title: Yulia Tymoshenko

text: During her second stint as prime-minister her ratings in opinion polls fell. In early 2008, in opinion polls for the 2009 Ukrainian presidential election, she stood at 30% but by late April 2009 that had shrunk to 15% According to a poll carried out between 29 January and 5 February 2009 by the Kyiv International Institute of Sociology, just over 43% of the Ukrainian voters believed Tymoshenko should leave her post, whereas just over 45% believed she should stay. According to an opinion poll carried out between 3 and 12 February 2009 by the "Sofia" Center for Social Studies, some 59.1% of those polled believed that the activities of (then) Prime Minister Yulia Tymoshenko were aimed at the defense of her own interests and that of her entourage, some 4.2% said her activities were aimed at the defense of interests of foreign states, and some 23.9% believed that Tymoshenko worked for the sake of national interests. 77.7% of the respondents were unsatisfied with the economic policy of the second Tymoshenko Government. Some 71.8% believed that this government was not able to lead the Ukrainian economy out of the 2008–09 Ukrainian financial crisis or even change the situation in Ukraine to better; 18.1% of respondents did think that the government could do that. Despite the neck-to-neck 2010 presidential race, many experts believed that Tymoshenko would win the vote due to her ability to "hike her popularity just before the voting day". JP Morgan Securities Inc. experts said that Tymoshenko's victory in presidential election would "bring stability in 2010, with budget consolidation, better terms of crediting and higher influx of capital. As a result, the economy will have better prospects of growing in the second half of 2010 and 2011".


title: Yulia Tymoshenko

text: Tymoshenko has been ranked three times by "Forbes" magazine among the most powerful women in the world. During her first term in 2005, she was ranked third (behind Condoleezza Rice and Wu Yi), in 2008 she was number 17 and in 2009 at number 47.


title: Yulia Tymoshenko

text: According to the Ukrainian magazine "Focus", Tymoshenko placed first in an annual ranking of the most influential women in Ukraine in 2006–2010 (five years). During the Orange Revolution, some Western media publications dubbed her the "Joan of Arc of the Revolution". In December 2011, Tymoshenko's party BYuT-Batkivschyna nominated her for the Nobel Peace Prize.


title: Yulia Tymoshenko

text: Russian prime minister Vladimir Putin has stated (in November 2009) he found it comfortable to work with his (then) Ukrainian counterpart Yulia Tymoshenko and also praised her for strengthening Ukrainian sovereignty and building stable ties with Moscow and called the second Tymoshenko Government "efficient and a force for stability". It has been suggested by Reuters that the Russian government, after seeing her opposition to Viktor Yushchenko, supported her since late 2008, although Putin denied it.


title: Yulia Tymoshenko

text: Former ally and President of Ukraine Victor Yushchenko stated in November 2009, "I am sure that every week spent by Yulia Tymoshenko in the post of prime minister leads the country to a catastrophe. Because of Yulia Tymoshenko, it is a crisis, a crisis in everything". Yushchenko has repeatedly accused his former ally turned rival Tymoshenko of acting in the interests of Russia, although she firmly denied the allegations. On 31 May 2010, Yushchenko stated that Tymoshenko was his "worst mistake", "The most serious mistake was to give the power to her twice". Expert in Ukrainian politics Dr. Taras Kuzio believes that he has always prioritized personal revenge against Tymoshenko over Ukraine's national interests. In her turn, Tymoshenko has blamed President Viktor Yushchenko for obstructing the government-proposed anti-crisis measures and efforts to form a broad coalition to battle the crisis. "The president is using flashy words today to deprive the nation, first of all its government, of the opportunity to counter the crisis, and to leave the nation without a government it logically needs" she said. "Viktor Yushchenko has no right to any criticism. He is the incumbent president. He only has the right to work and to serve Ukraine. He will have the right to criticize when he joins the opposition. Now he must work and answer for his moves".


title: Yulia Tymoshenko

text: Former Ukrainian Minister of Finance of Ukraine Viktor Pynzenyk has called Tymoshenko's decisions "normally guided by 'adventurous populism'", which she saw as a tool to "consolidate power in her own hands" and believed Tymoshenko should have "taken advantage of the opportunity presented by the 2008–2009 Ukrainian financial crisis to reform".


title: Yulia Tymoshenko

text: Party of Regions Deputy Head Borys Kolesnykov stated on 11 February 2010, "Tymoshenko was the most effective politician during the entire period of Ukraine's recent history". Former European High Representative for Common Foreign and Security Policy Javier Solana has called Tymoshenko "a patriot regardless of the position in which you have found yourself". President Viktor Yanukovych stated about Tymoshenko on 13 May 2010, "She likes to create a sensation. We have grown used to this extravagant woman".


title: Yulia Tymoshenko

text: Vitaly Chepinoha has closely collaborated with Tymoshenko during various elections for more than a decade.


title: Yulia Tymoshenko

text: In some newspapers and television programs, Tymoshenko has been referred to as Lady Yu (Ледi Ю, Леди Ю).


title: Yulia Tymoshenko

text: In 2006 "Korrespondent" magazine ranked Tymoshenko as its 2005 "Personality of the Year", naming her in the TOP 100 most influential politicians of Ukraine, 2nd place (Women with nimbus), Person of the year.


title: Yulia Tymoshenko

text: 2007 Yulia Tymoshenko, "Focus" magazine, the most influential women of Ukraine, 1st place. Yulia Tymoshenko, Korrespondent magazine, TOP 100 the most influential politics of Ukraine, 4th place (Woman-brand), Person of the year. Yulia Tymoshenko, Focus magazine, 200 the most influential Ukrainians, 2nd place.


title: Yulia Tymoshenko

text: 2009 Yulia Tymoshenko, "Korrespondent" magazine, TOP 100 the most influential Ukrainians, 1st place (Dream women). Yulia Tymoshenko, Focus magazine, the most influential women of Ukraine, 1st place. Yulia Tymoshenko, Focus magazine, TOP 200 the most influential politicians of Ukraine, 1st place.


title: Yulia Tymoshenko

text: Between 2007 and 2013 in Ukraine, Tymoshenko was the most popular politician on the Internet, in blogs and social networks. Yulia Tymoshenko was the most popular foreign politician in the Russian media.


title: Yulia Tymoshenko

text: In 2012 the national rating (28 December 2012) by the Razumkov Center and the "" recognised Yulia Tymoshenko as the best prime minister of Ukraine – 19.5%, compared with Viktor Yanukovych – 11.4%, Mykola Azarov – 8.6%, Leonid Kuchma – 5.6%, Viktor Yushchenko – 3.9%, Pavel Lazarenko – 2.2%.


title: Yulia Tymoshenko

text: According to the sociological group "Rating" Yulia Tymoshenko was ranked as third most trusted politician in early April 2021, behind President Volodymyr Zelenskyy and then-Chairman of the Verkhovna Rada Dmytro Razumkov.


title: Emily Brontë

text: Emily Jane Brontë (, ; 30 July 1818 – 19 December 1848) was an English novelist and poet who is best known for her only novel, "Wuthering Heights", now considered a classic of English literature. She also published a book of poetry with her sisters Charlotte and Anne titled "Poems by Currer, Ellis and Acton Bell" with her own poems finding regard as poetic genius. Emily was the second-youngest of the four surviving Brontë siblings, between the youngest Anne and her brother Branwell. She published under the pen name Ellis Bell.


title: Emily Brontë

text: Emily Brontë was born on 30 July 1818 to Maria Branwell and an Irish father, Patrick Brontë. The family was living on Market Street in the village of Thornton on the outskirts of Bradford, in the West Riding of Yorkshire, England. Emily was the second youngest of six siblings, preceded by Maria, Elizabeth, Charlotte and Branwell. In 1820, Emily's younger sister Anne, the last Brontë child, was born. Shortly thereafter, the family moved eight miles away to Haworth, where Patrick was employed as perpetual curate. In Haworth, the children would have opportunities to develop their literary talents.


title: Emily Brontë

text: When Emily was only three, and all six children under the age of eight, she and her siblings lost their mother, Maria, to cancer on 15 September 1821. The younger children were to be cared for by Elizabeth Branwell, their aunt and Maria's sister.


title: Emily Brontë

text: Emily's three elder sisters, Maria, Elizabeth, and Charlotte, were sent to the Clergy Daughters' School at Cowan Bridge. At the age of six, on 25 November 1824, Emily joined her sisters at school for a brief period. At school, however, the children suffered abuse and privations, and when a typhoid epidemic swept the school, Maria and Elizabeth became ill. Maria, who may actually have had tuberculosis, was sent home, where she died. Elizabeth died shortly after.


title: Emily Brontë

text: The four youngest Brontë children, all under ten years of age, had suffered the loss of the three eldest women in their immediate family.


title: Emily Brontë

text: Charlotte maintained that the school's poor conditions permanently affected her health and physical development and that it had hastened the deaths of Maria (born 1814) and Elizabeth (born 1815), who both died in 1825. After the deaths of his older daughters, Patrick removed Charlotte and Emily from the school. Charlotte would use her experiences and knowledge of the school as the basis for Lowood School in "Jane Eyre".


title: Emily Brontë

text: The three remaining sisters and their brother Branwell were thereafter educated at home by their father and aunt Elizabeth Branwell. A shy girl, Emily was very close to her siblings and was known as a great animal lover, especially for befriending stray dogs she found wandering around the countryside. Despite the lack of formal education, Emily and her siblings had access to a wide range of published material; favourites included Sir Walter Scott, Byron, Shelley, and "Blackwood's Magazine".


title: Emily Brontë

text: Inspired by a box of toy soldiers Branwell had received as a gift, the children began to write stories which they set in a number of invented imaginary worlds peopled by their soldiers as well as their heroes the Duke of Wellington and his sons, Charles and Arthur Wellesley. Little of Emily's work from this period survives, except for poems spoken by characters. Initially, all four children shared in creating stories about a world called Angria.


title: Emily Brontë

text: However, when Emily was 13, she and Anne withdrew from participation in the Angria story and began a new one about Gondal, a fictional island whose myths and legends were to preoccupy the two sisters throughout their lives. With the exception of their Gondal poems and Anne's lists of Gondal's characters and place-names, Emily and Anne's Gondal writings were largely not preserved. Among those that did survive are some "diary papers," written by Emily in her twenties, which describe current events in Gondal. The heroes of Gondal tended to resemble the popular image of the Scottish Highlander, a sort of British version of the "noble savage": romantic outlaws capable of more nobility, passion, and bravery than the denizens of "civilization". Similar themes of romanticism and noble savagery are apparent across the Brontë's juvenilia, notably in Branwell's "The Life of Alexander Percy", which tells the story of an all-consuming, death-defying, and ultimately self-destructive love and is generally considered an inspiration for "Wuthering Heights".


