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    Editor’s Note (9/4/20) best online viagra. Drugmakers worldwide are working overtime to produce vaccines for COVID-19. If delays emerge, they may need to rely on costly biotech such best online viagra as monoclonal antibodies. In this article, Scientific American details another approach making progress in Costa Rica, where inexpensive horse antibodies are being developed against the novel coronavirus. Development of the hundreds of vaccines and therapies for COVID-19 is by no means confined to metro areas surrounding San Francisco, Boston or Washington, D.C.

    Borrowing from decades of experience in producing snake antivenoms, scientists, veterinarians and technicians at a scientific and technical institute in Costa Rica have labored nonstop in recent months to produce a therapeutic formulation of equine antibodies against SARS-CoV-2, the coronavirus that causes best online viagra COVID-19. Similar efforts are underway in Brazil and Argentina to tide these countries over until the arrival of an effective vaccine. In late March, after the first case of COVID-19 was diagnosed in Costa Rica, Román Macaya—a biochemist and public health expert who heads the Costa Rican Social Security Fund, which runs the nation’s public clinics and hospitals—issued a call for the research community to join the fight against the then nascent pandemic. €œOur response to COVID-19 could not be only a health best online viagra care response,” Macaya says. €œIt had to be a scientific response as well.” In making his plea for help, he singled out the antivenom specialists at the University of Costa Rica’s Clodomiro Picado Institute, which is named after a renowned Costa Rican scientist.

    €œThe very next day we got a letter from Henning Jensen, then rector of the University of Costa Rica saying, ‘We’re in. Let's get best online viagra together and work on this,’” Macaya recalls. The effort’s objective was to harness the technology and experience the Clodomiro Picado Institute has acquired in its work using horse antibodies to fabricate antivenoms for snake bites during the past five decades. Every year, the antivenoms with purified equine antibodies produced at the institute save more than 500 people in Costa Rica and thousands more in other countries around the world. Equine antibodies made at The Clodomiro best online viagra Picado Institute’s production plant.

    Credit. Jenniffer Jiménez Oficina de Divulgación, Universidad de Costa Rica The Clodomiro Picado Institute has more than 100 horses that have developed strong immunity to snake venoms after being inoculated with small quantities of toxins over a period of weeks to months. Besides their use in antivenoms for snakes, scorpions and spiders, for decades, pharmaceutical preparations of equine antibodies have been employed worldwide as a treatment for rabies, botulism and diphtheria best online viagra. Clinical trials of the institute’s antivenoms conducted in Colombia, Nigeria and Papua New Guinea have shown that these antibodies are safe in humans and rarely induce severe adverse reactions. More recently, equine immunoglobulin therapy has emerged as a potential treatment for a range of viruses that have limited therapeutic options.

    Among them are the highly pathogenic avian influenza viruses H5N1 and best online viagra H7N9 and the coronavirus that causes Middle East Respiratory Syndrome (MERS). €œAll this inspired several research groups to find ways to produce safe and effective COVID-19 equine immunoglobulins,” explains Fan Hui Wen, a researcher and project manager at the Butantan Institute in Brazil, which also has long experience in manufacturing such antibodies. She was not involved with the research at the Clodomiro Picado Institute. The Costa Rican project has an air of familiarity best online viagra. €œThe idea behind the antibody therapy for patients with COVID-19 is similar to that of treating patients suffering from snakebite poisoning,” says Alberto Alape Girón, a microbiologist and lead researcher of the COVID-19 project at the Clodomiro Picado Institute.

    €œWe want to generate specific antibodies against viral structures in horses, purify the antibodies and give them to patients who are starting to fight the infection but whose immune system still does not produce enough antibodies to clear the viral particles, ” he adds. Private citizens who wanted to help with the research donated best online viagra six horses to the institute. The animals were inoculated with engineered proteins of the SARS-CoV-2 virus. Three of the horses received best online viagra only S1, a portion of the protein that makes up the protruding spikes that stick out from the pathogen’s surface. The other three animals received a combination of four proteins from the coronavirus, including S1.

    After four rounds of inoculations administered every two weeks, the horses produced the desired level of antibodies. At this point, their blood was extracted, and the best online viagra red blood cells were separated from the plasma and returned to the horses. €œPlasma is a very complex mixture that has hundreds of proteins,” Alape-Girón says. €œAntibodies are one of the most abundant proteins, but there are others.” At the pharmaceutical plant, researchers used a technology developed by the Clodomiro Picado Institute to separate the antibodies from other proteins in the plasma and then purified them to obtain the therapeutic formulation for human testing. In total, the plant produced 1,000 10-milliliter vials of purified equine antibodies best online viagra.

    Half of them had antibodies against the S1 protein, and the other half contained the four proteins present in the coronavirus. €œJust one 10-mL vial has about 80 times the quantity of antibodies you can find in 800 mL of convalescent plasma, which is the plasma donated by someone who has overcome an infection of SARS-CoV-2,” Alape-Girón says. To test the efficacy of the equine antibodies, a few vials best online viagra were shipped to George Mason University’s National Center for Biodefense and Infectious Diseases (NCBID). €œWe wanted to determine if the SARS-CoV-2 virus could be neutralized by the horse-produced antibodies,” says Charles Bailey, a professor of biology and executive director of the NCBID. €œThe test we performed on the samples is called a plaque reduction neutralization test, PRNTest.

    We exposed the antibodies produced in horses, at various dilutions, to the SARS-CoV-2 virus growing on cell culture best online viagra. The virus was neutralized.” The results of the research are expected to be published in the near future. The next step—testing the equine antibodies in COVID-19 patients—will begin with an accelerated clinical trial this month. The antibodies’ safety and efficacy will be examined in a group of 26 patients with COVID-19 who have been hospitalized best online viagra but not placed in an intensive care unit. The results are expected by the end of September.

    If they are positive, the research will then move to a large-scale trial with hundreds of patients. And if the equine antibodies are shown to best online viagra be effective, the Clodomiro Picado Institute could immunize more horses to scale up and produce enough of them to cover Costa Rica’s demand—and probably that of its neighbors. It received a $500,000 grant on Aug. 13 from the Central American Bank for Economic Integration to move ahead with equine antibody research. Unlike monoclonal antibodies, which are being developed to target a specific molecular best online viagra region, or epitope, on the surface of SARS-CoV-2 to elicit an immune response, horse polyclonal antibodies against SARS-CoV-2 recognize multiple epitopes.

    The lower specificity translates into a more inexpensive manufacturing process. Alape-Girón estimates that a vial of equine antibodies will cost $100 to produce, whereas a treatment with monoclonal antibodies could be best online viagra 10 times more expensive. €œIt’s not the highest technology,” Macaya says. €œIt’s not a monoclonal antibody, but it allows us the benefit of speed, and it’s a very pragmatic approach.” Further, “if this were a monoclonal antibody, you would need a big factory to produce them,” he adds. €œHere, the best online viagra horses are the factories—at least for the production part.

    Then comes the purification part, which is an industrial process, but the Clodomiro Picado Institute already has that infrastructure.” Fan says this description mirrors her experience at the Butantan Institute in Brazil. €œPolyclonal antibody products can be made in large quantities, and cost-effectively, to respond to large-scale pandemic situations, such as the infection by SARS-CoV-2”, she says. Currently, the best online viagra Butantan Institute is preparing horses to be immunized with portions of inactivated SARS-COV-2 virus, which were isolated, cultured and purified, using its expertise in the production of influenza virus vaccines. Even though the development protocols differ at the Brazilian and Costa Rican institutes, Fan predicts their antibodies “will have equivalent efficiency and safety in the treatment of COVID-19 patients.” Even farther south in South America, scientists in Argentina are also developing a potential therapy for COVID-19 patients using equine antibodies, while other researchers worldwide are exploring antibodies against SARS-CoV-2 from llamas and cows. The objective behind all of these projects is the same.

    To save lives while waiting best online viagra for a vaccine to become available. Costa Rica has more than 28,000 cases of COVID-19. "We have over 100 patients in the ICU," Macaya says. "And our ICU capacity, as with any country, best online viagra is limited." His hope is that equine antibodies will prove to be “a very valuable tool in keeping our health care system from collapsing at the ICU level and, obviously, preventing deaths. That’s the ultimate goal.” Read more about the coronavirus outbreak from Scientific American here.

    And read coverage from our international network of magazines here.Editor’s Note (9/4/20). Understanding how the immune system best online viagra goes awry in COVID-19 may help prevent the most severe and deadly cases. Earlier this year Scientific American explained how administering an antiviral protein called interferon at just the right time may help. When the immune system fights viruses, timing is key. And this maxim best online viagra may be especially true for its defense against the deadly severe form of COVID-19.

    Several new studies of immune response to SARS-CoV-2, the virus that causes the disease, suggest timing could be critical for a class of proteins known as interferons, which are being researched as potential treatments. These immune proteins suppress viral replication early in disease. Yet if they are active later, some scientists think they best online viagra can exacerbate the harmful inflammation that forces some COVID-19 patients onto life support. Interferons are “a double-edged sword,” says immunologist Eui-Cheol Shin of the Korea Advanced Institute of Science and Technology. Researchers have been looking at both of that sword’s edges.

    About a decade ago, when Shin was studying the viral disease hepatitis C, interferons were used best online viagra as a standard treatment. But examinations of some conditions suggested they should not be employed. For example, researchers in Paris found that too much of the proteins can lead to a diseases known as children’s interferonopathies best online viagra. In a sense, each of these two perceptions of interferons is correct. And understanding when, and to what extent, using them is warranted could be a critical factor in treating COVID-19.

    The researchers in Paris analyzed blood from 50 people with varying COVID-19 severity and best online viagra 18 healthy controls. They determined that severely ill patients had lower overall counts of lymphocytes (a type of white blood cell). Using techniques to analyze broad-based gene activity and measure specific proteins, two trends stood out. Compared with patients with milder forms of the disease, people with severe COVID-19 had an exaggerated inflammatory response, coupled with best online viagra a marked decrease in interferons. And among severe COVID-19 patients, the interferon deficiency was worse in those who died versus those who stabilized, the team reported on July 13 in Science.

    €œWe were surprised,” says Benjamin Terrier, a clinician-researcher at Cochin Hospital in Paris, who was co-senior author of the study. €œIt was not our hypothesis.” An analysis published in the May 28 issue of Cell by researchers at the Icahn School of Medicine at Mount Sinai turned best online viagra up a similar dual signature. Low interferon levels and elevated inflammatory proteins. Meanwhile, in another new study, Shin and his colleagues used single-cell RNA sequencing to analyze gene activity in immune cells. They analyzed blood samples from eight patients with mild or severe COVID-19, four healthy donors and five people with severe influenza—more than 59,000 cells in best online viagra total.

    The researchers employed computer algorithms to compare individual cells’ RNA, and they expected patterns to cluster by cell type. That is, they anticipated that T cells, lymphocytes that coordinate an immune response or kill invading pathogens, would look a lot alike, whether they were taken from patients with COVID-19 or influenza. But that best online viagra was not the case. Instead the cellular profiles grouped by disease. For example, T cells from COVID-19 patients did not resemble those from people with influenza.

    Rather they looked more like COVID-19 B cells, best online viagra Shin says. This curious observation prompted his team to search for molecules that might serve as a common mediator influencing various immune cells. Comparing gene activity profiles, the researchers first noticed a flu-COVID dichotomy. Influenza cells showed higher activity in genes regulated best online viagra by interferons, whereas inflammatory genes driven by so-called tumor necrosis factor (TNF) and interleukin-1 beta (IL-1β) predominated in COVID-19. They then compared severe versus mild COVID-19 samples and focused on a specific pool of immune cells called monocytes.

    In severe COVID-19 patients, these first-defender cells had increased activity in interferon-stimulated genes in addition to the TNF/IL-1β inflammatory genes. But mild COVID-19 monocytes best online viagra only had the TNF/IL-1β signature, Shin and his colleagues reported on July 10 in Science Immunology. At first glance, the recent French and South Korean papers seemed to reach contradictory conclusions—with severely ill COVID-19 patients showing weaker interferon responses in Terrier and his colleagues’ analysis and more interferon activity in Shin and his colleagues’ study. The difference could come down to technique best online viagra and timing. The French researchers analyzed RNA in samples containing mixtures of immune cells, whereas the South Korean team sequenced RNA in individual cells and observed interferon differences in monocytes.

    But because monocytes make up just a tenth of total make up less than a tenth of white blood cells, an increased signal in this population could be obscured by other cells in the French team’s bulk samples, Shin suggests. There is another side to best online viagra the coin, however. Multiple immune cells produce interferons and are presumably influenced by the proteins. Yet the Korean team’s single-cell profiling only looked at interferons’ effect on monocytes. €œWhat is the impact of a change in one small cell population on the best online viagra whole system?.

    It’s really complicated to interpret,” Terrier says. €œThe interferon response is a little bit tricky,” says Rudragouda Channappanavar, a viral immunologist at the University of Tennessee Health Science Center, who was not involved with the new studies. The response protects best online viagra the body from infections by thwarting viral replication. €œThe body needs it, without a doubt,” he says. €œBut viruses are smart.

    They have several proteins that can antagonize and suppress early interferon responses.” One of SARS-CoV-2’s own defenders, a viral protein called Nsp1, can shut down the host cell’s production of immune molecules, including interferons, best online viagra researchers in Munich reported on July 17 in Science. In earlier studies with Stanley Perlman of the University of Iowa, Channappanavar analyzed mouse models for the coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Those studies showed that “if the interferon response begins before viral replication peaks, we will have protective immunity,” he says. If the best online viagra viruses thwart this antiviral defense, however, the delayed interferon response becomes pathogenic—summoning too many monocytes, which secrete inflammatory molecules and cause tissue damage. €œIt’s the relative timing of interferon with virus replication that’s the key,” Channappanavar says.

    Therapeutically, the findings suggest that interferons matter in the initial phase of infection. €œIf you give interferon early, you can best online viagra really increase the antiviral response. This is where you gain the most,” says Miriam Merad, who directs the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai and was not involved with the new research. If a person with COVID-19 has already progressed to having inflammation, “and you go in and give interferon, you are going to make things worse,” she says. In an open-label preprint study in China, interferon nasal drops prevented the disease in at-risk medical staff best online viagra who had treated infected individuals.

    Early unpublished data from COVID-19 patients hospitalized in the U.K. Suggest that interferons inhaled directly into the lungs shortened hospital stays and increased odds of recovery. And a randomized trial in Iran is testing whether the proteins best online viagra can enhance a base therapeutic regimen in moderate to severe COVID-19 patients. Read more about the coronavirus outbreak from Scientific American here. And read coverage from our international network of magazines here..

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    As SARS-CoV-2 continues its global viagra capsule spread, it’s possible that one of the pillars of Covid-19 pandemic control — universal facial masking — viagra femenino might help reduce the severity of disease and ensure that a greater proportion of new infections are asymptomatic. If this hypothesis is borne out, universal masking could become a form of “variolation” that would generate immunity and thereby slow the spread of the virus in the United States and elsewhere, as we await a vaccine.One important reason for population-wide facial masking became apparent in March, when reports started to circulate describing the high rates of SARS-CoV-2 viral shedding from the noses and mouths of patients who were presymptomatic or asymptomatic — shedding rates equivalent to those among symptomatic patients.1 Universal facial masking seemed to be a possible way to prevent transmission from asymptomatic infected people. The Centers for Disease Control and Prevention (CDC) therefore recommended on April 3 that the public wear cloth face coverings in areas with high rates of community transmission — a viagra capsule recommendation that has been unevenly followed across the United States.Past evidence related to other respiratory viruses indicates that facial masking can also protect the wearer from becoming infected, by blocking viral particles from entering the nose and mouth.2 Epidemiologic investigations conducted around the world — especially in Asian countries that became accustomed to population-wide masking during the 2003 SARS pandemic — have suggested that there is a strong relationship between public masking and pandemic control.

