Interesting. Main point, the testing field is evolving rapidly and there is an urgent need for higher specificity testing to make enough people feel safe enough to enter that movie theater/board that airplane etc.
https://www.cell.com/action/showPdf?pii=S2666-6340%2820%2930016-7
https://doi.org/10.1016/j.medj.2020.08.001
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.”
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.
Source: https://khn.org/news/americas-obesity-epidemic-threatens-effectiveness-of-any-covid-vaccine/
Myasthenia Gravis Associated With SARS-CoV-2 Infection
Background: Some patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have neurologic symptoms (1–3). Some observers propose that these symptoms are caused by viral infection of nerve cells (4), but the possibility exists that these symptoms might be produced by autoimmune mechanisms (1–4). Myasthenia gravis is an autoimmune disease in which antibodies bind to acetylcholine receptors (AChRs) or to functionally related molecules in the postsynaptic membrane at the neuromuscular junction (5).
Objective: To describe 3 patients without previous neurologic or autoimmune disorders who were diagnosed with myasthenia gravis after the onset of coronavirus disease 2019 (COVID-19).
Case Report: Patient 1 was a 64-year-old man who had fever as high as 39 °C for 4 days. Five days after fever onset, he developed diplopia and muscular fatigability. Although his chest radiograph was normal, nasopharyngeal swab and real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing for COVID-19 showed a positive result. We suspected myasthenia gravis because of his symptoms. His neurologic examination was unremarkable. Computed tomography (CT) of the thorax excluded thymoma. Repetitive stimulation of the facial nerve showed a 57% decrement, confirming involvement of the postsynaptic neuromuscular junction, and the concentration of AChR antibodies in his serum was elevated (22.8 pmol/L; normal value, <0.4 pmol/L). We administered pyridostigmine bromide and prednisone, and the patient had a response typical for someone with myasthenia gravis.
Patient 2 was a 68-year-old man who had fever as high as 38.8 °C for 7 days. On day 7, he developed general muscular fatigability, diplopia, and dysphagia. Although his chest CT scan was normal, nasopharyngeal swab and RT-PCR testing for COVID-19 yielded positive results. We suspected myasthenia gravis because of his symptoms. His neurologic examination was normal, and his chest CT scan excluded thymoma. Repetitive nerve stimulation showed a postsynaptic deficit of neuromuscular transmission of the facial (52%) and ulnar (21%) nerves. His serum AChR antibody level was elevated (27.6 pmol/L). He improved after 1 cycle of intravenous immunoglobulin treatment.
Patient 3 was a 71-year-old woman who had a cough and fever to 38.6 °C for 6 days. Nasopharyngeal swab and RT-PCR testing for COVID-19 showed a negative result. Five days after her symptoms began, she developed bilateral ocular ptosis, diplopia, and hypophonia. Thorax CT revealed bilateral interstitial pneumonia and excluded thymoma. One day later, she developed dysphagia and respiratory failure and was transferred to the intensive care unit, where she received mechanical ventilation through a tracheostomy. Repetitive nerve stimulation showed a postsynaptic deficit of neuromuscular transmission of the ulnar nerve (56%), and her serum AChR antibody level was elevated (35.6 pmol/L). Five days later, she had a second nasopharyngeal swab test for COVID-19, and the result was positive. Plasmapheresis was started; she improved and was extubated. This patient received hydroxychloroquine the day after the onset of her first neurologic symptoms (withdrawn a day later), so we do not believe that it caused her symptoms of myasthenia gravis.
Additional information about these patients is provided in the Table.
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Discussion: We describe what we believe are the first 3 reported cases of AChR antibody–positive myasthenia gravis after COVID-19. These observations are consistent with reports of other infections that induce autoimmune disorders, as well as with the growing evidence of other neurologic disorders with presumed autoimmune mechanisms after COVID-19 onset (1–3). We note that symptoms of myasthenia gravis appeared within 5 to 7 days after fever onset in all 3 patients, and the time from presumed infection with SARS-CoV-2 to the beginning of myasthenia gravis symptoms is consistent with the time from infection to symptoms in other neurologic disorders triggered by infections (2, 3). Several possible explanations exist. For example, antibodies that are directed against SARS-CoV-2 proteins may cross-react with AChR subunits, because the virus has epitopes that are similar to components of the neuromuscular junction; this is known to occur in other neurologic autoimmune disorders after infection. Alternatively, COVID-19 infection may break immunologic self-tolerance.
This article was published at Annals.org on 10 August 2020
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.
Source: https://www.eurekalert.org/pub_releases/2020-07/ucl-iid070620.php
Neonatal outcome in 29 pregnant women with COVID-19: A retrospective study in Wuhan, China
Source: https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003195&type=printable
Abstract
Background
As of June 1, 2020, coronavirus disease 2019 (COVID-19) has caused more than 6,000,000 infected persons and 360,000 deaths globally. Previous studies revealed preg- nant women with COVID-19 had similar clinical manifestations to nonpregnant women. However, little is known about the outcome of neonates born to infected women.
Methods and findings
In this retrospective study, we studied 29 pregnant women with COVID-19 infection deliv- ered in 2 designated general hospitals in Wuhan, China between January 30 and March
10, 2020, and 30 neonates (1 set of twins). Maternal demographic characteristics, delivery course, symptoms, and laboratory tests from hospital records were extracted. Neonates were hospitalized if they had symptoms (5 cases) or their guardians agreed to a hospitalized quarantine (13 cases), whereas symptom-free neonates also could be discharged after birth and followed up through telephone (12 cases). For hospitalized neonates, laboratory test results and chest X-ray or computed tomography (CT) were extracted from hospital records. The presence of antibody of SARS-CoV-2 was assessed in the serum of 4 neonates.
Among 29 pregnant COVID-19-infected women (13 confirmed and 16 clinical diagnosed), the majority had higher education (56.6%), half were employed (51.7%), and their mean age was 29 years. Fourteen women experienced mild symptoms including fever (8), cough (9), shortness of breath (3), diarrhea (2), vomiting (1), and 15 were symptom-free.
Eleven of 29 women had pregnancy complications, and 27 elected to have a cesarean section delivery.
Of 30 neonates, 18 were admitted to Wuhan Children’s Hospital for quarantine and care, whereas the other 12 neonates discharged after birth without any symptoms and had normal follow-up. Five hospitalized neonates were diagnosed as COVID-19 infection (2 confirmed and 3 suspected). In addition, 12 of 13 other hospitalized neonates presented with radiologi- cal features for pneumonia through X-ray or CT screening, 1 with occasional cough and the others without associated symptoms. SARS-CoV-2 specific serum immunoglobulin M (IgM) and immunoglobulin G (IgG) were measured in 4 neonates and 2 were positive. The limited sample size limited statistical comparison between groups.
Conclusions
In this study, we observed COVID-19 or radiological features of pneumonia in some, but not all, neonates born to women with COVID-19 infection. These findings suggest that intrauterine or intrapartum transmission is possible and warrants clinical caution and further investigation.
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.
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