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Post by Admin on Nov 7, 2020 0:55:56 GMT
Fig. 3 IgG from COVID-19 patients potentiates thrombosis in mice. (A) Schematic shows thrombus initiation in the inferior vena cava (IVC) of mice by local electrolysis leading to free radical generation and activation of the endothelium. (B, C) Mice were administered IgG from healthy individuals (control), from patients with COVID-19 who had high or low aPS/PT antibodies or from patients with catastrophic antiphospholipid syndrome (CAPS). Just prior to intravenous administration of IgG, mice were subjected to local electrolysis in the inferior vena cava. Thrombus length (B) and weight (C) were determined 24 hours after IgG injection. Scatter plots with individual data points (each point represents a single mouse) are presented. (D) Shown are photographs of representative thrombi from the experiments presented in panels B and C. (E) Serum samples from mice in the experiments presented in panels B and C were tested for NET remnants measured by an ELISA that detected myeloperoxidase (MPO)-DNA complexes. Scatter plots with individual data points (each point represents a single mouse) are presented. OD, optical density. (F) Schematic shows thrombus initiation in the inferior vena cava (IVC) of mice by stenosis that was induced via placement of a fixed suture over a spacer that was subsequently removed. (G, H) Mice were treated intravenously with IgG from a healthy individual (control) or from a patient with COVID-19 with high aPS/PT antibodies. Just prior to intravenous administration of IgG, stenosis was induced. 24 hours later thrombus length (G) and weight (H) were determined. Scatter plots with individual data points (each point represents a single mouse) are presented. (I) Shown are photographs of representative thrombi from the experiments presented in panels G and H. (J) Serum samples from mice in the experiments presented in panels G and H were tested for NET remnants measured by an ELISA that detected MPO-DNA complexes. Scatter plots with individual data points (each point represents a single mouse) are presented. OD, optical density. Horizontal black bars represent the mean. Comparisons were by either one-way ANOVA with correction for multiple comparisons by Dunnett’s method (B, C, E) or unpaired t test (G, H, J): *p<0.05, **p<0.01, ***p<0.001, and ****p<0.0001. DISCUSSION Antiphospholipid autoantibodies (aPL antibodies) are a heterogeneous group of antibodies that underlie the pathogenesis of antiphospholipid syndrome via their interactions with phospholipid-binding plasma proteins such as β2GPI, prothrombin, thrombomodulin, plasminogen, antithrombin III, protein C, protein S, annexin II, annexin V, and likely others (22, 41–46). The association between various infections and the induction of aPL antibodies has long been recognized (47–52). For example, one study of 100 cases reported in Medline from 1983 to 2003 found the most commonly reported aPL antibody-associated infections to be skin infections (18%), pneumonia (14%), and urinary tract infections (10%); common pathogens included human immunodeficiency virus (17%), varicella-zoster virus (15%), and hepatitis C virus (13%) (50). Regarding specific aPL antibodies, aCL IgG and IgM (typically lacking anti-β2GPI antibody activity) have been most commonly reported (48, 52–57). The majority of these virus-associated aPL antibodies are thought to be transient (35, 54, 58). Although the clinical implications of transient virus-associated aPL antibodies remain to be fully defined, a recent review of 163 published cases of virus-associated aPL antibodies found thrombotic events in 116 cases (35). Even acknowledging the likelihood of sampling and publication bias, these data (along with the data presented here for individuals with severe COVID-19) suggest that some transient aPL antibodies may still have prothrombotic potential. Whether similar antibodies would be detected in patients with less symptomatic COVID-19 presentation—some of whom do experience thrombotic events—awaits further study. The most severe presentation of antiphospholipid syndrome is its catastrophic variant, which fortunately impacts only a minority of patients with antiphospholipid syndrome, typically at times of stress such as infection, surgery, or withdrawal of anticoagulants (59). Catastrophic