March 25, 2020
Since late last year, the novel SARS-CoV-2 coronavirus that causes the respiratory-related disease known as COVID-19 has spread to nearly every part of the globe. As the number of confirmed cases worldwide continues to rise, the hunt for effective treatments has intensified. Fortunately, insights gained from decades of scientific research on our immune system and how it responds to infectious disease and cancer are not only helping to inform treatment for COVID-19 today but may also lead to strategies to prevent future outbreaks of the virus.IMMUNOTHERAPY TO PREVENT INFECTION WITH NOVEL CORONAVIRUS
Preventive vaccines work by “teaching” the immune system to recognize specific threats before encountering them—in this case, the new coronavirus. Equipped with this information, the immune system prepares specialized T cells and antibody-producing B cells that stand ready to neutralize the threat should it appear. Whereas antibodies can bind to copies of the virus itself and mark them for destruction, T cells can recognize the cells in our body that have been infected and eliminate them before they enable spread of the virus to other cells.
According to a March 18 report by the Center for Disease Control (CDC), between 21-31% of patients confirmed to have been infected by the new coronavirus require hospitalization. Despite these alarming numbers, that means that, in the majority of people, their immune system naturally and successfully eliminated the virus. However, sometimes the immune response may not be strong or swift enough to reverse the spread of the virus within the body before the onset of symptoms or severe disease. Consequently, the preventive vaccine is designed to prime a patient’s immune system so that, should the virus be detected, it can be eliminated before it leads to disease.
A preventive vaccine developed by the U.S. National Institutes of Health (NIH) is currently in a phase 1 clinical trial involving healthy volunteers who have not been exposed to SARS-CoV-2. However, even if this experimental vaccine is shown to be safe and effective, it will likely take at least “a year to a year and a half” to reach the public, according to Anthony S. Fauci, M.D., who has served for three and a half decades as the director of the National Institute of Allergy and Infectious Diseases (NIAID) at the NIH.
IMMUNOTHERAPY TO TREAT COVID-19
When our immune system revs up in response to infection, overproduction of certain molecules involved in normal immune function can result in a dangerous condition called cytokine release syndrome (CRS). CRS is characterized by systemic hyperinflammation that damages patients’ own tissues, potentially leading to organ failure and death.
Initially observed in cancer patients whose immune systems rejected transplants of bone marrow (graft-versus-host disease) and later in cancer patients receiving a relatively new type of immunotherapy called CAR T cell therapy, CRS-like symptoms have now been observed in COVID-19 patients, and elevated levels of certain inflammatory cytokines were found to be a predictor of death due to the disease.
One of these inflammatory cytokines is interleukin-6 (IL-6). In treating cancer patients suffering from CRS, oncologists learned that blocking the activity of the IL-6 pathway can bring CRS under control. As a result of these lessons from cancer immunotherapy, doctors are now evaluating in at least one trial how the IL-6-blocking drug sarilumab can mitigate CRS in patients with severe COVID-19. Treatment with a modified fusion version of the CD24 protein designed to disrupt inflammatory signaling is also being tested against COVID-19.
Cell-based therapeutic vaccines are another potential option under investigation. One approach involves supplying patients with artificially engineered dendritic cells that have been primed to present viral protein targets to T cells as well as to stimulate T cell proliferation and activity. The other utilizes both dendritic cells and coronavirus-targeting T cells.
Another strategy uses what’s called inactivated convalescent plasma and involves taking the blood of patients who recovered from SARS-CoV-2 infection. The idea is to use the virus-targeting antibodies that these patients’ immune systems have already produced in order to help those who are currently afflicted by COVID-19. This approach is being deployed in New York City, where there are 25,000 active cases as of March 27. At Mount Sinai Hospital, they’re using it for people with moderate COVID-19 who had trouble breathing.
“The idea is to get to the right patients at the right time,” said David L. Reich, M.D., Mount Sinai’s president and chief operating officer. “It’s kind of difficult scientifically to know how valuable it is … until you try,” he added, “It’s not exactly a shot in the dark, but it’s not tried and true.”