    Recent data from Boston demonstrate that SARS-CoV-2 infections decreased among health care workers after universal masking was implemented in municipal hospitals in late March.SARS-CoV-2 has the protean ability to cause myriad clinical manifestations, ranging from a complete lack of symptoms to pneumonia, acute respiratory distress syndrome, and death. Recent virologic, epidemiologic, and ecologic data have led to the hypothesis that facial masking may also reduce the severity of disease among people who do become infected.3 This possibility is consistent with a long-standing theory of viagra capsule viral pathogenesis, which holds that the severity of disease is proportionate to the viral inoculum received. Since 1938, researchers have explored, primarily in animal models, the concept of the lethal dose of a virus — or the dose at which 50% of exposed hosts die (LD50).

    With viral infections in which host immune responses play a predominant role in viral pathogenesis, such as SARS-CoV-2, high doses of viral inoculum can overwhelm and dysregulate innate immune defenses, viagra capsule increasing the severity of disease. Indeed, down-regulating immunopathology is one mechanism by which dexamethasone improves outcomes in severe Covid-19 infection. As proof of concept of viral inocula influencing disease manifestations, higher doses of administered virus led to more severe manifestations of Covid-19 in a Syrian hamster model of SARS-CoV-2 infection.4If the viral inoculum matters in determining the severity of SARS-CoV-2 infection, an additional hypothesized reason for wearing facial masks would be to reduce the viral inoculum to which the wearer is exposed and the subsequent clinical impact of the disease.

    Since masks can filter out some virus-containing droplets (with viagra capsule filtering capacity determined by mask type),2 masking might reduce the inoculum that an exposed person inhales. If this theory bears out, population-wide masking, with any type of mask that increases acceptability and adherence,2 might contribute to increasing the proportion of SARS-CoV-2 infections that are asymptomatic. The typical rate of asymptomatic infection with SARS-CoV-2 was estimated to be 40% by the CDC in mid-July, but asymptomatic infection rates are reported to be higher than 80% in settings with universal facial masking, which viagra capsule provides observational evidence for this hypothesis.

    Countries that have adopted population-wide masking have fared better in terms of rates of severe Covid-related illnesses and death, which, in environments with limited testing, suggests a shift from symptomatic to asymptomatic infections. Another experiment in the Syrian hamster model simulated surgical masking of the animals and showed that with simulated masking, hamsters were less likely to get infected, and if they did get viagra capsule infected, they either were asymptomatic or had milder symptoms than unmasked hamsters.The most obvious way to spare society the devastating effects of Covid-19 is to promote measures to reduce both transmission and severity of illness. But SARS-CoV-2 is highly transmissible, cannot be contained by syndromic-based surveillance alone,1 and is proving difficult to eradicate, even in regions that implemented strict initial control measures.

    Efforts to increase testing and containment in the United States have been ongoing and variably successful, owing in part to the recent increase in demand for testing.The hopes for vaccines are pinned not just on infection prevention. Most vaccine trials include a viagra capsule secondary outcome of decreasing the severity of illness, since increasing the proportion of cases in which disease is mild or asymptomatic would be a public health victory. Universal masking seems to reduce the rate of new infections.

    We hypothesize that by reducing the viral inoculum, it would also increase the proportion of infected people who remain asymptomatic.3In an outbreak on a closed Argentinian cruise ship, for example, where passengers were provided with surgical masks and staff with N95 viagra capsule masks, the rate of asymptomatic infection was 81% (as compared with 20% in earlier cruise ship outbreaks without universal masking). In two recent outbreaks in U.S. Food-processing plants, where all workers were issued masks each day and were required to wear them, the proportion of asymptomatic infections among the more than 500 people who became infected was 95%, with only 5% in each outbreak experiencing mild-to-moderate symptoms.3 Case-fatality rates in countries with mandatory or enforced population-wide masking have remained low, even with resurgences of cases after lockdowns were lifted.Variolation was a process whereby people who were susceptible to smallpox were inoculated with material taken from a vesicle of a person with smallpox, viagra capsule with the intent of causing a mild infection and subsequent immunity.

    Variolation was practiced only until the introduction of the variola vaccine, which ultimately eradicated smallpox. Despite concerns regarding safety, worldwide distribution, and eventual uptake, the world has high hopes for a highly effective SARS-CoV-2 vaccine, and as of early September, 34 vaccine candidates were in clinical evaluation, with hundreds more in development.While we await the results of vaccine trials, however, any public health measure that could increase viagra capsule the proportion of asymptomatic SARS-CoV-2 infections may both make the infection less deadly and increase population-wide immunity without severe illnesses and deaths. Reinfection with SARS-CoV-2 seems to be rare, despite more than 8 months of circulation worldwide and as suggested by a macaque model.

    The scientific community has been clarifying for some time the humoral and cell-mediated components of the adaptive immune response to SARS-CoV-2 and the inadequacy of antibody-based seroprevalence studies to estimate the level of more durable T-cell and memory B-cell immunity to SARS-CoV-2. Promising data have been emerging in recent weeks suggesting that strong cell-mediated immunity results from even mild or asymptomatic SARS-CoV-2 infection,5 so any public health strategy that could reduce the severity of disease should increase population-wide immunity as well.To test our hypothesis that population-wide masking is one of those strategies, we need further studies comparing the rate of asymptomatic infection viagra capsule in areas with and areas without universal masking. To test the variolation hypothesis, we will need more studies comparing the strength and durability of SARS-CoV-2–specific T-cell immunity between people with asymptomatic infection and those with symptomatic infection, as well as a demonstration of the natural slowing of SARS-CoV-2 spread in areas with a high proportion of asymptomatic infections.Ultimately, combating the pandemic will involve driving down both transmission rates and severity of disease.

    Increasing evidence suggests that population-wide facial masking might benefit both components of the response.Trial viagra capsule Population Table 1. Table 1. Demographic Characteristics of the Participants in the NVX-CoV2373 Trial at viagra capsule Enrollment.

    The trial was initiated on May 26, 2020. 134 participants underwent randomization between May 27 and June 6, 2020, including 3 participants who were to serve as backups for sentinel dosing and who immediately withdrew from the trial without being vaccinated (Fig. S1).

    Of the 131 participants who received injections, 23 received placebo (group A), 25 received 25-μg doses of rSARS-CoV-2 (group B), 29 received 5-μg doses of rSARS-CoV-2 plus Matrix-M1, including three sentinels (group C), 28 received 25-μg doses of rSARS-CoV-2 plus Matrix-M1, including three sentinels (group D), and 26 received a single 25-μg dose of rSARS-CoV-2 plus Matrix-M1 followed by a single dose of placebo (group E). All 131 participants received their first vaccination on day 0, and all but 3 received their second vaccination at least 21 days later. Exceptions include 2 in the placebo group (group A) who withdrew consent (unrelated to any adverse event) and 1 in the 25-μg rSARS-CoV-2 + Matrix-M1 group (group D) who had an unsolicited adverse event (mild cellulitis.

    See below). Demographic characteristics of the participants are presented in Table 1. Of note, missing data were infrequent.

    Safety Outcomes No serious adverse events or adverse events of special interest were reported, and vaccination pause rules were not implemented. As noted above, one participant did not receive a second vaccination owing to an unsolicited adverse event, mild cellulitis, that was associated with infection after an intravenous cannula placement to address an unrelated mild adverse event that occurred during the second week of follow-up. Second vaccination was withheld because the participant was still recovering and receiving antibiotics.

    This participant remains in the trial. Figure 2. Figure 2.

    Solicited Local and Systemic Adverse Events. The percentage of participants in each vaccine group (groups A, B, C, D, and E) with adverse events according to the maximum FDA toxicity grade (mild, moderate, or severe) during the 7 days after each vaccination is plotted for solicited local (Panel A) and systemic (Panel B) adverse events. There were no grade 4 (life-threatening) events.

    Participants who reported 0 events make up the remainder of the 100% calculation (not displayed). Excluded were the three sentinel participants in groups C (5 μg + Matrix-M1, 5 μg + Matrix-M1) and D (25 μg + Matrix-M1, 25 μg + Matrix-M1), who received the trial vaccine in an open-label manner (see Table S7 for complete safety data on all participants).Overall reactogenicity was largely absent or mild, and second vaccinations were neither withheld nor delayed due to reactogenicity. After the first vaccination, local and systemic reactogenicity was absent or mild in the majority of participants (local.

    100%, 96%, 89%, 84%, and 88% of participants in groups A, B, C, D, and E, respectively. Systemic. 91%, 92%, 96%, 68%, and 89%) who were unaware of treatment assignment (Figure 2 and Table S7).

    Two participants (2%), one each in groups D and E, had severe adverse events (headache, fatigue, and malaise). Two participants, one each in groups A and E, had reactogenicity events (fatigue, malaise, and tenderness) that extended 2 days after day 7. After the second vaccination, local and systemic reactogenicity were absent or mild in the majority of participants in the five groups (local.

    100%, 100%, 65%, 67%, and 100% of participants, respectively. Systemic. 86%, 84%, 73%, 58%, and 96%) who were unaware of treatment assignment.

    One participant, in group D, had a severe local event (tenderness), and eight participants, one or two participants in each group, had severe systemic events. The most common severe systemic events were joint pain and fatigue. Only one participant, in group D, had fever (temperature, 38.1°C) after the second vaccination, on day 1 only.

    No adverse event extended beyond 7 days after the second vaccination. Of note, the mean duration of reactogenicity events was 2 days or less for both the first vaccination and second vaccination periods. Laboratory abnormalities of grade 2 or higher occurred in 13 participants (10%).

    9 after the first vaccination and 4 after the second vaccination (Table S8). Abnormal laboratory values were not associated with any clinical manifestations and showed no worsening with repeat vaccination. Six participants (5%.

    Five women and one man) had grade 2 or higher transient reductions in hemoglobin from baseline, with no evidence of hemolysis or microcytic anemia and with resolution within 7 to 21 days. Of the six, two had an absolute hemoglobin value (grade 2) that resolved or stabilized during the testing period. Four participants (3%), including one who had received placebo, had elevated liver enzymes that were noted after the first vaccination and resolved within 7 to 14 days (i.e., before the second vaccination).

    Vital signs remained stable immediately after vaccination and at all visits. Unsolicited adverse events (Table S9) were predominantly mild in severity (in 71%, 91%, 83%, 90%, and 82% of participants in groups A, B, C, D, and E, respectively) and were similarly distributed across the groups receiving adjuvanted and unadjuvanted vaccine. There were no reports of severe adverse events.

    Immunogenicity Outcomes Figure 3. Figure 3. SARS-CoV-2 Anti-Spike IgG and Neutralizing Antibody Responses.

    Shown are geometric mean anti-spike IgG enzyme-linked immunosorbent assay (ELISA) unit responses to recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) protein antigens (Panel A) and wild-type SARS-CoV-2 microneutralization assay at an inhibitory concentration greater than 99% (MN IC>99%) titer responses (Panel B) at baseline (day 0), 3 weeks after the first vaccination (day 21), and 2 weeks after the second vaccination (day 35) for the placebo group (group A), the 25-μg unadjuvanted group (group B), the 5-μg and 25-μg adjuvanted groups (groups C and D, respectively), and the 25-μg adjuvanted and placebo group (group E). Diamonds and whisker endpoints represent geometric mean titer values and 95% confidence intervals, respectively. The Covid-19 human convalescent serum panel includes specimens from PCR-confirmed Covid-19 participants, obtained from Baylor College of Medicine (29 specimens for ELISA and 32 specimens for MN IC>99%), with geometric mean titer values according to Covid-19 severity.

    The severity of Covid-19 is indicated by the colors of the dots for hospitalized patients (including those in intensive care), symptomatic outpatients (with samples collected in the emergency department), and asymptomatic patients who had been exposed to Covid-19 (with samples collected during contact and exposure assessment). Mean values (in black) for human convalescent serum are depicted next to (and of same color as) the category of Covid-19 patients, with the overall mean shown above the scatter plot (in black). For each trial vaccine group, the mean at day 35 is depicted above the scatterplot.ELISA anti-spike IgG geometric mean ELISA units (GMEUs) ranged from 105 to 116 at day 0.

    By day 21, responses had occurred for all adjuvanted regimens (1984, 2626, and 3317 GMEUs for groups C, D, and E, respectively), and geometric mean fold rises (GMFRs) exceeded those induced without adjuvant by a factor of at least 10 (Figure 3 and Table S10). Within 7 days after the second vaccination with adjuvant (day 28. Groups C and D), GMEUs had further increased by a factor of 8 (to 15,319 and 20,429, respectively) over responses seen with the first vaccination, and within 14 days (day 35), responses had more than doubled yet again (to 63,160 and 47,521, respectively), achieving GMFRs that were approximately 100 times greater than those observed with rSARS-CoV-2 alone.

    A single vaccination with adjuvant achieved GMEU levels similar to those in asymptomatic (exposed) patients with Covid-19 (1661), and a second vaccination with adjuvant achieved GMEU levels that exceeded those in convalescent serum from symptomatic outpatients with Covid-19 (7420) by a factor of at least 6 and rose to levels similar to those in convalescent serum from patients hospitalized with Covid-19 (53,391). The responses in the two-dose 5-μg and 25-μg adjuvanted vaccine regimens were similar, a finding that highlights the role of adjuvant dose sparing. Neutralizing antibodies were undetectable before vaccination and had patterns of response similar to those of anti-spike antibodies after vaccination with adjuvant (Figure 3 and Table S11).

    After the first vaccination (day 21), GMFRs were approximately 5 times greater with adjuvant (5.2, 6.3, and 5.9 for groups C, D, and E, respectively) than without adjuvant (1.1). By day 35, second vaccinations with adjuvant induced an increase more than 100 times greater (195 and 165 for groups C and D, respectively) than single vaccinations without adjuvant. When compared with convalescent serum, second vaccinations with adjuvant resulted in GMT levels approximately 4 times greater (3906 and 3305 for groups C and D, respectively) than those in symptomatic outpatients with Covid-19 (837) and approached the magnitude of levels observed in hospitalized patients with COVID-19 (7457).

    At day 35, ELISA anti-spike IgG GMEUs and neutralizing antibodies induced by the two-dose 5-μg and 25-μg adjuvanted vaccine regimens were 4 to 6 times greater than the geometric mean convalescent serum measures (8344 and 983, respectively). Figure 4. Figure 4.

    Correlation of Anti-Spike IgG and Neutralizing Antibody Responses. Shown are scatter plots of 100% wild-type neutralizing antibody responses and anti-spike IgG ELISA unit responses at 3 weeks after the first vaccination (day 21) and 2 weeks after the second vaccination (day 35) for the two-dose 25-μg unadjuvanted vaccine (group B. Panel A), the combined two-dose 5-μg and 25-μg adjuvanted vaccine (groups C and D, respectively.

    Panel B), and convalescent serum from patients with Covid-19 (Panel C). In Panel C, the severity of Covid-19 is indicated by the colors of the dots for hospitalized patients (including those in intensive care), symptomatic outpatients (with samples collected in the emergency department), and asymptomatic patients who had been exposed to Covid-19 (with samples collected during contact and exposure assessment).A strong correlation was observed between neutralizing antibody titers and anti-spike IgG GMEUs with adjuvanted vaccine at day 35 (correlation, 0.95) (Figure 4), a finding that was not observed with unadjuvanted vaccine (correlation, 0.76) but was similar to that of convalescent serum (correlation, 0.96). Two-dose regimens of 5-μg and 25-μg rSARS-CoV-2 plus Matrix-M1 produced similar magnitudes of response, and every participant had seroconversion according to either assay measurement.

    Reverse cumulative-distribution curves for day 35 are presented in Figure S2. Figure 5. Figure 5.

    RSARS-CoV-2 CD4+ T-cell Responses with or without Matrix-M1 Adjuvant. Frequencies of antigen-specific CD4+ T cells producing T helper 1 (Th1) cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 and for T helper 2 (Th2) cytokines interleukin-5 and interleukin-13 indicated cytokines from four participants each in the placebo (group A), 25-μg unadjuvanted (group B), 5-μg adjuvanted (group C), and 25-μg adjuvanted (group D) groups at baseline (day 0) and 1 week after the second vaccination (day 28) after stimulation with the recombinant spike protein. €œAny 2Th1” indicates CD4+ T cells that can produce two types of Th1 cytokines at the same time.