antiphospholipid syndrome involves derangements of both inflammatory and thrombotic pathways and impacts multiple organs in the body simultaneously (59). In the largest series of patients with catastrophic antiphospholipid syndrome assembled, the most commonly affected organs were kidneys (73%), lungs (60%), brain (56%), heart (50%), and skin (47%) (60). Whereas multi-organ failure certainly complicates severe cases of COVID-19, the lungs are typically the most severely affected organ. We speculate that local immune stimulation due to viral infection (including potentially the infection of endothelial cells) could synergize with circulating aPL antibodies and thereby lead to a particularly severe thrombo-inflammatory insult to the lungs of COVID-19 patients. Many studies from the general thrombosis literature have revealed that activated neutrophils, and in particular NET formation, contribute to the propagation of thrombi affecting arterial, venous, and microscopic vascular beds (61, 62). NETs have also been recently implicated in the pathogenesis of antiphospholipid syndrome. Our group has reported that serum samples from patients with antiphospholipid syndrome, as well as purified aPL antibodies, trigger neutrophils to release NETs (23). The potential in vivo relevance of this observation has been confirmed in mouse models of aPL antibody-mediated large-vein thrombosis in which either depletion of neutrophils or digestion of NETs was protective (38). Neutrophils from patients with antiphospholipid syndrome also appear to have increased adhesive potential, which is dependent upon the activated form of integrin Mac-1. This pro-adhesive phenotype amplifies neutrophil-endothelium interactions, potentiates NET formation, and potentially lowers the threshold for thrombosis (63). Therapies that target NET formation have the potential to treat thrombotic diseases. For example, selective agonism of the adenosine A2A receptor suppresses aPL antibody-mediated NETosis in a protein kinase A-dependent fashion (39). A2A receptor agonism also reduces thrombosis in the inferior vena cava of both control mice and mice treated with aPL antibodies. Dipyridamole, which is known to potentiate adenosine receptor signaling by increasing extracellular concentrations of adenosine and interfering with the breakdown of cAMP, also suppresses aPL antibody-mediated NETosis and mitigates venous thrombosis in mice (64). Interestingly, a small study from China showed that dipyridamole suppressed D-dimer elevation and improved platelet counts in patients with COVID-19 (65). Whereas we have demonstrated here that dipyridamole mitigated NET release mediated by IgG from COVID-19 patients, prospective randomized clinical trials (NCT04391179) are needed to evaluate clinical outcomes among COVID-19 patients treated with dipyridamole (64). aPL antibodies are defined based on their inclusion in the updated Sapporo classification criteria: namely, aCL IgG and IgM, aβ2GPI IgG and IgM, and lupus anticoagulant (25). Of these, lupus anticoagulant is generally accepted as the best indicator of a high-risk aPL antibody profile (66–71). There are certainly reports of patients with seronegative antiphospholipid syndrome, who have classic features of this disease but have tested negative for traditional aPL antibodies (72). Some non-criteria aPL antibodies discovered in the past 20 years have shown promising clinical utility in identifying antiphospholipid syndrome. Among those are aPS/PT IgG and IgM, as well as the IgA isotypes of aCL and aβ2GPI antibodies. Retrospective studies have suggested that aβ2GPI IgA is associated with thrombosis in lupus patients [odds ratio (OR) 2.8, 95% CI 1.3-6.2] (73). A recent review of 10 retrospective studies (1775 patients with lupus or primary antiphospholipid syndrome and 628 healthy controls) detected a strong association between aPS/PT antibodies and thrombotic events (OR 5.11; 95% CI 4.2-6.3) (74). Furthermore, serological agreement between aPS/PT IgG and IgM and high-risk aPL antibody profiles—especially the presence of lupus anticoagulant—has been demonstrated in a recent study of 95 well-characterized patients with primary antiphospholipid syndrome (75). Whereas the clinical implications of aPS/PT antibodies during viral infection remain to be comprehensively defined, we found here that IgG fractions