{"id":808,"date":"2020-05-22T11:23:16","date_gmt":"2020-05-22T05:53:16","guid":{"rendered":"http:\/\/www.potentialloops.org\/?p=808"},"modified":"2020-05-22T11:23:17","modified_gmt":"2020-05-22T05:53:17","slug":"preventing-cytokine-storm-may-ease-severe-covid-19-symptoms","status":"publish","type":"post","link":"https:\/\/www.potentialloops.org\/?p=808","title":{"rendered":"Preventing ‘cytokine storm’ may ease severe COVID-19 symptoms"},"content":{"rendered":"\n

Date: May 21, 2020 <\/p>\n\n\n\n

Source 1: Howard Hughes Medical Institute <\/p>\n\n\n\n

Source 2: www.sciencedaily.com<\/a><\/p>\n\n\n\n

Summary: A clinical trial in people with the new coronavirus is testing a drug that may halt an overactive immune response before it ramps up.<\/p>\n\n\n\n

For some COVID-19 patients, the body’s immune\n response may be as destructive as the virus that causes the disease. \nThe persistent high fevers, severe respiratory distress, and lung damage\n seen in some critically ill patients are all signs of an immune system \nin overdrive.<\/p>\n\n\n\n

Now, a new clinical trial will test a treatment that targets this \noveractive immune response, says Howard Hughes Medical Investigator Bert\n Vogelstein. He and his team at the Johns Hopkins University School of \nMedicine are currently recruiting individuals for the trial, which \nincludes patients ages 45 to 85 at the Johns Hopkins Hospital who have \nCOVID-19 but who aren’t on a ventilator or in the ICU.<\/p>\n\n\n\n

Their treatment, a common type of prescription drug called an alpha \nblocker, might break a cycle of hyperinflammation before it ramps up, \ntheir findings from mouse studies and a recent analysis of medical \nclaims data suggest.<\/p>\n\n\n\n

“The approach we’re advocating involves treating people who are at \nhigh risk early in the course of the disease, when you know they’re \ninfected but before they have severe symptoms,” says Vogelstein. If the \ntrial’s results suggest the drug is safe and effective against COVID-19,\n it could potentially help many people recover safely at home and lessen\n the strain on hospital resources, he says.<\/p>\n\n\n\n

Runaway reaction<\/strong><\/p>\n\n\n\n

A hyperactive immune response isn’t unique to COVID-19. People with \nautoimmune diseases and cancer patients receiving immunotherapy can \nexperience similar symptoms. These responses are referred to as \nmacrophage activation syndrome, cytokine release syndrome — or simply \n“cytokine storms.”<\/p>\n\n\n\n

When macrophages (and some other kinds of immune cells) detect virus \nparticles, they send out alert messages by releasing various proteins \nknown as cytokines. Those cytokines recruit other immune cells to the \nscene – an inflammatory response that, in moderation, helps the body \nfight off a virus. But macrophages can also release other signaling \nmolecules, called catecholamines, that amplify this response further, \ntriggering the release of more cytokines. The result is a runaway \nfeedback loop, like a snowball getting bigger as it barrels down a hill.<\/p>\n\n\n\n

“It seems that once this process starts, there’s this inability to \nproperly switch it off,” says Maximilian Konig, a rheumatologist at \nHopkins who is helping to coordinate the trial.<\/p>\n\n\n\n

Before COVID-19 hit, Vogelstein’s team was already exploring ways to \nease the hyperinflammatory immune response in cancer patients treated \nwith immunotherapy. The researchers were interested in drugs called \nalpha blockers, which are widely prescribed for prostate conditions and \nhigh blood pressure — and also interfere with the cell signaling that \ntriggers cytokine storms. In theory, alpha blockers might stop a \ncytokine storm before it starts.<\/p>\n\n\n\n

Giving mice with bacterial infections an alpha blocker lessened \ncytokine storms and decreased deaths, Vogelstein’s team reported in the \njournal Nature<\/em> in 2018. And, the researchers found, the treatment didn’t seem to harm other aspects of the immune response.<\/p>\n\n\n\n