title: Emily Brontë

text: At seventeen, Emily began to attend the Roe Head Girls' School, where Charlotte was a teacher, but suffered from extreme homesickness and left after only a few months. Charlotte wrote later that "Liberty was the breath of Emily's nostrils; without it, she perished. The change from her own home to a school and from her own very noiseless, very secluded but unrestricted and unartificial mode of life, to one of disciplined routine (though under the kindest auspices), was what she failed in enduring... I felt in my heart she would die if she did not go home, and with this conviction obtained her recall." Emily returned home and Anne took her place. At this time, the girls' objective was to obtain sufficient education to open a small school of their own.


title: Emily Brontë

text: Emily became a teacher at Law Hill School in Halifax beginning in September 1838, when she was twenty. Her always fragile health soon broke under the stress of the 17-hour work day and she returned home in April 1839. Thereafter she remained at home, doing most of the cooking, ironing, and cleaning at Haworth. She taught herself German out of books and also practised the piano.


title: Emily Brontë

text: In 1842, Emily accompanied Charlotte to the Héger Pensionnat in Brussels, Belgium, where they attended the girls' academy run by Constantin Héger in the hope of perfecting their French and German before opening their school. Unlike Charlotte, Emily was uncomfortable in Brussels, and refused to adopt Belgian fashions, saying "I wish to be as God made me", which rendered her something of an outcast. Nine of Emily's French essays survive from this period. Héger seems to have been impressed with the strength of Emily's character, writing that:


title: Emily Brontë

text: The two sisters were committed to their studies and by the end of the term had become so competent in French that Madame Héger proposed that they both stay another half-year, even, according to Charlotte, offering to dismiss the English master so that she could take his place. Emily had, by this time, become a competent pianist and teacher and it was suggested that she might stay on to teach music. However, the illness and death of their aunt drove them to return to their father and Haworth. In 1844, the sisters attempted to open a school in their house, but their plans were stymied by an inability to attract students to the remote area.


title: Emily Brontë

text: In 1844, Emily began going through all the poems she had written, recopying them neatly into two notebooks. One was labelled "Gondal Poems"; the other was unlabelled. Scholars such as Fannie Ratchford and Derek Roper have attempted to piece together a Gondal storyline and chronology from these poems.


title: Emily Brontë

text: In the autumn of 1845, Charlotte discovered the notebooks and insisted that the poems be published. Emily, furious at the invasion of her privacy, at first refused but relented when Anne brought out her own manuscripts and revealed to Charlotte that she had been writing poems in secret as well. As co-authors of Gondal stories, Anne and Emily were accustomed to read their Gondal stories and poems to each other, while Charlotte was excluded from their privacy. Around this time Emily had written one of her most famous poems "No coward soul is mine", probably as an answer to the violation of her privacy and her own transformation into a published writer. Despite Charlotte's later claim, it was not her last poem.


title: Emily Brontë

text: In 1846, the sisters' poems were published in one volume as "Poems by Currer, Ellis, and Acton Bell". The Brontë sisters had adopted pseudonyms for publication, preserving their initials: Charlotte was "Currer Bell", Emily was "Ellis Bell" and Anne was "Acton Bell". Charlotte wrote in the 'Biographical Notice of Ellis and Acton Bell' that their "ambiguous choice" was "dictated by a sort of conscientious scruple at assuming Christian names positively masculine, while we did not like to declare ourselves women, because... we had a vague impression that authoresses are liable to be looked on with prejudice". Charlotte contributed 19 poems, and Emily and Anne each contributed 21. Although the sisters were told several months after publication that only two copies had sold, they were not discouraged (of their two readers, one was impressed enough to request their autographs). "The Athenaeum" reviewer praised Ellis Bell's work for its music and power, singling out his poems as the best: "Ellis possesses a fine, quaint spirit and an evident power of wing that may reach heights not here attempted", and "The Critic" reviewer recognised "the presence of more genius than it was supposed this utilitarian age had devoted to the loftier exercises of the intellect."


title: Emily Brontë

text: Emily Brontë's solitary and reclusive nature has made her a mysterious figure and a challenge for biographers to assess. Except for Ellen Nussey and Louise de Bassompierre, Emily's fellow student in Brussels, she does not seem to have made any friends outside her family. Her closest friend was her sister Anne. Together they shared their own fantasy world, Gondal, and, according to Ellen Nussey, in childhood they were "like twins", "inseparable companions" and "in the very closest sympathy which never had any interruption". In 1845 Anne took Emily to visit some of the places she had come to know and love in the five years she spent as governess. A plan to visit Scarborough fell through and instead the sisters went to York where Anne showed Emily York Minster. During the trip the sisters acted out some of their Gondal characters.


title: Emily Brontë

text: Charlotte Brontë remains the primary source of information about Emily, although as an elder sister, writing publicly about her only shortly after her death, she is considered by certain scholars not to be a neutral witness. Stevie Davies believes that there is what might be called Charlotte's smoke-screen and argues that Emily evidently shocked her, to the point where she may even have doubted her sister's sanity. After Emily's death, Charlotte rewrote her character, history and even poems on a more acceptable (to her and the bourgeois reading public) model. Biographer Claire O'Callaghan suggests that the trajectory of Brontë's legacy was altered significantly by Elizabeth Gaskell’s biography of Charlotte, concerning not only because Gaskell did not visit Haworth until after Emily’s death, but also because Gaskell admits to disliking what she did know of Emily in her biography of Charlotte. As O'Callaghan and others have noted, Charlotte was Gaskell's primary source of information on Emily's life and may have exaggerated or fabricated Emily’s frailty and shyness to cast herself in the role of maternal saviour.


title: Emily Brontë

text: Charlotte presented Emily as someone whose "natural" love of the beauties of nature had become somewhat exaggerated owing to her shy nature, portraying her as too fond of the Yorkshire moors, and homesick whenever she was away. According to Lucasta Miller, in her analysis of Brontë biographies, "Charlotte took on the role of Emily's first mythographer." In the "Preface" to the Second Edition of "Wuthering Heights", in 1850, Charlotte wrote:


title: Emily Brontë

text: Emily's unsociability and extremely shy nature have subsequently been reported many times. According to Norma Crandall, her "warm, human aspect" was "usually revealed only in her love of nature and of animals". In a similar description, "Literary news" (1883) states: "[Emily] loved the solemn moors, she loved all wild, free creatures and things", and critics attest that her love of the moors is manifest in "Wuthering Heights". Over the years, Emily's love of nature has been the subject of many anecdotes. A newspaper dated 31 December 1899, gives the folksy account that "with bird and beast [Emily] had the most intimate relations, and from her walks she often came with fledgling or young rabbit in hand, talking softly to it, quite sure, too, that it understood". Elizabeth Gaskell, in her biography of Charlotte, told the story of Emily's punishing her pet dog Keeper for lying "on the delicate white counterpane" that covered one of the beds in the Parsonage. According to Gaskell, she struck him with her fists until he was "half-blind" with his eyes "swelled up". This story is apocryphal, and contradicts the following account of Emily's and Keeper's relationship:


title: Emily Brontë

text: In "Queens of Literature of the Victorian Era" (1886), Eva Hope summarises Emily's character as "a peculiar mixture of timidity and Spartan-like courage", and goes on to say, "She was painfully shy, but physically she was brave to a surprising degree. She loved few persons, but those few with a passion of self-sacrificing tenderness and devotion. To other people's failings she was understanding and forgiving, but over herself she kept a continual and most austere watch, never allowing herself to deviate for one instant from what she considered her duty."


title: Emily Brontë

text: Emily Brontë has often been characterised as a devout if somewhat unorthodox Christian, a heretic and a visionary "mystic of the moors".


title: Emily Brontë

text: Emily Brontë's "Wuthering Heights" was first published in London in 1847 by Thomas Cautley Newby, appearing as the first two volumes of a three-volume set that included Anne Brontë's "Agnes Grey". The authors were printed as being Ellis and Acton Bell; Emily's real name did not appear until 1850, when it was printed on the title page of an edited commercial edition. The novel's innovative structure somewhat puzzled critics.


title: Emily Brontë

text: "Wuthering Heights"s violence and passion led the Victorian public and many early reviewers to think that it had been written by a man. According to Juliet Gardiner, "the vivid sexual passion and power of its language and imagery impressed, bewildered and appalled reviewers." Literary critic Thomas Joudrey further contextualizes this reaction: "Expecting in the wake of Charlotte Brontë's "Jane Eyre" to be swept up in an earnest Bildungsroman, they were instead shocked and confounded by a tale of unchecked primal passions, replete with savage cruelty and outright barbarism." Even though the novel received mixed reviews when it first came out, and was often condemned for its portrayal of amoral passion, the book subsequently became an English literary classic. Emily Brontë never knew the extent of fame she achieved with her only novel, as she died a year after its publication, aged 30.


title: Emily Brontë

text: Although a letter from her publisher indicates that Emily had begun to write a second novel, the manuscript has never been found. Perhaps Emily or a member of her family eventually destroyed the manuscript, if it existed, when she was prevented by illness from completing it. It has also been suggested that, though less likely, the letter could have been intended for Anne Brontë, who was already writing "The Tenant of Wildfell Hall", her second novel.


title: Emily Brontë

text: Emily's health was probably weakened by the harsh local climate and by unsanitary conditions at home, where water was contaminated by run off from the church's graveyard. Branwell died suddenly, on Sunday, 24 September 1848. At his funeral service, a week later, Emily caught a severe cold that quickly developed into inflammation of the lungs and led to tuberculosis. Though her condition worsened steadily, she rejected medical help and all offered remedies, saying that she would have "no poisoning doctor" near her. On the morning of 19 December 1848, Charlotte, fearing for her sister, wrote:


title: Emily Brontë

text: At noon, Emily was worse; she could only whisper in gasps. With her last audible words she said to Charlotte, "If you will send for a doctor, I will see him now", but it was too late. She died that same day at about two in the afternoon. According to Mary Robinson, an early biographer of Emily, it happened while she was sitting on the sofa. However, Charlotte's letter to William Smith Williams where she mentions Emily's dog, Keeper, lying at the side of her dying-bed, makes this statement seem unlikely.


