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| The Coronavirus Patients Betrayed by Their Own Immune Systems | The Coronavirus Patients Betrayed by Their Own Immune Systems |
| (7 days later) | |
| The 42-year-old man arrived at a hospital in Paris on March 17 with a fever, cough and the “ground glass opacities” in both lungs that are a trademark of infection with the new coronavirus. | The 42-year-old man arrived at a hospital in Paris on March 17 with a fever, cough and the “ground glass opacities” in both lungs that are a trademark of infection with the new coronavirus. |
| Two days later, his condition suddenly worsened and his oxygen levels dropped. His body, doctors suspected, was in the grip of a cytokine storm, a dangerous overreaction of the immune system. The phenomenon has become all too common in the coronavirus pandemic, but it is also pointing to potentially helpful drug treatments. | Two days later, his condition suddenly worsened and his oxygen levels dropped. His body, doctors suspected, was in the grip of a cytokine storm, a dangerous overreaction of the immune system. The phenomenon has become all too common in the coronavirus pandemic, but it is also pointing to potentially helpful drug treatments. |
| When the body first encounters a virus or a bacterium, the immune system ramps up and begins to fight the invader. The foot soldiers in this fight are molecules called cytokines that set off a cascade of signals to cells to marshal a response. Usually, the stronger this immune response, the stronger the chance of vanquishing the infection, which is partly why children and younger people are less vulnerable over all to coronavirus. And once the enemy is defeated, the immune system is hard-wired to shut itself off. | When the body first encounters a virus or a bacterium, the immune system ramps up and begins to fight the invader. The foot soldiers in this fight are molecules called cytokines that set off a cascade of signals to cells to marshal a response. Usually, the stronger this immune response, the stronger the chance of vanquishing the infection, which is partly why children and younger people are less vulnerable over all to coronavirus. And once the enemy is defeated, the immune system is hard-wired to shut itself off. |
| “For most people and most infections, that’s what happens,” said Dr. Randy Cron, an expert on cytokine storms at the University of Alabama at Birmingham. | “For most people and most infections, that’s what happens,” said Dr. Randy Cron, an expert on cytokine storms at the University of Alabama at Birmingham. |
| But in some cases — as much as 15 percent of people battling any serious infection, according to Dr. Cron’s team — the immune system keeps raging long after the virus is no longer a threat. It continues to release cytokines that keep the body on an exhausting full alert. In their misguided bid to keep the body safe, these cytokines attack multiple organs including the lungs and liver, and may eventually lead to death. | But in some cases — as much as 15 percent of people battling any serious infection, according to Dr. Cron’s team — the immune system keeps raging long after the virus is no longer a threat. It continues to release cytokines that keep the body on an exhausting full alert. In their misguided bid to keep the body safe, these cytokines attack multiple organs including the lungs and liver, and may eventually lead to death. |
| In these people, it’s their body’s response, rather than the virus, that ultimately causes harm. | In these people, it’s their body’s response, rather than the virus, that ultimately causes harm. |
| Cytokine storms can overtake people of any age, but some scientists believe that they may explain why healthy young people died during the 1918 pandemic and more recently during the SARS, MERS and H1N1 epidemics. They are also a complication of various autoimmune diseases like lupus and Still’s disease, a form of arthritis. And they may offer clues as to why otherwise healthy young people with coronavirus infection are succumbing to acute respiratory distress syndrome, a common consequence of a cytokine storm. | Cytokine storms can overtake people of any age, but some scientists believe that they may explain why healthy young people died during the 1918 pandemic and more recently during the SARS, MERS and H1N1 epidemics. They are also a complication of various autoimmune diseases like lupus and Still’s disease, a form of arthritis. And they may offer clues as to why otherwise healthy young people with coronavirus infection are succumbing to acute respiratory distress syndrome, a common consequence of a cytokine storm. |
| Reports from China and Italy have described young patients with clinical outcomes that seem consistent with this phenomenon. It’s very likely that some of these patients developed a cytokine storm, Dr. Cron said. | Reports from China and Italy have described young patients with clinical outcomes that seem consistent with this phenomenon. It’s very likely that some of these patients developed a cytokine storm, Dr. Cron said. |
| In the case of the 42-year-old patient, the suspected cytokine storm led his doctors to eventually try tocilizumab, a drug they have sometimes used to soothe an immune system in distress. | In the case of the 42-year-old patient, the suspected cytokine storm led his doctors to eventually try tocilizumab, a drug they have sometimes used to soothe an immune system in distress. |
