Lung, immune function in kids could protect from severe COVID-19
July 8, 2020
Science Daily/University of Texas Health Science Center at Houston
Differences in lung physiology and immune function in children could be why they are more often spared from severe illness associated with COVID-19 than adults, according to pediatric and adult physicians at The University of Texas Health Science Center at Houston (UTHealth) and Baylor College of Medicine, who teamed up to investigate the disparity.
The perspectives paper was recently published in American Journal of Physiology-Lung Cellular and Molecular Physiology.
According to the paper, only about 1.7% of the first 149,082 cases in the U.S. were infants, children, and adolescents younger than 18 years old. Authors noted that children under 18 make up 22% of the U.S. population. Only three pediatric deaths were identified by the Centers for Disease Control and Prevention (CDC) as of April 2020.
"These profoundly decreased rates of symptomatic infection, hospitalization, and death are well beyond statistical significance, require further examination, and may hold the key to identifying therapeutic agents," the authors wrote.
Angiotensin-converting enzyme 2s, called ACE2, are the doors that allow SARS-CoV-2, the novel coronavirus that causes COVID-19, to enter the body's cells. Children naturally have less ACE2 in the lungs than adults.
"ACE2 are important for viral entry and there seems to be less of them in children, because they increase with age," said Matthew Harting, MD, MS, assistant professor in the Department of Pediatric Surgery at McGovern Medical School at UTHealth, pediatric surgeon with UT Physicians, and senior author of the paper. Harting is also director of the pediatric ECMO program providing advanced cardiac and respiratory support at Children's Memorial Hermann Hospital.
In addition to fewer ACE2 receptors, the authors note the immune system in children responds to viruses differently than that of adults, leaving less opportunity for severe illness in pediatric patients. There are several different mechanisms behind the differences, including the retention of T-cells in children, which are able to fight off or limit inflammation.
"T-cells have a viral response and also an immune modulator response. In severe cases of adult COVID-19 patients, we've seen that those T-cells are reduced, so the ability to fight the virus is also reduced. In kids, those T-cells seem to be maintained, so they are still able to prevent the virus," said Harry Karmouty-Quintana, PhD, an assistant professor in the Department of Biochemistry and Molecular Biology at McGovern Medical School, and a co-author of the paper.
Lung tissue in children naturally has a higher concentration of regulator T-cells. Patients with higher levels of T-cells also have higher levels of Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor, an anti-inflammatory cytokine.
"IL-10 inhibits the inflammation of other components like IL-6 that are detrimental. Adults tend to experience hyperinflammatory state, where kids do not," Karmouty-Quintana said. "In preclinical studies in mice, IL-10 has also shown to decrease with age."
The paper's findings were made possible through collaboration in a multidisciplinary group made up of pediatric and adult physicians and scientists in pediatric surgery, adult critical care, neonatology, and molecular biology.
"We, as physicians, have been challenged with the question of how to treat COVID-19 and we're learning in real time," said Bindu Akkanti, MD, associate professor of critical care medicine with McGovern Medical School, attending physician in critical care with Memorial Hermann-Texas Medical Center, and a study co-author. "I knew that to figure out the best way to treat adults, we needed to get a team together to get to the bottom of why children were being spared from severe illness related to the virus. So, I reached out to Dr. Karmouty-Quintana and we teamed up with Dr. Harting and two other physicians in the Texas Medical Center to start investigating." Akkanti also sees pulmonary patients at UT Physicians.
"Collaborations like this between adult and pediatric providers are really important and this disease highlights where we can learn a lot when we compare the way it behaves in younger kids with older people," Harting said. "Even now as we're learning about effective treatments, we're seeing younger people handle this disease better than older people. Moving forward, physicians and scientists need multidisciplinary collaboration to continue learning -- this is just another step in the right direction to attack this virus."
Krithika Lingappan, MBBS, was the first author of the paper and Jonathan Davies, MD, was a co-author. Both Lingappan and Davies are assistant professors of pediatrics at Baylor College of Medicine and neonatologists with Texas Children's Hospital.
As a result of the collaboration, the team has begun a new study using blood samples from patients in different stages of COVID-19 to continue to understand how to treat the virus and the disparities in disease progression between children and adults.
https://www.sciencedaily.com/releases/2020/07/200708155528.htm
Coronavirus linked to stroke in otherwise healthy young people
June 4, 2020
Science Daily/Thomas Jefferson University
Young patients with no risk factors for stroke may have an increased risk if they have contracted COVID-19, whether or not they are showing symptoms of the disease. Surgeons at Thomas Jefferson University and collaborators analyzed patients presenting with stroke from March 20th until April 10th at their institutions. The strokes they observed were unlike what they usually see.
"We were seeing patients in their 30s, 40s and 50s with massive strokes, the kind that we typically see in patients in their 70s and 80s," says Pascal Jabbour, MD, Chief of the Division of Neurovascular Surgery and Endovascular Surgery in the Vickie & Jack Farber Institute for Neuroscience -- Jefferson Health. He is a senior author of a study published in the journal Neurosurgery June 4th, that examines and characterizes strokes of patients who tested positive for COVID-19, done in collaboration with surgeons from NYU Langone Medical Center in New York.