title: Emily Brontë

text: It was less than three months after Branwell's death, which led Martha Brown, a housemaid, to declare that "Miss Emily died of a broken heart for love of her brother". Emily had grown so thin that her coffin measured only 16 inches (40 centimeters) wide. The carpenter said he had never made a narrower one for an adult. Her mortal remains were interred in the family vault in St Michael and All Angels' Church, Haworth.


title: Emily Brontë

text: The English folk group The Unthanks released "Lines", a trilogy of short albums, which includes settings of Brontë's poems to music and was recorded at the Brontës' parsonage home, using their own Regency era piano, played by Adrian McNally.


title: Emily Brontë

text: In the 2019 film "How to Build a Girl", Emily and Charlotte Brontë are among the historical figures in Johanna's wall collage.


title: Emily Brontë

text: In May 2021, the contents of the Honresfield library, a collection of rare books and manuscripts first assembled by Rochdale mill owners Alfred and William Law, re-emerged after being out of public view for nearly a century. In the collection were handwritten poems by Emily Brontë, as well as the Brontë family edition of Bewick's 'History of British Birds.' The collection was to be auctioned off at Sotheby's and was estimated to sell for £1 million.


title: Emily Brontë

text: In the 2022 film "Emily", written and directed by Frances O'Connor, Emma Mackey plays Emily before the publication of "Wuthering Heights". The film mixes known biographical details with imagined situations and relationships.


title: COVID-19 vaccine

text: A COVID19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 (COVID19).


title: COVID-19 vaccine

text: Prior to the COVID19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This knowledge accelerated the development of various vaccine platforms during early 2020. The initial focus of SARS-CoV-2 vaccines was on preventing symptomatic, often severe illness. In January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by March 2020, the global pharmaceutical industry announced a major commitment to address COVID19. In 2020, the first COVID19 vaccines were developed and made available to the public through emergency authorizations and conditional approvals. Initially, most COVID19 vaccines were two-dose vaccines, with the sole exception being the single-dose Janssen COVID-19 vaccine. However, immunity from the vaccines has been found to wane over time, requiring people to get booster doses of the vaccine to maintain immunity against COVID19.


title: COVID-19 vaccine

text: The COVID19 vaccines are widely credited for their role in reducing the spread of COVID19 and reducing the severity and death caused by COVID19. According to a June 2022 study, COVID19 vaccines prevented an additional 14.4 to 19.8 million deaths in 185 countries and territories from 8 December 2020 to 8 December 2021. Many countries implemented phased distribution plans that prioritized those at highest risk of complications, such as the elderly, and those at high risk of exposure and transmission, such as healthcare workers.


title: COVID-19 vaccine

text: Common side effects of COVID19 vaccines include soreness, redness, rash, inflammation at the injection site, fatigue, headache, myalgia (muscle pain), and arthralgia (joint pain), which resolve without medical treatment within a few days. COVID-19 vaccination is safe for people who are breastfeeding.


title: COVID-19 vaccine

text: , 12.7billion doses of COVID19 vaccines have been administered worldwide based on official reports from national public health agencies. By December 2020, more than 10 billion vaccine doses had been preordered by countries, with about half of the doses purchased by high-income countries comprising 14% of the world's population.


title: COVID-19 vaccine

text: Despite the extremely rapid development of effective mRNA and viral vector vaccines, worldwide vaccine equity has not been achieved. The development and use of whole inactivated virus (WIV) and protein-based vaccines have also been recommended, especially for use in developing countries. The United States Food and Drug Administration (FDA) has now authorized bivalent vaccines to protect against the original COVID-19 strain and its Omicron variant.


title: COVID-19 vaccine

text: Prior to COVID19, a vaccine for an infectious disease had never been produced in less than several yearsand no vaccine existed for preventing a coronavirus infection in humans. However, vaccines have been produced against several animal diseases caused by coronaviruses, including (as of 2003) infectious bronchitis virus in birds, canine coronavirus, and feline coronavirus. Previous projects to develop vaccines for viruses in the family "Coronaviridae" that affect humans have been aimed at severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Vaccines against SARS and MERS have been tested in non-human animals.


title: COVID-19 vaccine

text: According to studies published in 2005 and 2006, the identification and development of novel vaccines and medicines to treat SARS was a priority for governments and public health agencies around the world at that time. There is no cure or protective vaccine proven to be safe and effective against SARS in humans. There is also no proven vaccine against MERS. When MERS became prevalent, it was believed that existing SARS research might provide a useful template for developing vaccines and therapeutics against a MERS-CoV infection. As of March 2020, there was one (DNA-based) MERS vaccine which completed PhaseI clinical trials in humans, and three others in progress, all being viral-vectored vaccines: two adenoviral-vectored (ChAdOx1-MERS, BVRS-GamVac) and one MVA-vectored (MVA-MERS-S).


title: COVID-19 vaccine

text: Vaccines that use an inactive or weakened virus that has been grown in eggs typically take more than a decade to develop. In contrast, mRNA is a molecule that can be made quickly, and research on mRNA to fight diseases was begun decades before the COVID19 pandemic by scientists such as Drew Weissman and Katalin Karikó, who tested on mice. Moderna began human testing of an mRNA vaccine in 2015. Viral vector vaccines were also developed for the COVID19 pandemic after the technology was previously cleared for Ebola.


title: COVID-19 vaccine

text: As multiple COVID19 vaccines have been authorized or licensed for use, real-world vaccine effectiveness (RWE) is being assessed using case control and observational studies. A study is investigating the long-lasting protection against SARS-CoV-2 provided by the mRNA vaccines.


title: COVID-19 vaccine

text: As of July 2021, at least nine different technology platforms are under research and development to create an effective vaccine against COVID19. Most of the platforms of vaccine candidates in clinical trials are focused on the coronavirus spike protein (S protein) and its variants as the primary antigen of COVID19 infection, since the S protein triggers strong B-cell and T-cell immune responses. However, other coronavirus proteins are also being investigated for vaccine development, like the nucleocapsid, because they also induce a robust T-cell response and their genes are more conserved and recombine less frequently (compared to Spike). Future generations of COVID-19 vaccines that may target more and conserved genomic regions will also act as an insurance against the manifestation of catastrophic scenarios concerning the future evolutionary path of SARS-CoV-2, or any similar Coronavirus epidemic/pandemic.


title: COVID-19 vaccine

text: Platforms developed in 2020 involved nucleic acid technologies (nucleoside-modified messenger RNA and DNA), non-replicating viral vectors, peptides, recombinant proteins, live attenuated viruses, and inactivated viruses.


title: COVID-19 vaccine

text: Many vaccine technologies being developed for COVID19 are not like vaccines already in use to prevent influenza, but rather are using "next-generation" strategies for precise targeting of COVID19 infection mechanisms. Several of the synthetic vaccines use a 2P mutation to lock the spike protein into its prefusion configuration, stimulating an adaptive immune response to the virus before it attaches to a human cell. Vaccine platforms in development may improve flexibility for antigen manipulation, and effectiveness for targeting mechanisms of COVID19 infection in susceptible population subgroups, such as healthcare workers, the elderly, children, pregnant women, and people with weakened immune systems.


title: COVID-19 vaccine

text: Several COVID19 vaccines, including the Pfizer–BioNTech and Moderna vaccines, have been developed to use RNA to stimulate an immune response. When introduced into human tissue, the vaccine contains either self-replicating RNA or messenger RNA (mRNA), which both cause cells to express the SARS-CoV-2 spike protein. This teaches the body how to identify and destroy the corresponding pathogen. RNA vaccines often, but not always, use nucleoside-modified messenger RNA. The delivery of mRNA is achieved by a coformulation of the molecule into lipid nanoparticles which protect the RNA strands and help their absorption into the cells.


title: COVID-19 vaccine

text: RNA vaccines are the first COVID19 vaccines to be authorized in the United Kingdom, the United States and the European Union. Authorized vaccines of this type are the Pfizer–BioNTech<wbr /> and Moderna vaccines. The CVnCoV RNA vaccine from CureVac failed in clinical trials.


title: COVID-19 vaccine

text: Severe allergic reactions are rare. In December 2020, 1,893,360 first doses of Pfizer–BioNTech COVID19 vaccine administration resulted in 175 cases of severe allergic reaction, of which 21 were anaphylaxis. For 4,041,396 Moderna COVID19 vaccine dose administrations in December 2020 and January 2021, only ten cases of anaphylaxis were reported. Lipid nanoparticles (LNPs) were most likely responsible for the allergic reactions.


title: COVID-19 vaccine

text: These vaccines are examples of non-replicating viral vector vaccines, using an adenovirus shell containing DNA that encodes a SARS‑CoV‑2 protein. The viral vector-based vaccines against COVID19 are non-replicating, meaning that they do not make new virus particles, but rather produce only the antigen which elicits a systemic immune response.


title: COVID-19 vaccine

text: Authorized vaccines of this type are the Oxford–AstraZeneca COVID19 vaccine,<wbr /> the Sputnik V COVID19 vaccine, Convidecia, and the Janssen COVID19 vaccine.


title: COVID-19 vaccine

text: Convidecia and the Janssen COVID19 vaccine are both one-shot vaccines which offer less complicated logistics and can be stored under ordinary refrigeration for several months.


title: COVID-19 vaccine

text: Sputnik V uses Ad26 for its first dose, which is the same as Janssen's only dose, and Ad5 for the second dose, which is the same as Convidecia's only dose.


title: COVID-19 vaccine

text: In August 2021, the developers of Sputnik V proposed, in view of the Delta case surge, that Pfizer test the Ad26 component (termed its 'Light' version) as a booster shot:


title: COVID-19 vaccine

text: Inactivated vaccines consist of virus particles that are grown in culture and then killed using a method such as heat or formaldehyde to lose disease producing capacity, while still stimulating an immune response.


title: COVID-19 vaccine

text: Authorized vaccines of this type are the Chinese CoronaVac and the Sinopharm BIBP<wbr /> and WIBP vaccines; the Indian Covaxin; later this year the Russian CoviVac; the Kazakh vaccine QazVac; and the Iranian COVIran Barekat. Vaccines in clinical trials include the Valneva COVID19 vaccine.


title: COVID-19 vaccine

text: Subunit vaccines present one or more antigens without introducing whole pathogen particles. The antigens involved are often protein subunits, but can be any molecule that is a fragment of the pathogen.


