Houston Methodist Magazine | Methodology | Summer Issue 2020

METHODOLOGY

The Research and Education Magazine of Houston Methodist Special COVID-19 Edition Summer 2020

Fast-tracked

by FDA

Houston Methodist is First in Nation to Treat COVID-19 with Convalescent Plasma Therapy

FEATURES

Collaborating to Answer the Call 10

04

4

Producing an N95 Alternative

14

11

Calm in the Face of the Storm

3D Alternative to Assist Inhaler 12

Fast-tracked by the FDA

PPE: Keeping It Safe

06

13

Remdesivir Proves Promising

Innovative Helmet May Prevent Intubation

8

Intensivist Begins Two Clinical Trials 15

CytoSorb Trial Aims to Remove Toxins 16

08

Prototyping Protection

12

15

A Learning Health Care System Takes on COVID-19 16

The Retrospective Research Task Force and CURATOR 17

Surveillance Study Assesses Asymptomatic Workers

NEWS HIGHLIGHTS

10

6

18

News Briefs 20

Upcoming Events

Houston Methodist Academic Institute

FROM THE PRESIDENT As we welcomed a new decade in January 2020, no one could have foreseen that in the span of a few months, the world would be transformed by the SARS-CoV-2 virus. It is our commitment to providing Houston Methodist patients exceptional care that has sustained us through these challenging times, employing our spirit of innovation and collaboration.

With the rapid onset of the coronavirus disease 2019 (COVID-19), critical care physicians Faisal Masud, MD, and Deepa Gotur, MD, took immediate action to address the urgent need for effective, evidence-based therapies. They established strategies for managing treatment and measuring outcomes for all stages of COVID-19, and diligently tested new medical devices.

In addition, Kevin Grimes, MD, and Katherine Perez, PharmD, led the efforts for clinical trials of Remdesivir for moderate and severe COVID-19 patients.

H. Dirk Sostman, MD, FACR

Houston Methodist was the first academic medical center in the nation to receive FDA approval

President, Houston Methodist Academic Institute

to transfuse donated convalescent plasma from a recovered COVID-19 patient into a critically ill

Ernest Cockrell, Jr. Presidential Distinguished Chair Houston Methodist Emeritus Professor of Radiology

patient. Infectious disease experts Eric Salazar, MD, PhD, and James Musser, MD, PhD,

Weill Cornell Medical College

of the Department of Pathology & Genomic Medicine, led the trial.

Our EnMed collaboration with Texas A&M University enabled swift and creative prototype development that addressed PPE and patient assistive device shortages.

While never losing sight of our mission to deliver unparalleled patient care, the Academic Institute remained operational throughout the high point of the pandemic. Facing a disease without a vaccine or treatment, we balanced our commitment to essential research while minimizing the risks of exposure to colleagues, students and patients. In fact, we increased productivity, and as of this writing, have not had any documented infection among Academic Institute employees.

We are stronger and wiser as we forge ahead through the recovery period.

Edward A. Jones President and CEO Houston Methodist Research Institute Senior Vice President Houston Methodist

H. Dirk Sostman, MD, FACR President, Houston Methodist Academic Institute Ernest Cockrell, Jr. Presidential Distinguished Chair Houston Methodist Emeritus Professor of Radiology Weill Cornell Medical College

Board of Directors • Houston Methodist Research Institute

Timothy B. Boone, MD, PhD Craig C. Brown and Suzanne H. Smith Centennial Chair in Medical Education Director, Education Institute Chair, Department of Urology Houston Methodist

David C. Baggett, Jr.

Martin Craighead

Gregory V. Nelson

John F. Bookout, Jr.

Martha S. DeBusk

Mary Eliza Shaper

John F. Bookout, III (Chair)

Leslie Doggett

H. Dirk Sostman, MD

Marc L. Boom, MD

Antonio M. Gotto, Jr., MD, DPhil

Douglas E. Swanson, Jr.

Timothy Boone, MD, PhD

Edward A. Jones

David M. Underwood, Jr.

