Grant M. Gallagher

Eli Lilly and Company has announced the start of a phase 3 trial for prevention of SARS-CoV-2 infection in residents and staff at long-term care facilities in the United States, using a monoclonal antibody candidate known as LY-CoV555. Nursing homes and other long-term care facilities have been the nexus of the coronavirus disease 2019 (COVID-19) in the United States. As 

, they continue to be a source of concern. More than 40% of deaths caused by COVID-19 in the United States are linked to long-term care facilities.

The new study, named BLAZE-2, will enroll as many as 2400 residents and staff in nursing homes. The study team will use fleet custom mobile research units to conduct the trial on-site at various facilities.

In a press release, Lilly’s chief scientific officer highlighted the motivations for the study,” said Daniel Skovronsky, MD, PhD. “COVID-19 has had a devastating impact on nursing home residents. We’re working as fast as we can to create medicines that might stop the spread of the virus to these vulnerable individuals. While it’s not easy to conduct clinical trials in this setting, we're taking on the challenge in an effort to help those who need us the most. We are grateful to the NIAID team for their exceptional partnership on this innovative trial and we are deeply appreciative of the care facilities, their staff and the many residents who will be participating in this important study.”

The study will center on facilities that have had a recently diagnosed case of COVID-19 and are at risk of an outbreak. The study endpoints will be to evaluate the efficacy and safety of LY-CoV555 for the prevention of SARS-CoV-2 infection, assessing whether a single dose of LY-CoV555 reduces the rate of SARS-CoV-2 infection through 4 weeks, and seeing if the candidate reduces complications of COVID-19 through 8 weeks.

The mobile research units will use a retrofitted RV along with a trailer truck that will carry the medical supplies necessary to create an on-site infusion clinic. Additional staff will be at the facilities to help conduct a study in this unusual environment.

LY-CoV555 is a potent, neutralizing IgG1 monoclonal antibody directed against the spike protein of SARS-CoV-2. The antibody treatment candidate was identified from a blood sample taken from one of the first US patients to recover from COVID-19.

 across the country, amid a culture where sick staff were asked to show up for work, lawmakers in several states have also potentially disincentivized improvement of infection control standards by providing legal liability protections to these facilities ahead of time.

Direction of testing, PPE, and future authorized therapeutics (such as monoclonal antibody therapies) will be vital to reversing this course.

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Despite a clear record of violations across the country, amid a culture where sick staff were asked to show up for work, lawmakers in several states have also potentially disincentivized improvement of infection control standards in long-term care facilities by providing legal liability protections ahead of time.

Lily, NIAID Launch Phase 3 Prevention Trial Centered on Nursing Homes

SARS-CoV-2 is particularly difficult for health systems to respond to; the virus presents a perfect storm of largely mild and asymptomatic transmission dynamics combined with the danger for very severe infection in a sizable minority of at-risk individuals.

Efforts to adapt to the unique virologic profile of SARS-CoV-2 have been greatly frustrated by the paucity of effective treatment and prevention options. In order to improve clinical outcomes, a variety of investigational therapies are being studied for use among patients with COVID-19. Specialty medications like 

 have emerged from relative obscurity to garner intense media interest.

According to investigators from the Rensselaer Polytechnic Institute (RPI), an existing US Food and Drug Administration (FDA) approved anticoagulant called Heparin may lower the odds of SARS-CoV-2 infection. The analysis was published in 

SARS-CoV-2 uses its surface spike protein to bind to human cells. Heparin, a blood thinner also available in non-anticoagulant formulations, binds tightly with the coronavirus’ surface spike protein. A team led by Robert Linhardt, PhD, professor of chemistry and chemical biology at RPI, predicts that this tight binding might interfere with SARS-CoV-2 infection.

The investigators speculate that the medication could be introduced into the body using a nasal spray or nebulizer in order to run interference on the coronavirus’ binding processes, lowering the odds of infection. “Decoy” strategies have been previously used against Zika virus, influenza A, and dengue.

"This approach could be used as an early intervention to reduce the infection among people who have tested positive, but aren't yet suffering symptoms. But we also see this as part of a larger antiviral strategy," Linhardt said in a press release. “Ultimately, we want a vaccine, but there are many ways to combat a virus, and as we've seen with HIV, with the right combination of therapies, we can control the disease until a vaccine is found.”

Using a surface plasmon resonance direct binding assay, the study team discovered that SARS-CoV-2’s spike protein binds more tightly to immobilized heparin (KD = 40 pM VS 73 pM) than that of SARS-CoV and MERS-CoV (500 nM and 1 nM).

While the use of heparin as a COVID-19 treatment is currently theoretical, the study also serves a catalyst to further investigate the role of glycosaminoglycans in SARS-CoV-2 pathogenesis. Furthermore, the authors expressed hope that their findings provide a basis for further study of heparin-based interventions for COVID-19 patients exhibiting thrombotic complications.

An existing US Food and Drug Administration (FDA) approved anticoagulant called Heparin may lower the odds of SARS-CoV-2 infection.

FDA-Approved Anticoagulant May Stop Coronavirus From Binding to Human Cells

The debate about hydroxychloroquine’s effectiveness against COVID-19 continues, but for how long? A study unveiled yesterday added to the preponderance of evidence showing hydroxychloroquine isn’t effective. “We launched this trial not knowing what the answer was for the question: Does hydroxychloroquine prevent COVID-19 disease after exposure?” That’s what David Boulware, MD, MPH, told 

 found that hydroxychloroquine is not likely to be an effective prophylaxis against COVID-19. “We designed a double-blind placebo-controlled trial to find out what the answer was,” Boulware continued. “While we are disappointed that this did not work, we are pleased that we found the answer.”

