Category Archives: Covid-19

Medical student Camila Vernica Souza Freire

Brazilian medical student Camila Vernica Souza Freire is helping to research how the "infodemic" in science is similar to biological outbreaks, by analyzing behavior of the scientific publishing ecosystem during the Covid-19 pandemic.

Freire, who is currently a medical student at the Bahiana School of Medicine and Public Health and a junior researcher at the Brazilian Metascience Research Group (BMRG), says that during the pandemic there was a deluge of research and with the sheer quantity of papers, it was hard to make sense of whether quality research was being done.

"Globally, we were fighting a deluge of low-quality evidence," she says, adding that the project she is a part of at the BMRG is focused on analyzing a year's worth of published papers to see what happened with the volume and quality.

What the COVID infodemic project headed by Gabriel de Arajo Grisi and Joo de Deus Barreto Segundo found was that the infodemic was not just a media buzzword, it was real.

"In this emergency, we've been given the false idea that we need to slow down the rigor, for example, the review process is faster for Covid-19 papers."

"It has been interesting to observe the volume of publications during the pandemic and how it might have shaped health care policies," she says, adding that together with the political context in Brazil, the epidemic of fake news and problematic actions by the federal government based on low-quality evidence, was crucial to motivate a better understanding of the behavior of these publications.

Freiregrew up in Salvador, Bahia and says her grandfather encouraged her curiosity about the world.

"Although my grandfather was not an academic man, he used to prompt my questions about the world, the universe and how things work," she says, "he really believed I was the smartest kid in the world... not true, but very cute of him."

She says that this lead to her decision to pursue an undergraduate degree in relating to Science, Technology, Engineering, Mathematics and Medicine. In the end, she chose medicine, but she was sure that research would be the path she wanted to take.

Freire says her mentor Luis Cludio Correia, who is also the advisor of the meta-science project, has helped her "visualize science through purpose" and learn the value of the communication of science.

She says researchers from low-income and developing countries face disparities, fewer incentives and fewer opportunities to work in science within their own geographic location and especially in science centers of global importance.

"There is evidence that research from the Global South is viewed with bias by researchers, clinicians and institutions around the world," she says.

Freire says that globally female researchers are striving for the same conditions, opportunities and relevance, so adding the challenges of the Global South on top of that make it an even bigger challenge.

"Women researchers from Global South must strive to continue working, despite the discouragement and the statistics of gender inequality in science that do not ease," she says.

Professor Dr. Luis Cludio Correia (closest to the door), with the members of the Brazilian ... [+] Metascience Research Group. Picture of my science group (BMRG).

Another young Brazillian making a difference is Ester Borges Santos, who is a researcher at Brazilian web governance and freedom of speech think-tankInternetLaband a computer teacher and coordinator at Minas Programam.

She and her colleagues at Minas Programam are aiming to create more opportunities for young black women by developing a welcoming, inclusive virtual study group on gender, race, and technology.

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This Brazillian Med Student Is Unlocking Mysteries Of The Covid-19 Infodemic - Forbes

July 14, 2021

State grants will increase student engagement and support academic progress

Posted in: Homepage News, Science and Technology, University

Montclair State University will receive more than $1.4 million from the State of New Jersey to support programs that help address the impacts of COVID-19 on postsecondary students.

Governor Phil Murphy and Secretary of Higher Education Brian Bridges announced the grants July 12, with Montclair State among 35 public and public-mission private institutions receiving $30 million in state aid to implement vetted best practices that increase college completion, address barriers to student success, and develop sustainable systemic reforms.

In addition to a $100,000 grant to fight food insecurity among students, Montclair State was awarded:

These programs are designed to increase student engagement and support academic progress at a time when the challenges facing underrepresented and low-income students have been compounded by the global pandemic, explains President Susan A. Cole. Montclair State is steadfast in our resolve to meet those challenges in service to our students and the community.

Our institutions of higher education have provided a high quality of education to our students throughout the pandemic, despite challenging circumstances, said Governor Murphy. Supporting our institutions will continue to be a priority as they work to provide an equitable educational experience for students, prepare them for the jobs of the future and meet challenges ahead.

Through this critical federal funding, New Jersey is prioritizing students needs and ensuring our workforce will be ready to meet the challenges of tomorrows post-pandemic economy, said Secretary Bridges. We appreciate that institutions are committing to this challenge and look forward to learning from the innovative best practices implemented, as we strive to meet the states goal of 65 percent of residents earning a high-quality credential by 2025.

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University Awarded $1.4M To Address Impacts Of COVID-19 News Center - Montclaire News

A nurse holds a syringe containing a coronavirus vaccine made by the Beijing Institute of Biological Products, a unit of Sinopharm subsidiary China National Biotec Group (CNBG), at a vaccination center during a government-organized visit, in Beijing, China, April 15, 2021. REUTERS/Thomas Peter

BEIJING, July 14 (Reuters) - Several areas in China will start vaccinating teenagers this month against COVID-19, state media and local authorities said, as the country steps up its inoculation campaign.

China, which has managed to rein in domestic infections, has administered 1.4 billion vaccine doses, or two-fifths of the global total of 3.47 billion doses.

This month, the southwestern region of Guangxi and the city of Jingmen in the central province of Hubei will start vaccinating those aged between 15 and 17, and children between 12 and 14 in August, state media and local disease control officials said in reports on Tuesday.

By the end of October, authorities there aim to have fully vaccinated all eligible in the age group of 12 to 17.

China has approved two domestically developed vaccines, one produced by Sinovac Biotech (SVA.O) and the other produced by a Beijing firm affiliated with Sinopharm, for those aged between three and 17.

The world's most populous country, with a population of 1.4 billion, does not regularly disclose how many people have been fully vaccinated, but late last month a state broadcaster said the nationwide rate had exceeded 40%.

Several local authorities said this month that public places, from supermarkets to train stations, will check vaccination credentials and record personal details of unvaccinated visitors, to nudge more people to get doses.

China is expected to vaccinate at least 70% of target groups by the end of this year, Zeng Yixin, deputy director of the National Health Commission, told the official Xinhua news agency last month, without giving details of the groups.

Reporting by Roxanne Liu and Ryan Woo; Editing by Clarence Fernandez

Our Standards: The Thomson Reuters Trust Principles.

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China to start giving COVID-19 shots to teenagers this month - Reuters

THE HAGUE, Netherlands (AP) Coronavirus infections in the Netherlands skyrocketed by more than 500% over the last week, the countrys public health institute reported Tuesday. The surge follows the scrapping of almost all remaining lockdown restrictions and the reopening of night clubs in late June.

The weekly update showing that nearly 52,000 people in the Netherlands tested positive for COVID-19 over the past week came a day after caretaker Dutch Prime Minister Mark Rutte apologized for the June 26 lockdown relaxation and called it an error of judgment.

Rutte backtracked Friday and reintroduced some restrictions in an attempt to rein in the soaring infection rate. Bars again have to close at midnight, while discotheques and clubs were shuttered again until at least Aug. 13.

The Netherlands, along with other European nations, is facing a rise in infections fueled by the more contagious delta variant just as governments hoped to greatly ease or eliminate remaining pandemic restrictions during the summer holiday season.

With infections rising around France, President Emmanuel Macron on Monday cranked up pressure on people to get vaccinated and said special COVID passes would be required to go into restaurants and shopping malls starting next month.

The Dutch public health institute said that of the infections that could be traced to their source, 37% happened in a hospitality venue such as a bar or club. Infections among people ages 18-24 surged by 262%, followed by a 191% rise in 25-29 year-olds.