| After just two doses of the drug, spaced eight hours apart, the patient’s fever rapidly disappeared, his oxygen levels rose and a chest scan showed his lungs clearing. The case report, described in an upcoming paper in Annals of Oncology, joins dozens of accounts from Italy and China, all indicating that tocilizumab might be an effective antidote to the coronavirus in some people. | After just two doses of the drug, spaced eight hours apart, the patient’s fever rapidly disappeared, his oxygen levels rose and a chest scan showed his lungs clearing. The case report, described in an upcoming paper in Annals of Oncology, joins dozens of accounts from Italy and China, all indicating that tocilizumab might be an effective antidote to the coronavirus in some people. |
| On March 5, China approved the drug to treat serious cases of Covid-19, the disease caused by the coronavirus, and authorized clinical trials. On March 23, the U.S. Food and Drug Administration granted approval to the pharmaceutical company Roche to test the drug in hundreds of people with coronavirus infection. | On March 5, China approved the drug to treat serious cases of Covid-19, the disease caused by the coronavirus, and authorized clinical trials. On March 23, the U.S. Food and Drug Administration granted approval to the pharmaceutical company Roche to test the drug in hundreds of people with coronavirus infection. |
| Tocilizumab is approved to quieten the chatter of immune molecules in rheumatoid arthritis and in some types of cancer. It mutes the activity of a specific cytokine called interleukin-6 that is associated with an over-exuberant immune response. | Tocilizumab is approved to quieten the chatter of immune molecules in rheumatoid arthritis and in some types of cancer. It mutes the activity of a specific cytokine called interleukin-6 that is associated with an over-exuberant immune response. |
| “That’s the rationale for using the drug,” said Dr. Laurence Albiges, who cared for the patient at the Gustave Roussy Cancer Center in Paris. | “That’s the rationale for using the drug,” said Dr. Laurence Albiges, who cared for the patient at the Gustave Roussy Cancer Center in Paris. |
| Even as researchers look for treatments, they are trying to learn more about why some people’s immune systems go into this dangerous overdrive. Genetic factors explain the risk, at least in some kinds of cytokine storms. | Even as researchers look for treatments, they are trying to learn more about why some people’s immune systems go into this dangerous overdrive. Genetic factors explain the risk, at least in some kinds of cytokine storms. |
| There are many variations on the phenomenon, and they go by many names: systemic inflammatory response syndrome, cytokine release syndrome, macrophage activation syndrome, hemophagocytic lymphohistiocytosis. | There are many variations on the phenomenon, and they go by many names: systemic inflammatory response syndrome, cytokine release syndrome, macrophage activation syndrome, hemophagocytic lymphohistiocytosis. |
| Broadly speaking, they are all marked by an unbridled surge in immune molecules, and may all result in the fatal shutdown of multiple organs. | Broadly speaking, they are all marked by an unbridled surge in immune molecules, and may all result in the fatal shutdown of multiple organs. |
| But many doctors are unfamiliar with this niche concept or how to treat it, experts said. | But many doctors are unfamiliar with this niche concept or how to treat it, experts said. |
| “Everyone’s talking about cytokine storm as if it were a well-recognized phenomenon, but you could have asked medics two weeks ago and they wouldn’t have heard of it,” said Dr. Jessica Manson, an immunologist at University College London Hospital. | “Everyone’s talking about cytokine storm as if it were a well-recognized phenomenon, but you could have asked medics two weeks ago and they wouldn’t have heard of it,” said Dr. Jessica Manson, an immunologist at University College London Hospital. |
| A patient battling a cytokine storm may have an abnormally fast heart rate, fever and a drop in blood pressure. Apart from a surge in interleukin-6, the body may also show high swirling levels of molecules called interleukin-1, interferon-gamma, C-reactive protein and tumor necrosis factor-alpha. | A patient battling a cytokine storm may have an abnormally fast heart rate, fever and a drop in blood pressure. Apart from a surge in interleukin-6, the body may also show high swirling levels of molecules called interleukin-1, interferon-gamma, C-reactive protein and tumor necrosis factor-alpha. |
| This storm, if it develops, becomes obvious a few days into the infection. But the sooner doctors catch on to it and treat it, the more likely the patient is to survive. Too late, and the storm may be beyond control, or may already have caused too much damage. | This storm, if it develops, becomes obvious a few days into the infection. But the sooner doctors catch on to it and treat it, the more likely the patient is to survive. Too late, and the storm may be beyond control, or may already have caused too much damage. |
| Updated June 22, 2020 | |