Joseph R. "Rod" Canion

Evan H. Katz

Amy Waer, MD

David Chao

Edwin H. Knight

Joseph C. "Rusty" Walter, III

Stephen I. Chazen

Pastor Kenneth R. Levingston

Martha Walton

Augustine M.K. Choi, MD

Kevin J. Lilly

Judge Ewing Werlein, Jr. (Sr. Chair)

Ernest D. Cockrell, II

Steven S. Looke

John P. Cooke, MD, PhD

Vidal G. Martinez

Find videos and additional resources in our online edition: read.houstonmethodist.org/methodology.

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FEATURES

Fast-tracked by the FDA Houston Methodist is first in the U.S. to treat COVID-19 with convalescent plasma therapy

by Patti Muck

Houston Methodist received FDA approval on March 28, 2020, to become the first academic medical center in the nation to transfuse donated plasma from a recovered COVID-19 patient into a critically ill patient. The treatment was fast-tracked to the bedside over that weekend, as the death toll in the COVID-19 pandemic had just surpassed 1,000 people across the United States.

In anticipation of the FDA issuing regulatory

Plasma from an individual recovered from COVID-19 contains

guidelines, Houston Methodist physician

antibodies made by the immune system that may help to

scientists developed a protocol. Principal

kill the virus. Transfusing this antibody-rich plasma into a

investigator Eric Salazar, MD, PhD,

COVID-19 patient who is still fighting the virus may transform

assistant professor of pathology and

the antibodies into a healing, possibly life-saving therapy.

genomic medicine, Department of

Eric Salazar, MD, PhD

Pathology & Genomic Medicine, in

Known as convalescent serum therapy, the concept dates

collaboration with James M. Musser, MD,

back more than a century. Similar treatments were used

PhD, Fondren Foundation Distinguished

during the Spanish flu pandemic of 1918, a diphtheria outbreak

Presidential Endowed Chair, and Chair, Department of

in the 1920s, a flesh-eating bacteria epidemic in the 1930s,

Pathology & Genomic Medicine, designed and validated

and other outbreaks of infectious diseases. While literature

a COVID-19 molecular test and were prepared to begin

abounds on the theory that immunity can be transferred from

collecting data when COVID-19 patients started arriving.

a healthy individual to a sick individual using convalescent plasma, results have varied. In late March the Journal of the

The Houston Methodist Institutional Review Board reviewed

American Medical Association published a description of the

the treatment protocol rapidly, and the Regulatory Affairs

treatment for five patients in China, suggesting it was beneficial.

and Translational Management team, led by Christina Talley, worked expeditiously to secure FDA approval.

Under FDA guidelines, Houston Methodist’s convalescent serum therapy treatment is classified as an emergency

On Friday, March 27, the physician scientists began recruiting

investigational new drug protocol (eIND) that requires FDA

blood plasma donors from approximately 250 patients who

approval for each patient infused with donated convalescent

had tested positive for COVID-19 across the Houston

serum. Houston Methodist physician scientists will seek

Methodist system. Willing donors each gave a quart of blood

additional FDA approval for follow-up studies, possibly a

plasma in a procedure much like donating whole blood.

multicenter national trial on the effectiveness of convalescent serum therapy against the COVID-19 virus.

On the evening of Saturday, March 28, plasma from the first

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recovered COVID-19 patient to donate, who had been in

The initial trial results, published May 13, showed that 19 out

good health for more than two weeks, was transfused into

of 25 patients improved with the convalescent serum therapy,

a COVID-19 patient at Houston Methodist Hospital.

with 11 discharged from the hospital.

THANK YOU

Special Thanks to Our Supporters: Infectious Diseases Research Fund A multidisciplinary team of researchers and clinicians have worked tirelessly to find treatments for COVID-19 and help address PPE and ventilator shortages. Much of this work was made possible by generous support from Houston Methodist benefactors, who so far have invested more than $4.6 million in the Infectious Diseases Research Fund to support COVID-19 research, treatments and innovations. We offer our heartfelt thanks to the outstanding leaders who have supported our Houston Methodist frontline heroes and their innovative work.

In March 2020, Ann and John Bookout, Diane and David Modesett, and the Jerold B. Katz Foundation led an Infectious Diseases Research Fund challenge initiative to match every philanthropic dollar given, achieving their $2 million goal within two weeks.

