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Unproven Ivermectin resurfaces as treatment for long COVID patients

Michigan’s Dean Fritzemeier (52) got COVID in October 2020, and his life since then has been weighed down by the virus. He’s permanently tired, but can’t sleep. He once walked 5km daily, but now only gets outside in a wheelchair.

Like millions of others, he has long COVID, and after dozens of unsuccessful programmes, he turned to the unproven, controversial Ivermectin. His wife, Karen, heard about it from someone who said: “These people have the answers and the government is trying to kill us,” she said.

A horse dewormer and treatment for some human parasites, Ivermectin was initially promoted, despite the lack of research, as a way to treat COVID infections, reports STAT News. Now it is being marketed for long COVID, pushed by physicians with ties to political groups spreading anti-vaccine, anti-science messaging.

There’s no evidence supporting its use for this purpose, but anecdotes of Ivermectin as a miracle cure swirl around social media.

One patient posted that he started to feel better within two days of taking Ivermectin. “Don’t believe all the media lies,” he wrote, saying Big Pharma dismissed the drug because it’s cheap. Another patient said it cured her symptoms in 24 hours.

Though Karen Fritzemeier once worked as a respiratory therapist, is trained to weigh medical evidence, and knows to be sceptical, she said for those desperate for treatment, it’s hard to resist these stories.

Two physician-led groups, America’s Frontline Doctors (AFLDS) and Front Line COVID-19 Critical Care Alliance (FLCCC), have been particularly active in promoting the drug, charging $90 – and up to $1,650, to meet the founder of the alliance for online appointments for Ivermectin prescriptions.

Several doctors at long COVID clinics said there has been an increase in patients referred to them who had tried Ivermectin, most of whom got the drugs through networks of doctors co-ordinated by AFLDS and FLCCC.

With fears about acute COVID fading, but long COVID becoming a problem, there’s financial incentive for the doctors behind these groups to find new ways to advertise Ivermectin, said James Heathers, chief scientific officer at Cipher Skin and a scientific-integrity researcher, who has exposed fraudulent Ivermectin studies. “Some are true believers in its efficacy,” said Heathers, even if the evidence doesn’t stack up.

There’s more to this story, however, than mere greed. These groups’ leaders have achieved social media followings through ties to right-wing political organisations, including the Tea Party Patriots, and Trump administration officials. A recording of an April 2020 meeting of the Council for National Policy Action, an influential conservative group, shows political figures talking about assembling groups of doctors as spokespeople early in the pandemic, to push back against lockdowns and public health messaging perceived as damaging to Trump’s re-election chances.

These doctors, supported by political heavyweights, were promoted on right-wing media and helped create a counter-narrative encouraging distrust of pharmaceutical companies and health agencies.

Ivermectin has become a sword in that fight, said several doctors working to combat misinformation, playing on the same themes of distrust in science-based medicine.

Simone Gold, founder of America’s Frontline Doctors, launched her organisation with support from right-wing political figures. She was sentenced to 60 days in prison last month and fined $9,500 for storming the US Capitol in the 6 January 2021 insurrection.

Meanwhile, Pierre Kory, president of Frontline COVID-19 Critical Care Alliance, touted Ivermectin out of desperation to combat the virus, but has increasingly embraced vaccine scepticism and rejected Big Pharma and conventional medicine. He has a large online audience and, having resigned as a pulmonary/critical care specialist at Aurora St Luke’s Medical Centre in Milwaukee after saying they infringed on his freedom of speech, now flogs online appointments and access to Ivermectin.

Last month, the American Board of Internal Medicine wrote to Kory, warning it was considering revoking his board certification for promoting misinformation. In response, Kory tweeted he had “massive evidence to support each statement.”

Early in the pandemic, physicians scrambled to try existing drugs on the patients crowding hospitals, desperate for anything that could help. Ivermectin arose from that mayhem.

Kory was then a critical care doctor at University of Wisconsin Hospital and Clinics, but was frustrated with colleagues who wanted more evidence before giving drugs to the wards full of COVID-19 patients. He pushed numerous treatments, including steroids (since been proven effective) and intravenous vitamin C (which has not), then left for a position at Aurora St Luke’s in May 2020.

With Paul Marik, then chief of pulmonary and critical care medicine at Eastern Virginia Medical School, and several other doctors, he founded FLCCC, and they started pushing Ivermectin as a treatment for acute COVID-19. The medical community was frantically searching for something that could help: Ivermectin was cheap, widely available, and considered worth trying. Kory’s message was more forceful: Ivermectin was the pandemic’s answer.