containing high titers of these antibodies triggered NET release from neutrophils in vitro and accelerated thrombosis in vivo. Notably, IgG purified from COVID-19 patients with low aPS/PT serum titers demonstrated some activity in potentiating thrombosis (although high aPS/PT serum titer IgG fractions provided a more robust response). It is possible that aPL antibodies are but one species of a broader acute natural antibody response that is in fact prothrombotic in COVID-19 disease. The orchestration of autoimmunity against phospholipids in COVID-19 is likely a complex interplay between genetic predisposition, historical antigen exposures, and a hyperactivated host immune response in the setting of a unique environmental trigger—infection with SARS-CoV-2 (76). It is not surprising that aPL antibodies of the IgM isotype (which are designed for rapid mobilization) predominate in our COVID-19 patient cohort where they correlate with markers of neutrophil activation and NET release. The relationship between aPL antibodies and NETs in COVID-19 is potentially bidirectional. NETs are a known source of autoantigens, and cytokines released in parallel with NETosis may also facilitate NET-associated autoantibody propagation (77–80). An example of a cytokine that could play such a role is B cell activating factor (BAFF), an important mediator of the maturation of B cells into antibody-producing cells (81). For example, neutrophil-derived BAFF likely participates in the production of anti-double-stranded DNA antibodies in lupus (78). In COVID-19, it is possible that production of aPL antibodies potentiates NET formation and BAFF release. This may further enhance the survival and differentiation of phospholipid-reactive B cells, and in some cases class-switching to the IgG isotype. The interplay between COVID-19 and humoral immunity is clearly an area that merits further study. There are several potential clinical implications of these findings. Patients with catastrophic antiphospholipid syndrome are regularly treated with heparin, corticosteroids, and plasmapheresis (with the latter leading to a demonstrable improvement in outcomes) (82). Whereas both anticoagulation and corticosteroids have shown some promise to date in treatment of COVID-19, plasmapheresis has not been systematically explored. One wonders if this could provide benefit in the subgroup of COVID-19 patients with high titers of aPL antibodies. At the same time, convalescent plasma is receiving increasing attention as an approach to treating severe cases of COVID-19. Defining the extent to which convalescent plasma may contain aPL antibodies or other prothrombotic autoantibodies in addition to protective anti-SARS-CoV-2 antibodies, is another potential area for future investigation.
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Post by Admin on Nov 9, 2020 6:46:31 GMT
Many hopes for a return to a semi-normal life after COVID-19 revolve around vaccines, but those injections have limits — they’re harder to deploy in low-income and rural areas where there’s no guarantee of easy distribution. Science may offer a more accessible alternative, though. Columbia University researchers have developed a nasal spray that has successfully prevented COVID-19 infections in tests with ferrets as well as a 3D model of human lungs.
The lipopeptide (that is, a lipid and peptide combination) prevents the coronavirus from fusing with a target cell’s membrane by blocking a key protein from adopting a necessary shape. It should work immediately and last for at least 24 hours. It’s also affordable, lasts a long time, and doesn’t need refrigeration.
A spray like this is still some ways from reaching the public. There would need to be human clinical trials, not to mention large-scale production to provide enough access. Scientists are planning to “rapidly advance” to further testing, Columbia said.
The move could bring protection to many parts of the world where mass COVID-19 vaccinations would be difficult. It might also serve as a “complement” even in places where vaccines are readily available, key researchers Anne Moscona and Matteo Porotto said. People who can’t take vaccines, or those for whom vaccinations don’t work, could spray themselves daily knowing they’d be safe. That, in turn, could further limit the spread of the virus and hasten the end to the pandemic.
