Medicine

Neurological and Cardiovascular Complications in COVID-19

Abstract:

The COVID-19 pandemic has infected patients who have died of stroke and myocardial injury. The purpose of this study is to identify the neurological and cardiovascular complications of COVID-19. A systematic study has been performed on PubMed. Patients with a history of comorbidities (including stroke, cardiovascular disease, hypertension, and diabetes) are correlated with a higher severity and fatality rate. Neurological and cardiovascular complications seem to be caused by a thromboembolic storm, either triggered by direct invasion of the endothelium via the ACE2 receptor or COVID-19 infection-induced cytokine storm. Some patients that present cardiovascular and neurological complications are consistent with the COVID-19 theory of endotheliosis.

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Introduction:

According to the World Health Organization, the global pandemic SARS-CoV-2 has 20.4M cases and 745K deaths worldwide as of August 12, 2020. COVID-19 disease (COVID-19) is a respiratory disease that enters the body through respiratory droplets. The goal of society has been to “flatten the curve.” The U.S. has been working to prevent an overload of the U.S. healthcare system while awaiting the development of vaccines. Most young and healthy individuals who contract COVID-19 are able to recover at home without medical care; however, patients with a history of comorbidities tend to have more severe cases that require intensive care, potentially mechanical ventilation. Those families who have someone passed away due to they did not receive that kind of medical attention by the health institutions they seek, might be entitle to a compensation according to this wrongful death lawyer, contact him at the link.

The most serious comorbidities include cardiovascular disease, diabetes, hypertension, and stroke (1). Studies have reported acute cardiac injury, defined as a significant elevation of cardiac troponins, to be the most commonly reported cardiac abnormality in COVID-19 (2). Ischemic stroke is also a common outcome, with 31% of COVID-19 patients developing ischemic stroke (3). There are serious repercussions to ischemic stroke and acute myocardial injury. Ischemic stroke destroys brain cells through reduced blood flow and oxygen to the brain, which can cause death or permanent brain damage. Acute myocardial injury can lead to sudden death or severe cardiac dysfunction to the point where a heart transplant may be necessary. Therefore, it is very important to examine the outcomes of COVID-19 related to the development of ischemic strokes and acute myocardial injury. The purpose of this study is to identify the neurological and cardiovascular complications of COVID-19.

Methods

A systematic search was performed on PubMed with keywords “covid,” “stroke” and “cardiovascular.” A systematic review analyzed a series of studies on stroke, as well as cardiovascular and neurological manifestations and complications. Studies on irrelevant topics, containing too small a sample size, and dated before 2000 were excluded from this search list.

Results:

COVID-19 and Cardiovascular disease

Studies show that pre-existing cardiovascular comorbidities are associated with higher severity and fatality rate in COVID-19. A recent meta-analysis of eight studies from China measured comorbidities in 46,248 infected patients, resulting in 17% with hypertension, 8% with diabetes mellitus, and 5% with cardiovascular diseases (Table 1). The authors suggest that potential explanations may be cardiovascular disease being more prevalent in those with advancing age, a functionally impaired immune system, elevated levels of ACE2, or a predisposition to COVID-19 for those with cardiovascular disease (4).

Table 1

Comorbidities Present in 46,248 COVID-19 Patients (4)

Hypertension

17%

Diabetes

8%

Cardiovascular Disease

5%

The severity of COVID-19 is characterized by cardiovascular complications. Cardiovascular complications include acute myocardial injury, caused by acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest (1). Clerkin et al describe two patterns of myocardial injury in COVID-19. The first is related to the cytokine storm as a cause of myocardial injury.  They summarize a study where non-surviving COVID-19 patients exhibited a constant sustained rise in Troponin I levels up to 22 days.  There was a concurrent elevation in D-dimer, ferritin, interleukin 6, and lactate dehydrogenase suggesting inflammation-related causes. Meanwhile, the second pattern appears to be characterized by viral myocarditis. The authors report a 63-year old patient in China with no cardiac history who demonstrated signs of acute myocardial injury. After being treated with intravenous immunoglobulin and glucocorticoids, he recovered within three weeks with complete normalization of cardiac markers (4).

COVID-19 and Cerebrovascular disease

COVID-19 is seen to have a tropism for the central nervous system. In one case series, out of 214 COVID-19 patients, 36% presented with one or more neurological symptoms including headache, dizziness, myalgias, and anosmia, as well as cases of encephalopathy, encephalitis, necrotizing hemorrhagic encephalopathy, stroke, seizures, rhabdomyolysis, and Guillain-Barré syndrome (5,6). However, only 2.2% have a history of stroke, which is no different from the general population (6). In addition, studies also show that patients with a history of stroke have increased the rate of death due to COVID-19 by three times.

Gabriel and Galan propose four mechanisms for stroke due to COVID-19. The first is the invasion of vessel walls (i.e. endotheliitis) via the ACE2 receptor. The second is coagulation disorder where the virus causes thrombosis via immune system activation (i.e. cytokine storm). The third mechanism is cerebral embolism due to myocardial damage. The fourth proposed mechanism is the destabilization of atheromatous plaque leading to cerebral emboli (6).