He said “it basically obliterates transmission of this virus, and if you take it, you will not get sick”.

Months later, despite his own Ivermectin regimen, Kory got COVID. This didn’t diminish his belief in it; instead, he increased the dose to achieve maximum effectiveness.

When he and his associates started championing Ivermectin, there was legitimate scientific debate over whether it might work for patients with active infections. In June 2020, Australian researchers showed Ivermectin stopped the coronavirus from replicating – but in cell cultures in lab dishes, not humans.

Two years on, more advanced studies that tested Ivermectin in humans have been repeatedly found to be biased or fabricated. In one study, BuzzFeed News revealed that a hospital listed as participating had no record of it taking place. A study from Egyptian researchers was retracted after evidence of plagiarism and major data errors, including using the same medical records for multiple patients. And Kory’s own research on Ivermectin was retracted by a medical journal because of inaccurate hospital mortality data.

Overall, scientists investigating Ivermectin evidence, including Heathers, found more than a third of 26 studies had serious mistakes or potential fraud, while the others provided no evidence of the drug’s effectiveness. A meta-analysis of randomised controlled trials, published in March, found Ivermectin is not a viable COVID-19 treatment, and a large clinical trial of more than 3,500 patients, published in the New England Journal of Medicine in May, supported this.

And yet, Kory has dug in his heels – and shown hostility to COVID-19 vaccines.

When FLCCC launched, the group distanced itself from America’s Frontline Doctors. Over the years though, Kory’s rhetoric has gradually shifted, and FLCCC’s and America’s Frontline Doctors’ messaging have become more aligned. Last summer, Kory suggested pharmaceutical companies didn’t want to investigate Ivermectin for COVID because of the limited potential to profit from a generic drug.

He has also minimised the benefits of vaccines, and promoted conspiracy theories about children dying after shots.

FLCCC and AFLDS’ distrust of mainstream medicine and pharma, combined with vaccine scepticism, provides the foundation for promoting Ivermectin as a long COVID treatment. Without well-designed studies, it’s impossible to know whether Ivermectin is a valid treatment for long COVID. Given its inability to treat acute COVID though, physicians said it’s unlikely to work for long COVID, and shouldn’t be promoted as treatment without strong evidence.

There are clear financial incentives for continuing to sell Ivermectin, said Aaron Friedberg, an internal medicine physician at Ohio State University Wexner Medical Centre’s Post-COVID Recovery Programme.

“Financially, if you prescribe it as a long-term therapy, you can keep prescribing it, so keep having visits for it,” he said.

FLCCC does not cite specific studies promoting Ivermectin to treat long COVID, but describes it as “one of the safest drugs known”, and notes its discovery as a treatment for parasitic infections won a Nobel Prize. Although Ivermectin is relatively safe, it’s far from benign. Taken long term in large doses, it can cause severe rashes, stomach pain, diarrhoea, facial or limb swelling, a sudden drop in blood pressure, and liver injury.

Its demand has waned as people have become less fearful of acute COVID. From late 2020 until early 2022, monthly prescriptions surged to more than 100,000. That decreased in February, but dispensing it for long COVID helps maintain prescriptions above pre-pandemic levels: There were 78,723 prescriptions for the drug last month – 23% higher than in June 2019.

Doctors who offer it as long-COVID treatment often have no expertise treating pulmonary or chronic diseases. Isabel Bazan, a pulmonologist and critical care specialist at Yale University School of Medicine’s Post COVID Recovery Programme, said she saw one patient, in his 70s, who had been prescribed Ivermectin by a gynaecologist. “This doctor was prescribing this to multiple people as part of a long-COVID cure,” she said.

But this particular patient had never even tested positive for COVID in the first place and, after Bazan examined him, she discovered he had pneumonia and an aggressive bacterial infection. “COVID had nothing to do with it,” she said.

Ivermectin may help doctors get rich, but it’s not simply about the money. The drug’s appeal is intensely political.

“It taps into existing under-currents. It becomes an act of resistance to what some people see as coercive acts of governments and others call public health,” said Heathers, the scientist who exposes fraudulent research.

Right-wing politicians and doctors pushing unproven treatments have leaned on each other throughout the pandemic. The former have recruited physicians as an authoritative face for their policies and anti-public-health messaging. And the doctors have found a
devoted customer base.

Ivermectin’s popularity attracts patients sceptical of vaccines and those dissatisfied by conventional medical responses to long COVID.