title: COVID-19 vaccine

text: The authorized vaccines of this type are the peptide vaccine EpiVacCorona,<wbr /> ZF2001, MVC-COV1901, Corbevax, and the Sanofi–GSK vaccine. Vaccines with pending authorizations include the Novavax COVID19 vaccine, and Soberana 02 (a conjugate vaccine).


title: COVID-19 vaccine

text: The V451 vaccine was in clinical trials that were terminated after it was found that the vaccine may potentially cause incorrect results for subsequent HIV testing.<wbr />


title: COVID-19 vaccine

text: Additional types of vaccines that are in clinical trials include virus-like particle vaccines, multiple DNA plasmid vaccines,<wbr /> at least two lentivirus vector vaccines,<wbr /><wbr /> a conjugate vaccine, and a vesicular stomatitis virus displaying the SARS‑CoV‑2 spike protein.


title: COVID-19 vaccine

text: Scientists investigated whether existing vaccines for unrelated conditions could prime the immune system and lessen the severity of COVID19 infection. There is experimental evidence that the BCG vaccine for tuberculosis has non-specific effects on the immune system, but no evidence that this vaccine is effective against COVID19.


title: COVID-19 vaccine

text: Currently, all coronavirus vaccines available, regardless of the different types of technology they are based on, are administrated by injection. However, various other types of vaccine delivery methods have been studied for future coronavirus vaccines.


title: COVID-19 vaccine

text: Intranasal vaccines target mucosal immunity in the nasal mucosa which is a portal for viral entrance to the body. These vaccines are designed to stimulate nasal immune factors, such as IgA. In addition to inhibiting the virus, nasal vaccines provide ease of administration because no needles (and the accompanying needle phobia) are involved. Nasal vaccines have been approved for influenza, but not for COVID-19.


title: COVID-19 vaccine

text: A variety of intranasal COVID-19 vaccines are undergoing clinical trials. One is in use in China. Examples include a vaccine candidate which uses a modified avian virus as a vector to target SARS-CoV-2 spike proteins and an mRNA vaccine delivered via a nasal nanoparticle spray. In September 2022, India and China approved first nasal COVID-19 vaccines which may (as boosters) also reduce transmission (potentially via sterilizing immunity).


title: COVID-19 vaccine

text: Aivita Biomedical is developing an experimental autologous dendritic cell COVID19 vaccine kit where the vaccine is prepared and incubated at the point-of-care using cells from the intended recipient. The vaccine is undergoing small phase I and phase II clinical studies.


title: COVID-19 vaccine

text: A universal coronavirus vaccine is effective against all coronavirus (and possibly other) viruses. The concept was publicly endorsed by NIAID director Anthony Fauci, virologist Jeffery K. Taubenberger, and David M. Morens. In March 2022, the White House released the "National COVID-19 Preparedness Plan", which recommended to accelerate development of such vaccines.


title: COVID-19 vaccine

text: One strategy for developing such vaccines was developed at Walter Reed Army Institute of Research (WRAIR). It uses a spike ferritin-based nanoparticle (SpFN). This vaccine began a Phase I clinical trial in April 2022.


title: COVID-19 vaccine

text: Another strategy is to attach vaccine fragments from multiple strains to a nanoparticle scaffold. Universality is enhanced by targeting the receptor-binding domain rather than the spike protein.


title: COVID-19 vaccine

text: , eleven of the vaccine candidates in clinical development use adjuvants to enhance immunogenicity. An immunological adjuvant is a substance formulated with a vaccine to elevate the immune response to an antigen, such as the COVID19 virus or influenza virus. Specifically, an adjuvant may be used in formulating a COVID19 vaccine candidate to boost its immunogenicity and efficacy to reduce or prevent COVID19 infection in vaccinated individuals. Adjuvants used in COVID19 vaccine formulation may be particularly effective for technologies using the inactivated COVID19 virus and recombinant protein-based or vector-based vaccines. Aluminum salts, known as "alum", were the first adjuvant used for licensed vaccines, and are the adjuvant of choice in some 80% of adjuvanted vaccines. The alum adjuvant initiates diverse molecular and cellular mechanisms to enhance immunogenicity, including release of proinflammatory cytokines.


title: COVID-19 vaccine

text: Since January 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments.


title: COVID-19 vaccine

text: The urgency to create a vaccine for COVID19 led to compressed schedules that shortened the standard vaccine development timeline, in some cases combining clinical trial steps over months, a process typically conducted sequentially over several years. Public health programs have been described as in "[a] race to vaccinate individuals" with the early wave vaccines.


title: COVID-19 vaccine

text: Timelines for conducting clinical researchnormally a sequential process requiring yearsare being compressed into safety, efficacy, and dosing trials running simultaneously over months, potentially compromising safety assurance. As an example, Chinese vaccine developers and the government Chinese Center for Disease Control and Prevention began their efforts in January 2020, and by March were pursuing numerous candidates on short timelines, with the goal to showcase Chinese technology strengths over those of the United States, and to reassure the Chinese people about the quality of vaccines produced in China.


title: COVID-19 vaccine

text: The rapid development and urgency of producing a vaccine for the COVID19 pandemic was expected to increase the risks and failure rate of delivering a safe, effective vaccine. Additionally, research at universities is obstructed by physical distancing and closing of laboratories.


title: COVID-19 vaccine

text: Vaccines must progress through several phases of clinical trials to test for safety, immunogenicity, effectiveness, dose levels and adverse effects of the candidate vaccine. Vaccine developers have to invest resources internationally to find enough participants for PhaseII–III clinical trials when the virus has proved to be a "moving target" of changing transmission rates across and within countries, forcing companies to compete for trial participants. Clinical trial organizers also may encounter people unwilling to be vaccinated due to vaccine hesitancy or disbelief in the science of the vaccine technology and its ability to prevent infection. As new vaccines are developed during the COVID19 pandemic, licensure of COVID19 vaccine candidates requires submission of a full dossier of information on development and manufacturing quality.


title: COVID-19 vaccine

text: Internationally, the Access to COVID19 Tools Accelerator is a G20 and World Health Organization (WHO) initiative announced in April 2020. It is a cross-discipline support structure to enable partners to share resources and knowledge. It comprises four pillars, each managed by two to three collaborating partners: Vaccines (also called "COVAX"), Diagnostics, Therapeutics, and Health Systems Connector. The WHO's April 2020 "R&D Blueprint (for the) novel Coronavirus" documented a "large, international, multi-site, individually randomized controlled clinical trial" to allow "the concurrent evaluation of the benefits and risks of each promising candidate vaccine within 3–6 months of it being made available for the trial." The WHO vaccine coalition will prioritize which vaccines should go into PhaseII andIII clinical trials, and determine harmonized PhaseIII protocols for all vaccines achieving the pivotal trial stage.


title: COVID-19 vaccine

text: National governments have also been involved in vaccine development. Canada announced funding of 96 projects for development and production of vaccines at Canadian companies and universities with plans to establish a "vaccine bank" that could be used if another coronavirus outbreak occurs, and to support clinical trials and develop manufacturing and supply chains for vaccines.


title: COVID-19 vaccine

text: China provided low-rate loans to one vaccine developer through its central bank, and "quickly made land available for the company" to build production plants. Three Chinese vaccine companies and research institutes are supported by the government for financing research, conducting clinical trials, and manufacturing.


title: COVID-19 vaccine

text: The United Kingdom government formed a COVID19 vaccine task force in April 2020 to stimulate local efforts for accelerated development of a vaccine through collaborations of industry, universities, and government agencies. The UK's Vaccine Taskforce contributed to every phase of development from research to manufacturing.


title: COVID-19 vaccine

text: In the United States, the Biomedical Advanced Research and Development Authority (BARDA), a federal agency funding disease-fighting technology, announced investments to support American COVID19 vaccine development, and manufacture of the most promising candidates. In May 2020, the government announced funding for a fast-track program called Operation Warp Speed. By March 2021, BARDA had funded an estimated $19.3 billion in COVID19 vaccine development.


title: COVID-19 vaccine

text: Large pharmaceutical companies with experience in making vaccines at scale, including Johnson & Johnson, AstraZeneca, and GlaxoSmithKline (GSK), formed alliances with biotechnology companies, governments, and universities to accelerate progression toward effective vaccines.


title: COVID-19 vaccine

text: In November 2021, the full nucleotide sequences of the AstraZeneca and Pfizer/BioNTech vaccines were released by the UK Medicines and Healthcare products Regulatory Agency, in response to a freedom of information request.


title: COVID-19 vaccine

text: As of 2021, data suggests fully vaccinated individuals and those previously infected with SARS-CoV-2 have a low risk of subsequent infection for at least six months. There is currently insufficient data to determine an antibody titer threshold that indicates when an individual is protected from infection. Multiple studies show that antibody titers are associated with protection at the population level, but individual protection titers remain unknown. For some populations, such as the elderly and the immunocompromised, protection levels may be reduced after both vaccination and infection. Finally, current data suggests that the level of protection may not be the same for all variants of the virus.


title: COVID-19 vaccine

text: As of December 2021, there are no authorized or approved tests that providers or the public can use to reliably determine if a person is protected from infection.


title: COVID-19 vaccine

text: As of March 2022, elderly residents' protection against severe illness, hospitalization and death in English care homes was high immediately after vaccination, but protection declined significantly in the months following vaccination. Protection among care home staff, who were younger, declined much more slowly. Regular boosters are recommended for older people and boosters every six months for care home residents appear reasonable.


title: COVID-19 vaccine

text: The CDC recommends a fourth dose of the Pfizer mRNA vaccine , for "certain immunocompromised individuals and people over the age of 50".


title: COVID-19 vaccine

text: In contrast to other investigated prior variants, the SARS-CoV-2 Omicron variant and its BA.4/5 subvariants are evading immunity induced by vaccines, which may lead to breakthrough infections despite recent vaccination. Nevertheless, current vaccines are thought to provide a level of protection against severe illness, hospitalizations, and deaths due to Omicron.


title: COVID-19 vaccine

text: As of 2022, fully vaccinated individuals with breakthrough infections with SARS-CoV-2 delta (B.1.617.2) variant have peak viral load similar to unvaccinated cases and are able to transmit infection in household settings.


title: COVID-19 vaccine

text: According to studies, the combination of two different COVID19 vaccines, also called cross vaccination or mix-and-match method, provides protection equivalent to that of mRNA vaccines – including protection against the Delta variant. Individuals who receive the combination of two different vaccines produce strong immune responses, with side effects no worse than those caused by standard regimens.


