(Press-News.org) BOSTON -- Getting control of COVID-19 will take more than widespread vaccination; it will also require better understanding of why the disease causes no apparent symptoms in some people but leads to rapid multi-organ failure and death in others, as well as better insight into what treatments work best and for which patients.
To meet this unprecedented challenge, researchers at Massachusetts General Hospital (MGH), in collaboration with investigators from Brigham and Women's Hospital and the University of Cyprus, have created a mathematical model based on biology that incorporates information about the known infectious machinery of SARS-CoV-2, the virus that causes COVID-19, and about the potential mechanisms of action of various treatments that have been tested in patients with COVID-19.
The model and its important clinical applications are described in the journal Proceedings of the National Academy of Sciences (PNAS).
"Our model predicts that antiviral and anti-inflammatory drugs that were first employed to treat COVID-19 might have limited efficacy, depending on the stage of the disease progression," says corresponding author Rakesh K. Jain, PhD, from the Edwin L. Steele Laboratories in the Department of Radiation Oncology at MGH and Harvard Medical School (HMS).
Jain and colleagues found that in all patients, the viral load (the level of SARS-CoV-2 particles in the bloodstream) increases during early lung infection, but then may go in different directions starting after Day 5, depending on levels of key immune guardian cells, called T cells. T cells are the first responders of the immune system that effectively coordinate other aspects of immunity. The T cell response is known as adaptive immunity because it is flexible and responds to immediate threats.
In patients younger than 35 who have healthy immune systems, a sustained recruitment of T cells occurs, accompanied by a reduction in viral load and inflammation and a decrease in nonspecific immune cells (so-called "innate" immunity). All of these processes lead to lower risk for blood clot formation and to restoring oxygen levels in lung tissues, and these patients tend to recover.
In contrast, people who have higher levels of inflammation at the time of infection -- such as those with diabetes, obesity or high blood pressure -- or whose immune systems are tilted toward more active innate immune responses but less effective adaptive immune responses tend to have poor outcomes.
The investigators also sought to answer the question of why men tend have more severe COVID-19 compared with women, and found that although the adaptive immune response is not as vigorous in women as in men, women have lower levels of a protein called TMPRSS2 that allows SARS-CoV-2 to enter and infect normal cells.
Based on their findings, Jain and colleagues propose that optimal treatment for older patients -- who are likely to already have inflammation and impaired immune responses compared with younger patients -- should include the clot-preventing drug heparin and/or the use of an immune response-modifying drug (checkpoint inhibitor) in early stages of the disease, and the anti-inflammatory drug dexamethasone at later stages.
In patients with pre-existing conditions such as obesity, diabetes and high blood pressure or immune system abnormalities, treatment might also include drugs specifically targeted against inflammation-promoting substances (cytokines, such as interleukin-6) in the body, as well as drugs that can inhibit the renin-angiotensin system (the body's main blood pressure control mechanism), thereby preventing activation of abnormal blood pressure and resistance to blood flow that can occur in response to viral infections.
This work shows how tools originally developed for cancer research can be useful for understanding COVID-19: The model was first created to analyze involvement of the renin angiotensin system in the development of fibrous tissues in tumors, but was modified to include SARS-CoV-2 infection and COVID-19-specific mechanisms. The team is further developing the model and plans to use it to examine the dynamics of the immune system in response to different types of COVID-19 vaccines as well as cancer-specific comorbidities that might require special considerations for treatment.
INFORMATION:
Co-corresponding authors are Lance L. Munn, MGH, and Triantafyllos Stylianopoulos, University of Cyprus. Other authors are Chrysovalantis Voutouri, U. Cyprus; Mohammad Reza Nikmaneshi, Sharif University of Technology, Iran; C. Corey Hardin, Melin J. Khandekar and Sayon Dutta, all from MGH; and Ankit B. Patel and Ashish Verma from Brigham and Women's Hospital.
Jain's research is supported by an Investigator Award and grants from the National Foundation for Cancer Research, Jane's Trust Foundation, American Medical Research Foundation and Harvard Ludwig Cancer Center. Munn's research is supported by a National Institutes of Health grant. Stylianopoulos's research is supported by the European Research Council and Cyprus Research and Innovation Foundation. Patel is support by an American Society of Nephrology Joseph A. Carlucci Research Fellowship.
About the Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2020, Mass General was named #6 in the U.S. News & World Report list of "America's Best Hospitals."
Diabetes continues to be the leading cause of new cases of blindness among adults in the United States. But the current shortage of eye-care providers would make it impossible to keep up with demand to provide the requisite annual screenings for this population. A new study looks at the effectiveness of seven artificial intelligence-based screening algorithms to diagnose diabetic retinopathy, the most common diabetic eye disease leading to vision loss.
In a paper published Jan. 5 in Diabetes Care, researchers compared the algorithms against the diagnostic expertise of retina specialists. Five companies produced the tested algorithms - two in the United States (Eyenuk, Retina-AI Health), one in China (Airdoc), one in Portugal (Retmarker), ...