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Post by Admin on Nov 10, 2020 19:31:07 GMT
Twenty percent of coronavirus patients later develop a new mental illness, according to a study. The most common disorders experienced by COVID-19 survivors within 90 days of their diagnoses are anxiety, depression and insomnia, according to the study published in The Lancet Psychiatry journal. “People have been worried that COVID-19 survivors will be at greater risk of mental health problems, and our findings … show this to be likely,” said Paul Harrison, a professor of psychiatry at Britain’s Oxford University. The study looked at the electronic health records of over 62,000 coronavirus patients in the US. The study group was twice as likely to suffer from a new mental illness than other groups of patients during the same period, researchers said. COVID-19 and psychiatry: can electronic medical records provide the answers? Robert Yolken The COVID-19 pandemic has posed unprecedented challenges for health-care professionals, researchers, and policy makers, particularly in the area of serious mental illness. From the beginning of the pandemic, psychiatric symptoms have complicated medical care and contributed to morbidity and mortality.1 Conversely, individuals with serious mental illness are known to have a high prevalence of comorbid conditions associated with symptomatic COVID-19, including obesity, hypertension, smoking, and diabetes.2 Many individuals with psychiatric disorders also live in social conditions that result in high exposure to respiratory viruses, including seasonal coronaviruses.3 The sheer size and changing nature of the pandemic poses problems for investigators and policy planners investigating COVID-19 exposure and psychiatric disorders. This is particularly true in the USA, where the response to the pandemic has been hampered by the lack of a national medical care system and a patchwork of state and local public health agencies responsible for data collection and disease surveillance. The electronic medical record has become a part of many medical practices in the USA. Although this system has been approached with trepidation by many US health-care providers,4 data generated by electronic medical records has proven a useful tool for the analysis of somatic and mental health outcomes.5 In The Lancet Psychiatry, Maxime Taquet and colleagues6 report data collated from electronic medical records by the TriNetX Analytics Network from more than 69 million individuals who received care at 54 US health-care organisations between Jan 20, and Aug 1, 2020. This report provides evidence for what the authors characterise as a bidirectional association between COVID-19 and psychiatric disorders.6 The first association relates to an increase in newly recognised psychiatric disorders in individuals with COVID-19, with relative risks in the range of 2–3 for anxiety disorders, insomnia, and dementia. The other association characterises an increase in COVID-19 in individuals with pre-existing psychiatric disorders, with an overall relative risk of 1·65.6 The latter results are largely congruent with a previous study based on another electronic medical record database,7 although there are some differences in the reported relative risks associated with different psychiatric diagnoses and populations. Although potentially valuable for population-based studies, data derived from electronic medical records in the USA have limitations, most of which are noted in the report. Distinct from datasets based on national health-care systems, data derived from available electronic medical record-derived databases only capture events that occur in participating health-care organisations. Since the identity of participating health-care organisations and their relative contributions to the dataset are not disclosed, the generalisability of data derived from this population is difficult to assess. In this regard, although the 62 354 COVID-19 cases presented in this report is a large study population,6 they represent only a fraction of the number of cases reported in the USA during the same time period.8 In terms of psychiatric disorders, it is possible that the first entry of a diagnosis into the database might not represent the first occurrence of the condition, but rather the first time it is recognised by a health-care provider at a participating health-care organisation, making the timing of symptom onset relating to COVID-19 difficult to evaluate. Furthermore, data from electronic medical records are often lacking in information relevant to COVID-19. These data include detailed information relating to housing density, family size, current employment and immigration status, specific geographic location, and contact with others with COVID-19. Therefore, it is imperative that data derived from electronic medical records be supported by cohort studies that prospectively collect relevant information and biological samples. The changing nature of the COVID-19 pandemic presents a moving target for clinicians, investigators, readers of medical literature, and the general public. Infection rates in different areas are frequently changing. Additionally, new cases, clinical data, and analytic functionalities are being added to available databases. Conclusions based on any one dataset thus require frequent re-examination and re-interpretation. The recent retraction of articles on COVID-19 based on another database9 highlights the necessity of data sharing and transparency. More than 100 years have passed since the worldwide influenza pandemic that resulted in a markedly increased rate of neurological and psychiatric sequelae.10 Despite great advances in medical science, we are faced with some of the same issues relating to the characterisation of a rapidly changing pandemic occurring in different geopolitical environments. Learning to use new tools, such as electronic medical records efficiently should provide some of the essential information needed to understand and control the psychiatric consequences of this pandemic and plan for future ones. In these efforts, we should keep in mind the words of Sir William Osler that, “the best preparation for tomorrow is to do today's work superbly well.”
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Post by Admin on Mar 14, 2021 19:22:16 GMT
There was no reason to celebrate on Rachel Van Lear’s anniversary. The same day a global pandemic was declared, she developed symptoms of COVID-19. A year later, she’s still waiting for them to disappear. And for experts to come up with some answers.
The Texas woman is one of thousands of self-described long-haulers, patients with symptoms that linger or develop out of the blue months after they first became infected with coronavirus. Hers first arrived March 11, 2020.