Despite the alarming rise in confirmed cases, hospital admissions increased by a modest 11%, or 60 COVID-19 patients, over the week, the institute said. Twelve of the admissions were to intensive care units.

More than 46% of the Netherlands adult population is fully vaccinated, and more than 77% of the countrys adults have had at least one shot. Health authorities said more than 1.3 million people would receive their first or second doses this week.

Health Minister Hugo de Jonge said Monday that the late June loosening of restrictions combined with a lack of social distancing and the delta variant has had, of course, an accelerating effect. You can unfortunately see that with hindsight.

Other countries in Europe are scrambling to accelerate coronavirus vaccinations in the hope of outpacing the spread of the more infectious delta variant.

___

Follow all AP stories on the coronavirus pandemic at https://apnews.com/hub/coronavirus-pandemic

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Dutch COVID-19 infections soar by 500% in a week - Associated Press

JOHANNESBURGViolence and looting in parts of South Africa, triggered by the arrest of former President Jacob Zuma, are broadening to reflect more deep-seated problems in the continents most developed economy, where a third pandemic lockdown is exacerbating economic pain and joblessness that has disproportionately affected the poor.

Police,nowbolstered by asmalldeployment of soldiers, struggled for a third day to contain crowds ransacking warehouses and shopping centers in the economic capital of Johannesburg and the port city of Durban.In hospitals, doctors already stretched by a record wave of Covid-19 infectionshad trouble caringfor the injured, with many nurses and other staff unable to come to work because of roadblocks and the broader insecurity, officials said.

The countrys police ministry warned that the continued blockage of some of South Africas main transport routes could within days lead to shortages of food and other essentials and that mass gatherings could prompt a fresh rise in Covid-19 cases. At least 72 people have died amid the instability, officials said Tuesday, some trampled to death in shopping-center stampedes.

People are tired and frustrated with the whole situation, said Abram Lekganyane, who usually sells durags, sunglasses and masks at a stall at the Pan Africa Shopping Centre in the Johannesburg township of Alexandra. Mr. Lekganyane said he checked on his wares in a nearby storage facility and saw people leaving with everything from plasma televisions to sound systems and groceries.

The spark may have been Zuma. Now its a revolution against the lockdown, because nothing is being provided, he said.

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South Africas Looting, Violence Reflect Inequalities Exacerbated by Covid-19 Pandemic - The Wall Street Journal

Psaki and members of the White House COVID-19 response team have explained that the trusted messengers who will be going door to door to provide information about the vaccines will be doctors, faith and community leaders, and other volunteers not federal employees. She said the campaign is actually a continuation of an effort that has been ongoing since at least April.

So, those are the people who are the trusted messengers around the country. And we believe that we need to empower these individuals to continue to work in communities to make sure people know that these vaccines are safe, that they can save lives, Psaki said in a July 8 press briefing.

Even before the first vaccines were rolled out in mid-December, Biden himself said on Dec. 4 that he would not federally mandate that Americans get a vaccine when he became president.

No, I dont think it should be mandatory, then-President-elect Biden said in response to a question about possible vaccine mandates. I wouldnt demand it to be mandatory, but I would do everything in my power, just like I dont think masks have to be made mandatory nationwide, Ill do everything in my power as president of [the] United States to encourage people to do the right thing.

In a July 12 press briefing, Psaki reaffirmed that the federal government would not mandate vaccinations although, she said the administration would support entities that do require the shots.

Thats not a decision that we are making. Thats not a that is not our intention from the federal government, she said in response to a question about local mandates. There will be decisions made by private-sector entities, by universities, by educational institutions, and even perhaps by local leaders, should they decide that is how to keep their community safe. If they decide to make that decision, we certainly support them in that step.

We asked Greenes office for support for her claim that vaccinations would be required as part of the door-to-door campaign. We have not yet received a reply.

The freshman Republican congresswoman from Georgia made other claims in her tweet that we have previously addressed.

She said there have been 5,946 reported deaths after taking the #COVID19 vaccine, leaving the misleading impression that the deaths were caused by the vaccines.

It is true that 5,946 deaths were reported to the Vaccine Adverse Event Reporting System, as of July 6. But [r]eports of adverse events to VAERS following vaccination, including deaths, do not necessarily mean that a vaccine caused a health problem, the Centers for Disease Control and Prevention states on its website.

As weve written before, anyone can submit a report of an adverse event to VAERS regardless of whether the vaccine was a factor. In the case of deaths, health care providers are required to report any death after COVID-19 vaccination to VAERS, even if its unclear whether the vaccine was the cause, the CDC says.

A review of available clinical information, including death certificates, autopsy, and medical records, has not established a causal link to COVID-19 vaccines, the CDC said of death reports. However, recent reports indicate a plausible causal relationship between the J&J/Janssen COVID-19 Vaccine and TTS, a rare and serious adverse eventblood clots with low plateletswhich has caused deaths.

As of July 6, the Food and Drug Administration and CDC had identified 38 cases of the rare blood clotting condition, which is known as thrombosis with thrombocytopenia syndrome, or TTS. There have been three deaths from the condition among those cases, as of May 7.

Greene also tweeted that the vaccine is NOT FDA approved which is true, but misleading.

As weve noted, the FDA has authorized three COVID-19 vaccines including the one manufactured by Johnson & Johnson for emergency use. In order to grant an emergency use authorization, regulators must determine that the product may be effective and the known and potential benefits of a product outweigh its known and potential risks a standard that is typically less stringent than the standard full licensure, which is called a biologics license application, or BLA.

However, for the three COVID-19 vaccines, the FDA set up more rigorous EUA requirements that resemble the process for a BLA. The FDA required at least one well-designed Phase 3 clinical trial that demonstrates the vaccines safety and efficacy in a clear and compelling manner and wanted to see at least two months of follow-up data on half or more of the participants.

Greene disregards the rigorous clinical trials and real-world evidence that show the vaccines have been safe and effective.

According to CDC data, the seven-day rolling average of daily deaths from COVID-19 has declined by about 94% since the vaccines became available in the U.S. The seven-day average of daily deaths was 2,779 on Dec. 14; as of July 11, it was down to 176.

Pfizer, BioNTech and Moderna have filed for final approval of their vaccines.

Finally, while claiming that 33,631,656 Americans SURVIVED covid, Greene did not acknowledge that more than 600,000 U.S. deaths have been attributed to the disease. Even some individuals who have survived an infection have reported experiencing COVID-19 symptoms and side effects that persist for months.

Whats more, only a small percentage of recent COVID-19 deaths have been people who were vaccinated, according to government data.

In a July 1 White House COVID-19 response team briefing, CDC Director Dr. Rochelle Walensky said that preliminary data from a collection of states since January suggest 99.5% of deaths from COVID-19 in these states have occurred in unvaccinated people.

With vaccines available across the country, the suffering and loss we are now seeing is nearly entirely avoidable, she said.

Walenskys remarks are in line with an Associated Press analysis that found that nearly all of the people in the U.S. who died from COVID-19 in May were not vaccinated.

About 150 out of more than 18,000 COVID-19 deaths that month were in fully vaccinated people. That translates to about 0.8%, or five deaths per day on average, the AP reported.

The news service also said that fully vaccinated people accounted for less than 1,200 or about 1.1% of more than 107,000 COVID-19 related hospitalizations that month.

