Despite early comparisons between COVID-19 and influenza, the coronavirus would never be just another flu. It comes from a different family of viruses and has proven to be far more harmful and unpredictable. Nonetheless, “cytokine storms,” in which the immune system turns the body on by overreacting to a virus, were widely believed to be a critical factor in the 1918 influenza pandemic.
Not all historians and health professionals agree that cytokine storms caused as many deaths with the 1918 flu a century ago, and now a new study is asking how critical they were of COVID deaths. How big is the role of these potentially fatal hyperinflammatory immune responses in the coronavirus pandemic?
Less than 5% of COVID-19 patients in a new study, including some of the sickest people, had the life-threatening, hyperinflammatory immune response known as a "cytokine storm".
Around 500 million people, or a third of the world's population, were infected with the Spanish flu in 1918. It is estimated that 50 million people died worldwide, with about 675,000 deaths in the United States, according to the Centers for Disease Control and Prevention. As of Saturday, 53.7 million people worldwide were diagnosed with COVID-19 with 1.3 million deaths, including 245,453 in the United States.
These scientists wanted to find out. Most adults with moderate to severe COVID-19 have a suppressed viral immune response compared to influenza patients. This is based on research published Saturday by scientists at St. Jude Children's Research Hospital in Memphis, Tennessee and the Washington University School of Medicine in St. Louis, Mo.
“Less than 5% of the COVID-19 patients in this study, including some of the sickest individuals, had the life-threatening, hyperinflammatory immune response known as cytokine storm syndrome. Cytokines are small proteins that are secreted by blood cells that help coordinate the immune response and trigger inflammation. "
"We identified a subset of COVID-19 patients with the broadly upregulated range of cytokines, which is a hallmark of the cytokine storm," said co-author Paul Thomas, Ph.D., a member of St. Jude's Department of Immunology. “Overall, the average person with COVID-19 – even patients with moderate to severe illness – had less inflammation than the average person with the flu.
He said patients would benefit from a quick, reliable, and inexpensive test to measure cytokines and identify those most likely to benefit from immunosuppressive treatment. "The results suggest that treatment to suppress inflammation may only be effective in this minority of patients with a hyperinflammatory profile," added Thomas.
Medical staff treats a patient with coronavirus in the COVID-19 intensive care unit at the United Memorial Medical Center in Houston, Texas on November 10, 2020. COVID-19 infections rise in Houston, Texas has exceeded 1 million cases.
Go to Nakamura / Getty Images
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A hallmark of some viruses: an increase in immune cells and their activating compounds (known as "cytokines") effectively turned the body against itself, causing inflammation of the lungs, severe shortness of breath and making the body susceptible to secondary bacterial pneumonia. It has been seen as one reason why seemingly healthy people were so badly affected by the 1918 flu.
The study included 168 adults with COVID-19, 26 adults with influenza, and 16 healthy volunteers. More than 90% of COVID-19 patients have been hospitalized, around half in intensive care; 23% of the hospital population died. More than half of the flu patients were hospitalized, 35% in the intensive care unit and 8% of the hospitalized flu patients died.
The study found that the antiviral immune response in COVID-19 patients was "severely suppressed" compared to flu patients. In most cases, COVID-19 was not caused by widespread hyperinflammation from a cytokine storm. (However, the researchers found that the absence of hyperinflammation in most of these coronavirus patients did not mean they were less ill.)
Doctors and members of the public were immediately shocked by how strong and healthy people were who fell victim to the 1918 influenza, also mistakenly known as "Spanish flu." Many historians today attribute this to the "cytokine storm," the process by which the immune system in healthy people reacts so strongly that it hurts the body.
In most cases, COVID-19 wasn't caused by hyperinflammation from a cytokine storm, according to a new study in Science Advances. This was thought to be a feature of the 1918 pandemic influenza.
"There are two hypotheses that explain the high lethality of the 1918 strain: cytokine storms and secondary bacterial infections," said a 2018 editorial in Nature. "In a cytokine storm, the body's immune system overreacts and causes tissue and organ damage and even death." However, according to the editorial, it is more likely that secondary bacterial infections played a bigger role.
The Nature editorial cites this “fascinating” 2008 paper published in the Journal of Infectious Diseases. It examined and reviewed over 8,400 tissue samples from the 1918-1919 influenza deaths and found that “the majority of deaths in the 1918-1919 pandemic influenza are likely directly due to secondary bacterial pneumonia caused by common upper respiratory tract bacteria. "
This could coincide with the progression of this pandemic, with the second wave hitting even harder. "The second wave of Spanish flu in 1918 was even more devastating than the first," Ravina Kullar, an infectious disease expert with the Infectious Diseases Society of America and an additional faculty member at the University of California at Los Angeles, told MarketWatch.
Although the 1918 pandemic is forever linked to Spain, this strain of H1N1 influenza was actually discovered earlier in Germany, France, the UK and the US. Much like the Communist Party's response to the first cases of COVID-19 in Wuhan, China last December, World War I censorship buried or underestimated these earlier reports.
"It is important to see the deep connections between World War I and pandemic influenza not simply as simultaneous or sequential crises, but more deeply intertwined," wrote historian James Harris in around 1918. The public was shocked at how strong and healthy they were otherwise people fell victim to the 1918 influenza. A "cytokine storm" seemed a likely explanation.
"There are two hypotheses that explain the high lethality of the 1918 strain: cytokine storms and secondary bacterial infections," according to a 2018 editorial in Nature.
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The most recent study published on Saturday, published in Science Advances, a peer-reviewed open access journal for the American Association for Advancement of Science, suggests that the majority of COVID-19 patients are not candidates for treatment with steroids such as dexamethasone That, the researchers argue, can backfire in some patients.
However, dexamethasone has been shown to be effective in treating critically ill COVID-19 patients according to three studies published in JAMA in September. The researchers reported in mid-June that low dexamethasone doses played an important role in reducing deaths in hospitalized COVID-19 patients using ventilators by a third.
The majority of COVID-19 patients are not candidates for treatment with steroids like dexamethasone, the researchers argue, but it has been effective in treating critically ill patients.
Anthony Fauci, director of the National Institute for Allergies and Infectious Diseases, also credited dexamethasone with patient support. "We know that dexamethasone significantly lowers the death rate in people who require mechanical ventilation and / or in people who require high-flow oxygen," Fauci said during an interview with the American Medical Association last weekend.
Other research has found that cytokine storms remain a risk in elderly patients during the coronavirus pandemic. According to a study recently published in the Journal of Molecular and Cellular Cardiology, which makes SARS-CoV-2 appear to be the main factor in SARS-CoV-2's access to heart cells, which become more active with age and which can make them more prone to hyperinflammation.
The researchers found that "inflammation in the elderly can be more intense and cause organ damage," reported Johns Hopkins University. "Lung tissue becomes less elastic over time, making respiratory diseases like COVID-19 a particular problem for the elderly." Therefore, a cytokine storm in these patients can promote inflammation and acute respiratory distress syndrome.
In addition, a paper published in Frontiers in Immunology in September 2020 concluded: "Aberrant immune host response along with cytokine storm and lymphocytopenia (a disorder in which your blood does not have enough white blood cells), followed by acute shortness of breath, still relevant problems, that affect the severity of COVID-19. "
A similarity exists between 1918 and 2020: During the 1918 flu, cities that implemented non-pharmaceutical measures such as social distancing and school closings tended to have better economic outcomes, Francis Yared, Deutsche Bank's global head of interest rate research, wrote recently Note, "There has not been such a great trade-off between economic activity and public health."
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