title: COVID-19 vaccine

text: For most people, the side effects, also called "adverse effects", from COVID19 vaccines are mild and can be managed at home.


title: COVID-19 vaccine

text: All vaccines that are administered via intramuscular injection, including COVID19 vaccines, have side effects related to the mild trauma associated with the procedure and introduction of a foreign substance into the body. These include soreness, redness, rash, and inflammation at the injection site. Other common side effects include fatigue, headache, myalgia (muscle pain), and arthralgia (joint pain), all of which generally resolve without medical treatment within a few days. Also like any other vaccine, some people are allergic to one or more ingredients in COVID19 vaccines. Typical side effects are stronger and more common in younger people and in subsequent doses, and up to 20% of people report a disruptive level of side effects after the second dose of an mRNA vaccine. These side effects are less common or weaker in inactivated vaccines.


title: COVID-19 vaccine

text: COVID19 vaccination is safe for people who are breastfeeding. Temporary changes to the menstrual cycle in young women have been reported, although these changes are "small compared with natural variation and quickly reverse". In one study, women who received both doses of a two-dose vaccine during the same menstrual cycle (an atypical situation) may see their next period begin a couple of days late, and they have about twice the usual risk of a clinically significant delay (about 10% of these women, compared to about 4% of unvaccinated women). Cycle lengths return to normal after two menstrual cycles post-vaccination. Women who received doses in separate cycles had approximately the same natural variation in cycle lengths as unvaccinated women. Other temporary menstrual effects have been reported, such as heavier than normal menstrual bleeding after vaccination.


title: COVID-19 vaccine

text: Serious adverse events associated COVID19 vaccines are generally rare but of high interest to the public. The official databases of reported adverse events include the World Health Organization's VigiBase, the United States Vaccine Adverse Events Reporting System (VAERS) and the United Kingdom's Yellow Card Scheme. Increased public awareness of these reporting systems and the extra reporting requirements under US FDA Emergency Use Authorization rules have resulted in an increased volume of reported adverse events.


title: COVID-19 vaccine

text: The rate and type of side effects is also compared to the alternatives. For example, although vaccination may trigger some side effects, the effects experienced from an infection could be worse. Neurological side effects from getting COVID-19 are hundreds of times more likely than from vaccination.


title: COVID-19 vaccine

text: "Note about table in this section: Number and percentage of people who have received at least one dose of a COVID19 vaccine (unless noted otherwise). May include vaccination of non-citizens, which can push totals beyond 100% of the local population. Table is updated daily by a bot."


title: COVID-19 vaccine

text: Countries have extremely unequal access to the COVID-19 vaccine. Vaccine equity has not been achieved, or even approximated. The inequity has harmed both countries with poor access and countries with good access.


title: COVID-19 vaccine

text: Nations pledged to buy doses of the COVID19 vaccine before the doses were available. Though high-income nations represent only 14% of the global population, as of 15 November 2020, they had contracted to buy 51% of all pre-sold doses. Some high-income nations bought more doses than would be necessary to vaccinate their entire populations.


title: COVID-19 vaccine

text: In January 2021, WHO Director-General Tedros Adhanom Ghebreyesus warned of problems with equitable distribution: "More than 39 million doses of vaccine have now been administered in at least 49 higher-income countries. Just 25 doses have been given in one lowest-income country. Not 25 million; not 25 thousand; just 25."


title: COVID-19 vaccine

text: In March 2021, it was revealed the US attempted to convince Brazil not to purchase the Sputnik V COVID19 vaccine, fearing "Russian influence" in Latin America. Some nations involved in long-standing territorial disputes have reportedly had their access to vaccines blocked by competing nations; Palestine has accused Israel of blocking vaccine delivery to Gaza, while Taiwan has suggested that China has hampered its efforts to procure vaccine doses.


title: COVID-19 vaccine

text: A single dose of the COVID19 vaccine by AstraZeneca would cost 47 Egyptian pounds (EGP), and the authorities are selling it between 100 and 200 EGP. A report by Carnegie Endowment for International Peace cited the poverty rate in Egypt as around 29.7 percent, which constitutes approximately 30.5 million people, and claimed that about 15 million of the Egyptians would be unable to gain access to the luxury of vaccination. A human rights lawyer, Khaled Ali, launched a lawsuit against the government, forcing them to provide vaccination free of cost to all members of the public.


title: COVID-19 vaccine

text: According to immunologist Dr. Anthony Fauci, mutant strains of the virus and limited vaccine distribution pose continuing risks and he said: "we have to get the entire world vaccinated, not just our own country." Edward Bergmark and Arick Wierson are calling for a global vaccination effort and wrote that the wealthier nations' "me-first" mentality could ultimately backfire because the spread of the virus in poorer countries would lead to more variants, against which the vaccines could be less effective.


title: COVID-19 vaccine

text: In March 2021, the United States, Britain, European Union member states and some other members of the World Trade Organization (WTO) blocked a push by more than eighty developing countries to waive COVID19 vaccine patent rights in an effort to boost production of vaccines for poor nations. On 5 May 2021, the US government under President Joe Biden announced that it supports waiving intellectual property protections for COVID19 vaccines. The Members of the European Parliament have backed a motion demanding the temporary lifting of intellectual properties rights for COVID19 vaccines.


title: COVID-19 vaccine

text: In a meeting in April 2021, the World Health Organization's emergency committee addressed concerns of persistent inequity in the global vaccine distribution. Although 9 percent of the world's population lives in the 29 poorest countries, these countries had received only 0.3% of all vaccines administered as of May 2021. In March 2021, Brazilian journalism agency Agência Pública reported that the country vaccinated about twice as many people who declare themselves white than black and noted that mortality from COVID19 is higher in the black population.


title: COVID-19 vaccine

text: In May 2021, UNICEF made an urgent appeal to industrialized nations to pool their excess COVID19 vaccine capacity to make up for a 125-million-dose gap in the COVAX program. The program mostly relied on the Oxford–AstraZeneca COVID19 vaccine produced by Serum Institute of India, which faced serious supply problems due to increased domestic vaccine needs in India from March to June 2021. Only a limited amount of vaccines can be distributed efficiently, and the shortfall of vaccines in South America and parts of Asia are due to a lack of expedient donations by richer nations. International aid organizations have pointed at Nepal, Sri Lanka, and Maldives as well as Argentina and Brazil, and some parts of the Caribbean as problem areas, where vaccines are in short supply. In mid-May 2021, UNICEF was also critical of the fact that most proposed donations of Moderna and Pfizer vaccines were not slated for delivery until the second half of 2021, or early in 2022.


title: COVID-19 vaccine

text: In July 2021, the heads of the World Bank Group, the International Monetary Fund, the World Health Organization, and the World Trade Organization said in a joint statement: "As many countries are struggling with new variants and a third wave of COVID19 infections, accelerating access to vaccines becomes even more critical to ending the pandemic everywhere and achieving broad-based growth. We are deeply concerned about the limited vaccines, therapeutics, diagnostics, and support for deliveries available to developing countries." In July 2021, "The BMJ" reported that countries have thrown out over 250,000 vaccine doses as supply exceeded demand and strict laws prevented the sharing of vaccines. A survey by "The New York Times" found that over a million doses of vaccine had been thrown away in ten U.S. states because federal regulations prohibit recalling them, preventing their redistribution abroad. Furthermore, doses donated close to expiration often cannot be administered quickly enough by recipient countries and end up having to be discarded. To help overcome this problem, the Prime Minister of India, Narendra Modi announced that they would make their digital vaccination management platform CoWIN open to the global community. He also announced that India would also release the source code for contact tracing app Aarogya Setu for developers around the world. Around 142 countries including Afghanistan, Bangladesh, Bhutan, Maldives, Guyana, Antigua & Barbuda, St. Kitts & Nevis and Zambia expressed their interest in the application for COVID management.


title: COVID-19 vaccine

text: Amnesty International and Oxfam International have criticized the support of vaccine monopolies by the governments of producing countries, noting that this is dramatically increasing the dose price by five times and often much more, creating an economic barrier to access for poor countries. Médecins Sans Frontières (Doctors without Borders) has also criticized vaccine monopolies and repeatedly called from their suspension, supporting the TRIPS Waiver. The waiver was first proposed in October 2020, and has support from most countries, but delayed by opposition from EU (especially Germany – major EU countries such as France, Italy and Spain support the exemption), UK, Norway, and Switzerland, among others. MSF called for a Day of Action in September 2021 to put pressure on the WTO Minister's meeting in November, which was expected to discuss the TRIPS IP waiver.


title: COVID-19 vaccine

text: In August 2021, to reduce unequal distribution between rich and poor countries, the WHO called for a moratorium on a booster dose at least until the end of September. However, in August, the United States government announced plans to offer booster doses eight months after the initial course to the general population, starting with priority groups. Before the announcement, the WHO harshly criticized this type of decision, citing the lack of evidence for the need for boosters, except for patients with specific conditions. At this time, vaccine coverage of at least one dose was 58% in high-income countries and only 1.3% in low-income countries, and 1.14 million Americans already received an unauthorized booster dose. US officials argued that waning efficacy against mild and moderate disease might indicate reduced protection against severe disease in the coming months. Israel, France, Germany, and the United Kingdom have also started planning boosters for specific groups. In September 2021, more than 140 former world leaders, and Nobel laureates, including former President of France François Hollande, former Prime Minister of the United Kingdom Gordon Brown, former Prime Minister of New Zealand Helen Clark, and Professor Joseph Stiglitz, called on the candidates to be the next German chancellor to declare themselves in favour of waiving intellectual property rules for COVID19 vaccines and transferring vaccine technologies. In November 2021, nursing unions in 28 countries have filed a formal appeal with the United Nations over the refusal of the UK, EU, Norway, Switzerland, and Singapore to temporarily waive patents for Covid vaccines.


title: COVID-19 vaccine

text: During his first international trip, President of Peru Pedro Castillo spoke at the seventy-sixth session of the United Nations General Assembly on 21 September 2021, proposing the creation of an international treaty signed by world leaders and pharmaceutical companies to guarantee universal vaccine access, arguing "The battle against the pandemic has shown us the failure of the international community to cooperate under the principle of solidarity".