Editors note:SciChecks COVID-19/Vaccination Projectis made possible by a grant from the Robert Wood Johnson Foundation. The foundation hasno controlover our editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation. The goal of the project is to increase exposure to accurate information about COVID-19 and vaccines, while decreasing the impact of misinformation.

Biden, Joe. Remarks by President Biden on the COVID-19 Response and the Vaccination Program. Transcript. Whitehouse.gov. 6 Jul 2021.

Taylor Greene, Marjorie. @mtgreenee. 5,946 reported deaths after taking the #COVID19 vaccine. The vaccine is NOT FDA approved. 33,631,656 Americans SURVIVED covid. But Biden & the Dems are coming to your front door to force you to take the vax, schools say your healthy kids need it, and you still think your free? Twitter. 9 Jul 2021.

Psaki, Jen. Press Gaggle by Press Secretary Jen Psaki Aboard Air Force One En Route Crystal Lake, IL. Transcript. Whitehouse.gov. 7 Jul 2021.

Psaki, Jen. Press Briefing by Press Secretary Jen Psaki. Transcript. Whitehouse.gov. 12 Jul 2021.

CNN New Day. Transcript. 7 Jul 2021.

Zients, Jeff. Press Briefing by White House COVID-19 Response Team and Public Health Officials. Transcript. Whitehouse.gov. 8 Jul 2021.

Joe Biden Speech on 2020 Job Numbers & Economy. Video. Rev.com. 4 Dec 2020.

Centers for Disease Control and Prevention. Selected Adverse Events Reported after COVID-19 Vaccination. Cdc.gov. Accessed 11 Jul 2021.

Jaramillo, Catalina. Viral Posts Misuse VAERS Data to Make False Claims About COVID-19 Vaccines. FactCheck.org. 31 Mar 2021, updated 14 May 2021.

McDonald, Jessica. Q&A on COVID-19 Vaccines. FactCheck.org. 18 Dec 2020, updated 26 May 2021.

Pfizer and BioNTech Initiate Rolling Submission of Biologics License Application for U.S. FDA Approval of Their COVID-19 Vaccine. Press release. 7 May 2021.

Moderna Announces Initiation of Rolling Submission of Biologics License Application (BLA) with U.S. FDA for the Moderna COVID-19 Vaccine. Press release. 1 Jun 2021.

Centers for Disease Control and Prevention. Trends in Number of COVID-19 Cases and Deaths in the US Reported to CDC, by State/Territory. Cdc.gov. Accessed 12 Jul 2021.

Walensky, Rochelle. Press Briefing by White House COVID-19 Response Team and Public Health Officials. Transcript. Whitehouse.gov. 1 Jul 2021.

Johnson, Carla K. and Mike Stobbe. Nearly all COVID deaths in US are now among unvaccinated. Associated Press. 24 Jun 2021.

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Greene's Deceptive Claims of Forced COVID-19 Vaccinations and Vaccination 'Deaths' - FactCheck.org

Late last week, the U.S. Centers for Disease Control and Prevention released sweeping new guidance for public schools, prioritizing in-person learning and making masks optional for fully vaccinated students (a recommendation that Virginia will soon adopt, the Richmond Times-Dispatch reported).

The news came less than 24 hours after the states Department of Health announced that a second child under the age of 10 a boy from Stafford County had died from COVID-19. The risk of severe disease and hospitalization among children is still lower than it is for adults, according to the CDC. But for many public health experts, the upcoming school year is a looming reminder that children remain one of the most vulnerable populations for catching and spreading new cases of COVID-19.

Its going to depend so much on the local context of the school system, said Dr. Taison Bell, an infectious disease specialist at the University of Virginia. Children under 12 arent yet eligible for a shot, and likely wont be until later this fall. But growing research shows that vaccinations among adults can be key to protecting younger age groups.

For instance, Im in Charlottesville, and we have relatively high uptake rates, Bell continued. The teachers, the custodial staff and other adults in the building theyre much more likely to be protected. Thats a much lower-risk scenario compared to some areas of Virginia that still have low rates of vaccination.

Some of the clearest data comes from countries or regions with exceptionally high vaccination rates among the adult population. Israel, for example, has one of the highest per-capita vaccination rates in the world, and reopened most school buildings by March. But case rates still dropped dramatically among children younger than 11, as they did for people 16 and older.

Similar evidence came from Serrana, Brazil, where 98% of adults have been vaccinated. Research found that symptomatic infections dropped by roughly 80% among both adults and unvaccinated children as a result, according to reporting in Nature, an academic journal.

So, theres data showing that once vaccinations start picking up in adults, you actually have protection in children, Bell said. Children are less likely to be infected, and thats because the most common mode of transmission to a child is from an adult theyre in close contact with.

Experts are hoping the message will resonate as schools prepare for what, in some cases, will be the first return to full in-person learning since the start of the pandemic. Kids and young adults have made up a growing share of the states new infections since early April a trend that could be driven by the rise of more contagious variants. And while the risk of severe outcomes are lower for children, they can happen.

Students at Watkins Elementary in Chesterfield County attend class wearing masks. Chesterfield returned to all virtual learning after Thanksgiving.

A recent CDC study of hospitalizations among 12 to 17-year-olds found they were far more prevalent among Black and Latino children, as well as children with underlying medical conditions. Virginia has also recorded 76 cases of multisystem inflammatory syndrome in children, or MIS-C a rare COVID-associated condition thats also disproportionately affected Black and Latino youth.

For Bell, it underscores the importance of individual vaccination, a message many public health experts worry has gotten lost in the later stages of the state and national campaign. Much of the early messaging around vaccines focused on herd immunity the idea that with enough people vaccinated, COVID-19 would eventually stop circulating.

But some officials have become less than enamored with the concept as a way to promote vaccination. One reason, Bell said, is that theres no clear understanding of how many people need to be protected to actually attain herd immunity. The more contagious a disease, the larger theraising their estimates.

The problem is that it tends to simplify it down to, Whats the percent that we need to get protection? he said. And its much more complicated than that. It also tends to gloss over the impact that vaccinations can have at the local level. By early May, for example, researchers were estimating that Northern Virginia could avoid another surge in cases thanks to high uptake in the region.percentage of the population. And with variants now making up the vast majority of infections, officials have been

We put the focus so much on herd immunity that the importance of personal vaccination has kind of gotten lost, Bell said. And now the people we need to vaccinate are the ones who are reluctant or just dont feel that its necessary for them.

Protecting children who arent yet eligible for a dose is just one area where individual vaccination can make a significant difference. While the U.S. may never reach true herd immunity, the virus can be significantly curtailed as more people are immunized at the local level. Those protections extend to adults who in some rare cases cant receive the vaccine, or who may receive less protection due to pre-existing conditions.

Its especially important given the rise of the Delta variant, which now makes up just over 20% of sequenced cases among Virginians aged 0 to 19, according to data from VDH. Spokeswoman Melissa Gordon said those numbers are likely an undercount, given that not all samples of the virus are tested.

Delta, which can evade immune system protection, is more contagious than other forms of the virus. Preliminary research has also indicated it may cause more severe disease. A single dose of vaccine is much less protective against the variant, which makes high uptake rates and complete vaccination especially important for fighting the spread. Cases are currently surging in states like Missouri, where low vaccination rates and a lack of protective measures have allowed the virus to circulate widely.

Their ICUs are over capacity, Bell said. Their staff are overwhelmed. So for communities here with low vaccine uptake rates, Im very, very concerned about the fall and winter. I cant express it any better. The difference is that its truly preventable at this point.