A second challenge initiative, led by Diane and David Modesett, Freeport LNG, and the Ting Tsung and Wei Fong Chao Foundation, attained a second $2 million match goal in even less time.

In May 2020, Aramco Americas became a leading sponsor when it announced a $500,000 donation to advance Houston Methodist’s clinical research on convalescent plasma therapy, which includes a randomized controlled trial for validation and the application of innovative technology in the area of monoclonal antibodies that can be ready and available for use in therapy for COVID-19.

COVID-19 survivor Connor Scott has donated blood plasma multiple times. The antibodies his body made to fight COVID-19 may benefit Houston Methodist patients who are currently fighting the virus.

Salazar E, Perez KK, Ashraf M, Chen J, Castillo B, Christensen PC, Eubank T, Bernard DW, Eagar T, Long SW, Subedi S, Olsen RJ, Leveque C, Schwartz MR, Dey M, Chavez-East C, Rogers J, Shehabeldin A, Joseph D, Williams G, Thomas K, Masud F, Talley C, Dlouhy KG, Lopez B, Hampton C, Lavinder J, Gollihar JD, Maranhao AC, Ippolito GC, Saavedra MO, Cantu CC, Yerramilli P, Pruitt L and Musser JM. Treatment of COVID-19 patients with convalescent plasma in Houston, Texas. medRxiv. May 13, 2020. Preprint DOI: 10.1101/2020.05.08.20095471 This study was supported by funding from the National Institutes of Health (grants AI146771-01 and AI139369-01), the Fondren Foundation, the National Institute of Allergy and Infectious Diseases (Contract Number 75N93019C00050), the Army Research Office (Cooperative Agreement W911NF-12-1-0390), Houston Methodist Hospital and Houston Methodist Research Institute.

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FEATURES

Remdesivir Proves Promising

Houston’s first site for clinical trials sees patients’ rapid response to antiviral drug

by Lisa Merkl

COVID-19 patients in clinical trials at Houston Methodist Hospital have responded quickly to the antiviral drug Remdesivir. Early trial results suggest a faster rate of recovery with Remdesivir.

One of the most challenging aspects of COVID-19 is that it makes copies of itself after finding its way into the body.

It then begins to take over, sending a patient into respiratory distress and ultimately in need of intubation if not stopped early enough. Remdesivir has demonstrated a potent ability to inhibit this viral replication in human cells and is being Kevin Grimes, MD

Katherine Perez, PharmD

administered in clinical trials and compassionate use cases of patients with the SARS-CoV-2 virus that causes COVID-19. Houston Methodist was the first clinical trial site in Houston to test this investigational drug.

Working with pharmaceutical company Gilead Sciences, Remdesivir’s manufacturer and sponsor of the studies, Houston Methodist Hospital was the fifth site in the U.S. to join the clinical trials. It began enrolling and treating patients in mid-March. Initially, five patients received early access to Remdesivir on a compassionate use basis.

By the end of May, 98 patients had been enrolled in the clinical trial.

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The two Phase 3 clinical trials at Houston Methodist are

into overdrive and doing more harm than good by destroying

randomized, open-label, multicenter studies to evaluate the

cells in the lungs.

safety and efficacy of Remdesivir. One study tests either a 5-day or 10-day Remdesivir treatment for patients with

A broad-spectrum antiviral drug, Remdesivir was originally

moderate COVID-19. The second study evaluates a 10-day

developed to treat Ebola more than a decade ago. Known to

course of Remdesivir for patients with severe COVID-19,

be generally safe in humans and backed by a large body of

including those on mechanical ventilation. Infectious diseases

preclinical research, a number of studies have shown it to be

experts who are leading efforts for both clinical trials at

successful in stopping SARS and MERS, the viral cousins

Houston Methodist have been encouraged by the results.

of the new coronavirus strain.