"Although we have to stress that our observations are preliminary, and based on observations from 14 patients, what we have observed is worrying," says Dr. Jabbour. "Young people, who may not know they have the coronavirus, are developing clots that cause major stroke."
The researchers, including first author Ahmad Sweid, MD, examined 14 patients who had come into their Neurointerventional room for stroke. Eight patients were male, six were female, 50%, did not know they had the coronavirus, while the remainder were already being treated for other symptoms of the disease when they developed stroke.
Some of the paper's major points:
Patients with signs of stroke were delaying coming to the hospital for fear of getting the coronavirus. There's a small window of time in which strokes are treatable, so delays can be life threatening.
The mortality rate in these covid-19 stroke patients is 42.8%. The typical mortality from stroke is around 5 to 10%.
42% of the stroke coronavirus positive patients studied were under the age of 50. Most strokes, over 75% of all strokes in the US, occur in people over the age of 65.
The incidence of coronavirus in the stroke population was 31.5%, according to this sample of patients.
Patients observed had stroke in large vessels, in both hemispheres of the brain, and in both arteries and veins of the brain -- all of these observations are unusual in stroke patients.
Why is the coronavirus, which was assumed to be a disease of the lungs, causing blood clots that lead to a higher incidence of stroke? Researchers have shown that the coronavirus enters human cells via a very specific access point -- a protein on human cells called ACE2. But the coronavirus latches onto this protein and uses it to as a gateway into the cell, where the virus can replicate. Not all cells have the same amount of ACE2. This protein is very abundant on cells that line blood vessels, the heart, kidney, and of course, the lungs. Dr. Jabbour and colleagues speculate that the virus may be interfering with this receptor's normal function, which controls blood flow in the brain, in addition to using it as an entry point to the cell.
Another possibility is that the inflammation of the blood vessels causing vasculitis with injury to the cells lining the lumen of the vessel, called endothelium and causing micro thrombosis in small vessels.
"Our observations, though preliminary, can serve as a warning for medical personnel on the front lines, and for all of those at home," says Dr. Jabbour. "Stroke is occurring in people who don't know they have COVID-19, as well as those who feel sick from their infections. We need to be vigilant and respond q uickly to signs of stroke."
https://www.sciencedaily.com/releases/2020/06/200604095600.htm
ACE inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19
March 23, 2020
Science Daily/Louisiana State University Health Sciences Center
James Diaz, MD, MHA, MPH & TM, Dr PH, Professor and Head of Environmental Health Sciences at LSU Health New Orleans School of Public Health, has proposed a possible explanation for the severe lung complications being seen in some people diagnosed with COVID-19. The manuscript was published by Oxford University Press online in the Journal of Travel Medicine.
The SARS beta coronaviruses, SARS-CoV, which caused the SARS (Severe Acute Respiratory Syndrome) outbreak in 2003 and the new SARS-CoV-2, which causes COVID-19, bind to angiotensin converting enzyme 2 (ACE2) receptors in the lower respiratory tracts of infected patients to gain entry into the lungs. Viral pneumonia and potentially fatal respiratory failure may result in susceptible persons after 10-14 days.
"Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are highly recommended medications for patients with cardiovascular diseases including heart attacks, high blood pressure, diabetes and chronic kidney disease to name a few," notes Dr. Diaz. "Many of those who develop these diseases are older adults. They are prescribed these medications and take them every day."
Research in experimental models has shown an increase in the number of ACE2 receptors in the cardiopulmonary circulation after intravenous infusions of ACE inhibitors.
"Since patients treated with ACEIs and ARBS will have increased numbers of ACE2 receptors in their lungs for coronavirus S proteins to bind to, they may be at increased risk of severe disease outcomes due to SARS-CoV-2infections," explains Diaz.
Diaz writes, this hypothesis is supported by a recent descriptive analysis of 1,099 patients with laboratory-confirmed COVID-19 infections treated in China during the reporting period, December 11, 2019, to January 29, 2020. This study reported more severe disease outcomes in patients with hypertension, coronary artery disease, diabetes and chronic renal disease. All patients with the diagnoses noted met the recommended indications for treatment with ACEIs or ARBs. Diaz says that two mechanisms may protect children from COVID-19 infections -- cross-protective antibodies from multiple upper respiratory tract infections caused by the common cold-causing alpha coronaviruses, and fewer ACE2 receptors in their lower respiratory tracts to attract the binding S proteins of the beta coronaviruses.
He recommends future case-control studies in patients with COVID-19 infections to further confirm chronic therapy with ACEIs or ARBs may raise the risk for severe outcomes.
In the meantime he cautions, "Patients treated with ACEIs and ARBs for cardiovascular diseases should not stop taking their medicine, but should avoid crowds, mass events, ocean cruises, prolonged air travel, and all persons with respiratory illnesses during the current COVID-19 outbreak in order to reduce their risks of infection."
https://www.sciencedaily.com/releases/2020/03/200323101354.htm