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What's the best way to protect young Virginians from COVID-19? Experts say it's getting more adults immunized. - Fauquier Times

GWINNETT COUNTY, Ga. Blake Bargatze, 24, was the only one in his family to not get vaccinated and now he remains in a hospital ICU more than three months after contracting COVID-19, according to his family.

I just dont ever want anybody else to go through this, his mother Cheryl Nuclo told Channel 2s Matt Johnson.

Bargatze was infected with the virus in April while in Florida, his family says, and has needed a double lung transplant and months of intensive care at hospitals in three states.

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The Gwinnett County native vaped regularly, but his mother says he has no underlying conditions.

No diabetes, no hypertension, she said. Just a 24-year-old kid.

Bargatze is getting treatment at a Maryland hospital after being transferred there from Atlanta for his transplant. His family says he likely picked up the virus at an indoor concert.

He had called me that Friday when he got the results, Nuclo said, and hes like, Mom, youre going to be mad. I got COVID.

Doctors across the country say virtually all of their COVID-19 patients are unvaccinated.

He wanted to wait a few years to see you know, if theres any side effects or anything from it, said Paul Nuclo, his stepfather. As soon as he got in the hospital, though, he said he wished he had gotten the vaccine.

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As of Tuesday night in Georgia, 669 people are in hospitals battling the disease.

That number had been declining for months but its been slowly going up since late last month.

I do worry that we probably will expect some impacts in the Atlanta metro, said Dr. Amber Schmidtke with the University of St. Mary in Kansas. Were already seeing patient census for COVID-19 increase in hospital region D which is the Atlanta metro.

Case are up 23% in Georgia according to the latest White House COVID-19 Task Force report. Deaths are down 44%.

However, Dr. Patrick OCarroll with the Atlanta-based Task Force for Global Health worries about the more transmissible Delta variant amidst a rise in patients.

The people who havent been vaccinated are is as much in danger now because of the Delta variant than they were 12 months ago, Dr. OCarroll said.

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For Cheryl Nuclo, shes thankful her son is still fighting, and now pushing for others to get a shot.

Maybe if some people were kind of on the fence and swaying, he wants them to see what might be the extreme of what can happen, she said. Not using a fear tactic, but it can happen.

Friends of Bargatze are helping raise money for his medical expenses and his recovery. You can find out more about that here.

2021 Cox Media Group

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He wished he had gotten the vaccine: Local man battling COVID-19 from ICU for months - WSB Atlanta

INTRODUCTION

To date, very few treatments have been demonstrated to reduce the burden of morbidity and mortality from COVID-19. Although corticosteroids have been proven to reduce mortality in severe disease,1 there has been little convincing evidence on interventions that may prevent disease, reduce hospitalizations, and reduce the numbers of people progressing to critical disease and death.

Ivermectin is a well-known medicine that is approved as an antiparasitic by the World Health Organization and the US Food and Drug Administration. It is widely used in low- and middle-income countries (LMICs) to treat worm infections.2,3 Also used for the treatment of scabies and lice, it is one of the World Health Organizations Essential Medicines.4 With total doses of ivermectin distributed apparently equaling one-third of the present world population,5 ivermectin at the usual doses (0.20.4 mg/kg) is considered extremely safe for use in humans.6,7 In addition to its antiparasitic activity, it has been noted to have antiviral and anti-inflammatory properties, leading to an increasing list of therapeutic indications.8

Since the start of the SARS-CoV-2 pandemic, both observational and randomized studies have evaluated ivermectin as a treatment for, and as prophylaxis against, COVID-19 infection. A review by the Front Line COVID-19 Critical Care Alliance summarized findings from 27 studies on the effects of ivermectin for the prevention and treatment of COVID-19 infection, concluding that ivermectin demonstrates a strong signal of therapeutic efficacy against COVID-19.9 Another recent review found that ivermectin reduced deaths by 75%.10 Despite these findings, the National Institutes of Health in the United States recently stated that there are insufficient data to recommend either for or against the use of ivermectin for the treatment of COVID-19,11 and the World Health Organization recommends against its use outside of clinical trials.12

Ivermectin has exhibited antiviral activity against a wide range of RNA and some DNA viruses, for example, Zika, dengue, yellow fever, and others.13 Caly et al14 demonstrated specific action against SARS-CoV-2 in vitro with a suggested host-directed mechanism of action being the blocking of the nuclear import of viral proteins14,15 that suppress normal immune responses. However, the necessary cell culture EC50 may not be achievable in vivo.16 Other conjectured mechanisms include inhibition of SARS-CoV-2 3CLPro activity17,18 (a protease essential for viral replication), a variety of anti-inflammatory effects,19 and competitive binding of ivermectin with the viral S protein as shown in multiple in silico studies.20 The latter would inhibit viral binding to ACE-2 receptors suppressing infection. Hemagglutination via viral binding to sialic acid receptors on erythrocytes is a recently proposed pathologic mechanism21 that would be similarly disrupted. Both host-directed and virus-directed mechanisms have thus been proposed, the clinical mechanism may be multimodal, possibly dependent on disease stage, and a comprehensive review of mechanisms of action is warranted.

Developing new medications can take years; therefore, identifying existing drugs that can be repurposed against COVID-19 that already have an established safety profile through decades of use could play a critical role in suppressing or even ending the SARS-CoV-2 pandemic. Using repurposed medications may be especially important because it could take months, possibly years, for much of the world's population to get vaccinated, particularly among LMIC populations.

Currently, ivermectin is commercially available and affordable in many countries globally.6 A 2018 application for ivermectin use for scabies gives a direct cost of $2.90 for 100 12-mg tablets.22 A recent estimate from Bangladesh23 reports a cost of US$0.60US$1.80 for a 5-day course of ivermectin. For these reasons, the exploration of ivermectin's potential effectiveness against SARS-CoV-2 may be of particular importance for settings with limited resources.24 If demonstrated to be effective as a treatment for COVID-19, the cost-effectiveness of ivermectin should be considered against existing treatments and prophylaxes.

The aim of this review was to assess the efficacy of ivermectin treatment among people with COVID-19 infection and as a prophylaxis among people at higher risk of COVID-19 infection. In addition, we aimed to prepare a brief economic commentary (BEC) of ivermectin as treatment and as prophylaxis for COVID-19.25

The conduct of this review was guided by a protocol that was initially written using Cochrane's rapid review template and subsequently expanded to a full protocol for a comprehensive review.26

Two reviewers independently searched the electronic databases of Medline, Embase, CENTRAL, Cochrane COVID-19 Study Register, and Chinese databases for randomized controlled trials (RCTs) up to April 25, 2021 (see Appendix 13, Supplemental digital content 1, http://links.lww.com/AJT/A95); current guidance25 for the BEC was followed for a supplementary search of economic evaluations. There were no language restrictions, and translations were planned to be performed when necessary.

We searched the reference list of included studies, and of two other 2021 literature reviews on ivermectin,9 as well as the recent WHO report, which included analyses of ivermectin.12 We contacted experts in the field (Drs. Andrew Hill, Pierre Kory, and Paul Marik) for information on new and emerging trial data. In addition, all trials registered on clinical trial registries were checked, and trialists of 39 ongoing trials or unclassified studies were contacted to request information on trial status and data where available. Many preprint publications and unpublished articles were identified from the preprint servers MedRiv and Research Square, and the International Clinical Trials Registry Platform. This is a rapidly expanding evidence base, so the number of trials are increasing quickly. Reasons for exclusion were recorded for all studies excluded after full-text review.

