAAS) is a complex hormonal system that is involved in the contraction of renin, angiotensinogen, angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II, and aldosterone. In summary, RAAS is a framework that reacts to a physiologic condition of hypovolemia, hyponatremia, adrenergic, and hypotension and propels a vasoconstriction reaction and liquid maintenance. 36 The ACE2

receptor is located at the top respiratory tract cells and lung alveoli and is also the leading site of the virus's entrance into the body. 37 It is often found in various concentrations in other tissues, such as the gastrointestinal tract (which is presumably the cause for a typical diarrhea symptom) and the heart muscle (which may describe the cardiac symptoms of COVID-19).

The RAAS mechanism in viral entry makes it essential to understand the consequences of the system-modulating medications. Inhibitors of angiotensin transmitting enzymes (ACEi) and

antagonists of angiotensin receptors (ARBs) are popular medicines used to treat hypertension. In an extensive cohort survey of patients with COVID-19, an excess incidence of hypertension cases with unfavorable performance, indicating that these drugs could play a role in the morphology of the disease. 38 39 So, plasma tests of SARS-CoV-2 contaminated patients displayed a significantly elevated angiotensin II amount and were linearly correlated with viral load and liver disease. Even so, increased ACE activity and reduced ACE2 activity in mouse models are shown to lead to lung injury. 36 This recommends that meds like ACEi and ARBs, which diminishes ACE action and increment upregulation of ACE2, may benefit significantly. Subsequently, from a conceptual view, ACEi and ARBs may simplify viral passage into respiratory cells prompting viral interceded cell harm. However, these equivalent drugs may upregulate ACE2 and improve acute lung injury. Which of these behaviors are prevalent in people with COVID-19 is not apparent and more study is needed. In the meantime, most existing recommendations for cardiology say that sufferers with ACEi and ARBs should continue to take their drugs as usual and should not avoid using CoVID-19 disorder. The momentum suggestion is to beware of NSAIDs use in patients with COVID-19 illness. 41 Using corticosteroids in patients with COVID-19 can be destructive, and steroids can cause liquid maintenance, electrolyte disturbance, and hypertension. Moreover, SARS pieces of information dedicated to an expansion of viral shedding after steroid use. 42 However, treatment with methylprednisolone might be helpful if acute respiratory distress syndrome (ARDS) add to other disorders . 43 New investigations assess potential strange coagulation courses in extreme COVID-19 cases that may prompt microthrombi in many end organs, particularly the lungs. In those patients, a high D-dimer leads to a guarded prognosis and a high death rate. After prescription of 40-60 mg, enoxaparin/day, or unfractionated heparin 10,000-15,000 U/day, Tang, N. et al. reported a decrease of 28-day mortality in patients with high sepsis-induced coagulopathy (SIC) score more than four, or D-dimer over six-fold of the standard upper limit. 44 Recently realized antiviral and different medications have been taken a stab at patients without suitable preliminaries constrained by extreme ill patients and demise in affirmed cases with COVID-19 sickness.

Numerous examinations have at present been led researching the potential impact of the combination of Hydroxychloroquine and Azithromycin, immune therapy, Remdesivir, distinctive antiviral meds, and utilization of the relieved patients' plasma of COVID-19. 9,45-54 It should be borne in mind that some of these medications have many cardiac side effects. According to a brief French trial in COVID-19, Chloroquine and Hydroxychloroquine, a more potent engineered type of chloroquine, is utilized alongside Azithromycin, a macrolide anti-toxin, for experimental administration. 45, 46 Chloroquine can cause atrioventricular (AV) block, and alongside Azithromycin, increased QT distance. Hydroxychloroquine can also produce difficulty in cardiac conductions. Adverse effects of the simultaneous utilization of beta-blockers or calcium channel blockers can prompt bradycardia prompting cerebral hypoperfusion with syncope. 50 The current suggestion is to evaluate QT before beginning treatment and close checking in patients with extra danger components or patients utilizing different meds to upgrade the QT prolongation. 9 Moreover, electrolytes were observing, mainly hypokalemia result from the interactivity of 2019-nCoV with the renin-angiotensin-aldosterone system. 9 A new multicenter, randomized controlled trial (RCT) of Hydroxychloroquine including 150 adults admitted to the emergency clinic for COVID-19, announced no critical impact of the medication on quickening viral clearance. 53 Lopinavir/ritonavir are protease inhibitors that are affirmed for HIV-1 contamination treatment.