COVID-19 Endotheliitis

Recently, Chibale et al reported a case of a 66-year-old patient who presented with syncopal symptoms, but no respiratory symptoms. Based on elevated creatinine and troponins, she was found to have acute renal failure and myocardial injury. During hospitalization, she developed “right-sided cardiac overload and likely secondary to pulmonary embolism or extensive microvascular thrombosis.” She died within 2 days of an ischemic stroke and cardiorespiratory failure. Post-mortem testing confirmed COVID-19 infection. The authors state that “COVID-19-associated hypercoagulability and thromboembolisms may thus precede or present disproportionately to respiratory involvement, which is consistent with the concept of COVID-19 endotheliitis” (7).

Discussion

In summary, pre-existing cardiovascular comorbidities result in a higher fatality rate in patients with COVID-19, while a history of stroke raises the risk of mortality threefold. COVID-19 may cause stroke and myocardial injury through inflammation that results in hypercoagulability related to cytokine storm. In COVID-19 patients with cardiac disease, this was manifested by elevated levels of D-dimer, ferritin, interleukin 6, and lactate dehydrogenase. Similarly, Gabriel and Galan hypothesize that COVID-19 may cause a stroke by interfering with coagulation secondary to activation of the immune system leading to platelet and endothelial dysfunction. As a result, similar mechanisms exist in regards to the COVID-19 related causes of cardiovascular events and stroke (6).

COVID-19 endotheliitis may also play a role in hypercoagulability. COVID-19 endotheliitis is due to the direct invasion of endothelial cells through ACE-2 receptors. This can lead to a “thromboembolic storm” due to direct endothelial cell injury and systemic inflammation (cytokine storm), in accordance with Virchow’s triad (Figure 1). This can lead to multiorgan involvement, such as myocardial injury and ischemic stroke.

Figure 1: Schematic of COVID-19 Related Thromboembolic Storm

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Treatment of COVID-19 related cardiovascular and cerebrovascular disease is nuanced due to potential side effects. Because inflammation and hypercoagulability play a major role in the disease process, current treatments include corticosteroids in addition to anticoagulants. However, these therapies need to be carefully managed to avoid possible worsening infection or hemorrhage. There is also some concern that ACE inhibitors and angiotensin receptor blockers, which are beneficial in controlling hypertension, may contribute to COVID-19 infection due to the upregulation of ACE 2 receptors.

The limitations of this review are mainly due to small case studies and limited case reports of COVID-19 infection. Most of the studies published were conducted in hospitals. Reduced accessibility to hospitals by patients due to overcapacity or limited transportation may have an effect on the data as well. There is a need for further clinical studies to clearly define the effect of COVID-19 on the cardiovascular and neurological systems.

Conclusion

COVID-19 infection causes neurological and cardiovascular damage, especially in patients with a history of cardiovascular comorbidities. Evidence suggests that this occurs through direct viral tissue invasion and circulatory compromise due to endothelial injury and cytokine storm. Further studies are needed to establish the role of endotheliitis in COVID-19 infections.

Bibliography

  1. Kang, Yu, Tiffany Chen, David Mui, Victor Ferrari, Dinesh Jagasia, Marielle Scherrer-Crosbie, Yucheng Chen, and Yuchi Han. “Cardiovascular Manifestations and Treatment Considerations in COVID-19.” Heart 106, no. 15 (2020): 1132–41. https://doi.org/10.1136/heartjnl-2020-317056.
  2. Bansal, Manish. “Cardiovascular Disease and COVID-19.” Diabetes & Metabolic Syndrome: Clinical Research & Reviews 14, no. 3 (2020): 247–50. https://doi.org/10.1016/j.dsx.2020.03.013.
  3. Navi, B. “Strokes Occur More Frequently in Patients with COVID-19 Compared to Flu, but Overall Risk Is Low.” WCM Newsroom, 2022. https://news.weill.cornell.edu/news/2020/07/strokes-occur-more-frequently-in-patients-with-covid-19-compared-to-flu-but-overall.
  4. Clerkin, Kevin J., Justin A. Fried, Jayant Raikhelkar, Gabriel Sayer, Jan M. Griffin, Amirali Masoumi, Sneha S. Jain, et al. “COVID-19, and Cardiovascular Disease.” Circulation 141, no. 20 (2020): 1648–55. https://doi.org/10.1161/circulationaha.120.046941.
  5. Artal, Francisco Javier Carod. “Complicaciones Neurológicas Por Coronavirus y COVID-19.” Revista de Neurología 70, no. 09 (2020): 311. https://doi.org/10.33588/rn.7009.2020179.
  6. Trejo-Gabriel-Galán, J.m. “Ictus Como Complicación y Como Factor Pronóstico De COVID-19.” Neurología 35, no. 5 (2020): 318–22. https://doi.org/10.1016/j.nrl.2020.04.015.
  7. Chibane, S, G Gibeau, F Poulin, P Tessier, M Goulet, M Carrier, and S Lanthier. “Hyperacute multi-organ thromboembolic storm in COVID-19: a case report.” Journal of thrombosis and thrombolysis (2020):

About the Author

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Ethan Lee is a junior at the La Canada High School with a strong passion for medicine, specifically the field of ophthalmology. He has started a nonprofit for virtual shadowing of doctors and is intrigued by the current COVID-19 situation. He also runs for the school cross country and track teams and aims to be recruited for Division III.

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