    €œAll 3 Th1” indicates CD4+ T cells that produce IFN-γ, TNF-α, and interleukin-2 simultaneously. €œBoth Th2” indicates CD4+ T cells that can produce Th2 cytokines interleukin-5 and interleukin-13 at the same time.T-cell responses in 16 participants who were randomly selected from groups A through D, 4 participants per group, showed that adjuvanted regimens induced antigen-specific polyfunctional CD4+ T-cell responses that were reflected in IFN-γ, IL-2, and TNF-α production on spike protein stimulation. A strong bias toward this Th1 phenotype was noted.

    Th2 responses (as measured by IL-5 and IL-13 cytokines) were minimal (Figure 5).In recent months, epidemiologists in the United States and throughout the world have been asked the same question by clinicians, journalists, and members of the public, “When will we have a vaccine?. € The obvious answer to this question would be, “When a candidate vaccine is demonstrated to be safe, effective, and available. That can be determined only by scientific data, not by a target calendar date.” But we realize that such a response, although accurate, overlooks much of what people are ultimately seeking to understand.The emphasis on “we” reveals that most people want much more than an estimated vaccine-delivery date.

    Their inquiry typically involves three concerns. First, when will the public be able to have confidence that available vaccines are safe and effective?. Second, when will a vaccine be available to people like them?.

    And third, when will vaccine uptake be high enough to enable a return to prepandemic conditions?. Often, the inquiry is also assessing whether the biotech and vaccine companies, government agencies, and http://www.amisdepasteur.fr/viagra-online-purchase/ medical experts involved in developing, licensing, and recommending use of Covid-19 vaccines realize that the responses they provide now will influence what happens later. There is often a sense that messages regarding Covid-19 vaccines can have problematic framing (e.g., “warp speed”) and make assertions that involve key terms (e.g., “safe” and “effective”) for which experts’ definitions may vary and may differ considerably from those of the general public and key subpopulations.As Covid-19 vaccines move into phase 3 clinical trials, enthusiasm about the innovative and sophisticated technologies being used needs to be replaced by consideration of the actions and messages that will foster trust among clinicians and the public.

    Although vast investments have been made in developing safe and effective vaccines, it is important to remember that it is the act of vaccination itself that prevents harm and saves lives. Considered fully, the question “When will we have a Covid-19 vaccine?. € makes clear the many ways in which efforts related to both the “when” and the “we” can affect vaccination uptake.

    Recognizing the significance of both aspects of the question can help public health officials and scientists both to hone current messaging related to Covid-19 vaccines and to build a better foundation for clinicians who will be educating patients and parents about vaccination.The recently released guidelines from the Food and Drug Administration (FDA) on testing of Covid-19 vaccine candidates are scientifically sound and indicate that no compromises will be made when it comes to evaluating safety and efficacy.1 This commitment needs to be stated repeatedly, made apparent during the vaccine testing and approval process, and supported by transparency. Assurances regarding the warp speed effort to develop a vaccine or to issue emergency use authorizations accelerating availability must make clear the ways in which clinical trials and the review processes used by federal agencies (the FDA, the National Institutes of Health, and the Centers for Disease Control and Prevention [CDC]) will objectively assess the safety and effectiveness of vaccines developed using new platforms. Clinicians and the public should have easy access to user-friendly materials that reference publicly available studies, data, and presentations related to safety and effectiveness.

    The FDA’s and CDC’s plans for robust longer-term, postlicensure vaccine safety and monitoring systems will also need to be made visible, particularly to health care professionals, who are essential to the success of these efforts.2The second key part of this question pertains to when a safe and effective Covid-19 vaccine will become available to some, most, or all people who want one. This question has technical and moral components, and the answers on both fronts could foster or impede public acceptance of a vaccine. Data from antibody testing suggest that about 90% of people are susceptible to Covid-19.

    Accepting that 60 to 70% of the population would have to be immune, either as a result of natural infection or vaccination, to achieve community protection (also known as herd immunity), about 200 million Americans and 5.6 billion people worldwide would need to be immune in order to end the pandemic. The possibility that it may take years to achieve the vaccination coverage necessary for everyone to be protected gives rise to difficult questions about priority groups and domestic and global access.Given public skepticism of government institutions and concerns about politicization of vaccine priorities, the recent establishment of a National Academy of Medicine (NAM) committee to formulate criteria to ensure equitable distribution of initial Covid-19 vaccines and to offer guidance on addressing vaccine hesitancy is an important step. The NAM report should be very helpful to the CDC’s Advisory Committee on Immunization Practices, the group that traditionally develops vaccination recommendations in the United States.

    The NAM’s deliberations about which groups will be prioritized for vaccination involve identifying the societal values that should be considered, and the report will communicate how these values informed its recommendations. Will the people at greatest risk for disease — such as health care workers, nursing home residents, prison inmates and workers, the elderly, people with underlying health conditions, and people from minority and low-income communities — be the first to obtain access?. Alternatively, will the top priority be reducing transmission by prioritizing the public workforce, essential workers, students, and young people who may be more likely to spread infection asymptomatically?.

    And how will the United States share vaccine doses with other countries, where infections could ultimately also pose a threat to Americans?. Releasing expert-committee reports, however, should not be equated with successfully communicating with the public about vaccine candidates and availability.3 In the United States and many other countries, new vaccines and vaccination recommendations are rarely released with substantial public information and educational resources. Most investments in communication with clinicians and the public happen when uptake of newly recommended vaccines, such as the human papillomavirus vaccine or seasonal influenza vaccine, falls short of goals.

    Not since the March of Dimes’s polio-vaccination efforts in the 1950s has there been major investment in public information and advocacy for new vaccines. There is already a flood of misinformation on social media and from antivaccine activists about new vaccines that could be licensed for Covid-19. If recent surveys suggesting that about half of Americans would accept a Covid-19 vaccine4 are accurate, it will take substantial resources and active, bipartisan political support to achieve the uptake levels needed to reach herd immunity thresholds.5High uptake of Covid-19 vaccines among prioritized groups should also not be assumed.

    Many people in these groups will want to be vaccinated, but their willingness will be affected by what is said, the way it is said, and who says it in the months ahead. Providing compelling, evidence-based information using culturally and linguistically appropriate messages and materials is a complex challenge. Having trusted people, such as public figures, political leaders, entertainment figures, and religious and community leaders, endorse vaccination can be an effective way of persuading the portion of the public that is open to such a recommendation.

    Conversely, persuading people who have doubts about or oppose a particular medical recommendation is difficult, requires commitment and engagement, and is often not successful.Finally, surveys suggest that physicians, nurses, and pharmacists remain the most highly trusted professionals in the United States. Extensive, active, and ongoing involvement by clinicians is essential to attaining the high uptake of Covid-19 vaccines that will be needed for society to return to prepandemic conditions. Nurses and physicians are the most important and influential sources of vaccination information for patients and parents.

    Throughout the world, health care professionals will need to be well-informed and strong endorsers of Covid-19 vaccination.A more complete answer to the common question is therefore, “We will have a safe and effective Covid-19 vaccine when the research studies, engagement processes, communication, and education efforts undertaken during the clinical trial stage have built trust and result in vaccination recommendations being understood, supported, and accepted by the vast majority of the public, priority and nonpriority groups alike.” Efforts to engage diverse stakeholders and communities in Covid-19 vaccination education strategies, key messages, and materials for clinicians and the public are needed now.Specificity of SARS-CoV-2 Antibody Assays Both assays measuring pan-Ig antibodies had low numbers of false positives among samples collected in 2017. There were 0 and 1 false positives for the two assays among 472 samples, results that compared favorably with those obtained with the single IgM anti-N and IgG anti-N assays (Table S3). Because of the low prevalence of SARS-CoV-2 infection in Iceland, we required positive results from both pan-Ig antibody assays for a sample to be considered seropositive (see Supplementary Methods in Supplementary Appendix 1).

    None of the samples collected in early 2020 group were seropositive, which indicates that the virus had not spread widely in Iceland before February 2020. SARS-CoV-2 Antibodies among qPCR-Positive Persons Figure 2. Figure 2.

    Antibody Prevalence and Titers among qPCR-Positive Cases as a Function of Time since Diagnosis by qPCR. Shown are the percentages of samples positive for both pan-Ig antibody assays and the antibody titers. Red denotes the count or percentage of samples among persons during their hospitalization (249 samples from 48 persons), and blue denotes the count or percentage of samples among persons after they were declared recovered (1853 samples from 1215 persons).

    Vertical bars denote 95% confidence intervals. The dashed lines indicated the thresholds for a test to be declared positive. OD denotes optical density, and RBD receptor binding domain.Table 1.

    Table 1. Prevalence of SARS-CoV-2 Antibodies by Sample Collection as Measured by Two Pan-Ig Antibody Assays. Twenty-five days after diagnosis by qPCR, more than 90% of samples from recovered persons tested positive with both pan-Ig antibody assays, and the percentage of persons testing positive remained stable thereafter (Figure 2 and Fig.

    S2). Hospitalized persons seroconverted more frequently and quickly after qPCR diagnosis than did nonhospitalized persons (Figure 2 and Fig. S3).

    Of 1215 persons who had recovered (on the basis of results for the most recently obtained sample from persons for whom we had multiple samples), 1107 were seropositive (91.1%. 95% confidence interval [CI], 89.4 to 92.6) (Table 1 and Table S4). Since some diagnoses may have been made on the basis of false positive qPCR results, we determined that 91.1% represents the lower bound of sensitivity of the combined pan-Ig tests for the detection of SARS-CoV-2 antibodies among recovered persons.

    Table 2. Table 2. Results of Repeated Pan-Ig Antibody Tests among Recovered qPCR-Diagnosed Persons.

    Among the 487 recovered persons with two or more samples, 19 (4%) had different pan-Ig antibody test results at different time points (Table 2 and Fig. S4). It is notable that of the 22 persons with an early sample that tested negative for both pan-Ig antibodies, 19 remained negative at the most recent test date (again, for both antibodies).

    One person tested positive for both pan-Ig antibodies in the first test and negative for both in the most recent test. The longitudinal changes in antibody levels among recovered persons were consistent with the cross-sectional results (Fig. S5).

    Antibody levels were higher in the last sample than in the first sample when the antibodies were measured with the two pan-Ig assays, slightly lower than in the first sample when measured with IgG anti-N and IgG anti-S1 assays, and substantially lower than in the first sample when measured with IgM anti-N and IgA anti-S1 assays. IgG anti-N, IgM anti-N, IgG anti-S1, and IgA anti-S1 antibody levels were correlated among the qPCR-positive persons (Figs. S5 and S6 and Table S5).

    Antibody levels measured with both pan-Ig antibody assays increased over the first 2 months after qPCR diagnosis and remained at a plateau over the next 2 months of the study. IgM anti-N antibody levels increased rapidly soon after diagnosis and then fell rapidly and were generally not detected after 2 months. IgA anti-S1 antibodies decreased 1 month after diagnosis and remained detectable thereafter.

    IgG anti-N and anti-S1 antibody levels increased during the first 6 weeks after diagnosis and then decreased slightly. SARS-CoV-2 Infection in Quarantine Table 3. Table 3.

    SARS-CoV-2 Infection among Quarantined Persons According to Exposure Type and Presence of Symptoms. Of the 1797 qPCR-positive Icelanders, 1088 (61%) were in quarantine when SARS-CoV-2 infection was diagnosed by qPCR. We tested for antibodies among 4222 quarantined persons who had not tested qPCR-positive (they had received a negative result by qPCR or had simply not been tested).

    Of those 4222 quarantined persons, 97 (2.3%. 95% CI, 1.9 to 2.8) were seropositive (Table 1). Those with household exposure were 5.2 (95% CI, 3.3 to 8.0) times more likely to be seropositive than those with other types of exposure (Table 3).

    Similarly, a positive result by qPCR for those with household exposure was 5.2 (95% CI, 4.5 to 6.1) times more likely than for those with other types of exposure. When these two sets of results (qPCR-positive and seropositive) were combined, we calculated that 26.6% of quarantined persons with household exposure and 5.0% of quarantined persons without household exposure were infected. Those who had symptoms during quarantine were 3.2 (95% CI, 1.7 to 6.2) times more likely to be seropositive and 18.2 times (95% CI, 14.8 to 22.4) more likely to test positive with qPCR than those without symptoms.

    We also tested persons in two regions of Iceland affected by cluster outbreaks. In a SARS-CoV-2 cluster in Vestfirdir, 1.4% of residents were qPCR-positive and 10% of residents were quarantined. We found that none of the 326 persons outside quarantine who had not been tested by qPCR (or who tested negative) were seropositive.

    In a cluster in Vestmannaeyjar, 2.3% of residents were qPCR-positive and 13% of residents were quarantined. Of the 447 quarantined persons who had not received a qPCR-positive result, 4 were seropositive (0.9%. 95% CI, 0.3 to 2.1).

    Of the 663 outside quarantine in Vestmannaeyjar, 3 were seropositive (0.5%. 95% CI, 0.1 to 0.2%). SARS-CoV-2 Seroprevalence in Iceland None of the serum samples collected from 470 healthy Icelanders between February 18 and March 9, 2020, tested positive for both pan-Ig antibodies, although four were positive for the pan-Ig anti-N assay (0.9%), a finding that suggests that the virus had not spread widely in Iceland before March 9.

    Of the 18,609 persons tested for SARS-CoV-2 antibodies through contact with the Icelandic health care system for reasons other than Covid-19, 39 were positive for both pan-Ig antibody assays (estimated seroprevalence by weighting the sample on the basis of residence, sex, and 10-year age category, 0.3%. 95% CI, 0.2 to 0.4). There were regional differences in the percentages of qPCR-positive persons across Iceland that were roughly proportional to the percentage of people quarantined (Table S6).

    However, after exclusion of the qPCR-positive and quarantined persons, the percentage of persons who tested positive for SARS-CoV-2 antibodies did not correlate with the percentage of those who tested positive by qPCR. The estimated seroprevalence in the random sample collection from Reykjavik (0.4%. 95% CI, 0.3 to 0.6) was similar to that in the Health Care group (0.3%.

    95% CI, 0.2 to 0.4) (Table S6). We calculate that 0.5% of the residents of Iceland have tested positive with qPCR. The 2.3% with SARS-CoV-2 seroconversion among persons in quarantine extrapolates to 0.1% of Icelandic residents.

    On the basis of this finding and the seroprevalence from the Health Care group, we estimate that 0.9% (95% CI, 0.8 to 0.9) of the population of Iceland has been infected by SARS-CoV-2. Approximately 56% of all SARS-CoV-2 infections were therefore diagnosed by qPCR, 14% occurred in quarantine without having been diagnosed with qPCR, and the remaining 30% of infections occurred outside quarantine and were not detected by qPCR. Deaths from Covid-19 in Iceland In Iceland, 10 deaths have been attributed to Covid-19, which corresponds to 3 deaths per 100,000 nationwide.

    Among the qPCR-positive cases, 0.6% (95% CI, 0.3 to 1.0) were fatal. Using the 0.9% prevalence of SARS-CoV-2 infection in Iceland as the denominator, however, we calculate an infection fatality risk of 0.3% (95% CI, 0.2 to 0.6). Stratified by age, the infection fatality risk was substantially lower in those 70 years old or younger (0.1%.

    95% CI, 0.0 to 0.3) than in those over 70 years of age (4.4%. 95% CI, 1.9 to 8.4) (Table S7). Age, Sex, Clinical Characteristics, and Antibody Levels Table 4.

    Table 4. Association of Existing Conditions and Covid-19 Severity with SARS-CoV-2 Antibody Levels among Recovered Persons. SARS-CoV-2 antibody levels were higher in older people and in those who were hospitalized (Table 4, and Table S8 [described in Supplementary Appendix 1 and available in Supplementary Appendix 2]).

    Pan-Ig anti–S1-RBD and IgA anti-S1 levels were lower in female persons. Of the preexisting conditions, and after adjustment for multiple testing, we found that body-mass index, smoking status, and use of antiinflammatory medication were associated with SARS-CoV-2 antibody levels. Body-mass index correlated positively with antibody levels.

