Respiratory, organ failure and heart attacks responsible for Covid-19 deaths: Study

People with the novel coronavirus infection may die of a heart attack, respiratory failure, multiple organ failure or septic shock, but the cause of death is irrefutably for coronavirus, according to some scientists and clinisiscs, debunking attempts by some states to attribute fatalities to other reasons.

"Coronavirus or Covid-19 infected people killed by respiratory failure and cardiac arrest, just like any other severe pneumonia. The difference is lack of immunity against the new virus and greater severity of infection," said Dr Anurag Agrawal, director of the Institute of Genomics and Integrative Biology, New Delhi, reported Hindustan Times.

Earlier this week, a 78-year-old Italian woman in Gurugram's Medanta hospital was classified as a Covid-19 fatality after she died due to a heart attack, days after test results showed that she had managed to clear the Sars-Cov-2 infection for which she had been hospitalised.

"She died of multi-organ failure following a cardiac arrest, her kidney function was deranged when she was admitted to the hospital, and she was close to 80 years old; the mortality rate in such people with Sars-Cov-2 infection is close to 15%. The cause of death was Covid-19 because persistent infection is what led to the multi-organ failure," said Dr Yatin Mehta, chairman, anaestheology and critical care, Medata-The Medicity. The woman died on Thursday while 13 other Italians who were in her group recovered and were discharged form hospital two weeks ago.

Data from several countries that have been hit hard by the pandemic shows one in five people who contract Covid-19 become very ill. Chronic lung disease, cardiovascular disease and diabetes are the top three risk factors associated with potentially life-threatening complications.

In China, nearly all of the fatalities among 44,672 who were specifically studied ,were people who had such underlying conditions, according to what is the largest study yet of Covid-19 patients, published in the Journal of the American Medical Association (JAMA).

In the US, 78% of Covid-19 patients in intensive care units (ICUs) and 71% of those hospitalised had one or more reported underlying health conditions, compared to 27% among those who did not need hospitalisation, according to an analysis of records of hospitalised patients between February 12 and March 28 by the US Centers for Disease Control, which called the findings consistent with what has been seen in China and Italy, one of the other major hot spots of the disease.

Vulnerable heart

According to one of the studies from Wuhan, the ground zero of the pandemic, one in five patients showed signs of heart damage.

Cardiovascular conditions are often what kill patients, with "thromboembolic disease, hypercytokinaemia, secondary sepsis, hypovolaemia, and renal complications" being a toxic combination that doctors treating Covid-19 patients have to manage, according to a comment by Richard Horton, editor-in-chief of The Lancet, on April 11.

Horton mentions cardiac troponin I as a reliable indicator of heart damage in some of the fatalities. A thromboembolic disease refers to clots in blood vessels, hypercytokinaemia is a strong, potentially fatal immune reaction; while hypovolaemia refers to low levels of plasma, which is a critical component in the blood that contains antibodies and clotting factors.

Indian experts said heart damage could be explained by several reasons. "This could be because of causes ranging from acute cor pulmonale (heart working harder to pump blood as oxygen levels fall because of lung tissue freezing); heart muscles suffering hypoxic damage, leading to depressed function, and arrthythmias (irregular heartbeat), viral myocarditis (inflammation after virus directly invades heart cells); and possible rise in thrombosis (blood clots)," said Dr K Srinath Reddy, president, Public Health Foundation of India, and former head of cardiology at All India Institute of Medical Sciences (AIIMS), New Delhi.

Several other viral infections are known to disrupt blood flow to the heart, leading to irregular heartbeat and heart failure. During influenza outbreaks, more people die from heart complications than from pneumonia, according to a study in the journal JAMA Cardiology.

A 2018 study in the New England Journal of Medicine found the risk of heart attacks rising almost six-fold when a person has flu infection.

Lung onslaught

Smokers and people with COPD have also been identified as being at higher risk of infection and severe disease because their lungs and lower respiratory tract have cells showing a higher "expression" of ACE2, the portion of a cell through which the Sars-Cov-2 invades it, according to a study by the European Respiratory Journal. In mice, ACE2 has been shown to protect animals from severe lung injury related to breathing and sepsis.

"There is an increased ACE2 expression in airways of current (but not former) smokers and those with COPD... while the upregulation of ACE2 may be useful in protecting the host against acute lung injury, it predisposes them to increased risk of coronavirus infections, which uses this receptor to gain entrance into epithelial cells. This may in part explain the increased risk of viral respiratory tract infection in active smokers and virus-related exacerbations in those with COPD," said the study. Upregulation refers to a cell increasing the quantity of a cellular component, such as RNA or protein, in response to an external stimulus, such as a virus.

Protein connection

ACE2, or angiotensin-converting enzyme 2 (ACE2), is increasingly posing a challenge. ACE2 is a surface protein that is present at several key locations in the body: it covers cells in upper and lower respiratory tract, heart and the gastrointestinal tract, and plays a role in blood pressure, cardiac function and immune regulation. Targeting this protein is what makes the Sars-Cov-2 insidious in how it infects a body.

In response to this, the body mounts an immune attack by releasing small proteins called cytokines into the blood. But with the virus knocking ACE2 out, the immune response can go haywire, causing a cytokine storm that can lead to tissue and organ damage.

People with high blood pressure or heart disease are also prescribed ACE inhibitors or angiotensin receptor blockers (ARBs), which can inhibit ACE-2 action.

"The current consensus is that if people are already taking these medications, they should stay on them but they must consult their physicians. Depending on the severity of the infection and the clinical status of the patient, the medication may need to be modified," said Dr Reddy.