"Much of what we are learning about COVID-19 management

On April 29, 2020, the NIH reported results from the multi-site

is centered around preventing quick deterioration. Timing

clinical trial. It showed that patients with advanced COVID-19

is everything," said Katherine K. Perez, PharmD, BCPS-AQ ID,

and lung involvement who received Remdesivir recovered

assistant professor of allied health sciences, Departments of

faster than similar patients who received placebo. According

Pharmacy and Pathology & Genomic Medicine. "I can’t say

to preliminary data from the randomized, controlled trial involving

for certain they would have been intubated otherwise, but

1,063 patients in 68 sites, patients who received Remdesivir

it’s encouraging."

had a 31% faster time to recovery. (The median time to recovery was 11 days for patients treated with Remdesivir compared

Kevin Grimes, MD, MPH, agrees that acting quickly is critical.

with 15 days for those who received placebo.) Results also

The crucial turning point that makes COVID-19 become deadly

suggested a survival benefit, with an 8% mortality rate for the

is due to an extreme inflammatory response in the lungs. The

group receiving Remdesivir versus 11.6% for the placebo group.

patient's own immune system becomes hyperactive, going

“

If given early enough, we hope that Remdesivir interferes with the virus and blocks its ability to replicate in patients’ cells. The goal is that it staves off the deadly inflammatory cascade that leads to respiratory failure and the need to be intubated and put on a ventilator.

”

– Kevin

A. Grimes, MD, MPH Assistant Professor of Clinical Medicine Department of Medicine Houston Methodist

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FEATURES

Prototyping Protection Doctors develop an aerosol container to minimize risk during intubation

by LaVonne Carlson

When critically ill COVID-19 patients develop respiratory failure, they often need ventilator support, which requires intubation. The process of inserting an endotracheal tube when placing a patient on a ventilator causes a high rate of contaminated air to be expelled and form aerosols—creating a high-risk situation for health care workers.

Anticipating an increased occurrence for intubation, two Houston Methodist doctors began seeking safer delivery options for their fellow health care workers. Steven H. Hsu, MD, assistant professor of clinical medicine, Department of Medicine, and Faisal N. Masud, MD, medical director of critical care, Houston Methodist Hospital, and professor of clinical anesthesiology, Departments of Anesthesiology & Critical Care and Cardiovascular Sciences, DeBakey Heart & Vascular Center, developed a way to bring added safety to their co-workers. They designed the Houston Methodist Aerosol Container, or HMAC, a clear plastic box-like protective barrier enclosure that shields clinicians from expelled air when intubating a patient.

"The original design came from Dr. Lai Hsien Yung, an anesthesiologist in Christian Mennonite Hospital, Hualien, Taiwan, where I was born, and his family is living in Houston," said Hsu. "I found his design and thought 'This is a great idea to apply during this time of crisis.' “ Hsu and his colleagues at Houston Methodist made several modifications to the original enclosure to make it more clinician friendly. Along with Firas Zabaneh, director of system infection prevention and control, and Trevor Burt, vice president of education administration, they arranged to add a disposable surgical drape to cover the HMAC opening nearest to the patient’s torso, keeping the patient’s head and neck under the enclosure, to further prevent the aerosol from spreading. Another iteration upgraded the holes to be slightly larger for the clinician’s arms. And the final version includes a slanted top panel to enable easier view and control for the clinician. While enhancing the HMAC's utility and safety, these changes also allow the HMAC barrier to be used for bronchoscopy or even nasopharyngeal sampling.

The first prototype for testing was delivered on March 26. That same day, Randolph Steadman, MD, Chair, Department of Anesthesiology & Critical Care, DeBakey Heart & Vascular Center, coordinated testing the first prototype in the Houston Methodist ICU. An additional prototype was deployed to the Emergency Department for testing and intubation purposes. The HMAC continues to evolve during the testing phase. A new prototype, still being tested in the Houston Methodist Institute for Technology, Innovation & Education (MITIESM), adds a vacuum component to remove undesirable aerosol. Using smoke to test air flow in the model, the team confirmed that the vacuum prototype left no particulate matter on the hands while intubating the test dummy. This design is not yet approved for use in clinical care.

Requests for prototype improvements were met with flexibility by the Houston Methodist Machine Shop. The in-house machine shop, under the direction of lead machinist Juan Fernandez, produced 10 prototype boxes over seven days. Once the final version was selected, the machine shop delivered a total of 50 more HMACs across Houston Methodist’s hospitals within three weeks.