We extracted information or data on study design (including methods, location, sites, funding, study author declaration of interests, and inclusion/exclusion criteria), setting, participant characteristics (disease severity, age, gender, comorbidities, smoking, and occupational risk), and intervention and comparator characteristics (dose and frequency of ivermectin/comparator). The primary outcome for the intervention component of the review included death from any cause and presence of COVID-19 infection (as defined by investigators) for ivermectin prophylaxis. Secondary outcomes included time to polymerase chain reaction (PCR) negativity, clinical recovery, length of hospital stay, admission to hospital (for outpatient treatment), admission to ICU or requiring mechanical ventilation, duration of mechanical ventilation, and severe or serious adverse events, as well as post hoc assessments of improvement and deterioration. All of these data were extracted as measured and reported by investigators. Numerical data for outcomes of interest were extracted according to intention to treat.

If there was a conflict between data reported across multiple sources for a single study (eg, between a published article and a trial registry record), we contacted the authors for clarification. Assessments were conducted by 2 reviewers (T.L., T.D., A.B., or G.G.) using the Cochrane RCT risk-of-bias tool.27 Discrepancies were resolved by discussion.

Continuous outcomes were measured as the mean difference and 95% confidence intervalss (CI), and dichotomous outcomes as risk ratio (RR) and 95% CI.

We did not impute missing data for any of the outcomes. Authors were contacted for missing outcome data and for clarification on study methods, where possible, and for trial status for ongoing trials.

We assessed heterogeneity between studies by visual inspection of forest plots, by estimation of the I2 statistic (I2 60% was considered substantial heterogeneity),28 by a formal statistical test to indicate statistically significant heterogeneity,29 and, where possible, by subgroup analyses (see below). If there was evidence of substantial heterogeneity, the possible reasons for this were investigated and reported. We assessed reporting biases using funnel plots if more than 10 studies contributed to a meta-analysis.

We meta-analyzed data using the random effects model (DerSimonian and Laird method)30 using RevMan 5.4.1 software.27,31 The results used the inverse variance method for weighting.27 Some sensitivity analyses used other methods that are outlined below and some calculations were performed in R32 through an interface33 to the netmeta package.34 Where possible, we performed subgroup analyses grouping trials by disease severity, inpatients versus outpatients, and single dose versus multiple doses. We performed sensitivity analyses by excluding studies at high risk of bias. We conducted further post hoc sensitivity analyses using alternative methods to test the robustness of results in the presence of zero events in both arms in a number of trials35 and estimated odds ratios [and additionally RR for the MantelHaenszel (MH) method] using a fixed effects model. The models incorporate evidence from single-zero studies without having to resort to continuity corrections. However, double-zero studies are excluded from the analysis; so, the risk difference was also assessed using the MH method as this approach can adequately incorporate trials with double-zero events. This method can also use a random-effects component. A treatment-arm continuity correction was used, where the values 0.01, 0.1, and 0.25 were added where trials reported zero events in both arms. It has been shown that a nonfixed continuity correction is preferable to the usual 0.5.35 Other methods are available but were not considered due to difficulty in interpretation, sensitivity of assumptions, or the fact they are rarely used in practice.3640

When a meta-analysis is subjected to repeated statistical evaluation, there is an exaggerated risk that naive point estimates and confidence intervals will yield spurious inferences. In a meta-analysis, it is important to minimize the risk of making a false-positive or false-negative conclusion. There is a trade-off between the risk of observing a false-positive result (type I error) and the risk of observing a false-negative result (type II error). Conventional meta-analysis methods (eg, in RevMan) also do not take into account the amount of available evidence. Therefore, we examined the reliability and conclusiveness of the available evidence using trial sequential analyses (TSA).4143 The DerSimonianLaird (DL) method was used because this is most often used in meta-analytic practice and was also used in the primary meta-analysis.30

The TSA was used to calculate the required information size (IS) to demonstrate or reject a relative reduction in the risk (RRR) of death in the ivermectin group, as found in the primary meta-analysis. We assumed the estimated event proportion in the control group from the meta-analysis because this is the best and most representative available estimate. Recommended type I and II error rates of 5% and 10% were used, respectively (power of 90%),43 powering the result on the effect observed in the primary meta-analyses. We did not identify any large COVID-19 trials powered on all-cause mortality, so powering on some external meaningful difference was not possible. Any small RRR is meaningful in this context, given the scale of the pandemic, but the required IS would be unfeasibly high for this analysis if powered on a small difference. The only reliable data on ivermectin in its repurposed role for treatment against COVID-19 will be from the primary meta-analysis. Therefore, assuming it does not widely deviate from other published systematic reviews, a pragmatic decision was therefore made to power on the pooled meta-analysis effect estimate for all-cause mortality a priori. This is more reflective of a true meaningful difference. We used a model variance-based estimate to correct for heterogeneity. A continuity correction of 0.01 was used in trials that reported zero events in one or both arms. The required IS is the sample size required for a reliable and conclusive meta-analysis and is at least as large as that needed in a single powered RCT. The heterogeneity corrected required IS was used to construct sequential monitoring boundaries based on the O'BrienFleming type alpha-spending function for the cumulative z-scores (corresponding to the cumulative meta-analysis),43 analogous to interim monitoring in an RCT, to determine when sufficient evidence had been accrued. These monitoring boundaries are relatively insensitive to the number of repeated significance tests. They can be used to further contextualize the original meta-analysis and enhance our certainty around its conclusions. We used a two-sided test, so also considered futility boundaries (to test for no statistically significant difference) and the possibility that ivermectin could harm. Sensitivity analyses were performed excluding the trial of Fonseca,44 which was a cause of substantial heterogeneity (but retained in the core analysis because it was at low risk of bias). Its removal dramatically reduced I2 and D2 (diversity) estimates, thus reducing the model variance-based estimate to correct for heterogeneity. Two further sensitivity analyses were performed using 2 alternative random effect models, namely the BiggerstaffTweedie (BT) and SidikJonkman (SJ) methods.43

All outcomes have been assessed independently by 2 review authors (T.D. and A.B.) using the GRADE approach,45 which ranks the quality and certainty of the evidence. The results of the TSAs will also form part of the judgment for the primary all-cause mortality outcome. The results are presented in a summary of findings table. Any differences in judgments were resolved by discussion with the wider group. We used Cochrane Effective Practice and Organisation of Care guidance to interpret the evidence.46

The combined and preliminary deduplicated total was n = 583. We also identified 11 records from other sources (reference lists, etc). See PRISMA flow diagram for inclusion and exclusion details of these references (Figure 1).

Study flow diagram from search on 25 April 2021.

The supplementary search for the BEC identified 17 studies, of which 4 were retrieved in full. No full trial- or model-based economic evaluations (costutility analyses, costeffectiveness analyses, or costbenefit analyses) were identified.

Twenty-one trials in treatment and 2 trials in prophylaxis of COVID-19 met review inclusion. One further study47 reported separate treatment and prophylaxis components; we label this study Elgazzar under both questions. In effect, there were 22 trials in treatment and 3 in prophylaxis. All of these contributed data to at least one review outcome and meta-analysis. Fifteen trials contributed data for the primary outcome for ivermectin treatment (death); 3 studies reported the primary outcome for prophylaxis (COVID-19 infection). Characteristics of included studies are given in Table 1. Seventeen studies4763 were excluded as they were not RCTs and we identified 39 ongoing studies64102 and 2 studies103,104 are awaiting classification.

*Also administered doxycycline.

multiarm trial.

