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COVID-19 mostly kills through an overreaction of the immune system, whose function is precisely to fight infections, say scientists who have decoded the mechanisms, symptoms, and diagnosis of the disease caused by the SARS-Cov-2 coronavirus.

In a study published in the journal Frontiers in Public Health, the researchers explained step-by-step how the virus infects the airways, multiplies inside cells, and in severe cases causes the immune defences to overshoot with a "cytokine storm".

This storm is an over-activation of white blood cells, which release too-great amounts of cytokines -- inflammation-stimulating molecules --into the blood, they said.

"Similar to what happens after infection with SARS and MERS, data show that patients with severe COVID-19 may have a cytokine storm syndrome," said study author Daishun Liu, Professor at Zunyi Medical University in China.

"The rapidly increased cytokines attract an excess of immune cells such as lymphocytes and neutrophils, resulting in an infiltration of these cells into lung tissue and thus cause lung injury," Liu said.

The researchers explained that the cytokine storm ultimately causes high fever, excessive leakiness of blood vessels, and blood clotting inside the body.

It also causes extremely low blood pressure, lack of oxygen and excess acidity of the blood, and build-up of fluids in the lungs, they said.

The researchers noted that white blood cells are misdirected to attack and inflame even healthy tissue, leading to failure of the lungs, heart, liver, intestines, kidneys, and genitals.

This multiple organ dysfunction syndrome (MODS) may worsen and shutdown the lungs, a condition called acute respiratory distress syndrome, (ARDS), they said.

This, the researchers explained, happens due to the formation of a so-called hyaline membrane -- composed of debris of proteins and dead cells -- lining the lungs, which makes absorption of oxygen difficult.

Most deaths due to COVID-19 are therefore due to respiratory failure, they said.

The researchers explained that in the absence of a specific antiviral cure for COVID-19, the goal of treatment must be to the fight the symptoms, and lowering the mortality rate through intensive maintenance of organ function.

For example, an artificial liver blood purification system or renal replacement therapy can be used to filter the blood through mechanical means, they said.

The team noted that especially important are methods to supplement or replace lung function, for example with non-invasive mechanical ventilation through a mask, ventilation through a tube into the windpipe, the administration of heated and humidified oxygen via a tube in the nose, or a heart-lung bypass.

The researchers stressed the importance of preventing secondary infections.

They noted that SARS-Cov-2 also invades the intestines, where it causes inflammation and leakiness of the gut lining, allowing the opportunistic entry of other disease-causing microorganisms.

The researchers advocate that this should be prevented with nutritional support, for example with probiotics -- beneficial bacteria that protect against the establishment of harmful ones -- and nutrients and amino acids to improve the immune defences and function of the intestine.

"Because treatment for now relies on aggressive treatment of symptoms, preventative protection against secondary infections, such as bacteria and fungi, is particularly important to support organ function, especially in the heart, kidneys, and liver, to try and avoid further deterioration of their condition," Liu added.

Between 30-40 per cent of deaths from studies in intensive care units from different countries are people with diabetes, said Paul Zimmet, Professor of Diabetes, Monash University, Australia.

Zimmet, who is President International Diabetes Federation, added that the actual mechanism as to why COVID-19 may cause diabetes is as yet unknown, however, several possibilities exist. "COVID-19 is a very destructive and cunning virus and causes terrible damage to tissues including the lungs and pancreas," said Zimmet. Below are excerpts from an exclusive chat with IANS.

Why do you say Diabetes is dynamite if a person has been infected with COVID-19?

There have been many deaths in many countries, e.g. Italy, China, the UK and US among people with diabetes after infection with COVID-19 (SARS-Cov-2).

The mortality tends to be mainly in older Type 2 diabetics. Between 30-40 per cent of deaths from studies in intensive care units from different countries are people with diabetes. This outcome and other complications from the virus, particularly pneumonia, are more likely in people with diabetes which is poorly controlled with high blood sugars (poor metabolic control).

Diabetes is often associated with other chronic conditions, including obesity, hypertension and heart disease compounding the risk. These latter conditions all convey higher risk to COVID-19 infections.

ACE-2, which binds to SARS-Cov-2 and allows the virus to enter human cells is also located in organs and tissues involved in glucose metabolism. Is there solid evidence that virus after entering tissues may cause multiple and complex impairment of glucose metabolism?

The actual mechanism as to why COVID-19 may cause diabetes is as yet unknown.

However, several possibilities exist. Firstly, COVID-19 is a very destructive and cunning virus and causes terrible damage to tissues, including the lungs and pancreas.

A new study just published showed that in miniature lab-grown pancreas, and other cells such as liver, made using human stem cells, COVID-19 caused destruction of the pancreas beta cells that produce insulin.

It is possible that the virus causes disruption of the cells by disrupting cellular metabolism. This is possibly the way it brings about new-onset diabetes. ACE-2 exists in high concentration in the lung as this also explains the terrible lung side effects of COVID-19 infections.

Can COVID-19 lead to a new mechanism of diabetes? Probably a new form of diabetes or a new form of disease?

The COVID-19 virus has only been with us for about 5 months and there is a huge amount that we still must learn about its cunning and devastating ways. The purpose of the Global COVIDIAB Diabetes Registry, a joint initiative of Monash University in Australia, and King’s College London is to gain a much better understanding of how common is the appearance of COVID-19 related diabetes, what form does it take be it type 1 or type 2 or a new form, and how common are the complications that we already know e.g. diabetic keto-acidosis, hyperosmolar coma and high insulin requirements are causing high rates of ill health and mortality worldwide. The knowledge gained will aid our understanding for developing strategies to prevent and treat this terrible virus that has caused destruction globally.