    Smokers and users of antiinflammatory medication had lower antibody levels. With respect to clinical characteristics, antibody levels were most strongly associated with hospitalization and clinical severity, followed by clinical symptoms such as fever, maximum temperature reading, cough, and loss of appetite. Severity of these individual symptoms, with the exception of loss of energy, was associated with higher antibody levels.In a laboratory setting, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was inoculated into human bronchial epithelial cells.

    This inoculation, which was performed in a biosafety level 3 facility, had a multiplicity of infection (indicating the ratio of virus particles to targeted airway cells) of 3:1. These cells were then examined 96 hours after infection with the use of scanning electron microscopy. An en face image (Panel A) shows an infected ciliated cell with strands of mucus attached to the cilia tips.

    At higher magnification, an image (Panel B) shows the structure and density of SARS-CoV-2 virions produced by human airway epithelial cells. Virus production was approximately 3×106 plaque-forming units per culture, a finding that is consistent with a high number of virions produced and released per cell.Camille Ehre, Ph.D.Baric and Boucher Laboratories at University of North Carolina School of Medicine, Chapel Hill, NC [email protected].

    As SARS-CoV-2 continues its global spread, it’s possible that one of the pillars of Covid-19 pandemic control — universal facial masking — might Click This Link help reduce the severity of disease and ensure that a greater proportion of new infections are best online viagra asymptomatic. If this hypothesis is borne out, universal masking could become a form of “variolation” that would generate immunity and thereby slow the spread of the virus in the United States and elsewhere, as we await a vaccine.One important reason for population-wide facial masking became apparent in March, when reports started to circulate describing the high rates of SARS-CoV-2 viral shedding from the noses and mouths of patients who were presymptomatic or asymptomatic — shedding rates equivalent to those among symptomatic patients.1 Universal facial masking seemed to be a possible way to prevent transmission from asymptomatic infected people. The Centers for Disease Control and Prevention (CDC) therefore recommended on April best online viagra 3 that the public wear cloth face coverings in areas with high rates of community transmission — a recommendation that has been unevenly followed across the United States.Past evidence related to other respiratory viruses indicates that facial masking can also protect the wearer from becoming infected, by blocking viral particles from entering the nose and mouth.2 Epidemiologic investigations conducted around the world — especially in Asian countries that became accustomed to population-wide masking during the 2003 SARS pandemic — have suggested that there is a strong relationship between public masking and pandemic control.

    Recent data from Boston demonstrate that SARS-CoV-2 infections decreased among health care workers after universal masking was implemented in municipal hospitals in late March.SARS-CoV-2 has the protean ability to cause myriad clinical manifestations, ranging from a complete lack of symptoms to pneumonia, acute respiratory distress syndrome, and death. Recent virologic, epidemiologic, and ecologic data have led to the hypothesis that facial masking may also reduce the severity of best online viagra disease among people who do become infected.3 This possibility is consistent with a long-standing theory of viral pathogenesis, which holds that the severity of disease is proportionate to the viral inoculum received. Since 1938, researchers have explored, primarily in animal models, the concept of the lethal dose of a virus — or the dose at which 50% of exposed hosts die (LD50).

    With viral infections in which host immune responses play a predominant role in viral pathogenesis, such as SARS-CoV-2, high doses best online viagra of viral inoculum can overwhelm and dysregulate innate immune defenses, increasing the severity of disease. Indeed, down-regulating immunopathology is one mechanism by which dexamethasone improves outcomes in severe Covid-19 infection. As proof of concept of viral inocula influencing disease manifestations, higher doses of administered virus led to more severe manifestations of Covid-19 in a Syrian hamster model of SARS-CoV-2 infection.4If the viral inoculum matters in determining the severity of SARS-CoV-2 infection, an additional hypothesized reason for wearing facial masks would be to reduce the viral inoculum to which the wearer is exposed and the subsequent clinical impact of the disease.

    Since masks can filter out some virus-containing droplets (with best online viagra filtering capacity determined by mask type),2 masking might reduce the inoculum that an exposed person inhales. If this theory bears out, population-wide masking, with any type of mask that increases acceptability and adherence,2 might contribute to increasing the proportion of SARS-CoV-2 infections that are asymptomatic. The typical rate of asymptomatic infection with SARS-CoV-2 was estimated to be 40% by the CDC in mid-July, but asymptomatic infection rates are reported to be higher than 80% in settings with universal facial masking, which best online viagra provides observational evidence for this hypothesis.

    Countries that have adopted population-wide masking have fared better in terms of rates of severe Covid-related illnesses and death, which, in environments with limited testing, suggests a shift from symptomatic to asymptomatic infections. Another experiment in the Syrian hamster best online viagra model simulated surgical masking of the animals and showed that with simulated masking, hamsters were less likely to get infected, and if they did get infected, they either were asymptomatic or had milder symptoms than unmasked hamsters.The most obvious way to spare society the devastating effects of Covid-19 is to promote measures to reduce both transmission and severity of illness. But SARS-CoV-2 is highly transmissible, cannot be contained by syndromic-based surveillance alone,1 and is proving difficult to eradicate, even in regions that implemented strict initial control measures.

    Efforts to increase testing and containment in the United States have been ongoing and variably successful, owing in part to the recent increase in demand for testing.The hopes for vaccines are pinned not just on infection prevention. Most vaccine trials include a secondary outcome of decreasing the severity of illness, since increasing the proportion of cases in which disease is mild best online viagra or asymptomatic would be a public health victory. Universal masking seems to reduce the rate of new infections.

    We hypothesize that by best online viagra reducing the viral inoculum, it would also increase the proportion of infected people who remain asymptomatic.3In an outbreak on a closed Argentinian cruise ship, for example, where passengers were provided with surgical masks and staff with N95 masks, the rate of asymptomatic infection was 81% (as compared with 20% in earlier cruise ship outbreaks without universal masking). In two recent outbreaks in U.S. Food-processing plants, where all workers were issued masks best online viagra each day and were required to wear them, the proportion of asymptomatic infections among the more than 500 people who became infected was 95%, with only 5% in each outbreak experiencing mild-to-moderate symptoms.3 Case-fatality rates in countries with mandatory or enforced population-wide masking have remained low, even with resurgences of cases after lockdowns were lifted.Variolation was a process whereby people who were susceptible to smallpox were inoculated with material taken from a vesicle of a person with smallpox, with the intent of causing a mild infection and subsequent immunity.

    Variolation was practiced only until the introduction of the variola vaccine, which ultimately eradicated smallpox. Despite concerns regarding safety, worldwide distribution, and eventual uptake, the world has high hopes for a highly effective SARS-CoV-2 vaccine, and as of early September, 34 vaccine candidates were in clinical evaluation, with hundreds more in development.While we await the results of vaccine trials, however, any public health measure that could increase the proportion of asymptomatic SARS-CoV-2 best online viagra infections may both make the infection less deadly and increase population-wide immunity without severe illnesses and deaths. Reinfection with SARS-CoV-2 seems to be rare, despite more than 8 months of circulation worldwide and as suggested by a macaque model.

    The scientific community has been clarifying for some time the humoral and cell-mediated components of the adaptive immune response to SARS-CoV-2 and the inadequacy of antibody-based seroprevalence studies to estimate the level of more durable T-cell and memory B-cell immunity to SARS-CoV-2. Promising data have been emerging in recent weeks suggesting that strong cell-mediated immunity results from even mild or asymptomatic SARS-CoV-2 infection,5 so any public health strategy that could reduce the severity of disease should increase population-wide immunity as well.To test our hypothesis that population-wide best online viagra masking is one of those strategies, we need further studies comparing the rate of asymptomatic infection in areas with and areas without universal masking. To test the variolation hypothesis, we will need more studies comparing the strength and durability of SARS-CoV-2–specific T-cell immunity between people with asymptomatic infection and those with symptomatic infection, as well as a demonstration of the natural slowing of SARS-CoV-2 spread in areas with a high proportion of asymptomatic infections.Ultimately, combating the pandemic will involve driving down both transmission rates and severity of disease.

    Increasing evidence suggests that population-wide facial masking might benefit both components of the response.Trial best online viagra Population Table 1. Table 1. Demographic Characteristics of the Participants in the NVX-CoV2373 Trial at best online viagra Enrollment.

    The trial was initiated on May 26, 2020. 134 participants underwent randomization between May 27 and June 6, 2020, including 3 participants who were to serve as backups for sentinel dosing and who immediately withdrew from the trial without being vaccinated (Fig. S1).

    Of the 131 participants who received injections, 23 received placebo (group A), 25 received 25-μg doses of rSARS-CoV-2 (group B), 29 received 5-μg doses of rSARS-CoV-2 plus Matrix-M1, including three sentinels (group C), 28 received 25-μg doses of rSARS-CoV-2 plus Matrix-M1, including three sentinels (group D), and 26 received a single 25-μg dose of rSARS-CoV-2 plus Matrix-M1 followed by a single dose of placebo (group E). All 131 participants received their first vaccination on day 0, and all but 3 received their second vaccination at least 21 days later. Exceptions include 2 in the placebo group (group A) who withdrew consent (unrelated to any adverse event) and 1 in the 25-μg rSARS-CoV-2 + Matrix-M1 group (group D) who had an unsolicited adverse event (mild cellulitis.

    See below). Demographic characteristics of the participants are presented in Table 1. Of note, missing data were infrequent.

    Safety Outcomes No serious adverse events or adverse events of special interest were reported, and vaccination pause rules were not implemented. As noted above, one participant did not receive a second vaccination owing to an unsolicited adverse event, mild cellulitis, that was associated with infection after an intravenous cannula placement to address an unrelated mild adverse event that occurred during the second week of follow-up. Second vaccination was withheld because the participant was still recovering and receiving antibiotics.

    This participant remains in the trial. Figure 2. Figure 2.

    Solicited Local and Systemic Adverse Events. The percentage of participants in each vaccine group (groups A, B, C, D, and E) with adverse events according to the maximum FDA toxicity grade (mild, moderate, or severe) during the 7 days after each vaccination is plotted for solicited local (Panel A) and systemic (Panel B) adverse events. There were no grade 4 (life-threatening) events.

    Participants who reported 0 events make up the remainder of the 100% calculation (not displayed). Excluded were the three sentinel participants in groups C (5 μg + Matrix-M1, 5 μg + Matrix-M1) and D (25 μg + Matrix-M1, 25 μg + Matrix-M1), who received the trial vaccine in an open-label manner (see Table S7 for complete safety data on all participants).Overall reactogenicity was largely absent or mild, and second vaccinations were neither withheld nor delayed due to reactogenicity. After the first vaccination, local and systemic reactogenicity was absent or mild in the majority of participants (local.

    100%, 96%, 89%, 84%, and 88% of participants in groups A, B, C, D, and E, respectively. Systemic. 91%, 92%, 96%, 68%, and 89%) who were unaware of treatment assignment (Figure 2 and Table S7).

    Two participants (2%), one each in groups D and E, had severe adverse events (headache, fatigue, and malaise). Two participants, one each in groups A and E, had reactogenicity events (fatigue, malaise, and tenderness) that extended 2 days after day 7. After the second vaccination, local and systemic reactogenicity were absent or mild in the majority of participants in the five groups (local.

    100%, 100%, 65%, 67%, and 100% of participants, respectively. Systemic. 86%, 84%, 73%, 58%, and 96%) who were unaware of treatment assignment.

    One participant, in group D, had a severe local event (tenderness), and eight participants, one or two participants in each group, had severe systemic events. The most common severe systemic events were joint pain and fatigue. Only one participant, in group D, had fever (temperature, 38.1°C) after the second vaccination, on day 1 only.

    No adverse event extended beyond 7 days after the second vaccination. Of note, the mean duration of reactogenicity events was 2 days or less for both the first vaccination and second vaccination periods. Laboratory abnormalities of grade 2 or higher occurred in 13 participants (10%).

    9 after the first vaccination and 4 after the second vaccination (Table S8). Abnormal laboratory values were not associated with any clinical manifestations and showed no worsening with repeat vaccination. Six participants (5%.

    Five women and one man) had grade 2 or higher transient reductions in hemoglobin from baseline, with no evidence of hemolysis or microcytic anemia and with resolution within 7 to 21 days. Of the six, two had an absolute hemoglobin value (grade 2) that resolved or stabilized during the testing period. Four participants (3%), including one who had received placebo, had elevated liver enzymes that were noted after the first vaccination and resolved within 7 to 14 days (i.e., before the second vaccination).

    Vital signs remained stable immediately after vaccination and at all visits. Unsolicited adverse events (Table S9) were predominantly mild in severity (in 71%, 91%, 83%, 90%, and 82% of participants in groups A, B, C, D, and E, respectively) and were similarly distributed across the groups receiving adjuvanted and unadjuvanted vaccine. There were no reports of severe adverse events.

    Immunogenicity Outcomes Figure 3. Figure 3. SARS-CoV-2 Anti-Spike IgG and Neutralizing Antibody Responses.

    Shown are geometric mean anti-spike IgG enzyme-linked immunosorbent assay (ELISA) unit responses to recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) protein antigens (Panel A) and wild-type SARS-CoV-2 microneutralization assay at an inhibitory concentration greater than 99% (MN IC>99%) titer responses (Panel B) at baseline (day 0), 3 weeks after the first vaccination (day 21), and 2 weeks after the second vaccination (day 35) for the placebo group (group A), the 25-μg unadjuvanted group (group B), the 5-μg and 25-μg adjuvanted groups (groups C and D, respectively), and the 25-μg adjuvanted and placebo group (group E). Diamonds and whisker endpoints represent geometric mean titer values and 95% confidence intervals, respectively. The Covid-19 human convalescent serum panel includes specimens from PCR-confirmed Covid-19 participants, obtained from Baylor College of Medicine (29 specimens for ELISA and 32 specimens for MN IC>99%), with geometric mean titer values according to Covid-19 severity.

    The severity of Covid-19 is indicated by the colors of the dots for hospitalized patients (including those in intensive care), symptomatic outpatients (with samples collected in the emergency department), and asymptomatic patients who had been exposed to Covid-19 (with samples collected during contact and exposure assessment). Mean values (in black) for human convalescent serum are depicted next to (and of same color as) the category of Covid-19 patients, with the overall mean shown above the scatter plot (in black). For each trial vaccine group, the mean at day 35 is depicted above the scatterplot.ELISA anti-spike IgG geometric mean ELISA units (GMEUs) ranged from 105 to 116 at day 0.

    By day 21, responses had occurred for all adjuvanted regimens (1984, 2626, and 3317 GMEUs for groups C, D, and E, respectively), and geometric mean fold rises (GMFRs) exceeded those induced without adjuvant by a factor of at least 10 (Figure 3 and Table S10). Within 7 days after the second vaccination with adjuvant (day 28. Groups C and D), GMEUs had further increased by a factor of 8 (to 15,319 and 20,429, respectively) over responses seen with the first vaccination, and within 14 days (day 35), responses had more than doubled yet again (to 63,160 and 47,521, respectively), achieving GMFRs that were approximately 100 times greater than those observed with rSARS-CoV-2 alone.

    A single vaccination with adjuvant achieved GMEU levels similar to those in asymptomatic (exposed) patients with Covid-19 (1661), and a second vaccination with adjuvant achieved GMEU levels that exceeded those in convalescent serum from symptomatic outpatients with Covid-19 (7420) by a factor of at least 6 and rose to levels similar to those in convalescent serum from patients hospitalized with Covid-19 (53,391). The responses in the two-dose 5-μg and 25-μg adjuvanted vaccine regimens were similar, a finding that highlights the role of adjuvant dose sparing. Neutralizing antibodies were undetectable before vaccination and had patterns of response similar to those of anti-spike antibodies after vaccination with adjuvant (Figure 3 and Table S11).

    After the first vaccination (day 21), GMFRs were approximately 5 times greater with adjuvant (5.2, 6.3, and 5.9 for groups C, D, and E, respectively) than without adjuvant (1.1). By day 35, second vaccinations with adjuvant induced an increase more than 100 times greater (195 and 165 for groups C and D, respectively) than single vaccinations without adjuvant. When compared with convalescent serum, second vaccinations with adjuvant resulted in GMT levels approximately 4 times greater (3906 and 3305 for groups C and D, respectively) than those in symptomatic outpatients with Covid-19 (837) and approached the magnitude of levels observed in hospitalized patients with COVID-19 (7457).