title: COVID-19 vaccine

text: Optimizing the societal benefit of vaccination may benefit from a strategy that is tailored to the state of the pandemic, the demographics of a country, the age of the recipients, the availability of vaccines, and the individual risk for severe disease: In the UK, the interval between prime and boost dose was extended to vaccinate as many persons as early as possible, many countries are starting to give an additional booster shot to the immunosuppressed and the elderly, and research predicts an additional benefit of personalizing vaccine dose in the setting of limited vaccine availability when a wave of virus Variants of Concern hits a country.


title: COVID-19 vaccine

text: Despite the extremely rapid development of effective mRNA and viral vector vaccines, vaccine equity has not been achieved. The World Health Organization called for 70 per cent of the global population to be vaccinated by mid-2022, but as of March 2022 it was estimated that only one per cent of the 10 billion doses given worldwide had been administered in low-income countries. An additional 6 billion vaccinations may be needed to fill vaccine access gaps, particularly in developing countries. Given the projected availability of the newer vaccines, the development and use of whole inactivated virus (WIV) and protein-based vaccines are also recommended. Organizations such as the Developing Countries Vaccine Manufacturers Network could help to support the production of such vaccines in developing countries, with lower production costs and greater ease of deployment.


title: COVID-19 vaccine

text: While vaccines substantially reduce the probability and severity of infection, it is still possible for fully vaccinated people to contract and spread COVID19. Public health agencies have recommended that vaccinated people continue using preventive measures (wear face masks, social distance, wash hands) to avoid infecting others, especially vulnerable people, particularly in areas with high community spread. Governments have indicated that such recommendations will be reduced as vaccination rates increase and community spread declines.


title: COVID-19 vaccine

text: Vaccine inequity damages the global economy, disrupting the global supply chain. Most vaccines were being reserved for wealthy countries, , some of which have more vaccine than is needed to fully vaccinate their populations. When people, undervaccinated, needlessly die, experience disability, and live under lockdown restrictions, they cannot supply the same goods and services. This harms the economies of undervaccinated and overvaccinated countries alike. Since rich countries have larger economies, rich countries may lose more money to vaccine inequity than poor ones, though the poor ones will lose a higher percentage of GDP and experience longer-term effects. High-income countries would profit an estimated US$4.80 for every $1 spent on giving vaccines to lower-income countries.


title: COVID-19 vaccine

text: The International Monetary Fund sees the vaccine divide between rich and poor nations as a serious obstacle to a global economic recovery. Vaccine inequity disproportionately affects refuge-providing states, as they tend to be poorer, and refugees and displaced people are economically more vulnerable even within those low-income states, so they have suffered more economically from vaccine inequity.


title: COVID-19 vaccine

text: Several governments agreed to shield pharmaceutical companies like Pfizer and Moderna from negligence claims related to COVID19 vaccines (and treatments), as in previous pandemics, when governments also took on liability for such claims.


title: COVID-19 vaccine

text: In the US, these liability shields took effect on 4 February 2020, when the US Secretary of Health and Human Services Alex Azar published a notice of declaration under the Public Readiness and Emergency Preparedness Act (PREP Act) for medical countermeasures against COVID19, covering "any vaccine, used to treat, diagnose, cure, prevent, or mitigate COVID19, or the transmission of SARS-CoV-2 or a virus mutating therefrom". The declaration precludes "liability claims alleging negligence by a manufacturer in creating a vaccine, or negligence by a health care provider in prescribing the wrong dose, absent willful misconduct." In other words, absent "willful misconduct", these companies can not be sued for money damages for any injuries that occur between 2020 and 2024 from the administration of vaccines and treatments related to COVID19. The declaration is effective in the United States through 1October 2024.


title: COVID-19 vaccine

text: In the European Union, the COVID19 vaccines were granted a conditional marketing authorization which does not exempt manufacturers from civil and administrative liability claims. The EU conditional marketing authorizations were changed to standard authorizations in September 2022. While the purchasing contracts with vaccine manufacturers remain secret, they do not contain liability exemptions even for side-effects not known at the time of licensure.


title: COVID-19 vaccine

text: The Bureau of Investigative Journalism, a nonprofit news organization, reported in an investigation that unnamed officials in some countries, such as Argentina and Brazil, said that Pfizer demanded guarantees against costs of legal cases due to adverse effects in the form of liability waivers and sovereign assets such as federal bank reserves, embassy buildings or military bases, going beyond the expected from other countries such as the US. During the pandemic parliamentary inquiry in Brazil, Pfizer's representative said that its terms for Brazil are the same as for all other countries with which it has signed deals.


title: COVID-19 vaccine

text: On 13 December 2022, the governor of Florida, Ron DeSantis, said that he will petition the state supreme court to convene a grand jury to investigate possible violations in respect to COVID-19 vaccines, and declared that his government would be able to get "the data whether they [the companies] want to give it or not".


title: COVID-19 vaccine

text: In June 2021, a report revealed that the UB-612 vaccine, developed by the US-based COVAXX, was a for-profit venture initiated by the Blackwater founder Erik Prince. In a series of text messages to Paul Behrends, the close associate recruited for the COVAXX project, Prince described the profit-making possibilities in selling the COVID19 vaccines. COVAXX provided no data from the clinical trials on safety or efficacy it conducted in Taiwan. The responsibility of creating distribution networks was assigned to an Abu Dhabi-based entity, which was mentioned as "Windward Capital" on the COVAXX letterhead but was actually Windward Holdings. The firm's sole shareholder, which handled "professional, scientific and technical activities", was Erik Prince. In March 2021, COVAXX raised $1.35 billion in a private placement.


title: Diatomaceous earth

text: Diatomaceous earth (), diatomite (), or kieselgur/kieselguhr is a naturally occurring, soft, siliceous sedimentary rock that can be crumbled into a fine white to off-white powder. It has a particle size ranging from more than 3 μm to less than 1 mm, but typically 10 to 200 μm. Depending on the granularity, this powder can have an abrasive feel, similar to pumice powder, and has a low density as a result of its high porosity. The typical chemical composition of oven-dried diatomaceous earth is 80–90% silica, with 2–4% alumina (attributed mostly to clay minerals), and 0.5–2% iron oxide.


title: Diatomaceous earth

text: Diatomaceous earth consists of the fossilized remains of diatoms, a type of hard-shelled microalgae. It is used as a filtration aid, mild abrasive in products including metal polishes and toothpaste, mechanical insecticide, absorbent for liquids, matting agent for coatings, reinforcing filler in plastics and rubber, anti-block in plastic films, porous support for chemical catalysts, cat litter, activator in coagulation studies, a stabilizing component of dynamite, a thermal insulator, and a soil for potted plants and trees as in the art of bonsai.


title: Diatomaceous earth

text: Each deposit of diatomaceous earth is different, with varying blends of pure diatomaceous earth combined with other natural clays and minerals. The diatoms in each deposit contain different amounts of silica, depending on the sedimentation conditions, on the presence of other sediments (clay, sand, volcanic ashes), and on the age of the deposit (diagenesis, silica (SiO) dissolution/precipitation, diatoms tests ageing). The species of diatom may also differ among deposits. The species of diatom is dependent upon the age and paleoecology of the deposit. In turn, the shape of a diatom is determined by its species.


title: Diatomaceous earth

text: Many deposits throughout British Columbia, such as Red Lake Earth, are from the Miocene epoch and contain a species of diatom known as "Melosira granulata". These diatoms are approximately 12 to 13 million years old and have a small globular shape. A deposit containing diatoms from this epoch can provide certain benefits over others. For example, diatoms from the Eocene epoch (approximately 40 to 50 million years old) are not as effective in their ability to absorb fluids because as older diatoms recrystallize, their small pores become filled with silica.


title: Diatomaceous earth

text: Diatomite forms by the accumulation of the amorphous silica (opal, ) remains of dead diatoms (microscopic single-celled algae) in lake sediment or marine sediments. The fossil remains consist of a pair of symmetrical shells or frustules. Marine diatomites are found in association with a wide variety of other rock types but lacustrine diatomites are almost always associated with volcanic rock. Diatomaceous chert consists of diatomite that has been cemented with silica.


title: Diatomaceous earth

text: Diatoms are able to extract silica from water that is less than 1% saturated in amorphous silica (saturation index (SI): -2). Their frustules remain undissolved because they are surrounded by an organic matrix. Clay minerals may also precipitate on the frustules and protect them from dissolution in sea water. When the diatom dies, the frustule is stripped of its organic layer and exposed to sea water. As a result, only 1% to 10% of frustules survive long enough to be buried under sediments and some of this is dissolved within the sediments. Only an estimated 0.05% to 0.15% of the original amount of silica produced by diatoms is preserved in the sedimentary record.


title: Diatomaceous earth

text: In 1836 or 1837, German peasant Peter Kasten discovered diatomaceous earth (German: "Kieselgur") when sinking a well on the northern slopes of the Haußelberg hill, in the Lüneburg Heath in North Germany.


title: Diatomaceous earth

text: Until World War I, almost the entire worldwide production of diatomaceous earth was from this region.


title: Diatomaceous earth

text: In Poland diatomaceous earth deposits are found in Jawornik, and are composed mostly of diatomaceous skeletons (frustules)


title: Diatomaceous earth

text: In Germany, diatomaceous earth was also extracted at Altenschlirf on the Vogelsberg (Upper Hesse) and at Klieken (Saxony-Anhalt).


title: Diatomaceous earth

text: There is a layer of diatomaceous earth more than thick in the nature reserve of Soos in the Czech Republic.


title: Diatomaceous earth

text: In Colorado and in Clark County, Nevada, United States, there are deposits that are up to several hundred meters thick in places. Marine deposits have been worked in the Sisquoc Formation in Santa Barbara County, California near Lompoc and along the Southern California coast. This is the world's largest deposit of diatomite. Additional marine deposits have been worked in Maryland, Virginia, Algeria and the MoClay of Denmark. Freshwater lake deposits occur in Nevada, Oregon, Washington and California. Lake deposits also occur in interglacial lakes in the eastern United States, in Canada and in Europe in Germany, France, Denmark and the Czech Republic. The worldwide association of diatomite deposits and volcanic deposits suggests that the availability of silica from volcanic ash may be necessary for thick diatomite deposits.


title: Diatomaceous earth

text: Diatomaceous earth is sometimes found on desert surfaces. Research has shown that the erosion of diatomaceous earth in such areas (such as the Bodélé Depression in the Sahara) is one of the most important sources of climate-affecting dust in the atmosphere.