| A commentary published this month on the website of the British Journal of Sports Medicine points out that covering your face during exercise “comes with issues of potential breathing restriction and discomfort” and requires “balancing benefits versus possible adverse events.” Masks do alter exercise, says Cedric X. Bryant, the president and chief science officer of the American Council on Exercise, a nonprofit organization that funds exercise research and certifies fitness professionals. “In my personal experience,” he says, “heart rates are higher at the same relative intensity when you wear a mask.” Some people also could experience lightheadedness during familiar workouts while masked, says Len Kravitz, a professor of exercise science at the University of New Mexico. | |
| The steroid, dexamethasone, is the first treatment shown to reduce mortality in severely ill patients, according to scientists in Britain. The drug appears to reduce inflammation caused by the immune system, protecting the tissues. In the study, dexamethasone reduced deaths of patients on ventilators by one-third, and deaths of patients on oxygen by one-fifth. | The steroid, dexamethasone, is the first treatment shown to reduce mortality in severely ill patients, according to scientists in Britain. The drug appears to reduce inflammation caused by the immune system, protecting the tissues. In the study, dexamethasone reduced deaths of patients on ventilators by one-third, and deaths of patients on oxygen by one-fifth. |
| The coronavirus emergency relief package gives many American workers paid leave if they need to take time off because of the virus. It gives qualified workers two weeks of paid sick leave if they are ill, quarantined or seeking diagnosis or preventive care for coronavirus, or if they are caring for sick family members. It gives 12 weeks of paid leave to people caring for children whose schools are closed or whose child care provider is unavailable because of the coronavirus. It is the first time the United States has had widespread federally mandated paid leave, and includes people who don’t typically get such benefits, like part-time and gig economy workers. But the measure excludes at least half of private-sector workers, including those at the country’s largest employers, and gives small employers significant leeway to deny leave. | The coronavirus emergency relief package gives many American workers paid leave if they need to take time off because of the virus. It gives qualified workers two weeks of paid sick leave if they are ill, quarantined or seeking diagnosis or preventive care for coronavirus, or if they are caring for sick family members. It gives 12 weeks of paid leave to people caring for children whose schools are closed or whose child care provider is unavailable because of the coronavirus. It is the first time the United States has had widespread federally mandated paid leave, and includes people who don’t typically get such benefits, like part-time and gig economy workers. But the measure excludes at least half of private-sector workers, including those at the country’s largest employers, and gives small employers significant leeway to deny leave. |
| So far, the evidence seems to show it does. A widely cited paper published in April suggests that people are most infectious about two days before the onset of coronavirus symptoms and estimated that 44 percent of new infections were a result of transmission from people who were not yet showing symptoms. Recently, a top expert at the World Health Organization stated that transmission of the coronavirus by people who did not have symptoms was “very rare,” but she later walked back that statement. | So far, the evidence seems to show it does. A widely cited paper published in April suggests that people are most infectious about two days before the onset of coronavirus symptoms and estimated that 44 percent of new infections were a result of transmission from people who were not yet showing symptoms. Recently, a top expert at the World Health Organization stated that transmission of the coronavirus by people who did not have symptoms was “very rare,” but she later walked back that statement. |
| Touching contaminated objects and then infecting ourselves with the germs is not typically how the virus spreads. But it can happen. A number of studies of flu, rhinovirus, coronavirus and other microbes have shown that respiratory illnesses, including the new coronavirus, can spread by touching contaminated surfaces, particularly in places like day care centers, offices and hospitals. But a long chain of events has to happen for the disease to spread that way. The best way to protect yourself from coronavirus — whether it’s surface transmission or close human contact — is still social distancing, washing your hands, not touching your face and wearing masks. | Touching contaminated objects and then infecting ourselves with the germs is not typically how the virus spreads. But it can happen. A number of studies of flu, rhinovirus, coronavirus and other microbes have shown that respiratory illnesses, including the new coronavirus, can spread by touching contaminated surfaces, particularly in places like day care centers, offices and hospitals. But a long chain of events has to happen for the disease to spread that way. The best way to protect yourself from coronavirus — whether it’s surface transmission or close human contact — is still social distancing, washing your hands, not touching your face and wearing masks. |