Pointes are reported adverse effects. They can diminish serum convergence of the dynamic metabolites of clopidogrel, prasugrel while expanding that of ticagrelor and statins levels with the danger of rhabdomyolysis. Lopinavir/ritonavir potentiates the impacts of factor Xa inhibitors, for instance, apixaban and rivaroxaban, by the prohibition of CYP3A4, increased risk of bleeding. 47 Remdesivir is a mono-phosphor amidite prodrug of an adenosine analog that hinders viral RNA synthesis with a wide antiviral range, including paramyxoviruses, filoviruses, coronaviruses, and pneumo-viruses. There is restricted data on antagonistic impacts. Nonetheless, hypokalemia is a typical adverse effect 54 , and there was a patient who created hypotension and bradycardia when this drug was utilized to treat Ebola. 48 The security and adequacy of Remdesivir for the treatment of COVID-19 are being assessed in numerous progressing Phase 3 clinical preliminaries. In a new randomized, double-blind, multicenter preliminary study at ten medical clinics in Hubei, China, directed on adult admitted patients to an emergency clinic for extreme COVID-19 illness, Remdesivir did not show a significant profit clinically. Further studies need to justify a mathematical decrease to an approved clinical improvement. 54 Tocilizumab, a counter-acting agent for IL-6R, is known for its possible viability in decreasing inflammatory reactions, including the cytokine storm adding to ARDS and even death. 25 Reports illustrated the increment of cholesterol level notwithstanding, contradictory reports indicated its impact on morbidity and mortality during an extended period . 55

According to WHO, COVID-19 mass vaccination campaign first started in early December 2020. More than 13 different vaccines (across four platforms) have been administered.  Virus vaccines that use a form of the virus that has been inactivated or weakened so that it does not cause disease but still triggers an immune response.

 Protein-based vaccines, which safely produce an immune response by using harmless protein fragments or protein shells that resemble the COVID-19 virus.

 Viral vector vaccines, which use a non-pathogenic virus as a platform for producing coronavirus proteins and triggering an immune response.  RNA and DNA vaccines, a cutting-edge method that generates a protein from genetically modified RNA or DNA, safely trigger an immune response.

The prioritization of people who are eligible for the Covid vaccine can be seen in Figure 2 below.

As you can see, the prioritization of COVID vaccination is given to people who have a history of cardiovascular disease or related conditions. Therefore, it is difficult to evaluate the safety of the COVID vaccine regarding cardiovascular complications. Table 2 provides a comprehensive set of studies related to cardiac complications of the corona vaccine. In general, the most common complication was myocarditis, followed by cardiac arrhythmias.

Regardless of the origin, post-COVID-19 vaccine-associated cardiac diagnoses necessitate timely and thorough professional clinical management, as demonstrated by the few cardiovascular and cardiac-related deaths that have occurred following COVID-19 vaccination.

As a result, informed authorization for mRNA COVID-19 vaccines should include information about the rare but possible occurrence of myocarditis or pericarditis in the week after immunization, and subjects should be advised of potential symptoms and the need to seek immediate clinical care.

Although age (mostly, 30 years) and gender (mainly, male) may influence general perceptions of the rare risk of myocarditis following COVID-19 vaccination, an individual's personal risk should be considered based on their current health status, the impact of severe COVID-19 disease, and the risk of infection from locally circulating SARS-CoV-2 variants.

To this date, global safety monitoring data suggests that life-threatening serious adverse events are uncommon after COVID-19 vaccination, but they do necessitate close clinical vigilance, early detailed investigation, and clinical management because they can occur after all COVID-19 vaccine type, at first or second dose.

Significantly, at this early point, evaluations of these data and discussions by North American and European health organizations indicate that the advantages of COVID-19 vaccination outweigh the hazards in all demographics, including the rare risk of myocarditis, for all recommended age groups.

Additional research data may be valuable in determining a direct causal link between the host and the vaccine. Until then, no definite contraindication of COVID-19 immunization can be issued to the general public.

Vaccination is widely accepted as necessary for the general population since the benefits outweigh the hazards.

Any adverse event that arises from immunization must be handled the same way as any other conventional vehicle. There have been no specific post-vaccination cardiac care regimens proposed so far. Treatment procedures suited to each patient are recommended for the time being.

None of the authors have financial or proprietary interests in any of the materials or methods mentioned.

This review explained the cardiac problems of COVID-19 and discussed the crucial concepts of the virus and its interaction with cardiac therapies, particularly ACEi and ARBs. Further testing on different facets of this emerging coronavirus is underway, and physicians observe to understand as best as they are in the process. Data are presented as n (%).

Abbreviations: cTnI, cardiac Troponin I; ICU, intensive care unit.

* Patients presented heart palpitations as an initial symptom.

** Some patients died of myocarditis. 

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