I've had to eat more crow. Please see this Pundita post, just published: More from the physician re severe immune system reactions to COVID-19
END UPDATE
" ... an increasing number of experts believe a hyperactive immune response, rather than the virus, is what ultimately kills many Covid-19 patients."
-- The Wall Street Journal, Haywire Immune Response Eyed In Coronavirus Deaths, Treatment; April 9
"But I think most suggestive of all is that for some who are infected with COVID-19, their immune system goes crazy fighting the virus, which is exactly what happens with the most severe allergic reactions, both of which are life-threatening. It looks to me as if it could be the same situation, only that physicians do not associate the symptoms of COVID-19 infection with an allergic reaction."
-- Pundita, The worst COVID-19 symptoms remind me of severe allergic reaction; April 7
For those who asked why I didn't initially defend the argument I made in the April 7 post, because there was no defense for what I did. I lost my temper over a remark made to the press by a physician about COVID-19. Loss of temper is okay, but it's not okay for me to write for a public platform before I've calmed down. If I'd been thinking straight, I would've asked the physician I knew to review the post before I published it. Instead, I asked for help as an afterthought. So I was left to eat crow in public, which serves me right. (See the physician's remarks in the update to the April 7 post).
Doesn't matter that I believed my key point still held value. I was flagrantly wrong in certain respects. I take the physician's word for it that I misread the abstract I used in the attempt to shore my argument. The topper is that I didn't need the abstract to make my key point. And I shot off my sarcastic remark about the use of beta-antagonists without knowing what I was talking about; for that I certainly needed to be corrected. And yet my essay didn't need that remark.
All right, that's enough crow-eating. I want to move on to The Wall Street Journal report. From my reading it seems the scientists studying the coronavirus have yet to zero in on the striking similarity between hyperactive immune responses to allergens and the virus. But it looks as if they could be 15 minutes away from doing so. I'll have more to say about this is the next post; for now:
Haywire Immune Response Eyed In Coronavirus Deaths, Treatment
Researchers are looking at treatments to suppress ‘cytokine storm,’ increasingly linked to the most severe Covid-19 cases
By Joseph Walker and
Jared S. Hopkins
Jared S. Hopkins
April 9, 2020 7:00 am ET
The Wall Street Journal
Doctors have used the term “cytokine storm” to describe an overactive immune response triggered by external pathogens such as bacterial and viral infections.
An immune system gone haywire may be doing more damage than the coronavirus itself in patients with the severest forms of Covid-19, doctors and scientists say, a growing theory that could point the way to potential treatments.
Much remains unknown about the path the virus takes in the sickest patients, but an increasing number of experts believe a hyperactive immune response, rather than the virus, is what ultimately kills many Covid-19 patients.
The out-of-control immune response eventually causes the patients’ lungs to stop delivering oxygen to the rest of organs, leading to respiratory failure and in some cases death, the experts say. The malfunctioning immune system may be driving the rapid decline in lung function experienced by some patients, including younger and relatively healthy ones, after the initial onset of symptoms, doctors say.
[Graphic] Anatomy of a Cytokine Storm
An overactive immune response is thought to play a role in the disease progression of the sickest Covid-19 patients. [See WSJ site for the graphic.]
As scientists race to better understand the [phenomenon], pharmaceutical companies including Roche Holding AG are partnering with hospitals to explore whether drugs proven to tamp down an out-of-control immune response could help the sickest Covid-19 patients.
Some doctors are already administering the drugs to patients who are unable to breathe without the support of ventilators, or to prevent deterioration of patients who appear ready to slip into respiratory failure.
“You remove one piece of the storm, and it can quiet the whole thing,” said Kevin Tracey, president of the Feinstein Institutes for Medical Research at Northwell Health, which is testing Kevzara, an anti-inflammatory drug from Regeneron Pharmaceuticals Inc.
Doctors have used the term “cytokine storm” to describe an overactive immune response triggered by external pathogens such as bacterial and viral infections.
The Wall Street Journal
Doctors have used the term “cytokine storm” to describe an overactive immune response triggered by external pathogens such as bacterial and viral infections.
An immune system gone haywire may be doing more damage than the coronavirus itself in patients with the severest forms of Covid-19, doctors and scientists say, a growing theory that could point the way to potential treatments.