| A study by European scientists is the first to document a strong statistical link between genetic variations and Covid-19, the illness caused by the coronavirus. Having Type A blood was linked to a 50 percent increase in the likelihood that a patient would need to get oxygen or to go on a ventilator, according to the new study. | A study by European scientists is the first to document a strong statistical link between genetic variations and Covid-19, the illness caused by the coronavirus. Having Type A blood was linked to a 50 percent increase in the likelihood that a patient would need to get oxygen or to go on a ventilator, according to the new study. |
| The unemployment rate fell to 13.3 percent in May, the Labor Department said on June 5, an unexpected improvement in the nation’s job market as hiring rebounded faster than economists expected. Economists had forecast the unemployment rate to increase to as much as 20 percent, after it hit 14.7 percent in April, which was the highest since the government began keeping official statistics after World War II. But the unemployment rate dipped instead, with employers adding 2.5 million jobs, after more than 20 million jobs were lost in April. | The unemployment rate fell to 13.3 percent in May, the Labor Department said on June 5, an unexpected improvement in the nation’s job market as hiring rebounded faster than economists expected. Economists had forecast the unemployment rate to increase to as much as 20 percent, after it hit 14.7 percent in April, which was the highest since the government began keeping official statistics after World War II. But the unemployment rate dipped instead, with employers adding 2.5 million jobs, after more than 20 million jobs were lost in April. |
| States are reopening bit by bit. This means that more public spaces are available for use and more and more businesses are being allowed to open again. The federal government is largely leaving the decision up to states, and some state leaders are leaving the decision up to local authorities. Even if you aren’t being told to stay at home, it’s still a good idea to limit trips outside and your interaction with other people. | States are reopening bit by bit. This means that more public spaces are available for use and more and more businesses are being allowed to open again. The federal government is largely leaving the decision up to states, and some state leaders are leaving the decision up to local authorities. Even if you aren’t being told to stay at home, it’s still a good idea to limit trips outside and your interaction with other people. |
| Common symptoms include fever, a dry cough, fatigue and difficulty breathing or shortness of breath. Some of these symptoms overlap with those of the flu, making detection difficult, but runny noses and stuffy sinuses are less common. The C.D.C. has also added chills, muscle pain, sore throat, headache and a new loss of the sense of taste or smell as symptoms to look out for. Most people fall ill five to seven days after exposure, but symptoms may appear in as few as two days or as many as 14 days. | Common symptoms include fever, a dry cough, fatigue and difficulty breathing or shortness of breath. Some of these symptoms overlap with those of the flu, making detection difficult, but runny noses and stuffy sinuses are less common. The C.D.C. has also added chills, muscle pain, sore throat, headache and a new loss of the sense of taste or smell as symptoms to look out for. Most people fall ill five to seven days after exposure, but symptoms may appear in as few as two days or as many as 14 days. |
| If air travel is unavoidable, there are some steps you can take to protect yourself. Most important: Wash your hands often, and stop touching your face. If possible, choose a window seat. A study from Emory University found that during flu season, the safest place to sit on a plane is by a window, as people sitting in window seats had less contact with potentially sick people. Disinfect hard surfaces. When you get to your seat and your hands are clean, use disinfecting wipes to clean the hard surfaces at your seat like the head and arm rest, the seatbelt buckle, the remote, screen, seat back pocket and the tray table. If the seat is hard and nonporous or leather or pleather, you can wipe that down, too. (Using wipes on upholstered seats could lead to a wet seat and spreading of germs rather than killing them.) | If air travel is unavoidable, there are some steps you can take to protect yourself. Most important: Wash your hands often, and stop touching your face. If possible, choose a window seat. A study from Emory University found that during flu season, the safest place to sit on a plane is by a window, as people sitting in window seats had less contact with potentially sick people. Disinfect hard surfaces. When you get to your seat and your hands are clean, use disinfecting wipes to clean the hard surfaces at your seat like the head and arm rest, the seatbelt buckle, the remote, screen, seat back pocket and the tray table. If the seat is hard and nonporous or leather or pleather, you can wipe that down, too. (Using wipes on upholstered seats could lead to a wet seat and spreading of germs rather than killing them.) |
| If you’ve been exposed to the coronavirus or think you have, and have a fever or symptoms like a cough or difficulty breathing, call a doctor. They should give you advice on whether you should be tested, how to get tested, and how to seek medical treatment without potentially infecting or exposing others. | If you’ve been exposed to the coronavirus or think you have, and have a fever or symptoms like a cough or difficulty breathing, call a doctor. They should give you advice on whether you should be tested, how to get tested, and how to seek medical treatment without potentially infecting or exposing others. |
