For a world crippled by the coronavirus, salvation hinges on a vaccine.
But in the United States, where at least 4.6 million people have been infected and nearly 155,000 have died, the promise of that vaccine is hampered by a vexing epidemic that long preceded COVID-19: obesity.
Scientists know that vaccines engineered to protect the public from influenza, hepatitis B, tetanus and rabies can be less effective in obese adults than in the general population, leaving them more vulnerable to infection and illness. There is little reason to believe, obesity researchers say, that COVID-19 vaccines will be any different.
“Will we have a COVID vaccine next year tailored to the obese? No way,” said Raz Shaikh, an associate professor of nutrition at the University of North Carolina-Chapel Hill.
“Will it still work in the obese? Our prediction is no.”
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More than 107 million American adults are obese, and their ability to return safely to work, care for their families and resume daily life could be curtailed if the coronavirus vaccine delivers weak immunity for them.
In March, still early in the global pandemic, a little-noticed study from China found that heavier Chinese patients afflicted with COVID-19 were more likely to die than leaner ones, suggesting a perilous future awaited the U.S., whose population is among the heaviest in the world.
And then that future arrived.
As intensive care units in New York, New Jersey and elsewhere filled with patients, the federal Centers for Disease Control and Prevention warned that obese people with a body mass index of 40 or more — known as morbid obesity or about 100 pounds overweight — were among the groups at highest risk of becoming severely ill with COVID-19. About 9% of American adults are in that category.
As weeks passed and a clearer picture of who was being hospitalized came into focus, federal health officials expanded their warning to include people with a body mass index of 30 or more. That vastly expanded the ranks of those considered vulnerable to the most severe cases of infection, to 42.4% of American adults.
Obesity has long been known to be a significant risk factor for death from cardiovascular disease and cancer. But scientists in the emerging field of immunometabolism are finding obesity also interferes with the body’s immune response, putting obese people at greater risk of infection from pathogens such as influenza and the novel coronavirus. In the case of influenza, obesity has emerged as a factor making it more difficult to vaccinate adults against infection. The question is whether that will hold true for COVID-19.
A healthy immune system turns inflammation on and off as needed, calling on white blood cells and sending out proteins to fight infection. Vaccines harness that inflammatory response. But blood tests show that obese people and people with related metabolic risk factors such as high blood pressure and elevated blood sugar levels experience a state of chronic mild inflammation; the inflammation turns on and stays on.
Adipose tissue — or fat — in the belly, the liver and other organs is not inert; it contains specialized cells that send out molecules, like the hormone leptin, that scientists suspect induces this chronic state of inflammation. While the exact biological mechanisms are still being investigated, chronic inflammation seems to interfere with the immune response to vaccines, possibly subjecting obese people to preventable illnesses even after vaccination.
An effective vaccine fuels a controlled burn inside the body, searing into cellular memory a mock invasion that never truly happened.
Evidence that obese people have a blunted response to common vaccines was first observed in 1985 when obese hospital employees who received the hepatitis B vaccine showed a significant decline in protection 11 months later that was not observed in non-obese employees. The finding was replicated in a follow-up study that used longer needles to ensure the vaccine was injected into muscle and not fat.
Researchers found similar problems with the hepatitis A vaccine, and other studies have found significant declines in the antibody protection induced by tetanus and rabies vaccines in obese people.
“Obesity is a serious global problem, and the suboptimal vaccine-induced immune responses observed in the obese population cannot be ignored,” pleaded researchers from the Mayo Clinic’s Vaccine Research Group in a 2015 study published in the journal Vaccine.
Vaccines also are known to be less effective in older adults, which is why those 65 and older receive a supercharged annual influenza vaccine that contains far more flu virus antigens to help juice up their immune response.
By contrast, the diminished protection of the obese population — both adults and children — has been largely ignored.
“I’m not entirely sure why vaccine efficacy in this population hasn’t been more well reported,” said Catherine Andersen, an assistant professor of biology at Fairfield University who studies obesity and metabolic diseases. “It’s a missed opportunity for greater public health intervention.”
In 2017, scientists at UNC-Chapel Hill provided a critical clue about the limitations of the influenza vaccine. In a paper published in the International Journal of Obesity, they showed for the first time that vaccinated obese adults were twice as likely as adults of a healthy weight to develop influenza or flu-like illness.
Curiously, they found that adults with obesity did produce a protective level of antibodies to the influenza vaccine, but they still responded poorly.
“That was the mystery,” said Chad Petit, an influenza virologist at the University of Alabama.
One hypothesis, Petit said, is that obesity may trigger a metabolic dysregulation of T cells, white blood cells critical to the immune response. “It’s not insurmountable,” said Petit, who is researching COVID-19 in obese patients. “We can design better vaccines that might overcome this discrepancy.”
Historically, people with high BMIs often have been excluded from drug trials because they frequently have related chronic conditions that might mask the results. The clinical trials underway to test the safety and efficacy of a coronavirus vaccine do not have a BMI exclusion and will include people with obesity, said Dr. Larry Corey, of the Fred Hutchinson Cancer Research Center, who is overseeing the phase 3 trials sponsored by the National Institutes of Health.
