How does the new coronavirus kill patients? Clinicians track the virus ferociously throughout the body, from the brain to the toes

< br / > < br / > June 1, 2020 / < br / > BIOON / - - on the latest day, in a 20 bed intensive care unit (ICU), Joshua Denson, a pulmonary and intensive care physician at Tulane University School of medicine, evaluated two epileptic patients, many patients with respiratory failure, and others with dangerous renal landslidesA few days ago, his ward round was interrupted because his team failed to rescue a young woman whose heart had stopped beatingThese people have one thing in common, Denson said"They're all covid-19 positive."novel coronavirus SARS-CoV-2 has been used by clinicians and pathologists to understand the damage to human body as the number of COVID-19 confirmed cases exceeds 6 million and the death toll exceeds 360 thousandThey realized that although the lung is a ground zero, its influence can extend to many organs, including the heart and blood vessels, kidneys, intestines and brain< br / > < br / > according to Harlan Krumholz, a cardiologist at Yale New Haven Hospital Affiliated to Yale University School of medicine, "almost anything in the body can be attacked [by this disease] with devastating consequencesIts ferocity is shocking and suffocating" Krumholz is leading the collection of covid-19 clinical data< br / > < br / > pictures from science, 2020, doi:10.1126/science.abc3208 。 < br / >Does a dangerous, newly observed tendency to clot turn some mild cases into life-threatening emergencies? Does excessive immune response in severe cases mean that immunosuppressive drugs may be helpful? What causes some doctors to report that patients have surprisingly low blood oxygen but no asthma? "When we start to think about treatment, it may be beneficial to take a systematic approach," said nilam mangalmurti, a lung specialist at the University of Pennsylvania hospital < br / > < br / > the following is an understanding of how the virus attacks the rapid development of systemic cells, especially in about 5% of severe patientsAlthough more than 1000 papers are published on journals and preprint servers every week, we still can't get a clear understanding of the virus because of its role as a pathogen we've never seen beforeWithout the larger prospective control studies that are only now underway, scientists will have to extract information from small studies and case reports, which are often published at an alarming rate and are not peer-reviewed"With the development of this phenomenon, we need to keep a very open mind," said Nancy reau, a liver transplant doctor who treats patients with covid-19 at Rush University Medical Center in the United StatesWe are still learning" < br / >The virus has found a popular home in the lining of the nose, according to a paper published on the preprint server by scientists at the welcom Foundation's Sanger Institute and elsewhereThey found that the cells there were rich in a cell surface receptor called ACE2Throughout the body, the presence of ACE2 - which often helps regulate blood pressure - means that tissues are susceptible to infection because the virus needs the receptor to enter the cellOnce inside the cell, the virus hijacks the molecular machines in the cell and makes countless copies of itself, thus invading new cells< br / >There may not be any symptoms at this timeOr new victims of the virus may have symptoms of fever, dry cough, sore throat, loss of smell and taste, head and body pain< br / >The thin and far branches of the respiratory tree are called alveoli, each of which contains a layer of ACE2 receptor rich cells< br / > < br / > normally, oxygen enters the capillaries through the alveoli, i.ethe small blood vessels beside the air bags, and then delivers oxygen to other parts of the bodyBut when the immune system engages invaders, the battle itself destroys this healthy oxygen deliveryFrontline leukocytes release inflammatory molecules called chemokines, which in turn call on more immune cells to target and kill infected cells, leaving behind a mixture of liquid and dead cells pusThis is the basic pathology of pneumoniaThe corresponding symptoms are: cough, fever and rapid, shallow breathingSome patients with covid-19 can recover, sometimes just by breathing oxygen through the nasal cannula< br / > < br / > but there are also some patients whose condition worsens suddenly, which leads to a disease called acute respiratory distress syndrome (ARDS) Their blood oxygen levels plummeted and breathing became more difficult On X-ray and CT scans, their lungs are filled with white shadows that should have been black Usually, these patients end up relying on a ventilator to maintain their lives A lot of people died Autopsy results showed that their alveoli were filled with fluid, white blood cells, mucus and remnants of damaged lung cells < br / > But the virus, or the body's response to it, can harm many other organs Scientists are just beginning to explore the scope and nature of the