Fishermen contend with regulations, natural disasters, and the ups and downs of the stocks they fish, along with many other changes. As a result, fishing communities are quite resilient. That is, they can withstand, recover from, and adapt to change.
But how much pressure can they stand? The 2014-2016 North Pacific marine heatwave, known as the Blob, led to a harmful algal bloom of unprecedented scale. It necessitated substantial delays in the opening of the 2015-16 U.S. West Coast Dungeness crab fishery. The fishery is vital to West Coast communities. It produces around 26 percent of all annual fishing revenue and supports more than 30 percent of all commercial fishing vessels.
Understanding ...
Humans have consumed different types of fermented foods - from kimchi to yogurt - for thousands of years. Yet only recently, with the availability of new scientific techniques for analyzing their nutritional properties and microbiological composition, have scientists begun to understand exactly how the unique flavors and textures are created and how these foods benefit human health.
Now, 13 interdisciplinary scientists from the fields of microbiology, food science and technology, family medicine, ecology, immunology, and microbial genetics have come together to create the first international consensus definition of fermented ...
Hotel managers have something in common beyond their reputations for charming dispositions and excellent listening skills - they're predominantly men, despite women making up the majority of the accommodations workforce. New research led by the University of Houston Conrad N. Hilton College of Hotel and Restaurant Management suggests hotel companies that promote a woman over an equally qualified man are perceived as fairer and less discriminatory, creating a stronger organizational culture and higher financial performance.
Published in the International Journal of Contemporary Hospitality Management, the study is the first to address gender inequity in promotional opportunities for hotel employees. The researchers surveyed 87 hotel ...
DENVER/January 5, 2020 - Some English bulldogs diagnosed with a common cancer may instead have a newly described, non-cancerous syndrome called polyclonal B‐cell lymphocytosis. The discovery was made by Morris Animal Foundation-funded researchers at Colorado State University during a study to better understand B-cell chronic lymphocytic leukemia (BCLL). The team published their findings in the Journal of Veterinary Internal Medicine.
"This could save some dogs from being misdiagnosed, treated for cancer or even euthanized when they shouldn't be," said Dr. Anne Avery, Professor, Department of Microbiology, Immunology and Pathology at Colorado State University. "The dogs may look to their veterinarians like they ...
BOSTON - (January 4, 2021) - As they age, people with diabetes are more likely to develop Alzheimer's disease and other cognitive disorders than are people without diabetes. Scientists at Joslin Diabetes Center now have shown that routine eye imaging can identify changes in the retina that may be associated with cognitive disorders in older people with type 1 diabetes.
These results may open up a relatively easy method for early detection of cognitive decline in this population, providing better ways to understand, diagnose and ultimately treat the decline, said George L. King, MD, Joslin's Chief Scientific Officer and senior author on a paper about the study in the Journal of Clinical Endocrinology & Metabolism.
Previous research had demonstrated an association ...
To stop biodiversity loss, Canada recently committed to protecting 30% of its land and sea by 2030. But making conservation decisions about where to locate new protected areas is complicated. It depends on data both about biodiversity and about a range of benefits (e.g. freshwater, climate regulation, recreation) that people get from nature. Surprisingly, despite the size of the country, new mapping suggests that less than 1% of Canada's land (0.6% of total area or approximately 56,000 km2) is a hot spot, providing all these benefits in one place. Moreover, the study published today in Environmental Research Letters suggests that some of the most critical areas where people receive these key benefits from ...
Leipzig. The transition from the Medieval Warm Period to the Little Ice Age was apparently accompanied by severe droughts between 1302 and 1307 in Europe; this preceded the wet and cold phase of the 1310s and the resulting great famine of 1315-21. In the journal Climate of the Past, researchers from the Leibniz Institutes for the History and Culture of Eastern Europe (GWZO) and Tropospheric Research (TROPOS) write that the 1302-07 weather patterns display similarities to the 2018 weather anomaly, in which continental Europe experienced exceptional heat and drought. Both the medieval and recent weather patterns resemble the stable weather patterns that have occurred more frequently since the 1980s due to the increased warming of the Arctic. ...
A clear view of anatomical structures is vital for the success of surgery--especially in microsurgery where narrow anatomical cavities or proximity to vulnerable organs and tissues can pose significant risks to patient health. The surgical microscope has evolved to become a powerful tool for improving surgical visualization.
A END ...
TROY, N.Y. -- A loss of enzymatic processes within the body can increase a person's risk of bone fracture. This new insight was recently published in eLife by an international team of scientists and engineers led by Deepak Vashishth, the director of the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer Polytechnic Institute.
Enzymatic processes are essential to any number of chemical reactions that occur within the body, including the production of the extracellular matrix within bone that is critical for mechanical support. Phosphorylation -- one of those key enzymatic processes -- is the attachment of a phosphoryl to a protein, and is critical for ...