title: Diatomaceous earth

text: The siliceous frustules of diatoms accumulate in fresh and brackish wetlands and lakes. Some peats and mucks contain a sufficient abundance of frustules such that they can be mined. Most of Florida's diatomaceous earths have been found in the muck of wetlands or lakes. The American Diatomite Corporation, from 1935 to 1946, refined a maximum of 145 tons per year from their processing plant near Clermont, Florida. Muck from several locations in Lake County, Florida was dried and burned (calcined) to produce the diatomaceous earth. It was formerly extracted from Lake Mývatn in Iceland.


title: Diatomaceous earth

text: The commercial deposits of diatomite are restricted to Tertiary or Quaternary periods. Older deposits from as early as the Cretaceous Period are known, but are of low quality.


title: Diatomaceous earth

text: Diatomite deposits rich in fossils have been located in New Zealand, but mining of the Foulden Maar deposits on an industrial scale, for conversion to animal feed, has drawn strong opposition.


title: Diatomaceous earth

text: In 1866, Alfred Nobel discovered that nitroglycerin could be made much more stable if absorbed in diatomite (kieselguhr). This allowed a much safer transport and handling than pure nitroglycerin under the liquid form. Nobel patented this mixture as dynamite in 1867; the mixture is also called guhr dynamite by reference to the German term kieselguhr.


title: Diatomaceous earth

text: The Celle engineer, Wilhelm Berkefeld, recognized the ability of the diatomaceous earth to filter and developed tubular filters (known as filter candles) fired from diatomaceous earth. During the cholera epidemic in Hamburg in 1892, these Berkefeld filters were used successfully.


title: Diatomaceous earth

text: One form of diatomaceous earth is used as a filter medium, especially for swimming pools. It has a high porosity because it is composed of microscopically small, hollow particles. Diatomaceous earth (sometimes referred to by trademarked brand names such as Celite) is used in chemistry as a filtration aid, to increase flow rate, and filter very fine particles that would otherwise pass through or clog filter paper. It is also used to filter water, particularly in the drinking water treatment process and in fish tanks, and other liquids, such as beer and wine. It can also filter syrups, sugar, and honey without removing or altering their color, taste, or nutritional properties.


title: Diatomaceous earth

text: The oldest use of diatomite is as a very mild abrasive and has been used in toothpaste, metal polishes, and some facial scrubs.


title: Diatomaceous earth

text: Diatomite is of value as an insecticide because of its abrasive and physico-sorptive properties. The fine powder adsorbs lipids from the waxy outer layer of the exoskeletons of many species of insects; this layer acts as a barrier that resists the loss of water vapour from the insect's body. Damaging the layer increases the evaporation of water from their bodies, so that they dehydrate, often fatally.


title: Diatomaceous earth

text: Arthropods die as a result of the water pressure deficiency, based on Fick's laws of diffusion. This also works against gastropods and is commonly employed in gardening to defeat slugs. However, since slugs inhabit humid environments, efficacy is very low. Diatomaceous earth is sometimes mixed with an attractant or other additives to increase its effectiveness.


title: Diatomaceous earth

text: The shape of the diatoms contained in a deposit has not been proven to affect their functionality when it comes to the adsorption of lipids; however, certain applications, such as that for slugs and snails, do work best when a particularly shaped diatom is used, suggesting that lipid adsorption is not the whole story. For example, in the case of slugs and snails, large, spiny diatoms work best to lacerate the epithelium of the mollusk. Diatom shells will work to some degree on the vast majority of animals that undergo ecdysis in shedding cuticle, such as arthropods or nematodes. It also may have other effects on lophotrochozoans, such as mollusks or annelids.


title: Diatomaceous earth

text: Medical-grade diatomite has been studied for its efficacy as a deworming agent in cattle; in both studies cited the groups being treated with diatomaceous earth did not fare any better than control groups. It is commonly used in lieu of boric acid and can be used to help control and possibly eliminate bed bugs, house dust mite, cockroach, ant, and flea infestations.


title: Diatomaceous earth

text: In order to be effective as an insecticide, diatomaceous earth must be uncalcinated (i.e., it must not be heat-treated prior to application) and have a mean particle size below about 12 μm (i.e., food grade—see below).


title: Diatomaceous earth

text: Although considered to be relatively low-risk, pesticides containing diatomaceous earth are not exempt from regulation in the United States under the Federal Insecticide, Fungicide, and Rodenticide Act and must be registered with the Environmental Protection Agency.


title: Diatomaceous earth

text: Its thermal properties enable it to be used as the barrier material in some fire-resistant safes. It is also used in evacuated powder insulation for use with cryogenics. Diatomaceous earth powder is inserted into the vacuum space to aid in the effectiveness of vacuum insulation. It was used in the classical AGA cookers as a thermal heat barrier.


title: Diatomaceous earth

text: Diatomaceous earth also finds some use as a support for catalysts, generally serving to maximize a catalyst's surface area and activity. For example, nickel can be supported on the material—the combination is called Ni–Kieselguhr—to improve its activity as a hydrogenation catalyst.


title: Diatomaceous earth

text: Natural freshwater diatomaceous earth is used in agriculture for grain storage as an anticaking agent, as well as an insecticide. It is approved by the Food and Drug Administration as a feed additive to prevent caking.


title: Diatomaceous earth

text: Some believe it may be used as a natural anthelmintic (dewormer), although studies have not shown it to be effective. Some farmers add it to their livestock and poultry feed to prevent the caking of feed. "Food-Grade Diatomaceous Earth" is widely available in agricultural feed supply stores.


title: Diatomaceous earth

text: It is also used as a growing medium in potted plants, particularly as bonsai soil. Bonsai enthusiasts use it as a soil additive, or pot a bonsai tree in 100% diatomaceous earth. In vegetable gardening it is sometimes used as a soil conditioner, because like perlite, vermiculite, and expanded clay, it retains water and nutrients, while draining fast and freely, allowing high oxygen circulation within the growing medium.


title: Diatomaceous earth

text: Natural dried, not calcinated diatomaceous earth is regularly used in livestock nutrition research as a source of acid-insoluble ash (AIA), which is used as an indigestible marker. By measuring the content of AIA relative to nutrients in test diets and feces or digesta sampled from the terminal ileum (last third of the small intestine) the percentage of that nutrient digested can be calculated using the following equation:


title: Diatomaceous earth

text: Natural freshwater diatomaceous earth is preferred by many researchers over chromic oxide, which has been widely used for the same purpose, the latter being a known carcinogen and, therefore, a potential hazard to research personnel.


title: Diatomaceous earth

text: Spent diatomaceous earth from the brewing process can be added to ceramic mass for the production of red bricks with higher open porosity.


title: Diatomaceous earth

text: Diatomaceous earth is considered a very prominent inorganic non-metallic material that can be utilized for the production of various ceramics, including production of porous ceramics under low temperature hydrothermal technology.


title: Diatomaceous earth

text: Certain species of bacteria in oceans and lakes can accelerate the rate of dissolution of silica in dead and living diatoms by using hydrolytic enzymes to break down the organic algal material.


title: Diatomaceous earth

text: The Earth's climate is affected by dust in the atmosphere, so locating major sources of atmospheric dust is important for climatology. Recent research indicates that surface deposits of diatomaceous earth play an important role. Research shows that significant dust comes from the Bodélé Depression in Chad, where storms push diatomite gravel over dunes, generating dust by abrasion.


title: Diatomaceous earth

text: Inhalation of "crystalline" silica is harmful to the lungs, causing silicosis. "Amorphous" silica is considered to have low toxicity, but prolonged inhalation causes changes to the lungs. Diatomaceous earth is mostly amorphous silica but contains some crystalline silica, especially in the saltwater forms. In a 1978 study of workers, those exposed to natural diatomaceous earth for over five years had no significant lung changes while 40% of those exposed to the calcined form had developed pneumoconiosis. Today's common diatomaceous earth formulations are safer to use, as they are predominantly made up of amorphous silica and contain little or no crystalline silica.


title: Diatomaceous earth

text: The crystalline silica content of diatomaceous earth is regulated in the United States by the Occupational Safety and Health Administration (OSHA) and there are guidelines from the National Institute for Occupational Safety and Health that set maximum amounts allowable in the product (1%) and in the air near the breathing zone of workers, with a recommended exposure limit at 6 mg/m over an 8-hour workday. OSHA has set a permissible exposure limit for diatomaceous earth as 20 mppcf (80 mg/m/%SiO). At levels of 3,000 mg/m, diatomaceous earth is immediately dangerous to life and health.


title: Diatomaceous earth

text: In the 1930s, long-term occupational exposure among workers in the cristobalite diatomaceous earth industry who were exposed to high levels of airborne crystalline silica over decades were found to have an increased risk of silicosis.


title: Diatomaceous earth

text: Today, workers are required to use respiratory-protection measures when concentrations of silica exceed allowable levels.


title: Diatomaceous earth

text: Diatomite produced for pool filters is treated with high heat (calcination) and a fluxing agent (soda ash), causing the formerly harmless amorphous silicon dioxide to assume its crystalline form.


title: Selective serotonin reuptake inhibitor

text: Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.


title: Selective serotonin reuptake inhibitor

text: SSRIs increase the extracellular level of the neurotransmitter serotonin by limiting its reabsorption (reuptake) into the presynaptic cell. They have varying degrees of selectivity for the other monoamine transporters, with pure SSRIs having strong affinity for the serotonin transporter and only weak affinity for the norepinephrine and dopamine transporters.


title: Selective serotonin reuptake inhibitor

text: SSRIs are the most widely prescribed antidepressants in many countries. The efficacy of SSRIs in mild or moderate cases of depression has been disputed and may or may not be outweighed by side effects, especially in adolescent populations.


title: Selective serotonin reuptake inhibitor

text: The main indication for SSRIs is major depressive disorder; however, they are frequently prescribed for anxiety disorders, such as social anxiety disorder, generalized anxiety disorder, panic disorder, obsessive–compulsive disorder (OCD), eating disorders, chronic pain, and, in some cases, for posttraumatic stress disorder (PTSD). They are also frequently used to treat depersonalization disorder, although with varying results.


title: Selective serotonin reuptake inhibitor

text: Antidepressants are recommended by the UK National Institute for Health and Care Excellence (NICE) as a first-line treatment of severe depression and for the treatment of mild-to-moderate depression that persists after conservative measures such as cognitive therapy. They recommend against their routine use by those who have chronic health problems and mild depression.