The condition affects an uncertain number of survivors in a baffling variety of ways.
“We’re faced with a mystery,” said Dr. Francis Collins, chief of the National Institutes of Health.
Is it a condition unique to COVID-19, or just a variation of the syndrome that can occur after other infections? How many people are affected, and how long does it last? Is it a new form of chronic fatigue syndrome — a condition with similar symptoms?
Full Coverage: Coronavirus pandemic Or could some symptoms be unrelated to their COVID-19 but a physical reaction to the upheaval of this past pandemic year — the lockdowns, quarantines, isolation, job losses, racial unrest, political turmoil, not to mention overwhelming illness and deaths?
These are the questions facing scientists as they search for disease markers, treatments and cures. With $1 billion from Congress, Collins’ agency is designing and soliciting studies that aim to follow at least 20,000 people who’ve had COVID-19.
‘’We’ve never really been faced with a post-infectious condition of this magnitude so this is unprecedented,” Collins said Monday. “We don’t have time to waste.’’
With nearly 30 million U.S. cases of COVID-19 and 119 million worldwide, the impact could be staggering, even if only a small fraction of patients develop long-term problems.
Fatigue, shortness of breath, insomnia, trouble thinking clearly and depression are among the many reported symptoms. Organ damage, including lung scarring and heart inflammation, have also been seen. Pinpointing whether these symptom are directly linked to the virus or perhaps to some preexisting condition is among scientists’ tasks.
’’Is it just a very delayed recovery or is it something even more alarming and something that becomes the new normal?” Collins said.
There are a few working theories for what might be causing persistent symptoms. One is that the virus remains in the body at undetectable levels yet still causes tissue or organ damage. Or it overstimulates the immune system, keeping it from returning to a normal state. A third theory: Symptoms linger or arise anew when the virus attacks blood vessels, causing minute, undetectable blood clots that can wreak havoc throughout the body.
Some scientists think each of these may occur in different people.
Dr. Steven Deeks, an infectious disease specialist at the University of California, San Francisco, said researchers first need to create a widely accepted definition of the syndrome. Estimates are “all over the map because no one is defining it in the same way,” he said.
Deeks is leading one study, collecting blood and saliva samples from volunteers who will be followed for up to two years.
Some people develop long-term problems even when their initial infections were silent. Deeks said some evidence suggests that those who initially get sicker from a coronavirus infection might be more prone to persistent symptoms, and women seem to develop them more than men, but those observations need to be confirmed, Deeks said.
Van Lear says she was in great shape when she got sick. At 35, the suburban Austin woman had no other health issues and was a busy mother of three who often worked out. First came a chest cold, then a high fever. A flu test came back negative, so her doctor tested for COVID-19. Soon after she developed blinding headaches, debilitating fatigue and nausea so severe that she needed emergency room treatment.
’’I was very scared because no one could tell me what was going to happen to me,” Van Lear said.
Over the next several months, symptoms would come and go: burning lungs, a rapid heartbeat, dizzy spells, hand tremors and hair loss. While most have disappeared, she still deals with an occasional racing heartbeat. Heart monitoring, bloodwork and other tests have all been normal.
Fatigue, fever, and no taste or smell were Karla Jefferies’ first symptoms after testing positive last March. Then came brain fog, insomnia, a nagging smell of something burning that only recently disappeared, and intermittent ringing in her ears. Now she can’t hear out of her left ear.
Doctors can’t find anything to explain it, and she bristles when some doctors dismiss her symptoms.
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Post by Admin on Apr 8, 2021 19:39:23 GMT
TODAY Anchors Get Their COVID-19 Vaccinations Live On The Plaza | TODAY
Savannah Guthrie, Craig Melvin, Sheinelle Jones, Dylan Dreyer and Jenna Bush Hager are all eligible for the COVID-19 vaccine in New York now, and Dr. Dave Chokshi, New York City’s health commissioner, joins them outdoors on the plaza as they receive their shots live on the air from Walgreens pharmacists. “Nothing!” is what Savannah says she felt as she got her shot.
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