Much remains unknown about the path the virus takes in the sickest patients, but an increasing number of experts believe a hyperactive immune response, rather than the virus, is what ultimately kills many Covid-19 patients.
The out-of-control immune response eventually causes the patients’ lungs to stop delivering oxygen to the rest of organs, leading to respiratory failure and in some cases death, the experts say. The malfunctioning immune system may be driving the rapid decline in lung function experienced by some patients, including younger and relatively healthy ones, after the initial onset of symptoms, doctors say.
[Graphic] Anatomy of a Cytokine Storm
An overactive immune response is thought to play a role in the disease progression of the sickest Covid-19 patients. [See WSJ site for the graphic.]
As scientists race to better understand the [phenomenon], pharmaceutical companies including Roche Holding AG are partnering with hospitals to explore whether drugs proven to tamp down an out-of-control immune response could help the sickest Covid-19 patients.
Some doctors are already administering the drugs to patients who are unable to breathe without the support of ventilators, or to prevent deterioration of patients who appear ready to slip into respiratory failure.
“You remove one piece of the storm, and it can quiet the whole thing,” said Kevin Tracey, president of the Feinstein Institutes for Medical Research at Northwell Health, which is testing Kevzara, an anti-inflammatory drug from Regeneron Pharmaceuticals Inc.
Doctors have used the term “cytokine storm” to describe an overactive immune response triggered by external pathogens such as bacterial and viral infections.
Proteins called cytokines are part of the immune system’s arsenal for fighting disease. When too many are released into the bloodstream too quickly, however, it can have disastrous results, including organ failure and death.
As with other diseases, it is a mystery why cytokine storms are experienced by some but not all Covid-19 patients, doctors say. Genetics may be a factor.
In the most severe coronavirus patients, the disease appears to have two stages, doctors and researchers say. First the immune system fails to respond quickly or effectively enough to the virus. Then the immune response becomes too aggressive and floods the body with cytokines.
The surge of cytokines damages blood vessels and allows fluids to seep into the lungs, filling them up like water balloons, doctors say.
“The virus initiated it,” said Ya-Chi Ho, an assistant professor at the Yale School of Medicine who studies infectious diseases. “The second problem is our immune system handled it wrong, and induces this cytokine storm and clogs our lungs. That’s why patients die.”
Drugs called corticosteroids can be used to treat patients with cytokine storms, but studies are mixed on their effectiveness, with some studies indicating that Covid-19 patients may be at a higher risk of death when treated with steroids. Some doctors are reluctant to use steroids because they broadly dampen the immune response, which is risky in patients fighting infections.
Drugs targeting specific cytokines rather than the entire immune system may be more effective, doctors say.
Among the most promising targeted treatments, doctors say, is Roche’s rheumatoid-arthritis drug tocilizumab, which is marketed under the brand name Actemra. The drug was approved in 2017 to treat cytokine storms caused by cancer treatments known as CAR-T cell therapies.
On Tuesday, a federal agency that supports health research said it is committing $25 million to accelerate a late-stage study of Actemra in Covid-19 patients.
Last month, doctors from Seattle’s Swedish Health Services used Actemra to treat a 45-year-old emergency-room physician who was infected while caring for patients from a nursing home in Kirkland, Wash.
The man was transferred to Swedish and put on life support after his lungs and kidneys began to fail, said Samuel J. Youssef, a cardiothoracic surgeon at Swedish. Lab tests showed the man’s inflammation levels were 200 times greater than the normal range, indicating he might be suffering from a cytokine storm.
The doctors at Swedish decided to administer Actemra after discussing a small Chinese study that had shown that 21 Covid-19 patients with high levels of inflammation had been successfully treated with the drug.
Over the next two days, the patient’s inflammation levels began to decline and his blood-oxygen levels increased, Dr. Youssef said. After a week, he was well enough to be taken off life support on March 23, and was released from the hospital on Sunday.
“All we did was quiet the storm and support his body—his kidneys, his lungs, his heart—to give him the time to fight the virus,” said Dr. Youssef, who attributes the recovery both to Actemra as well as other interventions like being put on life support.
CytoDyn Inc., a Vancouver, Wash.-based biotech company, said 10 severely sick Covid-19 patients showed signs of recovering three days after being infused with its experimental HIV drug leronlimab, which may block the production of inflammatory cytokines. Three of the patients were taken off ventilators, including two who have since been discharged from care, according to CytoDyn.