SOC, standard of care; PR, peer review.

A risk-of-bias summary graph is given in Figure 2. Eleven studies23,24,44,47,105,106111 used satisfactory random sequence generation and allocation concealment. Two trials described satisfactory sequence generation, but it was unclear whether allocation was concealed.112,113

Risk-of-bias summary: review authors' judgments about each risk of bias item for each included study.

Ten trials reported adequate blinding of the participants/personnel and/or the outcome assessors.23,24,44,105,107,109,110,111,113,114 The others were either unclear or high risk for blinding. We considered blinding to be a less important criterion for evaluation of evidence related to the review's primary outcomes, namely death and laboratory-confirmed COVID-19 infection, which are objective outcomes.

We did not consider publication on preprint web sites to constitute a risk of bias because all studies were scrutinized and peer reviewed by us during the review process and, where additional information was needed, we contacted the authors for clarification.

Twenty-four RCTs (including 3 quasi-RCTs) involving 3406 participants were included, with sample sizes ranging from 24 to 476 participants. Twenty-two trials in treatment and 3 trials in prophylaxis met review inclusion, including the trial of Elgazzar et al, which reported both components. For trials of COVID-19 treatment, 16 evaluated ivermectin among participants with mild to moderate COVID-19 only; 6 trials included patients with severe COVID-19. Most compared ivermectin with placebo or no ivermectin; 3 trials included an active comparator (Table 1). Three RCTs involving 738 participants were included in the prophylaxis trials. Most trials were registered, self-funded, and undertaken by clinicians working in the field. There were no obvious conflicts of interest noted, with the exception of two trials.85,139

Twenty-two trials (2668 participants) contributed data to the comparison ivermectin treatment versus no ivermectin treatment for COVID-19 treatment.

Meta-analysis of 15 trials, assessing 2438 participants, found that ivermectin reduced the risk of death by an average of 62% (95% CI 27%81%) compared with no ivermectin treatment [average RR (aRR) 0.38, 95% CI 0.19 to 0.73; I2 = 49%]; risk of death 2.3% versus 7.8% among hospitalized patients in this analysis, respectively (SoF Table 2 and Figure 3). Much of the heterogeneity was explained by the exclusion of one trial44 in a sensitivity analysis (average RR 0.31, 95% CI 0.170.58, n = 2196, I2 = 22%), but because this trial was at low risk of bias, it was retained in the main analysis. The source of heterogeneity may be due to the use of active comparators in the trial design. The results were also robust to sensitivity analyses excluding 2 other studies with an active treatment comparator (average RR 0.41, 95% CI 0.230.74, n = 1809, I2 = 8%). The results were also not sensitive to the exclusion of studies that were potentially at higher risk of bias (average RR 0.29, 95% CI 0.100.80, 12 studies, n = 2095, I2 = 61%), but in subgroup analysis, it was unclear as to whether a single dose would be sufficient. The effect on reducing deaths was consistent across mild to moderate and severe disease subgroups. Subgrouping data according to inpatient and outpatient trials was not informative because few outpatient studies reported this serious outcome. The conclusions of the primary outcome were also robust to a series of alternative post hoc analyses that explored the impact of numerous trials that reported no deaths in either arm. Extreme sensitivity analyses using a treatment arm continuity correction of between 0.01 and 0.5 did not change the certainty of the evidence judgments (Table 3).

*Only one study contributed to the severe COVID-19 subgroup and subgroup data were not pooled due to subgroup differences.

Downgraded 1 for study design limitations.

Downgraded 1 for inconsistency.

Downgraded 1 for imprecision.

Downgraded 2 for imprecision/sparse data.

Downgraded 1 for indirectness.

Death due to any cause.

FE, fixed effects; IV, inverse variance; M-H, Mantel-Haenszel; RD, risk difference; RE, random effects; TACC, treatment arm continuity correction.

TSA, using the DL random-effects method, showed that there may have been sufficient evidence accrued before the end of 2020 to show significant benefit of ivermectin over control for all-cause mortality. The cumulative z-curve in Figure 8 crossed the trial sequential monitoring boundaries after reaching the required IS, implying that there is firm evidence for a beneficial effect of ivermectin use over no ivermectin use in mainly hospitalized participants with mild to moderate COVID-19 infection.

The TSA was used to calculate the IS required to demonstrate or reject a 62% RRR of death in the ivermectin group, as observed in the primary meta-analysis. This estimate is similar to effect estimates reported in other reviews.10 We assumed a 7.8% event proportion in the control group, which was the average control group event rate from the primary meta-analysis. We used a model variance-based estimate of 49.1% (diversity estimate) to correct for heterogeneity. The required IS was 1810 participants (Figure 8), which was exceeded by the total number of observed participants in the meta-analysis (n = 2438). In the TSA plots, the red dashed lines in Figure 8 represent the trial sequential monitoring boundaries using the O'BrienFleming alpha-spending function. The solid blue line is the cumulative z-curve and represents the observed trials in the cumulative meta-analysis. The adjusted significance boundaries for the cumulative z-curve were constructed under the assumption that significance testing may have been performed each time a new trial was added to the meta-analysis. In Figure 8, the z-curve crosses the boundary after reaching the required IS, thereby supporting the previous conclusion in RevMan 5.4.131 using the DL method that ivermectin is superior to control in reducing the risk of death.

Sensitivity analysis excluding the trial of Fonseca44 significantly reduced heterogeneity in the meta-analysis and thus the diversity estimate in the TSA using the DL model. This strengthened the suggestion in the primary core analysis that the required IS had been reached (Figure 9). Because the DL estimator could potentially underestimate the between-trials variance,43 we performed further sensitivity analyses using 2 alternative random-effects model approaches. The results of the primary TSA analysis were robust to sensitivity analysis using the BT method with the same parameters, excluding the Fonseca44 trial, which was a cause of substantial heterogeneity (Figure 10). The TSA comprehensively confirms the result of the conventional meta-analysis. The required IS was 1064.

The required IS was not reached in the TSA using the SJ method, largely because diversity from the model was high (Figure 11). The SJ estimator may overestimate the between-trials variance in meta-analyses with mild heterogeneity, thus producing artificially wide confidence intervals.43 When the diversity estimate was reduced to the same as in the DL model, the required IS was reached in the SJ model (data not shown). There was no evidence of futility using the SJ method in any scenario.

Overall, death from any cause, taking into account all composite analyses, was judged to provide moderate-certainty evidence (SoF Table 2 and Figures 411). A funnel plot corresponding to the primary outcome of death from any cause did not seem to suggest any evidence of publication bias (Figure 7). Furthermore, the ease with which trial reports can be uploaded as preprints should reduce this risk.

Death due to any cause, excluding an outlier study responsible for the heterogeneity.

Death due to any cause, excluding high risk-of-bias studies.

Death due to any cause, excluding studies with active controls.

Funnel plot of ivermectin versus control for COVID-19 treatment for all-cause death (subgrouped by severity).

Trial sequential analysis using DL random-effects method with parameter estimates of = 0.05, = 0.1, control rate = 7.8%, RRR = 62%, and diversity = 49.5%.

Sensitivity analysis excluding an outlier study responsible for the heterogeneity, showing trial sequential analysis using DL random-effects method with parameter estimates of = 0.05, = 0.1, control rate = 7.8%, = 62%, and diversity = 0%.

Sensitivity analysis excluding an outlier study responsible for the heterogeneity, showing trial sequential analysis using BiggerstaffTweedie random-effects method with parameter estimates of = 0.05, = 0.1, control rate = 7.8%, RRR = 62%, and diversity = 14.2%.