From Taiwan's design to the evolution of HMAC, the aerosol box concept provides frontline health care workers a protective, reusable and F aisal Masud, MD, (left) and Steven H. Hsu, MD, tested and adapted the HMAC, which the FDA approved for emergency use on May 1, 2020.

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low-cost solution to minimize exposure and risks during the pandemic.

Each aerosol containment device can be produced at a minimal cost (approximately $67) using acrylic or transparent polycarbonate sheet. Following each intubation, the HMAC can be reused after a thorough cleaning with 70% alcohol or bleach.

Download designs and a user guide for the HMAC at read.houstonmethodist.org/methodology.

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FEATURES

Collaborating to Answer the Call EnMed taps its engineering prowess to produce prototypes to avert potential shortages

by Laura Niles

As leaders and health care workers across the nation put out a call for PPE and other devices, Houston Methodist began working with our EnMed partners to devise alternatives. Driven by the expectation that a PPE supply chain crisis could occur and commercial versions would not be available, they developed several prototypes. Though in development, they are not FDA approved, and therefore not yet available for clinical use.

Producing an N95 Alternative To address the N95 mask shortage and protect Houston Methodist health care workers, faculty from EnMed worked with Houston Methodist clinicians to design a safe and efficient alternative to conventional N95 masks in mid-March. EnMed, the nation’s first and only program designed to offer both an MD and a master's in engineering in four years, is a collaborative endeavor between Texas A&M’s College of Engineering, College of Medicine and Houston Methodist.

Their goal was to create a 3D-printed alternative with N95 functionality, using commercial grade material produced from a type of plastic that would allow autoclaving (sterilization) for reuse. Air filtration using a smaller insert also offered more efficient use of standard material.

EnMed faculty from the College of Engineering submitted designs for five different masks. After input from their clinical colleagues at Houston Methodist, they moved forward with prototyping for the most promising mask. The preliminary prototype was demoed on March 25, then underwent a second round of modifications to improve fit, manufacturability and reusability.

“We worked diligently to optimize the design in anticipation of printing prototypes quickly,” said Roderic I. Pettigrew, MD, PhD, CEO of Engineering Health (EnHealth), executive dean for Engineering Medicine at Texas A&M, and adjunct professor of nanomedicine, Houston Methodist Center for Cardiovascular Regeneration. “Then we began the important next step of testing for clinical level functionality and assessing sterilization processes for multiple usage.”

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3D Alternative to Assist Inhaler Many COVID-19 patients require bronchodilator drugs to help ease breathing and increase airflow to the lungs. But bronchodilators often are administered by nebulizer, which converts the liquid medicine into a mist, potentially spreading the virus. The preferred option, inhalers, are in short supply and can be hard for patients to use.

The best option is a spacer, essentially a diffuser attached to an inhaler. These also were facing a critical shortage— until Houston Methodist’s EnMed partners at Texas A&M University helped develop a 3D printed spacer.

The engineering team produced three different spacer options, including one that used a common plastic bottle.

Based on feedback from Houston Methodist clinicians on the frontlines in the hospital, the most viable 3D printable option was chosen.

The spacer is cylindrical with a tapered slit that serves as a mouthpiece at one end; the other end attaches to the inhaler.

The bronchodilator is contained as it disperses into the chamber where the patient inhales through the mouthpiece.

Since patients in respiratory distress may have difficulty operating an inhaler, the spacer provides invaluable assistance.

“This device helps to assure that the patient is receiving the intended dose of medication, which is a best practice in the hospital setting,” said Daniel Metzen, PharmD, system director of pharmacy services at Houston Methodist.

In early April, Houston Methodist received 50 of the devices from Texas A&M, with an additional 150 ordered. The crisis has not grown grave enough to create a complete shortage of inhalers, so these 3D alternatives were not called to action.

But the EnMed and hospital teams continue to refine them, for the possibility of future use.

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FEATURES

PPE: Keeping It Safe Facing a need for PPE and an uncertain supply, the System Quality & Patient Safety team got creative

by LaVonne Carlson

With the increasing shortage of personal protective equipment for health care workers, Houston Methodist’s System Quality & Patient Safety team went to work exploring options for sterilizing and reusing PPE. The team considered three sterilization options: autoclave, UV light, and hydrogen peroxide vapor.