| If you’re sick and you think you’ve been exposed to the new coronavirus, the C.D.C. recommends that you call your healthcare provider and explain your symptoms and fears. They will decide if you need to be tested. Keep in mind that there’s a chance — because of a lack of testing kits or because you’re asymptomatic, for instance — you won’t be able to get tested. | If you’re sick and you think you’ve been exposed to the new coronavirus, the C.D.C. recommends that you call your healthcare provider and explain your symptoms and fears. They will decide if you need to be tested. Keep in mind that there’s a chance — because of a lack of testing kits or because you’re asymptomatic, for instance — you won’t be able to get tested. |
| There is a relatively simple, rapid and easily available test that can detect whether a patient’s body has been taken over by a cytokine storm. It looks for high levels of a protein called ferritin. | |
| But if the test does suggest a cytokine storm is underway, what then? | But if the test does suggest a cytokine storm is underway, what then? |
| The seemingly obvious solution is to quell the storm, Dr. Cron said: “If it’s the body’s response to the infection that’s killing you, you need to treat that.” | The seemingly obvious solution is to quell the storm, Dr. Cron said: “If it’s the body’s response to the infection that’s killing you, you need to treat that.” |
| The reality is trickier, especially given the lack of reliable data for Covid-19. But noting that drugs like tocilizumab are taken regularly by people with arthritis, Dr. Cron said the benefit would probably outweigh potential harm if someone is facing death. | The reality is trickier, especially given the lack of reliable data for Covid-19. But noting that drugs like tocilizumab are taken regularly by people with arthritis, Dr. Cron said the benefit would probably outweigh potential harm if someone is facing death. |
| “We need evidence-based data, but in a pandemic, where we’re flying by the seat of our pants, we always have to treat the patient in front of us,” he said. | “We need evidence-based data, but in a pandemic, where we’re flying by the seat of our pants, we always have to treat the patient in front of us,” he said. |
| Other drugs might also be useful against cytokine storms. For example, a drug called anakinra mutes interleukin-1, another of the wayward proteins. Clinical trials of anakinra for Covid-19 are also underway. A report published this week suggested that hydroxychloroquine, a much-spotlighted malaria drug that also calms an overactive immune response, might also be effective as a treatment for those who are mildly ill from coronavirus. | Other drugs might also be useful against cytokine storms. For example, a drug called anakinra mutes interleukin-1, another of the wayward proteins. Clinical trials of anakinra for Covid-19 are also underway. A report published this week suggested that hydroxychloroquine, a much-spotlighted malaria drug that also calms an overactive immune response, might also be effective as a treatment for those who are mildly ill from coronavirus. |
| Doctors could also turn to corticosteroids, which broadly turn down the entire immune response. That poses its own danger, by exposing the patient to other opportunistic infections, especially in a hospital. “It’s about getting the balance right between suppression of the over-exuberant immune response and still allowing the immune response to fight the virus,” Dr. Manson said. | Doctors could also turn to corticosteroids, which broadly turn down the entire immune response. That poses its own danger, by exposing the patient to other opportunistic infections, especially in a hospital. “It’s about getting the balance right between suppression of the over-exuberant immune response and still allowing the immune response to fight the virus,” Dr. Manson said. |
| A group of experts convened two weeks ago to discuss the best ways to collect more data and to treat patients who appear to have cytokine storm. It’s already clear that the complexities of the immune system and the course of coronavirus mean there is no single best treatment. | A group of experts convened two weeks ago to discuss the best ways to collect more data and to treat patients who appear to have cytokine storm. It’s already clear that the complexities of the immune system and the course of coronavirus mean there is no single best treatment. |
| At the Gustave Roussy Cancer Center, doctors treated another coronavirus patient with tocilizumab. That individual did not show any improvement with the drug. | At the Gustave Roussy Cancer Center, doctors treated another coronavirus patient with tocilizumab. That individual did not show any improvement with the drug. |
| “The response to the pathogen, the virus, is totally different in different individuals,” said Dr. Fabrice André, an oncologist at the center. “The trials will determine in which patients it works.” | “The response to the pathogen, the virus, is totally different in different individuals,” said Dr. Fabrice André, an oncologist at the center. “The trials will determine in which patients it works.” |
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