Coronaviruses like SARS-CoV2 – which is responsible for COVID-19 – cause illness by infecting the lungs. But the impact of these viruses can be far wider. The truth is, COVID-19 can be heartbreaking.
Any time a new health issue develops, our understanding of the condition changes over time. COVID-19 is no different as recommendations on social distancing and the need for face masks have evolved as more research is done.
One fact that has remained since the earliest reports of COVID-19 is the risk cardiovascular disease presents. People with cardiovascular disease are more likely to contract COVID-19 and have a more severe illness1. Studies show ~40% of people hospitalized for COVID-19 have cardiovascular disease2 and they are up to 4-times more likely to be admitted to the ICU than those without cardiovascular conditions3.
Outcomes from COVID-19 patients with cardiovascular disease are particularly poor. In some studies the mortality rate was 5-times higher in patients with cardiovascular disease, a rate that was 1.5-times higher than even people with chronic respiratory diseases4.
The Heart as a Target
The heart isn’t just a problem for COVID-19 patients. It’s also a target.
Cardiac troponins, molecules in the blood that are measured to diagnose a heart attack, were increased in patients with COVID-19 and correlated with severity of illness and risk of death. Almost a quarter of individuals with a severe form of COVID-19 developed heart failure5. In one study cardiac arrhythmias like atrial fibrillation or heart blocks were detected in 17% of patients hospitalized for COVID-196. In the ICU the number of patients with arrhythmias rose to almost half of all patients. No matter how it is measured, there are clear signs the heart is injured in many people afflicted with COVID-19.
Injury to the heart is not dependent on individuals already having cardiovascular disease. However, in those with pre-existing conditions cardiac damage adds an extra stressor that the body must deal with and weakens the ability to fight off infection.
The Missing Link
It is clear that cardiovascular disease worsens outcomes for people infected with SARS-CoV2, but the question is “how?”.
One mechanism is direct damage of cardiovascular tissues by the virus itself. SARS-CoV-2 enters cells using a protein called ACE2. Once inside the cell the virus hijacks the cell machinery and uses it to reproduce. As new viruses are released from the cell and allowed to go on to infect other cells, it leaves behind a dead or dying cell7. Up to 30% of patients with COVID-19 show signs of cardiac injury that is not linked to pre-existing cardiovascular disease8.
In the heart where muscle cells normally do not regenerate SARS-CoV2 infection may decrease heart muscle and impair the ability of the heart to contract. Under normal circumstances this is a problem, but for people with pre-existing cardiovascular disease it may be enough to cause a catastrophic heart failure.
Not only does cardiovascular disease put people on the edge, it may also provide the shove. Some cardiovascular diseases increase the amount of ACE2 protein expressed in the heart9,10. The increase in cardiac ACE2 levels could increase the opportunity for SARS-CoV2 to enter cells, but this has not been tested.
Too Much of a Good Thing
Another way the cardiovascular system can be damaged in COVID-19 is by what is called a “cytokine storm”. When the body is invaded with a foreign entity like a virus or bacteria the immune system fights the infection. Molecules called “cytokines” are critical to activating and controlling the immune cells that remove the infectious threat.
In some people infected with SARS-CoV2 the levels of cytokines rise to very high levels and the immune system becomes overactive. In this hyperactive state immune cells mistakenly attack the body’s own tissues and cause damage or even kill cells, impairing the function of critical organs like the heart.
The cytokine storm can worsen cardiovascular diseases and increase the risk of death. An excessive inflammatory response destabilizes fatty plaques that line the blood vessels of people with atherosclerosis. These dislodged pieces travel through the vascular system until they get stuck and block the flow of blood. If the blockage occurs in the brain it causes a stroke, and if it occurs in the blood vessels of the heart it results in a heart attack.
Targeting the Eye of the Storm
The reason for immune system hyperreactivity is not known although some studies suggest that mutations in some genes increase the risk for a cytokine storm and that COVID-19 unveils this problem. Some early studies found results showing that anti-inflammatory drugs like tocilizumab (Actemra) helped COVID-19 patients recover. These therapies are included in some of the clinical trials underway to find a treatment for COVID-19.
In The Long Run
Cytokines that increase during COVID-19 can cause long-term damage to the cardiovascular system and increase the risk of atherosclerosis and heart failure after recovery7. The recent emergence of SARS-CoV2 has prevented monitoring patients over the months or years these conditions may take to develop, so it is important that COVID-19 patients be followed for the development of cardiovascular complications.
The long-terms effects of COVID-19 on cardiovascular disease are not known, but the effects of other coronarvirus outbreaks provide clues into what the future may hold. In some people infected during the 2004 SARS outbreak circulating lipids remained disrupted 12 years after infection, which increases the risk of developing cardiovascular disease11. These findings suggest that long after the pandemic as subsided the impact of COVID-19 may remain.
Even though the outcomes of COVID-19 in people with cardiovascular disease are concerning, there are steps that can be taken to reduce the risks. Social distancing and wearing masks in public help decrease the spread of SARS-CoV2 and protect those who are most vulnerable.
Early rumours suggested that some cardiovascular medications, specifically treatments for high blood pressure, increased the risk of infection. These reports proved to be unfounded. Taking medications as prescribed help control cardiovascular conditions and strength the ability of the body to fight off infection.
These simple actions can go a long way to protecting people against COVID-19. Taking them to heart just might save a life.
Glen Pyle, PhD is a Professor of Molecular Cardiology at the University of Guelph and an Associate Member of the IMPART Team Canada Investigator Network at Dalhousie Medicine.
- 1. Ganatra S et al. Trend Cardiovasc Med. May 28, 2020.
- 2. Chen N et al. Lancet. 395: 507-513. 2020.
- 3. Kuster GM et al. Eu Heart J. 41: 157. 2020.
- 4. Madjid M et al. JAMA Cardiology. March 27, 2020.
- 5. Zhou F et al. Lancet. 395: 104-1062. 2020.
- 6. Wang D et al. JAMA. 323: 1061-1069. 2020.
- 7. Guzik TJ et al Cardiovasc Res. April 30, 2020.
- 8. Zheng Y-Y et al. Nat Rev Cardiol. 17: 259-260. 2020.
- 9. Ohtsuki M et al. Int J Cardiol. 145: 333-334. 2010.
- 10. Nicin L et al. Eu Heart J. 41: 1804-1806. 2020.
- 11. Wu Q et al. Sci Rep, 7: 9110. 2017.
Category: Fundamental Science