Much of this political sentiment is shared online. Kory spreads his message through a newsletter, with thousands of paying subscribers, writes STAT News.

The crusade’s origin was carefully co-ordinated, rather than springing from the grassroots. The Council for National Policy (CNP), a secretive organisation formed in 1981 to promote Christian fundamental ideas, with funding from fossil fuel interests, first discussed the importance of physicians as figureheads of political messaging soon after the pandemic started. A leaked recording from the April 2020 meeting of CNP Action, an affiliate of CNP, shared with Associated Press by the Centre for Media & Democracy, showed participants discussing the importance of physician-led groups to combat the prospect of lockdowns, seen as damaging to the economy and Trump’s campaign.

Doctors “have a 92% trust rate with the American people according to polling”, conservative activist Nancy Schulze said. “There is a coalition of pro-Trump doctors and doctors’ coalition, who have been preparing for the war ahead in the campaign on healthcare.”

Study 1 details
Ivermectin for the Treatment of Coronavirus Disease 2019: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Yuani M Roman, Paula Alejandra Burela, Vinay Pasupuleti, Alejandro Piscoya, Jose E Vidal, Adrian V Hernandez

Published in the National Library of Medicine on 23 March 2022

Abstract

Background
We systematically assessed benefits and harms of the use of ivermectin (IVM) in patients with coronavirus disease 2019 (COVID-19).

Methods
Published and preprint randomised controlled trials (RCTs) assessing the effects of IVM on adult patients with COVID-19 were searched until 22 March 2021 in 5 engines. Primary outcomes were all-cause mortality rate, length of hospital stay (LOS), and adverse events (AEs). Secondary outcomes included viral clearance and severe AEs (SAEs). The risk of bias (RoB) was evaluated using the Cochrane Risk of Bias 2.0 tool. Inverse variance random effect meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods.

Results
Ten RCTs (n = 1173) were included. The controls were the standard of care in 5 RCTs and placebo in 5. COVID-19 disease severity was mild in 8 RCTs, moderate in 1, and mild and moderate in 1. IVM did not reduce all-cause mortality rates compared with controls (relative risk [RR], 0.37 [95% confidence interval, .12-1.13]; very low QoE) or LOS compared with controls (mean difference, 0.72 days [95% confidence interval, -.86 to 2.29 days]; very low QoE). AEs, SAEs, and viral clearance were similar between IVM and control groups (low QoE for all outcomes). Subgroups by severity of COVID-19 or RoB were mostly consistent with main analyses; all-cause mortality rates in 3 RCTs at high RoB were reduced with IVM.

Conclusions
Compared with the standard of care or placebo, IVM did not reduce all-cause mortality, LOS, or viral clearance in RCTs in patients with mostly mild COVID-19. IVM did not have an effect on AEs or SAEs and is not a viable option to treat patients with COVID-19.

Study 2 details
Effect of Early Treatment with Ivermectin among Patients with Covid-19

Gilmar Reis, Eduardo A.S.M. Silva, Daniela C.M. Silva, Lehana Thabane, Aline C. Milagres, Thiago S. Ferreira, Castilho V.Q. dos Santos, Vitoria H.S. Campos, Ana M.R. Nogueira, Ana P.F.G. de Almeida, Eduardo D. Callegari, Adhemar D.F. Neto,

Published in the New England Journal of Medicine on 20 March 2022

Abstract

Background
The efficacy of ivermectin in preventing hospitalisation or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear.

Methods
We conducted a double-blind, randomised, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2–positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 μg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalisation due to Covid-19 within 28 days after randomisation or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomisation.

Results
A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events.

Conclusions
Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19.

 

NEJM article – Effect of Early Treatment with Ivermectin among Patients with Covid-19 (Open access)

 

STAT News article – Encouraged by right-wing doctor groups, desperate patients turn to ivermectin for long Covid (Open access)

 

National Library of Medicine article – Ivermectin for the Treatment of Coronavirus Disease 2019: A Systematic Review and Meta-analysis of Randomized Controlled Trials (Open access)

 

See more from MedicalBrief archives:

 

Largest yet Ivermectin trial fails to show benefit in COVID outpatients

 

Ivermectin: When desperate patients litigate for unproven treatments

 

Largest study yet: Ivermectin ‘not clinically effective’ for COVID hospitalisation

 

Withdrawn: Mexican Ivermectin paper claiming reduced COVID hospitalisation

 

Increased human use of veterinary Ivermectin reflected in Oregon Poison Centre calls

 

 

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