Diabetes is one of the most prevalent chronic diseases in India. According to a recent study, sugar levels of diabetic persons increased by 20 per cent during nationwide lockdown in India to contain COVID-19 outbreak. Even after lockdown was lifted, many people are confined within their home. Do you think lack of physical activity will create more problems for diabetics?

My own major research has been on studying populations with high rates of diabetes, including ethnic Indian communities including India, Mauritius, and Fiji so I am very well aware of this. It is now well established that along with diabetes, that associated poor metabolic control of their diabetes places these people at the highest risk for COVID infection and its devastating complications and the associated morbidity and mortality. And these communities have high prevalence of heart disease as well.

Lockdown not only has deleterious effects on metabolic control of the diabetes through reduced opportunities for exercise to be protective serious consequences of SARS-CoV-2 infection, lockdown usually results in disruption of the regular medical care and the regular monitoring of metabolic control. This may also be partly due to the stress and poor compliance, or inability to afford their medications such as insulin. It may also be compounded by inability to access the care during the pandemic. Nevertheless, we now know that poor metabolic control heightens their risk as described above.

You have said diabetes is itself a pandemic just like Covid-19, and the two pandemics could be clashing. How could governments address this problem?

These are “The Times of COVID-19”. Most nations of the world were totally unprepared for a pandemic of this magnitude. They underestimated its potential impact and the destructive nature of the viral infection. This should prompt all countries to upgrade their guidelines to take into account the lessons learnt on infection control including training of staff specialising in infectious diseases and improved public education and taking their communities into their confidence about the terrible nature of COVID-19. The risks of COVID-19 infection need a much higher priority in the general community, particularly for people with chronic conditions such as diabetes, obesity, and cardiac conditions.

Governments are faced with chronic diseases (NCDs) like diabetes and communicable diseases (CDs) like viral and enteric diseases and TB. In general WHO gives the highest priority to communicable diseases and much less attention and funding to chronic diseases like diabetes (I was an adviser to WHO for many years (about 30) on diabetes and obesity and it was very frustrating to deal with this situation).

This attitude to diabetes, for example, has a flow down effect so that diabetes funding in countries by governments, rich and poor, suffered and was insufficient.

So now we have a COVID-19 pandemic and who are those at highest risk, yes people with diabetes and other NCDs, it is very important that now the two, Diabetes and COVID-19 are clashing face-to-face. This is a major issue that WHO and national governments have to face with equal priority’

Stressed people suffering from diabetes run a greater risk of poor blood glucose levels, what do you suggest to these people?

As mentioned in the answer above, stress is an important factor in upsetting the blood sugar (metabolic) control of diabetes. Additive to this is poor compliance with medications and diet. These and potential associated comorbidities due to other chronic conditions are part of the dynamic dynamite mixture.

Jan 31: Cervical cancer could be eliminated worldwide as a public health issue within the next 100 years, according to two studies which may lead to better strategies for screening and vaccination against the malignant disease.

According to the studies, published in the journal The Lancet, more than 74 million cervical cancer cases, and 60 million deaths could be averted, and the disease eliminated in the 78 countries which have the highest disease burden.

The researchers, including those from Laval University in Canada, said cervical cancer is the second most frequent cancer among women in low-income and lower-middle-income countries (LMICs) with 2,90,000 (51 per cent) of the 5,70,000 new cases worldwide reported in women living in LMICs.

In the current studies, the scientists used the WHO draft strategy of cervical cancer elimination which defines plans for vaccination against the disease's causative agent, the human papillomavirus (HPV).

These plans, they explained, call for 90 per cent of girls to be vaccinated against HPV by 2030, and for 70 per cent of women to be screened for cervical cancer once or twice in their lifetime.

About 90 per cent of women with precancerous lesions, or cervical cancer are also advised to receive appropriate treatment, according to the WHO draft strategy, the scientists said.

In the second study, the research team analysed the impact of three elements of the WHO strategy on deaths from cervical cancer -- modelling the impact of scaling up cancer treatment, as well as vaccination and screening

"Our findings emphasise the importance of acting immediately to combat cervical cancer on all three fronts," said Karen Canfell from the University of Sydney in Australia, who co-led both the studies.

"In just 10 years, it's possible to reduce deaths from the disease by a third and, over the next century, more than 60 million women's lives could be saved. This would represent an enormous gain in terms of both quality of life, and lives saved," Canfell said.

By adding the two screening tests, and with the treatment of precancerous cervical lesions, cases of the cancer may drop by 97 per cent, and 72 million cervical cancer cases could be averted over the next century, the researchers said.

Scaling-up of appropriate cancer treatment could avert 62 million cervical cancer deaths, the study noted.

"For the first time, we've estimated how many cases of cervical cancer could be averted if WHO's strategy is rolled out and when elimination might occur," said Marc Brisson, study co-author from Laval University.

"Our results suggest that to eliminate cervical cancer it will be necessary to achieve both high vaccination coverage, and a high uptake of screening and treatment, especially in countries with the highest burden of the disease," Brisson added.

Based on the results of the studies, WHO's cervical cancer elimination strategy has been updated which will be presented for adoption at the World Health Assembly in May 2020, the scientists noted.

"If the strategy is adopted and applied by member states, cervical cancer could be eliminated in high income countries by 2040, and across the globe within the next century, which would be a phenomenal victory for women's health," Brisson said.

"However, this can only be achieved with considerable international financial and political commitment, in order to scale-up prevention and treatment," he added.