Protocol for Autoclaving N95s, the highly protective masks worn by health care workers to protect them from COVID-19 droplets, were of particular concern for the System Quality & Patient Safety team when developing a new protocol to enable reuse of the N95 respirator masks. They experimented with various types of masks and different sterilization techniques, testing afterward for fit and cleanliness, and found

Circulating UV Light

the best results using an autoclave device for immediate-use

Houston Methodist also led a sterilization study that explored

steam sterilization.

the use of ultraviolet (UV) light for sterilizing N95 masks. It used UV light sterilization robots, automated to move through ICUs, to

Under the direction of Firas Zabaneh, MT, CIC, CIE, MBA, director

expose everything to sterilizing UV light when not in use. EnMed

of system infection prevention and control at Houston Methodist,

contributed its design expertise by devising a rack where the masks

the team developed an autoclaving process that allows reuse of

could hang in the middle of the room (see below). The robots then

the masks without destroying their structural integrity, which is what

circulated to expose all areas and parts of the masks to sterilize

makes them effective at protecting their wearer. Their new protocol,

them with UV light. While initially experimenting with 30-minute

published online in Infection Control & Hospital Epidemiology by

intervals of exposure, a formal protocol is under development.

Cambridge University Press on April 17, 2020, is entitled “Immediateuse steam sterilization sterilizes N95 masks without mask damage.”

STERIS for Hydrogen Peroxide Vapor Another option for sterilization of surgical gowns is vaporized hydrogen peroxide. But procuring the equipment—a STERIS sterilization machine—can be difficult. When the STERIS method was approved by the FDA and recommended by the CDC, the Academic Institute was fortunate to have a STERIS machine available. The Comparative Medicine team donated their backup STERIS sterilization machine to System Infection Prevention & Control for sterilization of surgical gowns. The CM team also programmed the machine, set it up with reagents, and trained Houston Methodist clinical staff in its proper use.

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Innovative Helmet May Prevent Intubation Only the most severe COVID-19 patients require a stay in the ICU, often when they display respiratory symptoms. Their care may begin with nasal cannula oxygen, but soon progresses to intubation, when a tube is inserted through the nose or mouth to help patients breathe— and requiring a ventilator. Performing intubation puts health care providers at risk. And some patients may require reintubation.

With these concerns in mind, Faisal N. Masud, MD, medical director of critical care, Houston Methodist Hospital, and professor of clinical anesthesiology, Departments of Anesthesiology & Critical Care and Cardiovascular Sciences, DeBakey Heart & Vascular Center, began seeking clinical alternatives Faisal N. Masud, MD

to ventilators for COVID-19 patients. One innovation

was brought to his attention by Houston Methodist Chief Academic Officer, Dirk Sostman, MD, who learned about the potential device on March 31 and immediately acquired three.

Called simply “the helmet,” the device is made of lightweight, transparent plastic that resembles a spacesuit hood. Produced by Sea-Long Medical Systems in Waxahachie, Texas, it is the only one in the U.S. that meets FDA requirements and has been validated in a clinical study for acute respiratory syndrome.

Houston Methodist’s respiratory therapy team began testing the three helmets as soon as they arrived. They confirmed the helmets met specific requirements: a secure seal, an easily attached viral filter and the ability to provide 60 liters of oxygenation. In addition to being more comfortable for patients, the helmet also allows easy access for giving inhaled medicines.

Led by Masud, the health care staff began using the helmets for ICU patients with low oxygenation levels due to COVID-19. They hope to see rapid improvement and, ideally, avoid intubation. The helmet also is used for a special group of COVID-19 patients who are taken off ventilators—during the critical first 48 hours when aiming to avoid reintubation.

Jason Bordelon, director of respiratory care services, tests the fit and seal of the Sea-Long helmet.

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FEATURES

Calm in the Face of the Storm

by LaVonne Carlson

With the rapid onset of COVID-19, only limited national and international guidelines existed for approaches to treatment. Responding to the urgent need for effective, evidence-based therapies, Houston Methodist's critical care physicians immediately began observing and tracking protocolized treatments.