Although trial coordinators are not specifically focused on obesity as a potential complication, Corey said, participants’ BMI will be documented and results evaluated.
Dr. Timothy Garvey, an endocrinologist and director of diabetes research at the University of Alabama, was among those who stressed that, despite the lingering questions, it is still safer for obese people to get vaccinated than not.
“The influenza vaccine still works in patients with obesity, but just not as well,” Garvey said. “We still want them to get vaccinated. Continue reading
Neurological complications of Covid-19 can include delirium, brain inflammation, stroke and nerve damage, finds a new UCL and UCLH-led study.
Published in the journal Brain, the research team identified one rare and sometimes fatal inflammatory condition, known as ADEM, which appears to be increasing in prevalence due to the pandemic.
Some patients in the study did not experience severe respiratory symptoms, and the neurological disorder was the first and main presentation of Covid-19.
Joint senior author Dr Michael Zandi (UCL Queen Square Institute of Neurology and University College London Hospitals NHS Foundation Trust) said: “We identified a higher than expected number of people with neurological conditions such as brain inflammation, which did not always correlate with the severity of respiratory symptoms.
“We should be vigilant and look out for these complications in people who have had Covid-19. Whether we will see an epidemic on a large scale of brain damage linked to the pandemic – perhaps similar to the encephalitis lethargica outbreak in the 1920s and 1930s after the 1918 influenza pandemic – remains to be seen.”
The study provides a detailed account of neurological symptoms of 43 people (aged 16-85) treated at the National Hospital for Neurology and Neurosurgery, UCLH, who had either confirmed or suspected Covid-19.
The researchers identified 10 cases of transient encephalopathies (temporary brain dysfunction) with delirium, which corresponds with other studies finding evidence of delirium with agitation. There were also 12 cases of brain inflammation, eight cases of strokes, and eight others with nerve damage, mainly Guillain-Barré syndrome (which usually occurs after a respiratory or gastrointestinal infection).
Most (nine out of 12 cases) of those with brain inflammation conditions were diagnosed with acute disseminated encephalomyelitis (ADEM). ADEM is rare and typically seen in children and can be triggered by viral infections: the team in London normally sees about one adult patient with ADEM per month, but that increased to at least one per week during the study period, which the researchers say is a concerning increase.
The virus causing Covid-19, SARS-CoV-2, was not detected in the cerebrospinal brain fluid of any of the patients tested, suggesting the virus did not directly attack the brain to cause the neurological illness. Further research is needed to identify why patients were developing these complications.
In some patients, the researchers found evidence that the brain inflammation was likely caused by an immune response to the disease, suggesting that some neurological complications of Covid-19 might come from the immune response rather than the virus itself.
The findings add clinical descriptions and detail to another recent study, which also involved Dr Zandi and co-author Dr Hadi Manji (UCL Queen Square Institute of Neurology) identifying 153 people with neurological complications from Covid-19. This paper also confirms the previously reported findings of a higher than expected number of patients with stroke which results from the excessive stickiness of the blood in COVID-19 patients.
Joint first author Dr Ross Paterson (UCL Queen Square Institute of Neurology) said: “Given that the disease has only been around for a matter of months, we might not yet know what long-term damage Covid-19 can cause.
“Doctors needs to be aware of possible neurological effects, as early diagnosis can improve patient outcomes. People recovering from the virus should seek professional health advice if they experience neurological symptoms,” he added.
Joint first author Dr Rachel Brown (UCL Queen Square Institute of Neurology and UCL Infection & Immunity) said: “Our study advances understanding of the different ways in which Covid-19 can affect the brain, which will be paramount in the collective effort to support and manage patients in their treatment and recovery.”
Joint senior author Dr Hadi Manji said: “Our study amalgamates, for the first time, the clinical presentations of patients with Covid-19 neurological disease with MRI and laboratory features including, in one case, a brain biopsy.
“This now sets up a template for other researchers around the world, facilitating coordinated research to optimise the diagnosis and treatments of these complications, which to date, has proved difficult. In addition, patients are going to require long term follow up.”
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The researchers were supported by the National Institute for Health Research UCL/UCLH Biomedical Research Centre, Medical Research Council, Alzheimer’s Association, and the UK Dementia Research Institute. Continue reading
How come only scientists? From ‘brain fog’ to heart damage, COVID-19’s lingering problems alarm scientists Source: https://www.sciencemag.org/news/2020/07/brain-fog-heart-damage-covid-19-s-lingering-problems-alarm-scientists
TRAVEL MAP: CROSS STATE TRAVEL COUNTIES AS OF JULY 24, 2020 (MODIFIED JULY 27, 2020)
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Maurice Preter, MD is a European and U.S. educated psychiatrist, psychotherapist, psychopharmacologist, neurologist, and medical-legal expert in private practice in Manhattan. He is also the principal of Fifth Avenue Concierge Medicine, PLLC, a medical concierge service and health advisory for select individuals and families.
Maurice Preter, MD is a European and U.S. educated psychiatrist, psychotherapist, psychopharmacologist, neurologist, and medical-legal expert in private practice in Manhattan. He is also the principal of Fifth Avenue Concierge Medicine, PLLC, a medical concierge service and health advisory for select individuals and families.