    At day 35, ELISA anti-spike IgG GMEUs and neutralizing antibodies induced by the two-dose 5-μg and 25-μg adjuvanted vaccine regimens were 4 to 6 times greater than the geometric mean convalescent serum measures (8344 and 983, respectively). Figure 4. Figure 4.

    Correlation of Anti-Spike IgG and Neutralizing Antibody Responses. Shown are scatter plots of 100% wild-type neutralizing antibody responses and anti-spike IgG ELISA unit responses at 3 weeks after the first vaccination (day 21) and 2 weeks after the second vaccination (day 35) for the two-dose 25-μg unadjuvanted vaccine (group B. Panel A), the combined two-dose 5-μg and 25-μg adjuvanted vaccine (groups C and D, respectively.

    Panel B), and convalescent serum from patients with Covid-19 (Panel C). In Panel C, the severity of Covid-19 is indicated by the colors of the dots for hospitalized patients (including those in intensive care), symptomatic outpatients (with samples collected in the emergency department), and asymptomatic patients who had been exposed to Covid-19 (with samples collected during contact and exposure assessment).A strong correlation was observed between neutralizing antibody titers and anti-spike IgG GMEUs with adjuvanted vaccine at day 35 (correlation, 0.95) (Figure 4), a finding that was not observed with unadjuvanted vaccine (correlation, 0.76) but was similar to that of convalescent serum (correlation, 0.96). Two-dose regimens of 5-μg and 25-μg rSARS-CoV-2 plus Matrix-M1 produced similar magnitudes of response, and every participant had seroconversion according to either assay measurement.

    Reverse cumulative-distribution curves for day 35 are presented in Figure S2. Figure 5. Figure 5.

    RSARS-CoV-2 CD4+ T-cell Responses with or without Matrix-M1 Adjuvant. Frequencies of antigen-specific CD4+ T cells producing T helper 1 (Th1) cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 and for T helper 2 (Th2) cytokines interleukin-5 and interleukin-13 indicated cytokines from four participants each in the placebo (group A), 25-μg unadjuvanted (group B), 5-μg adjuvanted (group C), and 25-μg adjuvanted (group D) groups at baseline (day 0) and 1 week after the second vaccination (day 28) after stimulation with the recombinant spike protein. €œAny 2Th1” indicates CD4+ T cells that can produce two types of Th1 cytokines at the same time.

    €œAll 3 Th1” indicates CD4+ T cells that produce IFN-γ, TNF-α, and interleukin-2 simultaneously. €œBoth Th2” indicates CD4+ T cells that can produce Th2 cytokines interleukin-5 and interleukin-13 at the same time.T-cell responses in 16 participants who were randomly selected from groups A through D, 4 participants per group, showed that adjuvanted regimens induced antigen-specific polyfunctional CD4+ T-cell responses that were reflected in IFN-γ, IL-2, and TNF-α production on spike protein stimulation. A strong bias toward this Th1 phenotype was noted.

    Th2 responses (as measured by IL-5 and IL-13 cytokines) were minimal (Figure 5).In recent months, epidemiologists in the United States and throughout the world have been asked the same question by clinicians, journalists, and members of the public, “When will we have a vaccine?. € The obvious answer to this question would be, “When a candidate vaccine is demonstrated to be safe, effective, and available. That can be determined only by scientific data, not by a target calendar date.” But we realize that such a response, although accurate, overlooks much of what people are ultimately seeking to understand.The emphasis on “we” reveals that most people want much more than an estimated vaccine-delivery date.

    Their inquiry typically involves three concerns. First, when will the public be able to have confidence that available vaccines are safe and effective?. Second, when will a vaccine be available to people like them?.

    And third, when will vaccine uptake be high enough to enable a return to prepandemic conditions?. Often, the inquiry is also assessing whether the biotech and vaccine companies, government agencies, and medical experts involved in developing, licensing, and recommending use of Covid-19 vaccines realize that the responses they provide now will influence what happens later. There is often a sense that messages regarding Covid-19 vaccines can have problematic framing (e.g., “warp speed”) and make assertions that involve key terms (e.g., “safe” and “effective”) for which experts’ definitions may vary and may differ considerably from those of the general public and key subpopulations.As Covid-19 vaccines move into phase 3 clinical trials, enthusiasm about the innovative and sophisticated technologies being used needs to be replaced by consideration of the actions and messages that will foster trust among clinicians and the public.

    Although vast investments have been made in developing safe and effective vaccines, it is important to remember that it is the act of vaccination itself that prevents harm and saves lives. Considered fully, the question “When will we have a Covid-19 vaccine?. € makes clear the many ways in which efforts related to both the “when” and the “we” can affect vaccination uptake.

    Recognizing the significance of both aspects of the question can help public health officials and scientists both to hone current messaging related to Covid-19 vaccines and to build a better foundation for clinicians who will be educating patients and parents about vaccination.The recently released guidelines from the Food and Drug Administration (FDA) on testing of Covid-19 vaccine candidates are scientifically sound and indicate that no compromises will be made when it comes to evaluating safety and efficacy.1 This commitment needs to be stated repeatedly, made apparent during the vaccine testing and approval process, and supported by transparency. Assurances regarding the warp speed effort to develop a vaccine or to issue emergency use authorizations accelerating availability must make clear the ways in which clinical trials and the review processes used by federal agencies (the FDA, the National Institutes of Health, and the Centers for Disease Control and Prevention [CDC]) will objectively assess the safety and effectiveness of vaccines developed using new platforms. Clinicians and the public should have easy access to user-friendly materials that reference publicly available studies, data, and presentations related to safety and effectiveness.

    The FDA’s and CDC’s plans for robust longer-term, postlicensure vaccine safety and monitoring systems will also need to be made visible, particularly to health care professionals, who are essential to the success of these efforts.2The second key part of this question pertains to when a safe and effective Covid-19 vaccine will become available to some, most, or all people who want one. This question has technical and moral components, and the answers on both fronts could foster or impede public acceptance of a vaccine. Data from antibody testing suggest that about 90% of people are susceptible to Covid-19.

    Accepting that 60 to 70% of the population would have to be immune, either as a result of natural infection or vaccination, to achieve community protection (also known as herd immunity), about 200 million Americans and 5.6 billion people worldwide would need to be immune in order to end the pandemic. The possibility that it may take years to achieve the vaccination coverage necessary for everyone to be protected gives rise to difficult questions about priority groups and domestic and global access.Given public skepticism of government institutions and concerns about politicization of vaccine priorities, the recent establishment of a National Academy of Medicine (NAM) committee to formulate criteria to ensure equitable distribution of initial Covid-19 vaccines and to offer guidance on addressing vaccine hesitancy is an important step. The NAM report should be very helpful to the CDC’s Advisory Committee on Immunization Practices, the group that traditionally develops vaccination recommendations in the United States.

    The NAM’s deliberations about which groups will be prioritized for vaccination involve identifying the societal values that should be considered, and the report will communicate how these values informed its recommendations. Will the people at greatest risk for disease — such as health care workers, nursing home residents, prison inmates and workers, the elderly, people with underlying health conditions, and people from minority and low-income communities — be the first to obtain access?. Alternatively, will the top priority be reducing transmission by prioritizing the public workforce, essential workers, students, and young people who may be more likely to spread infection asymptomatically?.

    And how will the United States share vaccine doses with other countries, where infections could ultimately also pose a threat to Americans?. Releasing expert-committee reports, however, should not be equated with successfully communicating with the public about vaccine candidates and availability.3 In the United States and many other countries, new vaccines and vaccination recommendations are rarely released with substantial public information and educational resources. Most investments in communication with clinicians and the public happen when uptake of newly recommended vaccines, such as the human papillomavirus vaccine or seasonal influenza vaccine, falls short of goals.

    Not since the March of Dimes’s polio-vaccination efforts in the 1950s has there been major investment in public information and advocacy for new vaccines. There is already a flood of misinformation on social media and from antivaccine activists about new vaccines that could be licensed for Covid-19. If recent surveys suggesting that about half of Americans would accept a Covid-19 vaccine4 are accurate, it will take substantial resources and active, bipartisan political support to achieve the uptake levels needed to reach herd immunity thresholds.5High uptake of Covid-19 vaccines among prioritized groups should also not be assumed.

    Many people in these groups will want to be vaccinated, but their willingness will be affected by what is said, the way it is said, and who says it in the months ahead. Providing compelling, evidence-based information using culturally and linguistically appropriate messages and materials is a complex challenge. Having trusted people, such as public figures, political leaders, entertainment figures, and religious and community leaders, endorse vaccination can be an effective way of persuading the portion of the public that is open to such a recommendation.

    Conversely, persuading people who have doubts about or oppose a particular medical recommendation is difficult, requires commitment and engagement, and is often not successful.Finally, surveys suggest that physicians, nurses, and pharmacists remain the most highly trusted professionals in the United States. Extensive, active, and ongoing involvement by clinicians is essential to attaining the high uptake of Covid-19 vaccines that will be needed for society to return to prepandemic conditions. Nurses and physicians are the most important and influential sources of vaccination information for patients and parents.

    Throughout the world, health care professionals will need to be well-informed and strong endorsers of Covid-19 vaccination.A more complete answer to the common question is therefore, “We will have a safe and effective Covid-19 vaccine when the research studies, engagement processes, communication, and education efforts undertaken during the clinical trial stage have built trust and result in vaccination recommendations being understood, supported, and accepted by the vast majority of the public, priority and nonpriority groups alike.” Efforts to engage diverse stakeholders and communities in Covid-19 vaccination education strategies, key messages, and materials for clinicians and the public are needed now.Specificity of SARS-CoV-2 Antibody Assays Both assays measuring pan-Ig antibodies had low numbers of false positives among samples collected in 2017. There were 0 and 1 false positives for the two assays among 472 samples, results that compared favorably with those obtained with the single IgM anti-N and IgG anti-N assays (Table S3). Because of the low prevalence of SARS-CoV-2 infection in Iceland, we required positive results from both pan-Ig antibody assays for a sample to be considered seropositive (see Supplementary Methods in Supplementary Appendix 1).

    None of the samples collected in early 2020 group were seropositive, which indicates that the virus had not spread widely in Iceland before February 2020. SARS-CoV-2 Antibodies among qPCR-Positive Persons Figure 2. Figure 2.

    Antibody Prevalence and Titers among qPCR-Positive Cases as a Function of Time since Diagnosis by qPCR. Shown are the percentages of samples positive for both pan-Ig antibody assays and the antibody titers. Red denotes the count or percentage of samples among persons during their hospitalization (249 samples from 48 persons), and blue denotes the count or percentage of samples among persons after they were declared recovered (1853 samples from 1215 persons).

    Vertical bars denote 95% confidence intervals. The dashed lines indicated the thresholds for a test to be declared positive. OD denotes optical density, and RBD receptor binding domain.Table 1.

    Table 1. Prevalence of SARS-CoV-2 Antibodies by Sample Collection as Measured by Two Pan-Ig Antibody Assays. Twenty-five days after diagnosis by qPCR, more than 90% of samples from recovered persons tested positive with both pan-Ig antibody assays, and the percentage of persons testing positive remained stable thereafter (Figure 2 and Fig.

    S2). Hospitalized persons seroconverted more frequently and quickly after qPCR diagnosis than did nonhospitalized persons (Figure 2 and Fig. S3).

    Of 1215 persons who had recovered (on the basis of results for the most recently obtained sample from persons for whom we had multiple samples), 1107 were seropositive (91.1%. 95% confidence interval [CI], 89.4 to 92.6) (Table 1 and Table S4). Since some diagnoses may have been made on the basis of false positive qPCR results, we determined that 91.1% represents the lower bound of sensitivity of the combined pan-Ig tests for the detection of SARS-CoV-2 antibodies among recovered persons.

    Table 2. Table 2. Results of Repeated Pan-Ig Antibody Tests among Recovered qPCR-Diagnosed Persons.

    Among the 487 recovered persons with two or more samples, 19 (4%) had different pan-Ig antibody test results at different time points (Table 2 and Fig. S4). It is notable that of the 22 persons with an early sample that tested negative for both pan-Ig antibodies, 19 remained negative at the most recent test date (again, for both antibodies).

    One person tested positive for both pan-Ig antibodies in the first test and negative for both in the most recent test. The longitudinal changes in antibody levels among recovered persons were consistent with the cross-sectional results (Fig. S5).

    Antibody levels were higher in the last sample than in the first sample when the antibodies were measured with the two pan-Ig assays, slightly lower than in the first sample when measured with IgG anti-N and IgG anti-S1 assays, and substantially lower than in the first sample when measured with IgM anti-N and IgA anti-S1 assays. IgG anti-N, IgM anti-N, IgG anti-S1, and IgA anti-S1 antibody levels were correlated among the qPCR-positive persons (Figs. S5 and S6 and Table S5).

    Antibody levels measured with both pan-Ig antibody assays increased over the first 2 months after qPCR diagnosis and remained at a plateau over the next 2 months of the study. IgM anti-N antibody levels increased rapidly soon after diagnosis and then fell rapidly and were generally not detected after 2 months. IgA anti-S1 antibodies decreased 1 month after diagnosis and remained detectable thereafter.

    IgG anti-N and anti-S1 antibody levels increased during the first 6 weeks after diagnosis and then decreased slightly. SARS-CoV-2 Infection in Quarantine Table 3. Table 3.

    SARS-CoV-2 Infection among Quarantined Persons According to Exposure Type and Presence of Symptoms. Of the 1797 qPCR-positive Icelanders, 1088 (61%) were in quarantine when SARS-CoV-2 infection was diagnosed by qPCR. We tested for antibodies among 4222 quarantined persons who had not tested qPCR-positive (they had received a negative result by qPCR or had simply not been tested).

    Of those 4222 quarantined persons, 97 (2.3%. 95% CI, 1.9 to 2.8) were seropositive (Table 1). Those with household exposure were 5.2 (95% CI, 3.3 to 8.0) times more likely to be seropositive than those with other types of exposure (Table 3).

    Similarly, a positive result by qPCR for those with household exposure was 5.2 (95% CI, 4.5 to 6.1) times more likely than for those with other types of exposure. When these two sets of results (qPCR-positive and seropositive) were combined, we calculated that 26.6% of quarantined persons with household exposure and 5.0% of quarantined persons without household exposure were infected. Those who had symptoms during quarantine were 3.2 (95% CI, 1.7 to 6.2) times more likely to be seropositive and 18.2 times (95% CI, 14.8 to 22.4) more likely to test positive with qPCR than those without symptoms.

    We also tested persons in two regions of Iceland affected by cluster outbreaks. In a SARS-CoV-2 cluster in Vestfirdir, 1.4% of residents were qPCR-positive and 10% of residents were quarantined. We found that none of the 326 persons outside quarantine who had not been tested by qPCR (or who tested negative) were seropositive.

    In a cluster in Vestmannaeyjar, 2.3% of residents were qPCR-positive and 13% of residents were quarantined. Of the 447 quarantined persons who had not received a qPCR-positive result, 4 were seropositive (0.9%. 95% CI, 0.3 to 2.1).

    Of the 663 outside quarantine in Vestmannaeyjar, 3 were seropositive (0.5%. 95% CI, 0.1 to 0.2%). SARS-CoV-2 Seroprevalence in Iceland None of the serum samples collected from 470 healthy Icelanders between February 18 and March 9, 2020, tested positive for both pan-Ig antibodies, although four were positive for the pan-Ig anti-N assay (0.9%), a finding that suggests that the virus had not spread widely in Iceland before March 9.

    Of the 18,609 persons tested for SARS-CoV-2 antibodies through contact with the Icelandic health care system for reasons other than Covid-19, 39 were positive for both pan-Ig antibody assays (estimated seroprevalence by weighting the sample on the basis of residence, sex, and 10-year age category, 0.3%. 95% CI, 0.2 to 0.4). There were regional differences in the percentages of qPCR-positive persons across Iceland that were roughly proportional to the percentage of people quarantined (Table S6).