title: Selective serotonin reuptake inhibitor

text: There has been controversy regarding the efficacy of SSRIs in treating depression depending on its severity and duration.


title: Selective serotonin reuptake inhibitor

text: In 2018, a systematic review and network meta-analysis comparing the efficacy and acceptability of 21 antidepressant drugs showed escitalopram to be one of the most effective.


title: Selective serotonin reuptake inhibitor

text: In children, there are concerns around the quality of the evidence on the meaningfulness of benefits seen. If a medication is used, fluoxetine appears to be first line.


title: Selective serotonin reuptake inhibitor

text: Some SSRIs are effective for social anxiety disorder, although their effects on symptoms is not always robust and their use is sometimes rejected in favor of psychological therapies. Paroxetine was the first drug to be approved for social anxiety disorder and it is considered effective for this disorder, sertraline and fluvoxamine were later approved for it, too, escitalopram and citalopram are used off label with acceptable efficacy, while fluoxetine is not considered to be effective for this disorder.


title: Selective serotonin reuptake inhibitor

text: PTSD is relatively hard to treat and generally treatment is not highly effective; SSRIs are no exception. They are not very effective for this disorder and only two SSRI are FDA approved for this condition, paroxetine and sertraline. Paroxetine has slightly higher response and remission rates for PTSD than sertraline, but both are not fully effective for many patients. Fluoxetine is used off label, but with mixed results; venlafaxine, an SNRI, is considered somewhat effective, although used off label, too. Fluvoxamine, escitalopram and citalopram are not well tested in this disorder. Paroxetine remains the most suitable drug for PTSD as of now, but with limited benefits.


title: Selective serotonin reuptake inhibitor

text: SSRIs are recommended by the National Institute for Health and Care Excellence (NICE) for the treatment of generalized anxiety disorder (GAD) that has failed to respond to conservative measures such as education and self-help activities. GAD is a common disorder of which the central feature is excessive worry about a number of different events. Key symptoms include excessive anxiety about multiple events and issues, and difficulty controlling worrisome thoughts that persists for at least 6 months.


title: Selective serotonin reuptake inhibitor

text: Antidepressants provide a modest-to-moderate reduction in anxiety in GAD, and are superior to placebo in treating GAD. The efficacy of different antidepressants is similar.


title: Selective serotonin reuptake inhibitor

text: In Canada, SSRIs are a first-line treatment of adult obsessive–compulsive disorder (OCD). In the UK, they are first-line treatment only with moderate to severe functional impairment and as second line treatment for those with mild impairment, though, as of early 2019, this recommendation is being reviewed. In children, SSRIs can be considered a second line therapy in those with moderate-to-severe impairment, with close monitoring for psychiatric adverse effects. SSRIs, especially fluvoxamine, which is the first one to be FDA approved for OCD, are efficacious in its treatment; patients treated with SSRIs are about twice as likely to respond to treatment as those treated with placebo. Efficacy has been demonstrated both in short-term treatment trials of 6 to 24 weeks and in discontinuation trials of 28 to 52 weeks duration.


title: Selective serotonin reuptake inhibitor

text: Paroxetine CR was superior to placebo on the primary outcome measure. In a 10-wk randomized controlled, double-blind trial escitalopram was more effective than placebo. Fluvoxamine, another SSRI, has shown positive results. However, evidence for their effectiveness and acceptability is unclear.


title: Selective serotonin reuptake inhibitor

text: Antidepressants are recommended as an alternative or additional first step to self-help programs in the treatment of bulimia nervosa. SSRIs (fluoxetine in particular) are preferred over other anti-depressants due to their acceptability, tolerability, and superior reduction of symptoms in short-term trials. Long-term efficacy remains poorly characterized.


title: Selective serotonin reuptake inhibitor

text: Similar recommendations apply to binge eating disorder. SSRIs provide short-term reductions in binge eating behavior, but have not been associated with significant weight loss.


title: Selective serotonin reuptake inhibitor

text: Clinical trials have generated mostly negative results for the use of SSRIs in the treatment of anorexia nervosa. Treatment guidelines from the National Institute of Health and Clinical Excellence recommend against the use of SSRIs in this disorder. Those from the American Psychiatric Association note that SSRIs confer no advantage regarding weight gain, but that they may be used for the treatment of co-existing depressive, anxiety, or OCD.


title: Selective serotonin reuptake inhibitor

text: SSRIs have been used off-label in the treatment of stroke patients, including those with and without symptoms of depression. A 2019 meta-analysis of randomized, controlled clinical trials found a statistically significant effect of SSRIs on dependence, neurological deficit, depression, and anxiety but the studies had a high risk of bias. No reliable evidence points to their routine use to promote recovery following stroke. Thrombosis risk is reduced because SSRIs limit serotonin availability to platelets, so benefits, such as stroke recovery, of reduced clotting go up, with SSRIs.


title: Selective serotonin reuptake inhibitor

text: SSRIs are effective for the treatment of premature ejaculation. Taking SSRIs on a chronic, daily basis is more effective than taking them prior to sexual activity. The increased efficacy of treatment when taking SSRIs on a daily basis is consistent with clinical observations that the therapeutic effects of SSRIs generally take several weeks to emerge. Sexual dysfunction ranging from decreased libido to anorgasmia is usually considered to be a significantly distressing side effect which may lead to noncompliance in patients receiving SSRIs. However, for those with premature ejaculation, this very same side effect becomes the desired effect.


title: Selective serotonin reuptake inhibitor

text: SSRIs can cause various types of sexual dysfunction such as anorgasmia, erectile dysfunction, diminished libido, genital numbness, and sexual anhedonia (pleasureless orgasm). Sexual problems are common with SSRIs. While initial trials showed side effects in 5-15% of users (based on spontaneous reporting by users), later studies (based on asking patients directly) have shown side effect rates from 36% to 98%. Poor sexual function is also one of the most common reasons people stop the medication.


title: Selective serotonin reuptake inhibitor

text: In some cases, symptoms of sexual dysfunction may persist after discontinuation of SSRIs. This combination of symptoms is sometimes referred to as Post-SSRI Sexual Dysfunction (PSSD). On the 11th of June 2019 the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency concluded that a possible relationship exists between SSRI use and persistent sexual dysfunction after cessation of use. The committee concluded that a warning should be added to the label of SSRIs and SNRIs regarding this possible risk.


title: Selective serotonin reuptake inhibitor

text: The mechanism by which SSRIs may cause sexual side effects is not well understood . The range of possible mechanisms includes (1) nonspecific neurological effects (e.g., sedation) that globally impair behavior including sexual function; (2) specific effects on brain systems mediating sexual function; (3) specific effects on peripheral tissues and organs, such as the penis, that mediate sexual function; and (4) direct or indirect effects on hormones mediating sexual function. Management strategies include: for erectile dysfunction the addition of a PDE5 inhibitor such as sildenafil; for decreased libido, possibly adding or switching to bupropion; and for overall sexual dysfunction, switching to nefazodone.


title: Selective serotonin reuptake inhibitor

text: A number of non-SSRI drugs are not associated with sexual side effects (such as bupropion, mirtazapine, tianeptine, agomelatine and moclobemide).


title: Selective serotonin reuptake inhibitor

text: While trazodone (an antidepressant with alpha adrenergic receptor blockade) is a notorious cause of priapism, cases of priapism have also been reported with certain SSRIs (e.g. fluoxetine, citalopram).


title: Selective serotonin reuptake inhibitor

text: Certain antidepressants may cause emotional blunting, characterized by reduced intensity of both positive and negative emotions as well as symptoms of apathy, indifference, and amotivation. It may be experienced as either beneficial or detrimental depending on the situation. This side effect has been particularly associated with serotonergic antidepressants like SSRIs and SNRIs, but may be less with atypical antidepressants like bupropion, agomelatine, and vortioxetine. Higher doses of antidepressants seem to be more likely to produce emotional blunting than lower doses. It can be decreased by reducing dosage, discontinuing the medication, or switching to a different antidepressant that may have less propensity for causing this side effect.


title: Selective serotonin reuptake inhibitor

text: Researcher David Healy and others have reviewed available data, concluding that SSRIs increase violent acts, in adults and children, both on therapy and during withdrawal. This view is also shared by some patient activist groups.


title: Selective serotonin reuptake inhibitor

text: Acute narrow-angle glaucoma is the most common and important ocular side effect of SSRIs, and often goes misdiagnosed.


title: Selective serotonin reuptake inhibitor

text: SSRIs do not appear to affect the risk of coronary heart disease (CHD) in those without a previous diagnosis of CHD. A large cohort study suggested no substantial increase in the risk of cardiac malformations attributable to SSRI usage during the first trimester of pregnancy. A number of large studies of people without known pre-existing heart disease have reported no EKG changes related to SSRI use. The recommended maximum daily dose of citalopram and escitalopram was reduced due to concerns with QT prolongation. In overdose, fluoxetine has been reported to cause sinus tachycardia, myocardial infarction, junctional rhythms and trigeminy. Some authors have suggested electrocardiographic monitoring in patients with severe pre-existing cardiovascular disease who are taking SSRIs.


title: Selective serotonin reuptake inhibitor

text: SSRIs directly increase the risk of abnormal bleeding by lowering platelet serotonin levels, which are essential to platelet-driven hemostasis.


title: Selective serotonin reuptake inhibitor

text: SSRIs interact with anticoagulants, like warfarin, and antiplatelet drugs, like aspirin. This includes an increased risk of GI bleeding, and post operative bleeding. The relative risk of intracranial bleeding is increased, but the absolute risk is very low. SSRIs are known to cause platelet dysfunction. This risk is greater in those who are also on anticoagulants, antiplatelet agents and NSAIDs (nonsteroidal anti-inflammatory drugs), as well as with the co-existence of underlying diseases such as cirrhosis of the liver or liver failure.


title: Selective serotonin reuptake inhibitor

text: Evidence from longitudinal, cross-sectional, and prospective cohort studies suggests an association between SSRI usage at therapeutic doses and a decrease in bone mineral density, as well as increased fracture risk, a relationship that appears to persist even with adjuvant bisphosphonate therapy. However, because the relationship between SSRIs and fractures is based on observational data as opposed to prospective trials, the phenomenon is not definitively causal. There also appears to be an increase in fracture-inducing falls with SSRI use, suggesting the need for increased attention to fall risk in elderly patients using the medication. The loss of bone density does not appear to occur in younger patients taking SSRIs.