Why does this matter? Because Boulware’s findings came to light just a day after 

 assessment of hydroxychloroquine based on potentially faulty data from Surgisphere

Boulware’s trial consisted of non-hospitalized adults who indicated a high-risk or moderate-risk exposure to COVID-19 through the household or an occupational setting. They were provided the study drug or placebo by mail within 4 days of exposure. This leaves the prophylactic treatment to take place before symptoms typically develop.

The trial consisted of non-hospitalized adults who indicated a high-risk or moderate-risk exposure to COVID-19 through the household or an occupational setting. They were provided the study drug or placebo by mail within 4 days of exposure. This leaves the prophylactic treatment to take place before symptoms typically develop.

The randomized placebo-controlled trial launched on March 17. The trial enrolled 821 participants from across Canada and the United States. Half of the participants received 5 days of hydroxychloroquine while the other half received 5 days of a placebo.

Out of 821 participants, COVID-19 like-illness developed in 107 (13%) participants.

Notably, polymerase-chain-reaction assay confirmation was only available for about 3% of participants. Incidence of likely COVID-19, however, did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]).

Side effects were more common in patients receiving hydroxychloroquine (40.1%) than placebo (16.8%), but no serious adverse effects (including serious heart complications) were reported.

“Our team at the University of Minnesota has just concluded the first randomized, placebo-controlled, double-blind clinical trial of hydroxychloroquine as post-exposure prophylaxis in SARS-CoV-2,” the study’s second author, Matthew Pullen, MD, said. “After examining the data of our 821 participants, we did not find a significant difference in the risk of infection following exposure in those taking hydroxychloroquine and those taking placebo. We also did not find an association between hydroxychloroquine and serious adverse effects in our study population.”

 published alongside the results in the 

questioned how the results would impact clinical trials going forward.

“On June 1, 2020, ClinicalTrials.gov listed a remarkable 203 Covid-19 trials with hydroxychloroquine, 60 of which were focused on prophylaxis,” wrote Myron S. Cohen, MD, in the editorial. “An important question is to what extent the article by Boulware et al. should affect planned or ongoing hydroxychloroquine trials?”

Matthew Pullen, MD: “After examining the data of our 821 participants, we did not find a significant difference in the risk of infection following exposure in those taking hydroxychloroquine and those taking placebo."

Hydroxychloroquine Fails to Show Efficacy for COVID-19 Prophylaxis

Navigating shifting guidelines and recommendations about COVID-19 is a central challenge for clinicians on the frontlines of the COVID-19 pandemic response.

 partnered with Physicians’ Education Resource

to host a live CME-certified webinar. The program offered a diverse look at just what it’s like on the frontlines of the COVID-19 pandemic-from the ICU to the lab. 

, PhD, MPH, MA, CIC, a hospital epidemiologist and infection preventionist. Popescu opened the discussion by providing an infection preventionist’s perspective.

As the US Centers for Disease Control and Prevention and World Health Organization guidance changes, infection prevention efforts have become complicated. Each state in the United States is facing a different and unique challenge.

Learning as we go requires being communicative and empathetic, Popescu explained.

, MD, MS, FACP, assistant professor of medicine, University of Nebraska Medical Center, was the first speaker. She shared her experiences working in a critical care role.

Cawcutt also emphasized the theme of navigating ever-changing information. In particular, she highlighted debates about mechanisms of COVID-19 transmission. This focused on the complexities of aerosolization and droplet versus airborne personal protective equipment precautions.

Cawcutt added that the shortage of ventilators and sedative medications used during intubation points to concerns about early guidance which suggested ICU patients be placed on a ventilator as soon as possible. Cawcutt also suggested that noninvasive ventilation should be explored further as an option.

Following Cawcutt, there was a presentation on hydroxychloroquine by Matthew F. Pullen, MD, infectious diseases and international medicine physician at the University of Minnesota.

Pullen is part of a group conducting a randomized control trial of hydroxychloroquine as a post-exposure preventative measure for COVID-19. After the original Severe Acute Respiratory Syndrome outbreak, hydroxychloroquine was found useful against SARS-CoV-1 

There are only, so far, small studies presenting human data. Pullen emphasized the need to operate based on evidence, bringing up his ongoing trial.

The last presentation was by Mohini Lata, RN, MSN, registered nurse at Kaiser Permanente in the ICU.

Lata’s presentation emphasized that frontline health care workers are the heart of a health care organization. Patients don’t have families visiting and patients are scared and feel alone, Lata explained. Because of this, it helps to remember that a patient is someone’s loved one and treat them accordingly.

The panic on social media that treats COVID-19 as a death sentence is counterproductive to these efforts, Lata pointed out.

If a patient loses the battle in their mind, that’s half of the clinical battle lost, she said. Reassuring patients and families is vital to patients maintaining the energy needed to overcome their illness.

The presentations were followed by a Q&A from the clinician audience.

Grant M. Gallagher

Articles

Lily, NIAID Launch Phase 3 Prevention Trial Centered on Nursing Homes

FDA-Approved Anticoagulant May Stop Coronavirus From Binding to Human Cells

Hydroxychloroquine Fails to Show Efficacy for COVID-19 Prophylaxis

Webinar Recap: COVID-19 As Seen by Those on the Frontlines