    However, after exclusion of the qPCR-positive and quarantined persons, the percentage of persons who tested positive for SARS-CoV-2 antibodies did not correlate with the percentage of those who tested positive by qPCR. The estimated seroprevalence in the random sample collection from Reykjavik (0.4%. 95% CI, 0.3 to 0.6) was similar to that in the Health Care group (0.3%.

    95% CI, 0.2 to 0.4) (Table S6). We calculate that 0.5% of the residents of Iceland have tested positive with qPCR. The 2.3% with SARS-CoV-2 seroconversion among persons in quarantine extrapolates to 0.1% of Icelandic residents.

    On the basis of this finding and the seroprevalence from the Health Care group, we estimate that 0.9% (95% CI, 0.8 to 0.9) of the population of Iceland has been infected by SARS-CoV-2. Approximately 56% of all SARS-CoV-2 infections were therefore diagnosed by qPCR, 14% occurred in quarantine without having been diagnosed with qPCR, and the remaining 30% of infections occurred outside quarantine and were not detected by qPCR. Deaths from Covid-19 in Iceland In Iceland, 10 deaths have been attributed to Covid-19, which corresponds to 3 deaths per 100,000 nationwide.

    Among the qPCR-positive cases, 0.6% (95% CI, 0.3 to 1.0) were fatal. Using the 0.9% prevalence of SARS-CoV-2 infection in Iceland as the denominator, however, we calculate an infection fatality risk of 0.3% (95% CI, 0.2 to 0.6). Stratified by age, the infection fatality risk was substantially lower in those 70 years old or younger (0.1%.

    95% CI, 0.0 to 0.3) than in those over 70 years of age (4.4%. 95% CI, 1.9 to 8.4) (Table S7). Age, Sex, Clinical Characteristics, and Antibody Levels Table 4.

    Table 4. Association of Existing Conditions and Covid-19 Severity with SARS-CoV-2 Antibody Levels among Recovered Persons. SARS-CoV-2 antibody levels were higher in older people and in those who were hospitalized (Table 4, and Table S8 [described in Supplementary Appendix 1 and available in Supplementary Appendix 2]).

    Pan-Ig anti–S1-RBD and IgA anti-S1 levels were lower in female persons. Of the preexisting conditions, and after adjustment for multiple testing, we found that body-mass index, smoking status, and use of antiinflammatory medication were associated with SARS-CoV-2 antibody levels. Body-mass index correlated positively with antibody levels.

    Smokers and users of antiinflammatory medication had lower antibody levels. With respect to clinical characteristics, antibody levels were most strongly associated with hospitalization and clinical severity, followed by clinical symptoms such as fever, maximum temperature reading, cough, and loss of appetite. Severity of these individual symptoms, with the exception of loss of energy, was associated with higher antibody levels.In a laboratory setting, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was inoculated into human bronchial epithelial cells.

    This inoculation, which was performed in a biosafety level 3 facility, had a multiplicity of infection (indicating the ratio of virus particles to targeted airway cells) of 3:1. These cells were then examined 96 hours after infection with the use of scanning electron microscopy. An en face image (Panel A) shows an infected ciliated cell with strands of mucus attached to the cilia tips.

    At higher magnification, an image (Panel B) shows the structure and density of SARS-CoV-2 virions produced by human airway epithelial cells. Virus production was approximately 3×106 plaque-forming units per culture, a finding that is consistent with a high number of virions produced and released per cell.Camille Ehre, Ph.D.Baric and Boucher Laboratories at University of North Carolina School of Medicine, Chapel Hill, NC [email protected].

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    Elon Musk on Friday unveiled a coin-sized prototype of a is viagra safe for 20 year olds brain implant developed by his startup Neuralink to enable people who are paralyzed to operate smartphones and robotic limbs with their thoughts — and said the company had worked to “dramatically simplify” the device since presenting an earlier version last summer.In an event live-streamed on YouTube to more than 150,000 viewers at one point, the company staged a demonstration in which it trotted out a pig named Gertrude that was said to have had the company’s device implanted in its head two months ago. The live stream showed what Musk claimed to be Gertrude’s real-time brain activity as it sniffed around a pen. At no point, though, did he provide evidence that the signals — rendered in beeps and bright blue wave patterns on screen — were, in fact, emanating from the pig’s brain.A pig presented at a Neuralink demonstration was said to have one is viagra safe for 20 year olds of the company’s brain implants in its head. YouTube screenshot“This is obviously sounding increasingly like a Black Mirror episode,” Musk said at one point during the event as he responded affirmatively to a question about whether the company’s implant could eventually be used to save and replay memories.

    €œThe future’s going to be weird.”advertisement Musk said that in July Neuralink received a breakthrough device designation from the Food and Drug Administration — a regulatory pathway that could allow the company is viagra safe for 20 year olds to soon start a clinical trial in people with paraplegia and tetraplegia. The big reveal came after four former Neuralink employees told STAT that the company’s leaders have long fostered an internal culture characterized by rushed timelines and the “move fast and break things” ethos of a tech company — a pace sometimes at odds with the slow and incremental pace that’s typical of medical device development. Advertisement Friday’s event began, 40 minutes late, with a glossy video about the company’s work — and then panned to Musk, standing in front of is viagra safe for 20 year olds a blue curtain beside a gleaming new version of the company’s surgical “sewing machine” robot that could easily have been mistaken for a giant Apple device. Musk described the event as a “product demo” and said its primary purpose was to recruit potential new employees.

    It was unclear whether the demonstration was taking place at the company’s Fremont, Calif., headquarters or elsewhere is viagra safe for 20 year olds. Musk proceeded to reveal the new version of Neuralink’s brain implant, which he said was designed to fit snugly into the top of the skull. Neuralink’s technological design has changed significantly since its last big update in July 2019 is viagra safe for 20 year olds. At that time, the company’s brain implant system involved a credit-card sized device designed to be positioned behind the back of a person’s ear, with several wires stretching to the top of the skull.

    After demonstrating the pig’s brain is viagra safe for 20 year olds activity at Friday’s event, Musk showed video footage of a pig walking on a treadmill and said Neuralink’s device could be used to “predict the position of limbs with high accuracy.” That capability would be critical to allowing someone using the device to do something like controlling a prosthetic limb, for example.Neuralink for months has signaled that it initially plans to develop its device for people who are paralyzed. It said at its July 2019 event that it wanted to start human testing by the end of 2020. Receiving the breakthrough device designation from the FDA — designed to speed up the is viagra safe for 20 year olds lengthy regulatory process — is a step forward, but it by no means guarantees that a device will receive a green light, either in a short or longer-term time frame. After Musk’s presentation, a handful of the company’s employees — all wearing masks, but seated only inches apart — joined him to take questions submitted on Twitter or from the small audience in the room.In typical fashion for a man who in 2018 sent a Tesla Roadster into space, Musk didn’t hesitate to use the event to cross-promote his electric car company.

    Asked whether the Neuralink is viagra safe for 20 year olds chip would allow people to summon their Tesla telepathically, Musk responded. €œDefinitely — of course.”Matthew MacDougall, the company’s head neurosurgeon, appearing in scrubs, said the company had so far only implanted its technology into the brain’s cortical surface, the coaster-width layer enveloping the brain, but added that it hoped to go deeper in the future. Still, Musk said is viagra safe for 20 year olds. €œYou could solve blindness, you could solve paralysis, you could solve hearing — you can solve a lot just by interfacing with the cortex.”Musk and MacDougall said they hoped to eventually implant Neuralink’s devices — which they referred to on stage simply as “links” — in the deeper structures of the brain, such as in the hypothalamus, which is believed to play a critical role in mental illnesses including depression, anxiety, and PTSD.There were no updates at the event of Neuralink’s research in monkeys, which the company has been conducting in partnership with the University of California, Davis since 2017.

    At last July’s event, Musk said — without providing evidence — that a monkey had controlled a computer with its brain.At that same July 2019 event, Neuralink released a preprint paper — published a few is viagra safe for 20 year olds months later — that claimed to show that a series of Neuralink electrodes implanted in the brains of rats could record neural signals. Critically, the work did not show where in the brain the implanted electrodes were recording from, for how long they were recording, or whether the recordings could be linked to any of the rats’ bodily movements.In touting Friday’s event — and Neuralink’s technological capabilities — on Twitter in recent weeks, Musk spoke of “AI symbiosis while u wait” and referenced the “matrix in the matrix” — a science-fiction reference about revealing the true nature of reality. The progress the company reported on Friday fell far is viagra safe for 20 year olds short of that. Neuralink’s prototype is ambitious, but it has yet to show evidence that it can match up to the brain-machine interfaces developed by academic labs and other companies.

    Other groups have shown that they can listen in on neural activity and allow primates and people to control a computer cursor with their brain — so-called “read-out” technology — and have also shown that they can use electrical stimulation to input is viagra safe for 20 year olds information, such as a command or the heat of a hot cup of coffee, using “write-in” technology. Neuralink said on Friday that its technology would have both read-out and write-in capabilities.Musk acknowledged that Neuralink still has a long way to go. In closing is viagra safe for 20 year olds the event after more than 70 minutes, Musk said. €œThere’s a tremendous amount of work to be done to go from here to a device that is widely available and affordable and reliable.”Following the news this week of what appears to have been the first confirmed case of a Covid-19 reinfection, other researchers have been coming forward with their own reports.

    One in Belgium, another is viagra safe for 20 year olds in the Netherlands. And now, one in Nevada.What caught experts’ attention about the case of the 25-year-old Reno man was not that he appears to have contracted SARS-CoV-2 (the name of the virus that causes Covid-19) a second time. Rather, it’s that his second bout was more serious than his first.Immunologists had expected is viagra safe for 20 year olds that if the immune response generated after an initial infection could not prevent a second case, then it should at least stave off more severe illness. That’s what occurred with the first known reinfection case, in a 33-year-old Hong Kong man.advertisement Still, despite what happened to the man in Nevada, researchers are stressing this is not a sky-is-falling situation or one that should result in firm conclusions.

    They always presumed people would become vulnerable to Covid-19 again some time after recovering from an initial case, based on how our immune systems respond to other respiratory viruses, including is viagra safe for 20 year olds other coronaviruses. It’s possible that these early cases of reinfection are outliers and have features that won’t apply to the tens of millions of other people who have already shaken off Covid-19.“There are millions and millions of cases,” said Michael Mina, an epidemiologist at Harvard’s T.H. Chan School is viagra safe for 20 year olds of Public Health. The real question that should get the most focus, Mina said, is, “What happens to most people?.

    €advertisement But with more reinfection reports likely is viagra safe for 20 year olds to make it into the scientific literature soon, and from there into the mainstream press, here are some things to look for in assessing them.What’s the deal with the Nevada case?. The Reno resident in question first tested positive for SARS-CoV-2 in April after coming down with a sore throat, cough, and headache, as well as nausea and diarrhea. He got is viagra safe for 20 year olds better over time and later tested negative twice. But then, some 48 days later, the man started experiencing headaches, cough, and other symptoms again.

    Eventually, he became so sick that he had to be hospitalized and was found to have pneumonia.Researchers sequenced virus samples from both of his infections and found they were different, providing evidence that this was a new infection distinct from the first. What happens when we get Covid-19 is viagra safe for 20 year olds in the first case?. Researchers are finding that, generally, people who get Covid-19 develop a healthy immune response replete with both antibodies (molecules that can block pathogens from infecting cells) and T cells (which help wipe out the virus). This is what happens after other viral infections.In addition to fending off the virus the first time, that immune response also creates memories of the virus, should it try to is viagra safe for 20 year olds invade a second time.

    It’s thought, then, that people who recover from Covid-19 will typically be protected from another case for some amount of time. With other coronaviruses, protection is thought to last for perhaps a little less than a year to about three years.But researchers can’t tell is viagra safe for 20 year olds how long immunity will last with a new pathogen (like SARS-CoV-2) until people start getting reinfected. They also don’t know exactly what mechanisms provide protection against Covid-19, nor do they know what levels of antibodies or T cells are required to signal that someone is protected through a blood test. (These are is viagra safe for 20 year olds called the “correlates of protection.”) Why do experts expect second cases to be milder?.

    With other viruses, protective immunity doesn’t just vanish one day. Instead, it wanes is viagra safe for 20 year olds over time. Researchers have then hypothesized that with SARS-CoV-2, perhaps our immune systems might not always be able to prevent it from getting a toehold in our cells — to halt infection entirely — but that it could still put up enough of a fight to guard us from getting really sick. Again, this is what happens with other respiratory pathogens.And it’s why some researchers is viagra safe for 20 year olds actually looked at the Hong Kong case with relief.

    The man had mild to moderate Covid-19 symptoms during the first case, but was asymptomatic the second time. It was is viagra safe for 20 year olds a demonstration, experts said, of what you would want your immune system to do. (The case was only detected because the man’s sample was taken at the airport when he arrived back in Hong Kong after traveling in Europe.)“The fact that somebody may get reinfected is not surprising,” Malik Peiris, a virologist at the University of Hong Kong, told STAT earlier this week about the first reinfection. €œBut the reinfection didn’t cause disease, so that’s the first point.”The Nevada case, then, provides a is viagra safe for 20 year olds counterexample to that.

    What kind of immune response did the person who was reinfected generate initially?. Earlier, we is viagra safe for 20 year olds described the robust immune response that most people who have Covid-19 seem to mount. But that was a generalization. Infections and the immune responses they is viagra safe for 20 year olds induce in different people are “heterogeneous,” said Sarah Cobey, an epidemiologist and evolutionary biologist at the University of Chicago.Older people often generate weaker immune responses than younger people.

    Some studies have also indicated that milder cases of Covid-19 induce tamer immune responses that might not provide as lasting or as thorough of a defense as stronger immune responses. The man in Hong Kong, is viagra safe for 20 year olds for example, did not generate antibodies to the virus after his first infection, at least to the level that could be detected by blood tests. Perhaps that explains why he contracted the virus again just about 4 1/2 months after recovering from his initial infection.In the Nevada case, researchers did not test what kind of immune response the man generated after the first case.“Infection is not some binary event,” Cobey said. And with reinfection, “there’s going to be some viral replication, but the question is is viagra safe for 20 year olds how much is the immune system getting engaged?.

    €What might be broadly meaningful is when people who mounted robust immune responses start getting reinfected, and how severe their second cases are. Are people who have Covid-19 a is viagra safe for 20 year olds second time infectious?. As discussed, immune memory can prevent reinfection. If it can’t, it is viagra safe for 20 year olds might stave off serious illness.

    But there’s a third aspect of this, too.“The most important question for reinfection, with the most serious implications for controlling the pandemic, is whether reinfected people can transmit the virus to others,” Columbia University virologist Angela Rasmussen wrote in Slate this week.Unfortunately, neither the Hong Kong nor the Reno studies looked at this question. But if most people who get is viagra safe for 20 year olds reinfected don’t spread the virus, that’s obviously good news. What happens when people broadly become susceptible again?. Whether it’s six months after the first infection or nine months or a year or longer, at some point, protection for most people who recover from is viagra safe for 20 year olds Covid-19 is expected to wane.

    And without the arrival of a vaccine and broad uptake of it, that could change the dynamics of local outbreaks.In some communities, it’s thought that more than 20% of residents have experienced an initial Covid-19 case, and are thus theoretically protected from another case for some time. That is is viagra safe for 20 year olds still below the point of herd immunity — when enough people are immune that transmission doesn’t occur — but still, the fewer vulnerable people there are, the less likely spread is to occur.On the flip side though, if more people become susceptible to the virus again, that could increase the risk of transmission. Modelers are starting to factor that possibility into their forecasts.A crucial question for which there is not an answer yet is whether what happened to the man in Reno, where the second case was more severe than the first, remains a rare occurrence, as researchers expect and hope. As the Nevada researchers wrote, “the generalizability of this finding is unknown.”An advocacy group has asked the Department of Defense to investigate what it called “an apparent failure” by Moderna (MRNA) to disclose millions of dollars in awards received from the Defense Advanced Research Projects Agency in patent applications the company filed for vaccines.In a letter to the agency, Knowledge Ecology International explained that a review of dozens of patent applications found the company received approximately $20 million from the federal government in grants several years ago and the funds “likely” led to the creation is viagra safe for 20 year olds of its vaccine technology.

