Coronavirus: Three markers in blood could identify mortality risk

Scientists have identified three biological clues in COVID-19 patients’ blood samples to predict their risk of death with up to 90 per cent accuracy.

Chinese researchers used machine learning to analyse blood samples of patients in Wuhan and identify the three biomarkers of mortality risk 10 days early.

High levels of both an enzyme associated with tissue breakdown and a protein produced during inflammation, as well as low levels of lymphocyte white blood cells, were the key predictors. 

Using these markers for an early diagnosis of risk of death among people with COVID-19 is vital to prioritise care for the patients who are most at risk.

A blood sample can quickly predict patients at the highest riskof death from COVID-19, allowing them to be prioritisedin hospitals worldwide

The research provides a method to quickly predict patients at the highest risk, allowing them to receive urgent treatment and potentially reduce the mortality rate.

‘The three key features – LDH, lymphocytes and hs-CRP – can be easily collected in any hospital,’ the researchers write in Nature Machine Intelligence. 

‘In crowded hospitals, and with shortages of medical resources, this simple model can help to quickly prioritise patients, especially during a pandemic when limited healthcare resources have to be allocated.’

As an increase in COVID-19 cases puts pressure on healthcare services worldwide, fast, accurate and early clinical assessment of the disease severity is vital, the researchers write.

Vials with blood samples seen at a medical centre. The this makes use of a database of blood samples from 485 infected patients in the region of Wuhan, China

Vials with blood samples seen at a medical centre. The this makes use of a database of blood samples from 485 infected patients in the region of Wuhan, China

It has been reported that somewhere between 13.8 per cent to 19.1 per cent of COVID-19 patients in Wuhan, China, where the disease originated, became severely ill.

But in overworked hospitals, there had been no prognostic biomarker to distinguish patients that require immediate medical attention.

To remedy this, the researchers used a database of blood samples from 485 infected patients in the region of Wuhan between January 10 and February 18 this year

By February 18, 375 of this total with a ‘definite outcome’ – 201 survived and 174 had died – were used to develop an algorithm.

By collecting medical information of both sets of patients in machine learning software, the researchers were able to identify the most common characteristics in the patients who had died.

An artist's illustration of lymphocytes. Low levels of lymphocytes in the blood - known as lymphopenia - is a common feature in patients with COVID-19 and might be a critical factor associated with disease severity and mortality

An artist’s illustration of lymphocytes. Low levels of lymphocytes in the blood – known as lymphopenia – is a common feature in patients with COVID-19 and might be a critical factor associated with disease severity and mortality

The model was able to accurately identify the outcome of patients, regardless of their original diagnosis upon hospital admission.

On average, the accuracy of our algorithm was 90 per cent and could be applied to any blood sample taken throughout a patient’s stay in hospital.

The model selected the three biomarkers that predict the mortality of individual patients more than 10 days in advance of death or discharge – firstly, lactic dehydrogenase (LDH), an enzyme found in nearly all living cells.

In particular, relatively high levels of LDH alone seem to play a crucial role in distinguishing the vast majority of cases that require immediate medical attention, the team said.

Blood sample tube for lactate dehydrogenase or LDH test, diagnosis for tissue damage or cellular destruction, and one of the three markers

Blood sample tube for lactate dehydrogenase or LDH test, diagnosis for tissue damage or cellular destruction, and one of the three markers

This is consistent with current medical knowledge that high LDH levels are associated with tissue breakdown occurring in various diseases, including pulmonary disorders such as pneumonia.

The second marker was low levels of a type of white blood cell called lymphocytes – a condition known as lymphopenia. 

Lymphocytes are of ‘fundamental importance’ in the immune system because they determine immune response to infectious microorganisms and other foreign substances, such as the SARS-CoV-2 virus, the team said. 

In human adults, lymphocytes make up roughly 20 to 40 percent of the total number of white blood cell and are concentrated in central lymphoid organs and tissues, such as the spleen, tonsils, and lymph nodes, where initial immune response is likely to occur. 

Chemical structure of C-reactive protein (CRP) molecule. Increased blood levels of this protein indicate the presence of inflammation or infection

Chemical structure of C-reactive protein (CRP) molecule. Increased blood levels of this protein indicate the presence of inflammation or infection

The third marker was an increase in high-sensitivity C-reactive proteins (hs-CRP) – a protein in the blood that increases when inflammation is present.

The increase of hs-CRP is an important marker for poor prognosis in acute respiratory distress syndrome and reflects a persistent state of inflammation, the team said.

The result of this persistent inflammatory response is large grey-white lesions in the lungs of patients with COVID-19, as observed in autopsies.

The data in the study was obtained at an early period in the emergence of the disease, meaning a relatively small handful of patient data was used. 

Researchers conclude that their technique can easily be repeated to obtain more accurate models as more data become available. 

COVID-19 has infected more than 4.8 million people and killed 319,000, as of Tuesday. 

How is China preventing a second wave of COVID-19 infections?

The country where the coronavirus pandemic began has been working to prevent a second wave of the outbreak looming in hindsight.

Chinese officials have warned that a surge of ‘imported cases’ from inbound travellers and asymptomatic patients could trigger a new epidemic, spoiling the nation’s progress of containing the crisis.

Overseas Chinese citizens have rushed to return home as China is now deemed to be a safe harbour during the escalating coronavirus pandemic.

The picture shows workers wearing protective suits checking information of an inbound passenger at Shanghai Pudong International Airport on March 27

The picture shows workers wearing protective suits checking information of an inbound passenger at Shanghai Pudong International Airport on March 27

China have heavily restricted international flights and tightened border controls in a move to avoid a second wave of the outbreak. 

All passengers who fly into China will be quarantined for 14 days. Beijing also opened a dedicated coronavirus hospital in late March to quarantine people arriving from abroad.

By April 8, China has closed all entry and exit points on its 2,670 mile border with Russia, after 40 new COVID-19 cases were recorded at the China-Russia border in one day.

People passing through security at the railway station in Wuhan, a body temperature checking feature is also used

People passing through security at the railway station in Wuhan, a body temperature checking feature is also used

Suifenhe, a Chinese port city of 70,000 residents, went under Wuhan-style lockdown on the same day. An emergency makeshift hospital was built in the boarder city after six days of construction.

The Inner Mongolian city of Manzhouli – the largest land border between the neighbours – also closed in the evening of April 8, stretching its quarantine and testing capacity ‘beyond limit’ as tens of thousands of Chinese flooded back in.

From the start of April, China have been giving daily reports about the coronavirus patients who show no symptoms amid fears that they could lead to a second wave of infections.

Authorities also ordered all cities to isolate such patients in quarantine centres for 14 days, according to a previous directive from Wuhan. People in close contact with them face two weeks of medical observation.

Meanwhile, officials from Guangzhou have pledged to deport any ‘foreigners’ who refuse to cooperate amid the coronavirus crisis after the southern Chinese city has seen a spike of ‘imported cases’. 

Despite China has eased travel restrictions on most parts of the country, residents are required to show a dedicated green code on their phones to prove they are virus-free when travelling or entering public places.

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