Sensitivity analysis excluding an outlier study responsible for the heterogeneity, showing trial sequential analysis using SidikJonkman random-effects method with parameter estimates of = 0.05, = 0.1, control rate = 7.8%, RRR = 62%, and diversity = 71.9%.

Secondary outcomes provided low to very low certainty evidence (SoF Table 2). Low-certainty findings suggested that there may be no benefit with ivermectin for need for mechanical ventilation, whereas effect estimates for improvement and deterioration favored ivermectin but were graded as low certainty due to study design limitations and inconsistency (Figures 1214). All other secondary outcome findings were assessed as very low certainty.

Need for mechanical ventilation.

Improvement.

Deterioration.

Meta-analysis of 11 trials, assessing 1533 participants, found that there was no significant difference between ivermectin and control in the risk of severe adverse events (aRR 1.65, 95% CI 0.446.09; I2 = 0%; low certainty evidence, downgraded for imprecision and study design limitations). Seven severe adverse events were reported in the ivermectin group and 2 in controls. The SAEs were as follows: 2 patients in the Mahmud trial107 had esophagitis (this is a known side effect of doxycycline, which was coadministered with ivermectin in this trial); one patient in the study by Krolewiecki et al106 had hyponatremia (this trial used high-dose ivermectin for 5 days); and 2 patients in a study from Turkey115 had serious delirium-like behavior, agitation, aggressive attitude, and altered state of consciousness, which the authors attributed to metabolic insufficiencies in MDR-1/ABCB1 or CYP3A4 genes, screening for which was a study feature. In the Lopez-Medina et al85 trial, there were 2 SAEs in each arm (SoF Table 2).

Three studies involving 738 participants evaluated ivermectin for COVID-19 prophylaxis among health care workers and COVID-19 contacts. Meta-analysis of these 3 trials, assessing 738 participants, found that ivermectin prophylaxis among health care workers and COVID-19 contacts probably reduces the risk of COVID-19 infection by an average of 86% (79%91%) (3 trials, 738 participants; aRR 0.14, 95% CI 0.090.21; 5.0% vs. 29.6% contracted COVID-19, respectively; low-certainty evidence; downgraded due to study design limitations and few included trials) (Figure 15). In 2 trials involving 538 participants, no severe adverse events were recorded (SoF Table 4).

COVID-19 infection (prophylaxis studies).

GRADE working group grades of evidence; High quality: Further research is very unlikely to change our confidence in the estimate of effect; Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; Very low quality: We are very uncertain about the estimate.

*The basis for the assumed risk (eg, the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

Downgraded 2 for study design limitations.

NNT, number needed to treat.

The findings indicate with moderate certainty that ivermectin treatment in COVID-19 provides a significant survival benefit. Our certainty of evidence judgment was consolidated by the results of trial sequential analyses, which show that the required IS has probably already been met. Low-certainty evidence on improvement and deterioration also support a likely clinical benefit of ivermectin. Low-certainty evidence suggests a significant effect in prophylaxis. Overall, the evidence also suggests that early use of ivermectin may reduce morbidity and mortality from COVID-19. This is based on (1) reductions in COVID-19 infections when ivermectin was used as prophylaxis, (2) the more favorable effect estimates for mild to moderate disease compared with severe disease for death due to any cause, and (3) on the evidence demonstrating reductions in deterioration.

The evidence on severe adverse events in this review was graded as low certainty, partly because there were too few events to reach statistical significance. Evidence from a recent systematic review of ivermectin use among people with parasitic infections suggests that ivermectin administered at the usual doses (0.2 or 0.4 mg/kg) is safe and could be safe at higher doses.7,116 A recent World Health Organization document on ivermectin use for scabies found that adverse events with ivermectin were primarily minor and transient.22

We restricted the included studies to the highest level of evidence, that is, RCTs, as a policy. This was despite there being numerous observational but nonrandomized trials of ivermectin, which one could argue could also be considered in an emergency. We included preprint and unpublished data from completed but not yet published trials due to the urgency related to evidence synthesis in the context of a global pandemic.117 Although there is the potential for selective reporting of outcomes and publication bias, we have factored in these considerations in interpreting results and forming conclusions. We adhered to PRISMA guidelines and the WHO statement on developing global norms for sharing data and results during public health emergencies.117

There are a number of limitations with this review. Several of the studies contributing data did not provide full descriptions of methods, so assessing risk of bias was challenging. Where descriptions of study methods were sparse or unclear, we attempted to contact authors to clarify methods, but lack of information led us to downgrade findings in several instances. Overall interpretation of findings was hampered due to variability in the participants recruited, treatment regimen, and the care offered to those in control groups. We have tried to take this variation into account through subgroup and sensitivity analyses. Nevertheless, dosing and treatment regimens and the use of ivermectin with other components of standard care require further research. We did not include laboratory outcome measures, such as viral clearance. The latter and other biochemical outcomes have been reported in several studies and reviews and tend to favor ivermectin.10,47,105,108 Several trials reported continuous data, such as length of hospital stay, as medians and interquartile ranges; therefore, we were unable to include these data in meta-analysis. Because we did not undertake in our protocol to perform narrative evidence synthesis, and because these data tended to favor ivermectin, the certainty of the effects of ivermectin on these continuous outcomes may be underestimated.

At least 5 other reviews of ivermectin use for COVID-19 have been published, including one coauthored with Nobel Laureate Professor Satoshi mura, discoverer of ivermectin,9,10,118,119,120 but only 3 have been peer-reviewed9,118,120 and only 2 attempt full systematic review.10,119 We applied AMSTAR 2,121 a critical appraisal tool for systematic reviews of health care interventions, to the 2 nonpeered systematic reviews10,119 and both were judged to be of low quality (Table 5). However, there was also a suggestion that ivermectin reduced the risk of death in treatment of COVID-19 in these reviews.

*Not documented or inadequately reported.

Participant population, description of comparator interventions, and time frame for follow-up were not described or inadequately reported.

No summary of risk-of-bias assessment was given in the main text in the review, other than stating trials were of poor, fair, or high quality. There were some further details about bias in the discussion, but these were largely generic and did not follow the recommended Cochrane tool used to assess risk of bias in RCTs.

There was some further details about bias in the discussion, but this was largely generic and did not follow the recommended Cochrane tool used to assess risk of bias in RCTs. Similarly, in terms of certainty/quality of the evidence, the authors used terms in a summary table that included good, fair, and limited, without offering any explanation or justification.

Outcomes were reported but lacked definitions.

#A significant number of pertinent RCTs have not been included in the review. Given the adequate due diligence of review process, the comprehensive nature of the search strategy is questionable.

**No description of risk-of-bias assessment in any domain apart from missing outcome data but attrition rates not documented to justify judgment.

Authors did not report data from RCTs that we obtained from various sources and some conclusions were not reflective of the observed data. It was reported that in an analysis of 4 preprint retrospective studies at high risk of bias, ivermectin was not associated with reduced mortality (logRR 0.89, 95% CI 0.091.70, P = 0.04). Although the caveat of studies being at high risk of bias and statistical heterogeneity should be added to any interpretation, it is incorrect to interpret these results as not demonstrating a potential association based on the observed result. Furthermore, the high risk of bias judgment is not adequately justified.