    This was used to develop vaccines to combat different viruses, such as Zika and, later, the virus that causes Covid-19.In arguing for an investigation, the advocacy group maintained Moderna is obligated under federal law to disclose the grants that led to nearly a dozen specific patent applications and explained the financial support means the U.S. Government would have certain rights is viagra safe for 20 year olds over the patents. In other words, U.S. Taxpayers would have an ownership stake in vaccines developed by the company.advertisement “This clarifies the public’s right in the inventions,” said Jamie Love, who heads Knowledge Ecology International, a nonprofit that tracks patents and access is viagra safe for 20 year olds to medicines issues.

    €œThe disclosure (also) changes the narrative about who has financed the inventive activity, often the most risky part of development.” advertisement One particular patent assigned to Moderna concerns methods and compositions that can be used specifically against coronaviruses, including COVID-19. The patent names a Moderna scientist and a former Moderna scientist as inventors, both of which acknowledged performing work under the DARPA awards in two academic papers, according to the report by the advocacy group.The group examined the 126 patents assigned to Moderna or ModernaTx as well as 154 patent applications. €œDespite the evidence that multiple inventions were conceived in the course of research supported by the DARPA is viagra safe for 20 year olds awards, not a single one of the patents or applications assigned to Moderna disclose U.S. Federal government funding,” the report stated.We asked Moderna and the Department of Defense for comment and will update you accordingly.The missive to the Department of Defense follows a recent analysis by Public Citizen, another advocacy group, indicating the National Institutes of Health may own mRNA-1273, the Moderna vaccine candidate for Covid-19.

    The advocacy group noted the federal government filed multiple patents is viagra safe for 20 year olds covering the vaccine and two patent applications, in particular, list federal scientists as co-inventors.The analyses are part of a larger campaign among advocacy groups and others in the U.S. And elsewhere to ensure that Covid-19 medical products are available to poor populations around the world. The concern reflects the unprecedented global demand for therapies and is viagra safe for 20 year olds vaccines, and a race among wealthy nations to snap up supplies from vaccine makers. In the U.S., the effort has focused on the extent to which the federal government has provided taxpayer dollars to different companies to help fund their discoveries.

    In some cases, advocates argue that federal funding matters because it clarifies the is viagra safe for 20 year olds rights that the U.S. Government has to ensure a therapy or vaccine is available to Americans on reasonable terms.One example has been remdesivir, the Gilead Sciences (GILD) treatment being given to hospitalized Covid-19 patients. The role is viagra safe for 20 year olds played by the U.S. Government in developing remdesivir to combat coronaviruses involved contributions from government personnel at such agencies as the U.S.

    Army Medical Research Institute of Infectious Diseases.As for the Moderna vaccine, earlier this month, the company was awarded a $1.525 billion contract by the Department of Defense and the Department of Health and Human Services to manufacture and deliver 100 million doses of is viagra safe for 20 year olds its Covid-19 vaccine. The agreement also includes an option to purchase another 400 million doses, although the terms were not disclosed. In announcing the is viagra safe for 20 year olds agreement, the government said it would ensure Americans receive the Covid-19 vaccine at no cost, although they may be charged by health care providers for administering a shot.In this instance, however, Love said the “letter is not about price or profits. It’s about (Moderna) not owning up to DARPA funding inventions.

    If the is viagra safe for 20 year olds U.S. Wants to pay for all of the development of Moderna’s vaccine, as Moderna now acknowledges, and throw in a few more billion now, and an option to spend billions more, it’s not unreasonable to have some transparency over who paid for their inventions.”This is not the first time Moderna has been accused of insufficient disclosure. Earlier this is viagra safe for 20 year olds month, Knowledge Ecology International and Public Citizen maintained the company failed to disclose development costs in a $955 million contract awarded by BARDA for its Covid-19 vaccine. In all, the federal government has awarded the company approximately $2.5 billion to develop the vaccine.The coming few weeks represent a crucial moment for an ambitious plan to try to secure Covid-19 vaccines for roughly 170 countries around the world without the deep pockets to compete for what will be scarce initial supplies.Under the plan, countries that want to pool resources to buy vaccines must notify the World Health Organization and other organizers — Gavi, the Vaccine Alliance, as well as the Coalition for Epidemic Preparedness Innovations — of their intentions by Monday.

    That means it’s fish-or-cut-bait time for the so-called COVAX facility.Already, wealthy countries — is viagra safe for 20 year olds the United States, the United Kingdom, Japan, Canada, and Australia, among others, as well as the European Union — have opted to buy their own vaccine, signing bilateral contracts with manufacturers that have secured billions of doses of vaccine already. That raises the possibility that less wealthy countries will be boxed out of supplies.advertisement And yet Richard Hatchett, the CEO of CEPI, insists there is a path to billions of doses of vaccine for the rest of the world in 2021. STAT spoke is viagra safe for 20 year olds with Hatchett this week. A transcript of the conversation, lightly edited for clarity and length, follows.

    You said this is a critical is viagra safe for 20 year olds time for CEPI. Can you explain what needs to happen between now and mid-September for this joint purchasing approach to be a success?. Advertisement The critical moment is now for countries is viagra safe for 20 year olds to commit to the COVAX facility, because that will enable us to secure ample quantities of vaccine and then to be able to convey when that vaccine is likely to become available based on current information.What we’re now here asking countries to do is to indicate their intent to participate by Aug. 31, and to make a binding commitment by Sept.

    18. And to provide funds in support of that binding commitment by early October. Our negotiations with companies are already taking place and it will be important for us from a planning purpose that countries indicate their intent to participate.Those binding commitments we think will be sufficient to allow us to then secure the advance purchase agreements, particularly with those companies that don’t have a prior contractual obligation to COVAX. And then obviously, we need the funds to live up to those advance purchase agreements.Is it possible this thing could still fall apart?.

    There appears to be some concern COVAX has been boxed out by rich countries. There was always a possibility that there wouldn’t be sufficient uptake. But I think we’re very encouraged at this point by the level of commitment, both from countries that would be beneficiaries of the advance market commitment — that’s the lower-income, lower-middle-income countries — as well as the self-financing countries. To have over 170 countries expressing interest in participating — they see the value.We’re much more encouraged now that it’s not going to fall apart.

    We still need to bring it off to maximize its value. And we’re right at the crunch moment where countries are going to have to make these commitments. So, the next month is really absolutely critical to the facility. I am confident at this point that the world recognizes the value and wants it to work.I’ve been keeping tabs on advance purchase agreements that have been announced.

    And at this point, a small number of rich countries have nailed down a lot of vaccine — more than 3 billion doses. How hard does that make your job?. The fact that they’re doing it creates anxiety among other countries. And that in itself can accelerate the pace.

    So, I’m not going to say that we’re not watching that with concern.I will say that for COVAX and the facility, this is absolutely critical moment. I think we still have a window of opportunity between now and mid-September — when we’re asking that the self-financing countries to make their commitments — to make the facility real and to make it work. Between doses that are committed to COVAX through the access agreements and other agreements — these are discussions with partners that CEPI has funded as well as partners that CEPI has not funded — we still see a pathway for COVAX to well over 3 billion doses in 2021.I think it’s really important to bear in mind is that there are at least a few countries — and I think the U.S. And the U.K.

    Most publicly — that may be in a situation of significant oversupply. I believe the U.S. And U.K. Numbers, if you add them together, would result in enough vaccine for 600 million people to receive two doses of vaccine each.

    And, you know, there is no possible way that the U.S. Or the U.K. Can use that much vaccine.So, there may be a lot of extra supply that looks like it’s been tied up sloshing around later. I don’t think that the bilateral deals that have been struck are going to prevent COVAX from achieving its goals.But if so much vaccine has been pre-ordered by rich countries, can countries in the COVAX pool get enough for their needs?.

    One of the things that we’ve argued through COVAX is that to control the pandemic or to end the acute phase of the pandemic to allow normalcy to start to reassert itself, you don’t have to vaccinate 100% of your population.You need to vaccinate those at greatest risk for bad outcomes and you need to vaccinate certain critical workers, particularly your health care workforce. And if you can achieve that goal, which for most countries means vaccinating between 20% and maybe 30% of the population, then you can transform the pandemic into something that is much more manageable. Then you can buy yourself time to vaccinate everybody who wants to be vaccinated.We’ve argued the COVAX facility really offers the world the best shot at doing that globally in the fastest possible way, as well as providing for equitable access. This is a case where doing the equitable thing is also doing the efficient thing.CEPI has provided funding to nine vaccines.

    Is it true that all those manufacturers aren’t required to provide the COVAX facility with vaccine?. That is correct. One of the things that we did, and I think it was an important role that CEPI played early on, was that we moved money very, very quickly, in small increments. You know, some of the early contracts were only $5 million or $10 million, to get programs up and running while we potentially put in place much larger-scale, longer-term contracts.If you were doing it over again, would you have given money without strings attached?.

    Yes, I think I would have. I think that was critically important to initiating programs.Our contract with Moderna was established in about 48 hours. And that provided critical funding to them to manufacture doses that got them into clinical trials within nine weeks of the genetic sequences [of the SARS-CoV-2 virus] being released.And if you look at the nine programs that we’ve invested in, seven are in clinical trials. Two — the AstraZeneca program now and the Moderna program — are among the handful in Phase 3 clinical trials.

    And, I think the number of projects that that we funded initially, which started in kind of a biotech or academic phase that have now been picked up by large multinational corporations, there’s at least four. The Themis program being picked up by Merck, Oxford University by AstraZeneca, the University of Queensland by CSL, and Clover being in partnership with GSK, I think that speaks to the quality of the programs that we selected.So, I think that combination of rapid review, speed of funding, getting those programs started, getting them oriented in the right direction, I think all of that is critical to where we are now.Companies that got money from CEPI to build out production capacity — that money came with strings attached, right?. Yes, exactly. So, where CEPI has made investments that create manufacturing, or secure manufacturing capacity, the commitment has been that the capacity that is attributable to the CEPI investment is committed — at least right of first refusal — to the global procurement facility.WASHINGTON — The Trump administration removed a top Food and Drug Administration communications official from her post on Friday in the wake of several controversial agency misstatements, a senior administration official confirmed to STAT.The spokeswoman, Emily Miller, had played a lead role in defending the FDA commissioner, Stephen Hahn, after he misrepresented data regarding the use of blood plasma from recovered Covid-19 patients.

    The New York Times first reported Miller’s ouster. Miller’s tenure at as the top FDA spokeswoman lasted only 11 days. Her appointment was viewed with alarm by agency officials who felt her presence at the agency was emblematic of broader political pressure from the Trump administration, STAT first reported earlier this week.advertisement Before joining the FDA, Miller had no experience in health or medicine. Her former role as assistant commissioner for media affairs is typically not an appointment filled by political appointees.

    The FDA’s communications arm typically maintains a neutral, nonpolitical tone.Miller’s appointment particularly alarmed FDA staff and outside scientists given her history in right-wing political advocacy and conservatism journalism. Her résumé included a stint as a Washington Times columnist, where she penned columns with titles that include “New Obamacare ads make young women look like sluts,” and a 2013 book on gun rights titled “Emily Gets Her Gun. But Obama Wants to Take Yours.”advertisement She also worked as a reporter for One America News Network, a right-wing cable channel that frequently espouses conspiracy theories and has declared an open alliance with President Trump.Miller quickly made her presence known at the FDA. In the wake of Hahn’s misstatements on blood plasma, she aggressively defended the commissioner, falsely claiming in a tweet that the therapy “has shown to be beneficial for 35% of patients.” An FDA press release on blood plasma, issued less than a week after her appointment, similarly alarmed agency insiders by trumpeting the emergency authorization as “Another Achievement in Administration’s Fight Against [the] Pandemic.”.

    Elon Musk on Friday unveiled a coin-sized prototype of a brain implant developed by his startup Neuralink to enable people who are paralyzed to operate smartphones and robotic limbs with their thoughts — and said the company had worked to “dramatically simplify” the device since presenting an earlier version last summer.In an event live-streamed on YouTube best online viagra to more than 150,000 viewers at one point, the company staged a demonstration in which it trotted out a pig named Gertrude that was said to have had the company’s device implanted in its head two months ago. The live stream showed what Musk claimed to be Gertrude’s real-time brain activity as it sniffed around a pen. At no point, though, did he provide evidence that the signals — rendered in beeps and bright blue wave patterns on screen — were, in fact, emanating from the pig’s brain.A pig presented at a Neuralink demonstration was said to have one of best online viagra the company’s brain implants in its head. YouTube screenshot“This is obviously sounding increasingly like a Black Mirror episode,” Musk said at one point during the event as he responded affirmatively to a question about whether the company’s implant could eventually be used to save and replay memories.

    €œThe future’s going to be weird.”advertisement Musk said that in July Neuralink received a breakthrough device designation from the Food and best online viagra Drug Administration — a regulatory pathway that could allow the company to soon start a clinical trial in people with paraplegia and tetraplegia. The big reveal came after four former Neuralink employees told STAT that the company’s leaders have long fostered an internal culture characterized by rushed timelines and the “move fast and break things” ethos of a tech company — a pace sometimes at odds with the slow and incremental pace that’s typical of medical device development. Advertisement Friday’s event began, 40 minutes late, with a glossy video about the company’s work — and then panned to Musk, standing in front of a blue curtain beside a gleaming new version of the company’s surgical “sewing machine” robot that could easily have been mistaken for a best online viagra giant Apple device. Musk described the event as a “product demo” and said its primary purpose was to recruit potential new employees.

    It was unclear whether the best online viagra demonstration was taking place at the company’s Fremont, Calif., headquarters or elsewhere. Musk proceeded to reveal the new version of Neuralink’s brain implant, which he said was designed to fit snugly into the top of the skull. Neuralink’s technological design has changed significantly since its best online viagra last big update in July 2019. At that time, the company’s brain implant system involved a credit-card sized device designed to be positioned behind the back of a person’s ear, with several wires stretching to the top of the skull.

    After demonstrating the pig’s brain best online viagra activity at Friday’s event, Musk showed video footage of a pig walking on a treadmill and said Neuralink’s device could be used to “predict the position of limbs with high accuracy.” That capability would be critical to allowing someone using the device to do something like controlling a prosthetic limb, for example.Neuralink for months has signaled that it initially plans to develop its device for people who are paralyzed. It said at its July 2019 event that it wanted to start human testing by the end of 2020. Receiving the breakthrough device designation from the FDA — designed to speed up the lengthy regulatory process — is a step forward, but it by no means best online viagra guarantees that a device will receive a green light, either in a short or longer-term time frame. After Musk’s presentation, a handful of the company’s employees — all wearing masks, but seated only inches apart — joined him to take questions submitted on Twitter or from the small audience in the room.In typical fashion for a man who in 2018 sent a Tesla Roadster into space, Musk didn’t hesitate to use the event to cross-promote his electric car company.

    Asked whether the Neuralink chip would best online viagra allow people to summon their Tesla telepathically, Musk responded. €œDefinitely — of course.”Matthew MacDougall, the company’s head neurosurgeon, appearing in scrubs, said the company had so far only implanted its technology into the brain’s cortical surface, the coaster-width layer enveloping the brain, but added that it hoped to go deeper in the future. Still, Musk said best online viagra. €œYou could solve blindness, you could solve paralysis, you could solve hearing — you can solve a lot just by interfacing with the cortex.”Musk and MacDougall said they hoped to eventually implant Neuralink’s devices — which they referred to on stage simply as “links” — in the deeper structures of the brain, such as in the hypothalamus, which is believed to play a critical role in mental illnesses including depression, anxiety, and PTSD.There were no updates at the event of Neuralink’s research in monkeys, which the company has been conducting in partnership with the University of California, Davis since 2017.