harm < br / > For the eyes, conjunctivitis is more common in the most serious patients For the nose, some patients lose their sense of smell Scientists speculate that the virus may move up the nerve endings of the nose, damaging cells For the lungs, the cross-section shows that the immune cells are packed with inflamed alveoli, or air sacs Under the attack of this virus, the walls of the air sacs will rupture, reducing the absorption of oxygen The patient coughs, has a fever, and has difficulty breathing For the heart and blood vessels, the virus enters the cells (possibly including those in the vascular intima) by binding to ACE2 receptors on the cell surface The virus infection also promotes blood clotting, heart attacks and heart inflammation For the liver, as many as half of the patients in hospital have enzyme levels indicating liver dysfunction Over speed of the immune system, coupled with antiviral drugs, may be the cause of liver damage For kidneys, in severe cases, kidney damage is common and makes death more likely The virus may directly attack the kidneys, or renal failure may be part of a systemic event such as a drop in blood pressure For the gut, patient reports and biopsy data indicate that the virus can infect the lower gastrointestinal tract, which is rich in ACE2 receptors More than 20% of patients have diarrhea < br / > < br / > some clinicians speculate that the driving force for the deterioration of many severe patients is the catastrophic overreaction of the immune system, namely cytokine storm, which can also be triggered by other virus infections Cytokines are the chemical signaling molecules that guide the healthy immune response, but in the cytokine storm, the level of some cytokines soared far beyond what is needed, and immune cells began to attack healthy tissues Blood vessels leak, blood pressure drops, blood clots form, and catastrophic organ failure will follow < br / > Jamie Garfield, a pulmonary surgeon who cares for COVID-19 patients at Temple University hospital, said: "the real incidence rate and mortality rate of this disease may be caused by excessive inflammation of the virus." < br / > < br / > but others are not convinced Joseph Levitt, a pulmonary intensive care physician at Stanford University School of medicine, said, "it seems that someone soon associated covid-19 with these high inflammatory states I haven't seen such convincing data " < br / > < br / > he is also concerned that efforts to inhibit cytokine responses will backfire Several drugs targeting specific cytokines are in clinical trials in patients with covid-19 But Levitt worries that the drugs may inhibit the body's immune response to the virus "It's risky that we allow more virus replication," Levitt said < br / > < br / > at the same time, other scientists are targeting a completely different organ system - the heart and blood vessels - which they say is the cause of some patients' rapid deterioration < br / > Further tests showed that the heart was swollen and scarred, and the left ventricle - usually the heart's power chamber - was so fragile that it pumped only a third of its normal blood volume But when doctors injected dye into coronary arteries, looking for blockages that mark a heart attack, they did not find them Another test showed the cause: the woman had covid-19 < br / > < br / > how the virus attacks the heart and blood vessels is a mystery, but dozens of preprinted articles and papers prove that this damage is common A paper published in the Journal of JAMA Cardiology on March 25 recorded that nearly 20% of 416 patients hospitalized for covid-19 in Wuhan, China had heart injury In another study conducted in Wuhan, 44% of 36 ICU patients admitted to the hospital had arrhythmias < br / > < br / > the heart damage seems to extend to the blood itself According to a paper published in the Journal of thrimbosis research on April 10, 38% of 184 patients with covid-19 in an intensive care unit in the Netherlands have abnormal blood clots, and nearly 1 / 3 of them have already developed blood clots Blood clots can rupture and stay in the lungs, blocking vital arteries, a condition known as pulmonary embolism, which has reportedly resulted in the death of patients with covid-19 Blood clots in arteries also deposit in the brain, leading to < br / > strokes < br / > Behnood bikdeli, a researcher in cardiovascular medicine at Columbia University Medical Center, said many patients had "significantly" high levels of D-dimer, a byproduct of blood clots "The more we look at it, the more likely we are to think that clots play an important role in the severity and mortality of covid-19," bikdeli said < br / > < br / > infection can also cause vasoconstriction It has been reported that finger and toe ischemia - reduced blood flow can cause swelling, pain and tissue death in the fingers < br / > < br / > in the lungs, vasoconstriction may help explain a puzzling phenomenon in the pneumonia caused by covid-19: some patients have extremely low blood oxygen levels, but none