The company is studying its drug in a trial for patients with mild-to-moderate symptoms and expects to start one for severely sick patients.
Swedish Orphan Biovitrum AB expects results in July from a study evaluating its rheumatoid-arthritis drug Kineret in combination with an antibody called emapalumab in patients in Italy, said Milan Zdravkovic, Sobi’s head of research and development.
Novartis AG and Incyte Corp. said they plan to start clinical trials of their drug ruxolitinib in Covid-19 patients with cytokine storm. The drug, marketed as Jakafi in the U.S., is approved to treat rare blood cancers.
Write to Joseph Walker at joseph.walker@wsj.com and Jared S. Hopkins at jared.hopkins@wsj.com
[END REPORT]
As with other diseases, it is a mystery why cytokine storms are experienced by some but not all Covid-19 patients, doctors say. Genetics may be a factor.
In the most severe coronavirus patients, the disease appears to have two stages, doctors and researchers say. First the immune system fails to respond quickly or effectively enough to the virus. Then the immune response becomes too aggressive and floods the body with cytokines.
The surge of cytokines damages blood vessels and allows fluids to seep into the lungs, filling them up like water balloons, doctors say.
“The virus initiated it,” said Ya-Chi Ho, an assistant professor at the Yale School of Medicine who studies infectious diseases. “The second problem is our immune system handled it wrong, and induces this cytokine storm and clogs our lungs. That’s why patients die.”
Drugs called corticosteroids can be used to treat patients with cytokine storms, but studies are mixed on their effectiveness, with some studies indicating that Covid-19 patients may be at a higher risk of death when treated with steroids. Some doctors are reluctant to use steroids because they broadly dampen the immune response, which is risky in patients fighting infections.
Drugs targeting specific cytokines rather than the entire immune system may be more effective, doctors say.
Among the most promising targeted treatments, doctors say, is Roche’s rheumatoid-arthritis drug tocilizumab, which is marketed under the brand name Actemra. The drug was approved in 2017 to treat cytokine storms caused by cancer treatments known as CAR-T cell therapies.
On Tuesday, a federal agency that supports health research said it is committing $25 million to accelerate a late-stage study of Actemra in Covid-19 patients.
Last month, doctors from Seattle’s Swedish Health Services used Actemra to treat a 45-year-old emergency-room physician who was infected while caring for patients from a nursing home in Kirkland, Wash.
The man was transferred to Swedish and put on life support after his lungs and kidneys began to fail, said Samuel J. Youssef, a cardiothoracic surgeon at Swedish. Lab tests showed the man’s inflammation levels were 200 times greater than the normal range, indicating he might be suffering from a cytokine storm.
The doctors at Swedish decided to administer Actemra after discussing a small Chinese study that had shown that 21 Covid-19 patients with high levels of inflammation had been successfully treated with the drug.
Over the next two days, the patient’s inflammation levels began to decline and his blood-oxygen levels increased, Dr. Youssef said. After a week, he was well enough to be taken off life support on March 23, and was released from the hospital on Sunday.
“All we did was quiet the storm and support his body—his kidneys, his lungs, his heart—to give him the time to fight the virus,” said Dr. Youssef, who attributes the recovery both to Actemra as well as other interventions like being put on life support.
CytoDyn Inc., a Vancouver, Wash.-based biotech company, said 10 severely sick Covid-19 patients showed signs of recovering three days after being infused with its experimental HIV drug leronlimab, which may block the production of inflammatory cytokines. Three of the patients were taken off ventilators, including two who have since been discharged from care, according to CytoDyn.
The company is studying its drug in a trial for patients with mild-to-moderate symptoms and expects to start one for severely sick patients.
Swedish Orphan Biovitrum AB expects results in July from a study evaluating its rheumatoid-arthritis drug Kineret in combination with an antibody called emapalumab in patients in Italy, said Milan Zdravkovic, Sobi’s head of research and development.
Novartis AG and Incyte Corp. said they plan to start clinical trials of their drug ruxolitinib in Covid-19 patients with cytokine storm. The drug, marketed as Jakafi in the U.S., is approved to treat rare blood cancers.
Write to Joseph Walker at joseph.walker@wsj.com and Jared S. Hopkins at jared.hopkins@wsj.com
[END REPORT]
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