Staving off the storm<\/strong><\/p>\n\n\n\n

As the COVID-19 pandemic escalated in the United States over the past\n few months and severely ill patients presented with cytokine storm \nsymptoms, the idea of testing alpha blockers in humans has become more \nurgent, Vogelstein’s team recently argued in the Journal of Clinical Investigation<\/em>.<\/p>\n\n\n\n

To obtain approval for an alpha blocker clinical trial, Vogelstein’s \nteam first surveyed medical claims data. They combed through records \nfrom people hospitalized for pneumonia and acute respiratory distress \nand analyzed whether patients’ outcomes were better if they had been \ntaking alpha blockers for unrelated conditions. The team’s tentative \nconclusion: taking alpha blocker drugs correlated to a lower risk of \ndeath from respiratory distress.<\/p>\n\n\n\n

On its own, that’s not strong enough evidence to prescribe the drug \nfor a wholly new disease like COVID-19, says Susan Athey, an economist \nat Stanford University who collaborated with Vogelstein’s team on the \nclaims analysis. But it helps bolster the case for the team’s clinical \ntrial.<\/p>\n\n\n\n

In the trial, COVID-19 patients will take gradually increasing doses \nof an alpha blocker called prazosin, sold under the brand name \nMinipress, over six days, says Chetan Bettegowda, a neurosurgeon at \nHopkins who is helping to design and run the trials. Then, the team will\n evaluate whether people who received this treatment had a lower ICU \nadmission rate or ventilator use than patients who received the standard\n treatment. They’ll follow each patient for 60 days, but preliminary \ndata from the first patients could be available within weeks to months, \nBettegowda says.<\/p>\n\n\n\n

If the trial’s results suggest alpha blockers are safe and effective,\n the team hopes to run a second trial with patients who have been \ndiagnosed with COVID-19 but are not yet hospitalized. They’re also \nencouraging colleagues at other hospitals to join their clinical trial \nefforts, to gather patient data more quickly.<\/p>\n\n\n\n

This treatment, if it works, would be a secondary form of prevention,\n Vogelstein says, mitigating symptoms before they become severe, rather \nthan stopping infection in the first place. “Eventually, hopefully, a \nvaccine will be produced, and that will be the essence of prevention,” \nhe says. “But until vaccines are available, secondary prevention makes a\n lot of sense.”<\/p>\n\n\n\n

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Story Source:<\/strong><\/p>\n\n\n\n

Materials<\/a> provided by Howard Hughes Medical Institute<\/strong><\/a>. Note: Content may be edited for style and length.<\/em><\/p>\n\n\n\n

www.sciencedaily.com<\/a><\/p>\n\n\n\n

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Journal References<\/strong>:<\/p>\n\n\n\n

  1. Maximilian F. Konig, Michael A. Powell, Verena Staedtke, Ren-Yuan \nBai, David L. Thomas, Nicole M. Fischer, Sakibul Huq, Adham M. \nKhalafallah, Allison Koenecke, Ruoxuan Xiong, Brett Mensh, Nickolas \nPapadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Joshua T. Vogelstein,\n Susan Athey, Shibin Zhou, Chetan Bettegowda. Preventing cytokine storm syndrome in COVID-19 using \u03b1-1 adrenergic receptor antagonists<\/strong>. Journal of Clinical Investigation<\/em>, 2020; DOI: 10.1172\/JCI139642<\/a>\n<\/li>
  2. Joshua T. Vogelstein, Michael Powell, Allison Koenecke, Ruoxuan \nXiong, Nicole Fischer, Sakibul Huq, Adham M. Khalafallah, Brian Caffo, \nElizabeth A. Stuart, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert \nVogelstein, Shibin Zhou, Chetan Bettegowda, Maximilian F. Konig, Brett \nMensh, Susan Athey. Alpha-1 adrenergic receptor antagonists for \npreventing acute respiratory distress syndrome and death from cytokine \nstorm syndrome<\/strong>. arXiv.org<\/em>, April 21, 2020; [link<\/a>]<\/li><\/ol>\n\n\n\n
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