OTHER APPROACHES TO PREVENT OR TREAT CORONAVIRUS INFECTION
Clinical trials are also exploring a variety of preventive and therapeutic approaches that do not directly involve the immune system, including: hydroxychloroquine, an anti-malarial drug, in combination with the antibiotic azithromycin; remdesivir, an anti-viral drug that has shown activity against other coronaviruses such as SARS and MERS; losartan, a drug for high blood pressure; and aviptadil, a vasodilator used for erectile dysfunction.
Overall, as of March 22, there were more than 100 trials worldwide, including at least 11 in the U.S., investigating both preventive and therapeutic strategies against SARS-CoV-2 and COVID-19.
PROTECTING OURSELVES AND OUR COMMUNITIES
As we strive for long-term scientific solutions against COVID-19, our immediate focus must be to slow the virus’ spread in our local communities.
A recently published study led by Lauren Ancel Meyers, Ph.D., a professor of integrative biology at the University of Texas, Austin, found that pre-symptomatic people can spread the new coronavirus, which, like the flu, appears be transmitted from person-to-person via virus-containing respiratory droplets. In such droplets, which can be expelled in coughs or sneezes, the new coronavirus can survive in the air for three hours and on metal and plastic for two to three days, another study found.
Our actions as individuals—and as families, communities, and nations—will be crucial when it comes to saving as many lives as possible. Protective guidelines from the Centers for Disease Control and Prevention and protocols like “social distancing” are designed to break the lines of transmission and protect the most vulnerable among us—particularly the elderly, those with pre-existing health conditions, and those with weakened immune systems, among other high-risk groups.
People with cancer, in particular, are believed to be at higher risk of coronavirus-related complications for at least two reasons, according to Steve Pergram, M.D., M.P.H., of the Fred Hutchinson Cancer Research Center.
First, the cancer itself may be contributing to a general immunosuppressive state, rendering people more susceptible to infection. This is especially applicable for people with blood cancers—such as leukemia, lymphoma, and myeloma—as these cancers can directly interfere with the development of certain immune cells and the functioning of the immune system as a whole. People with lung cancer may also be at higher risk given the pneumonia and other lung-related issues that can arise in severe cases.
Second, certain treatments, including chemotherapies and bone marrow transplants, can also leave patients immunocompromised and susceptible to infection.
Whether ongoing treatment-related decisions should be altered in light of the current coronavirus situation is an issue that that is still up for discussion, one that patients must conduct with their medical team. (For more information about this, see the American Society of Clinical Oncology (ASCO)’s FAQs.) For example, Drew Griffin, a colorectal cancer patient, spoke to his oncologist about appropriate precautions, tapped into his network of friends and family for assistance, and prepared for life in Seattle during an outbreak.
While the virus is much more likely to be severe or fatal to people in certain high-risk groups, it cannot be emphasized enough that everyone—even young, healthy people—can become infected and experience severe disease. As of March 19, the CDC revealed that of one-fifth of all U.S. patients hospitalized for the new coronavirus were between the ages of 20-44.
Clearly, this current situation is unlike anything that any of us alive today have encountered before. While the challenge it presents is immense and multifaceted, we are more than capable of overcoming it through intense scientific effort as well as a comprehensive commitment to better social behaviors, at least for the near future.
“Today’s coronavirus pandemic will ultimately subside,” predicts CRI CEO and Director of Scientific Affairs Jill O’Donnell-Tormey, Ph.D., “thanks largely to the relentless efforts of medical professionals on the frontlines, scientists searching for better treatments and ways to prevent future outbreaks, and the generosity of those who fund their work.”
At the Cancer Research Institute, we remain committed to funding scientists studying the immune system and how its protective powers can be harnessed to fight not only cancer, but also autoimmune and infectious diseases. Now more than ever, their work is vital to all our futures
Fonte: Cancer Research InstituteAs informações e sugestões contidas neste blog são meramente informativas e não devem substituir consultas com médicos especialistas.
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