    At last July’s event, Musk said — without providing evidence — that a monkey had controlled a computer with its brain.At that same July 2019 event, Neuralink released a preprint paper — published a few months later — that claimed to show that best online viagra a series of Neuralink electrodes implanted in the brains of rats could record neural signals. Critically, the work did not show where in the brain the implanted electrodes were recording from, for how long they were recording, or whether the recordings could be linked to any of the rats’ bodily movements.In touting Friday’s event — and Neuralink’s technological capabilities — on Twitter in recent weeks, Musk spoke of “AI symbiosis while u wait” and referenced the “matrix in the matrix” — a science-fiction reference about revealing the true nature of reality. The progress the company reported on Friday best online viagra fell far short of that. Neuralink’s prototype is ambitious, but it has yet to show evidence that it can match up to the brain-machine interfaces developed by academic labs and other companies.

    Other groups have shown that they can listen in on neural activity and allow primates and people to control a computer cursor with their brain — so-called “read-out” technology — and have also shown that they can use electrical stimulation to input information, such as a command or the best online viagra heat of a hot cup of coffee, using “write-in” technology. Neuralink said on Friday that its technology would have both read-out and write-in capabilities.Musk acknowledged that Neuralink still has a long way to go. In closing the event best online viagra after more than 70 minutes, Musk said. €œThere’s a tremendous amount of work to be done to go from here to a device that is widely available and affordable and reliable.”Following the news this week of what appears to have been the first confirmed case of a Covid-19 reinfection, other researchers have been coming forward with their own reports.

    One in Belgium, best online viagra another in the Netherlands. And now, one in Nevada.What caught experts’ attention about the case of the 25-year-old Reno man was not that he appears to have contracted SARS-CoV-2 (the name of the virus that causes Covid-19) a second time. Rather, it’s that his second bout was more serious than his first.Immunologists had expected that if the immune response generated after an initial infection could not prevent a second best online viagra case, then it should at least stave off more severe illness. That’s what occurred with the first known reinfection case, in a 33-year-old Hong Kong man.advertisement Still, despite what happened to the man in Nevada, researchers are stressing this is not a sky-is-falling situation or one that should result in firm conclusions.

    They always presumed people would become vulnerable to Covid-19 again some time after recovering from an initial case, based best online viagra on how our immune systems respond to other respiratory viruses, including other coronaviruses. It’s possible that these early cases of reinfection are outliers and have features that won’t apply to the tens of millions of other people who have already shaken off Covid-19.“There are millions and millions of cases,” said Michael Mina, an epidemiologist at Harvard’s T.H. Chan School best online viagra of Public Health. The real question that should get the most focus, Mina said, is, “What happens to most people?.

    €advertisement But with more reinfection reports likely to make it into best online viagra the scientific literature soon, and from there into the mainstream press, here are some things to look for in assessing them.What’s the deal with the Nevada case?. The Reno resident in question first tested positive for SARS-CoV-2 in April after coming down with a sore throat, cough, and headache, as well as nausea and diarrhea. He got better over time and later tested best online viagra negative twice. But then, some 48 days later, the man started experiencing headaches, cough, and other symptoms again.

    Eventually, he became so sick that he had to be hospitalized and was found to have pneumonia.Researchers sequenced virus samples from both of his infections and found they were different, providing evidence that this was a new infection distinct from the first. What happens when best online viagra we get Covid-19 in the first case?. Researchers are finding that, generally, people who get Covid-19 develop a healthy immune response replete with both antibodies (molecules that can block pathogens from infecting cells) and T cells (which help wipe out the virus). This is what happens after other viral infections.In addition to fending off the virus best online viagra the first time, that immune response also creates memories of the virus, should it try to invade a second time.

    It’s thought, then, that people who recover from Covid-19 will typically be protected from another case for some amount of time. With other coronaviruses, protection is thought to last for perhaps a little less than a year to about three years.But best online viagra researchers can’t tell how long immunity will last with a new pathogen (like SARS-CoV-2) until people start getting reinfected. They also don’t know exactly what mechanisms provide protection against Covid-19, nor do they know what levels of antibodies or T cells are required to signal that someone is protected through a blood test. (These are called the “correlates of protection.”) Why do experts expect second cases to be best online viagra milder?.

    With other viruses, protective immunity doesn’t just vanish one day. Instead, it wanes over time best online viagra. Researchers have then hypothesized that with SARS-CoV-2, perhaps our immune systems might not always be able to prevent it from getting a toehold in our cells — to halt infection entirely — but that it could still put up enough of a fight to guard us from getting really sick. Again, this is what happens with other respiratory pathogens.And it’s why some researchers actually looked at the Hong Kong case best online viagra with relief.

    The man had mild to moderate Covid-19 symptoms during the first case, but was asymptomatic the second time. It was a demonstration, experts said, of what you would want your immune system to best online viagra do. (The case was only detected because the man’s sample was taken at the airport when he arrived back in Hong Kong after traveling in Europe.)“The fact that somebody may get reinfected is not surprising,” Malik Peiris, a virologist at the University of Hong Kong, told STAT earlier this week about the first reinfection. €œBut the reinfection didn’t cause disease, so best online viagra that’s the first point.”The Nevada case, then, provides a counterexample to that.

    What kind of immune response did the person who was reinfected generate initially?. Earlier, we described the robust immune response that most people who have Covid-19 seem best online viagra to mount. But that was a generalization. Infections and the immune responses they induce in different people are “heterogeneous,” said Sarah Cobey, an epidemiologist and evolutionary biologist at the University best online viagra of Chicago.Older people often generate weaker immune responses than younger people.

    Some studies have also indicated that milder cases of Covid-19 induce tamer immune responses that might not provide as lasting or as thorough of a defense as stronger immune responses. The man in Hong Kong, for example, did not generate antibodies to the virus after his first infection, at least to the level that could be detected by best online viagra blood tests. Perhaps that explains why he contracted the virus again just about 4 1/2 months after recovering from his initial infection.In the Nevada case, researchers did not test what kind of immune response the man generated after the first case.“Infection is not some binary event,” Cobey said. And with reinfection, “there’s going to be some viral replication, but the question is how much is the immune system best online viagra getting engaged?.

    €What might be broadly meaningful is when people who mounted robust immune responses start getting reinfected, and how severe their second cases are. Are people who have Covid-19 a second time infectious? best online viagra. As discussed, immune memory can prevent reinfection. If it can’t, it might stave off best online viagra serious illness.

    But there’s a third aspect of this, too.“The most important question for reinfection, with the most serious implications for controlling the pandemic, is whether reinfected people can transmit the virus to others,” Columbia University virologist Angela Rasmussen wrote in Slate this week.Unfortunately, neither the Hong Kong nor the Reno studies looked at this question. But if most best online viagra people who get reinfected don’t spread the virus, that’s obviously good news. What happens when people broadly become susceptible again?. Whether it’s six months best online viagra after the first infection or nine months or a year or longer, at some point, protection for most people who recover from Covid-19 is expected to wane.

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    This was used to develop vaccines to combat different viruses, such as Zika and, later, the virus that causes Covid-19.In arguing for an investigation, the advocacy group maintained Moderna is obligated under federal law to disclose the grants that led to nearly a dozen specific patent applications and explained the financial support means the U.S. Government would have certain rights over the best online viagra patents. In other words, U.S. Taxpayers would have an ownership stake in vaccines developed by the company.advertisement best online viagra “This clarifies the public’s right in the inventions,” said Jamie Love, who heads Knowledge Ecology International, a nonprofit that tracks patents and access to medicines issues.

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    In some cases, advocates best online viagra argue that federal funding matters because it clarifies the rights that the U.S. Government has to ensure a therapy or vaccine is available to Americans on reasonable terms.One example has been remdesivir, the Gilead Sciences (GILD) treatment being given to hospitalized Covid-19 patients. The role played best online viagra by the U.S. Government in developing remdesivir to combat coronaviruses involved contributions from government personnel at such agencies as the U.S.

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    If the best online viagra U.S. Wants to pay for all of the development of Moderna’s vaccine, as Moderna now acknowledges, and throw in a few more billion now, and an option to spend billions more, it’s not unreasonable to have some transparency over who paid for their inventions.”This is not the first time Moderna has been accused of insufficient disclosure. Earlier this month, Knowledge Ecology International and Public Citizen maintained the company failed to best online viagra disclose development costs in a $955 million contract awarded by BARDA for its Covid-19 vaccine. In all, the federal government has awarded the company approximately $2.5 billion to develop the vaccine.The coming few weeks represent a crucial moment for an ambitious plan to try to secure Covid-19 vaccines for roughly 170 countries around the world without the deep pockets to compete for what will be scarce initial supplies.Under the plan, countries that want to pool resources to buy vaccines must notify the World Health Organization and other organizers — Gavi, the Vaccine Alliance, as well as the Coalition for Epidemic Preparedness Innovations — of their intentions by Monday.

    That means it’s fish-or-cut-bait time for the so-called COVAX facility.Already, wealthy countries — the United States, the best online viagra United Kingdom, Japan, Canada, and Australia, among others, as well as the European Union — have opted to buy their own vaccine, signing bilateral contracts with manufacturers that have secured billions of doses of vaccine already. That raises the possibility that less wealthy countries will be boxed out of supplies.advertisement And yet Richard Hatchett, the CEO of CEPI, insists there is a path to billions of doses of vaccine for the rest of the world in 2021. STAT spoke best online viagra with Hatchett this week. A transcript of the conversation, lightly edited for clarity and length, follows.

    You said this is a critical time for CEPI best online viagra. Can you explain what needs to happen between now and mid-September for this joint purchasing approach to be a success?. Advertisement The critical moment is now for countries to commit to the COVAX facility, because that will enable us to secure ample quantities of vaccine and then to be able to convey when that vaccine is likely to become available based on current best online viagra information.What we’re now here asking countries to do is to indicate their intent to participate by Aug. 31, and to make a binding commitment by Sept.

    18. And to provide funds in support of that binding commitment by early October. Our negotiations with companies are already taking place and it will be important for us from a planning purpose that countries indicate their intent to participate.Those binding commitments we think will be sufficient to allow us to then secure the advance purchase agreements, particularly with those companies that don’t have a prior contractual obligation to COVAX. And then obviously, we need the funds to live up to those advance purchase agreements.Is it possible this thing could still fall apart?.

    There appears to be some concern COVAX has been boxed out by rich countries. There was always a possibility that there wouldn’t be sufficient uptake. But I think we’re very encouraged at this point by the level of commitment, both from countries that would be beneficiaries of the advance market commitment — that’s the lower-income, lower-middle-income countries — as well as the self-financing countries. To have over 170 countries expressing interest in participating — they see the value.We’re much more encouraged now that it’s not going to fall apart.

    We still need to bring it off to maximize its value. And we’re right at the crunch moment where countries are going to have to make these commitments. So, the next month is really absolutely critical to the facility. I am confident at this point that the world recognizes the value and wants it to work.I’ve been keeping tabs on advance purchase agreements that have been announced.

    And at this point, a small number of rich countries have nailed down a lot of vaccine — more than 3 billion doses. How hard does that make your job?. The fact that they’re doing it creates anxiety among other countries. And that in itself can accelerate the pace.

    So, I’m not going to say that we’re not watching that with concern.I will say that for COVAX and the facility, this is absolutely critical moment. I think we still have a window of opportunity between now and mid-September — when we’re asking that the self-financing countries to make their commitments — to make the facility real and to make it work. Between doses that are committed to COVAX through the access agreements and other agreements — these are discussions with partners that CEPI has funded as well as partners that CEPI has not funded — we still see a pathway for COVAX to well over 3 billion doses in 2021.I think it’s really important to bear in mind is that there are at least a few countries — and I think the U.S. And the U.K.

    Most publicly — that may be in a situation of significant oversupply. I believe the U.S. And U.K. Numbers, if you add them together, would result in enough vaccine for 600 million people to receive two doses of vaccine each.

    And, you know, there is no possible way that the U.S. Or the U.K. Can use that much vaccine.So, there may be a lot of extra supply that looks like it’s been tied up sloshing around later. I don’t think that the bilateral deals that have been struck are going to prevent COVAX from achieving its goals.But if so much vaccine has been pre-ordered by rich countries, can countries in the COVAX pool get enough for their needs?.

    One of the things that we’ve argued through COVAX is that to control the pandemic or to end the acute phase of the pandemic to allow normalcy to start to reassert itself, you don’t have to vaccinate 100% of your population.You need to vaccinate those at greatest risk for bad outcomes and you need to vaccinate certain critical workers, particularly your health care workforce. And if you can achieve that goal, which for most countries means vaccinating between 20% and maybe 30% of the population, then you can transform the pandemic into something that is much more manageable. Then you can buy yourself time to vaccinate everybody who wants to be vaccinated.We’ve argued the COVAX facility really offers the world the best shot at doing that globally in the fastest possible way, as well as providing for equitable access. This is a case where doing the equitable thing is also doing the efficient thing.CEPI has provided funding to nine vaccines.

    Is it true that all those manufacturers aren’t required to provide the COVAX facility with vaccine?. That is correct. One of the things that we did, and I think it was an important role that CEPI played early on, was that we moved money very, very quickly, in small increments. You know, some of the early contracts were only $5 million or $10 million, to get programs up and running while we potentially put in place much larger-scale, longer-term contracts.If you were doing it over again, would you have given money without strings attached?.

    Yes, I think I would have. I think that was critically important to initiating programs.Our contract with Moderna was established in about 48 hours. And that provided critical funding to them to manufacture doses that got them into clinical trials within nine weeks of the genetic sequences [of the SARS-CoV-2 virus] being released.And if you look at the nine programs that we’ve invested in, seven are in clinical trials. Two — the AstraZeneca program now and the Moderna program — are among the handful in Phase 3 clinical trials.

    And, I think the number of projects that that we funded initially, which started in kind of a biotech or academic phase that have now been picked up by large multinational corporations, there’s at least four. The Themis program being picked up by Merck, Oxford University by AstraZeneca, the University of Queensland by CSL, and Clover being in partnership with GSK, I think that speaks to the quality of the programs that we selected.So, I think that combination of rapid review, speed of funding, getting those programs started, getting them oriented in the right direction, I think all of that is critical to where we are now.Companies that got money from CEPI to build out production capacity — that money came with strings attached, right?. Yes, exactly. So, where CEPI has made investments that create manufacturing, or secure manufacturing capacity, the commitment has been that the capacity that is attributable to the CEPI investment is committed — at least right of first refusal — to the global procurement facility.WASHINGTON — The Trump administration removed a top Food and Drug Administration communications official from her post on Friday in the wake of several controversial agency misstatements, a senior administration official confirmed to STAT.The spokeswoman, Emily Miller, had played a lead role in defending the FDA commissioner, Stephen Hahn, after he misrepresented data regarding the use of blood plasma from recovered Covid-19 patients.

    The New York Times first reported Miller’s ouster. Miller’s tenure at as the top FDA spokeswoman lasted only 11 days. Her appointment was viewed with alarm by agency officials who felt her presence at the agency was emblematic of broader political pressure from the Trump administration, STAT first reported earlier this week.advertisement Before joining the FDA, Miller had no experience in health or medicine. Her former role as assistant commissioner for media affairs is typically not an appointment filled by political appointees.

    The FDA’s communications arm typically maintains a neutral, nonpolitical tone.Miller’s appointment particularly alarmed FDA staff and outside scientists given her history in right-wing political advocacy and conservatism journalism. Her résumé included a stint as a Washington Times columnist, where she penned columns with titles that include “New Obamacare ads make young women look like sluts,” and a 2013 book on gun rights titled “Emily Gets Her Gun. But Obama Wants to Take Yours.”advertisement She also worked as a reporter for One America News Network, a right-wing cable channel that frequently espouses conspiracy theories and has declared an open alliance with President Trump.Miller quickly made her presence known at the FDA. In the wake of Hahn’s misstatements on blood plasma, she aggressively defended the commissioner, falsely claiming in a tweet that the therapy “has shown to be beneficial for 35% of patients.” An FDA press release on blood plasma, issued less than a week after her appointment, similarly alarmed agency insiders by trumpeting the emergency authorization as “Another Achievement in Administration’s Fight Against [the] Pandemic.”.

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