A sensitivity analysis was performed excluding those studies without adjustment for confounding but no details are provided. Given that there was some evidence of a potential association with ivermectin treatment and survival in 4 retrospective studies (although downplayed as no association due to concerns about attrition), it is highly implausible that any sensitivity analysis would not remove any suggestion of association.

The recently updated WHO therapeutics guidelines12 included 7 trials and 1419 people in the analysis of mortality. Reporting a risk reduction of 81% (odds ratio 0.19, 95% CI 0.090.36), the effect estimate favoring ivermectin was downgraded by 2 levels for imprecision, although the justification for this is unclear as the reported CI is precise (64%91%).

In addition to the evidence from systematic reviews, the findings of several controlled observational studies are consistent with existing evidence and suggest improved outcomes with ivermectin treatment.55,57,59 Similarly, with respect to ivermectin prophylaxis of frontline workers and those at risk, controlled observational studies from Bangladesh and Argentina (the latter which involved 1195 health care workers) have shown apparent reductions in COVID-19 transmission with ivermectin prophylaxis, including in some reports total protection (zero infections) where infection rates in the control group exceeded 50%.122,123 A very large trial of ivermectin prophylaxis in health care workers in India124 covered 3532 participants and reported risk ratios not significantly different from this meta-analysis (prophylaxis outcome).

Clarifying ivermectin safety in pregnancy is a key question in patient acceptability for pregnant women contracting COVID-19. A recent meta-analysis5 found little evidence of increased risk of abnormal pregnancies but similarly weak evidence of absence of risk. For (pre-exposure) prophylaxis in pregnancy, where vaccines may be contraindicated, the alternative of hydroxychloroquine has been advocated.125,126 In addition to safety and relative efficacy, different riskbenefit judgments may be presented for prophylaxis (pre- and post-exposure), and for treatment, with pregnancy a high-risk status for COVID-19.

RCTs in this review did not specifically examine use of ivermectin in the elderly, although this is a known high-risk group for severe COVID-19. In the setting of care homes, it is also notorious for rapid contagion. A standard indication for ivermectin in the elderly is scabies. We identified 2 recent reports suggesting that ivermectin may be efficacious as prevention and treatment of COVID-19 in this age group.50,127 A letter on positive experience in 7 elder care facilities in Virginia covering 309 patients was sent to NIH127 and has recently been submitted for publication.

There is also evidence emerging from countries where ivermectin has been implemented. For example, Peru had a very high death toll from COVID-19 early on in the pandemic.128 Based on observational evidence, the Peruvian government approved ivermectin for use against COVID-19 in May 2020.128 After implementation, death rates in 8 states were reduced between 64% and 91% over a two-month period.128 Another analysis of Peruvian data from 24 states with early ivermectin deployment has reported a drop in excess deaths of 59% at 30+ days and of 75% at 45+ days.129 However, factors such as change in behavior, social distancing, and face-mask use could have played a role in this reduction.

Other considerations related to the use of ivermectin treatment in the COVID-19 pandemic include people's values and preferences, equity implications, acceptability, and feasibility.130 None of the identified reviews specifically discussed these criteria in relation to ivermectin. However, in health care decision making, evidence on effectiveness is seldom taken in isolation without considering these factors. Ultimately, if ivermectin is to be more widespread in its implementation, then some considerations are needed related to these decision-making criteria specified in the GRADE-DECIDE framework.130

There are numerous emerging ongoing clinical trials assessing ivermectin for COVID-19. The trade-off with policy and potential implementation based on evidence synthesis reviews and/or RCTs will vary considerably from country to country. Certain South American countries, Indian states, and, more recently, Slovakia and other countries in Europe have implemented its use for COVID-19.129,131,132,133,134 A recent survey of global trends118 documents usage worldwide. Despite ivermectin being a low-cost medication in many countries globally, the apparent shortage of economic evaluations indicates that economic evidence on ivermectin for treatment and prophylaxis of SARS-CoV-2 is currently lacking. This may impact more on LMICs that are potentially waiting for guidance from organizations like the WHO.

Given the evidence of efficacy, safety, low cost, and current death rates, ivermectin is likely to have an impact on health and economic outcomes of the pandemic across many countries. Ivermectin is not a new and experimental drug with an unknown safety profile. It is a WHO Essential Medicine already used in several different indications, in colossal cumulative volumes. Corticosteroids have become an accepted standard of care in COVID-19, based on a single RCT of dexamethasone.1 If a single RCT is sufficient for the adoption of dexamethasone, then a fortiori the evidence of 2 dozen RCTs supports the adoption of ivermectin.

Ivermectin is likely to be an equitable, acceptable, and feasible global intervention against COVID-19. Health professionals should strongly consider its use, in both treatment and prophylaxis.

This work was inspired by the prior literature review of Dr Pierre Kory.

The authors thank Information Specialist, Jo Platt, of the Cochrane Gynaecological, Neuro-oncology, and Orphan Cancer (CGNOC) group for designing the search strategy and running the search, as well as Anna Noel Storr for reviewing the strategy. The authors also thank Isabella Rushforth for her voluntary assistance with the preparation of the reference lists.

The authors thank Gill Gyte for detailed comments, feedback, and involvement in this review, and Michael Grayling and David Tovey for useful peer review comments before submission. The authors also thank the external peer reviewers for their helpful comments and Peter Manu for the opportunity to publish our findings.

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Ivermectin for Prevention and Treatment of COVID-19... : American Journal of Therapeutics - LWW Journals

One of the main factors driving differences in COVID-19 vaccination rates across the country is partisanship. Our surveys consistently find that Democrats are much more likely to report having been vaccinated than Republicans, and Republicans are much more likely to say that they definitely do not want to get vaccinated. In May, just as vaccine supply was starting to outstrip demand, we examined average vaccination rates by county and found that rates were lower in counties that voted for Trump in the 2020 Presidential election compared to those that voted for Biden. Now, two months later, we find that not only does this remain the case, the gap has grown.

We obtained data on the share of the population fully vaccinated by county from the Centers for Disease Control and Preventions (CDC)COVID-19 Integrated County View and data on the 2020 Presidential election results by county from here (for more detailed methods, see: https://www.kff.org/coronavirus-covid-19/issue-brief/vaccination-is-local-covid-19-vaccination-rates-vary-by-county-and-key-characteristics/). To create a longer time series, we also looked at vaccination rates in April 2021.

While the share of the total population that is fully vaccinated has increased for both county groups, it has increased faster in counties that voted for Biden, resulting in a widening gap. Three months ago, as of April 22, the average vaccination rate in counties that voted for Trump was 20.6% compared to 22.8% in Biden counties, yielding a relatively small gap of 2.2 percentage points. By May 11, the gap had increased to 6.5% and by July 6, 11.7%, with the average vaccination rate in Trump counties at 35% compared to 46.7% in Biden counties. See Figures 1 and 2.

Although there has been an overall significant slow-down in COVID-19 vaccination rates in the U.S., these findings show a widening divide of communities at risk for COVID-19 along partisan lines. A key component of any effort to boost vaccination rates among Republicans will be identifying the right messengers. According to our Vaccine Monitor, which tracks the publics attitudes and experiences with COVID-19 vaccinations, Republicans are most likely to trust their doctors and employers to provide reliable information on COVID-19 vaccines, while government sources are less trusted. Going forward, efforts that focus on these messengers, including President Bidens recent announcement to augment vaccination distribution through doctors offices, may help, but there is a hardcore group of vaccine resisters who are disproportionately Republican and will be difficult to move.

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The Red/Blue Divide in COVID-19 Vaccination Rates is Growing - Kaiser Family Foundation