Houston Methodist clinicians chart a path for best practice protocols, innovative treatments and evidence-based outcomes to confront the cytokine storm

“

Leading the effort were Faisal N. Masud, MD, medical director of critical care, Houston Methodist Hospital, and professor of clinical anesthesiology, Departments of Anesthesiology & Critical Care and Cardiovascular Sciences, DeBakey Heart & Vascular Center, and Deepa B. Gotur, MD, intensivist and associate professor of clinical medicine, Department of Medicine.

They took a special interest in best practices for managing acute respiratory distress syndrome (ARDS), characterized by rapid onset of inflammation and fluid accumulation in the lungs. ARDS initiates respiratory failure that is a leading cause of death in COVID-19 patients.

Many of the most severe COVID-19 cases occur in patients with a heightened immune response: Their overly active immune system produces an excess of cytokines to fight off the viral infection. Called a “cytokine storm,” it attacks the patient’s own vital organs and the resulting complications are severe.

It puts patients at high risk of worsening ARDS, as well as renal and cardiac dysfunction, which require an ICU level of care.

Many people are already experiencing a cytokine storm by the time they arrive at the hospital. We quickly realized we needed to stop this process—as early as possible—to prevent patients from being intubated or going on life support.

”

– Deepa

Bangalore Gotur, MD Associate Professor of Clinical Medicine Department of Medicine Houston Methodist

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Intensivist Begins Two Clinical Trials Deepa Bangalore Gotur, MD, is looking at existing drugs used for various autoimmune diseases as a possibility for treating COVID-19. After studying the options, Gotur proposed clinical trials to offer treatment options for patients with ARDS brought on by COVID-19. On May 6, she was approved by Houston Methodist’s Institutional Review Board to move forward with two clinical trials.

Gotur is now enrolling patients in a clinical trial of Tocilizumab, a drug designed as an active agent against interleukin 6, the protein associated with the inflammatory cascade linked to the body’s overactive immune Deepa Bangalore Gotur, MD

response. The trial will measure levels of cytokines both before and after the medication is administered to assess whether it has blocked interleukin 6. The goal is to determine the right amount of dosing for COVID-19 patients, including those with cancer.

Gotur’s second clinical trial is designed to study a cytokine pathway with a different target in the chain of cytokine responses as part of a cytokine storm. It will explore a different immune blocking medication known as I-Mab, which was developed by Biopharma. This medication will block GM-CSF. Designed for a severely ill patient population, the randomized, placebo controlled clinical trial will soon be initiated.

CytoSorb Trial Aims to Remove Toxins In approximately 5% of confirmed cases, COVID-19 causes severe complications that require an ICU level of care.

ICU care often includes advanced life-support interventions such as extracorporeal membrane oxygenation (ECMO) to aid heart and lung functions and continuous renal replacement therapy (CRRT) to support kidney function.

Steven H. Hsu, MD, a medical intensive care unit (MICU) intensivist and assistant professor of clinical medicine, Department of Medicine, is exploring another option for trying to control the cytokine storm. Called CytoSorb, it is Steven H. Hsu, MD

a device that uses a dialysis machine to clean the blood of toxic cytokines created by the body’s immune system.

Though traditionally used for patients with sepsis, it now may be applied to help patients with COVID-19.

Hsu has developed a COVID-19 study based on CytoSorb, which uses a specialized cartridge designed to clean and actively clear the cytokines from the blood of severely infected patients. Recently, the device was approved by the FDA for emergency use. CytoSorb may serve as a crucial adjunct to COVID-19 patients with worsening organ dysfunction due to cytokine storm by halting, reversing and possibly improving organ dysfunction and outcomes.

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FEATURES

A Learning Health Care System Takes on COVID-19 The Center for Outcomes Research develops an informatics driven learning health care system

by LaVonne Carlson

The sudden arrival of SARS-CoV-2 challenged Houston Methodist to make real time data about patient diagnosis, treatment, enrollment in clinical trials, and outcomes available for research. The Center for Outcomes Research met the challenge, paving the way for evidence-based conclusions about the best ways to test for, control the spread of, and treat COVID-19.

The Retrospective Research Task Force and CURATOR Receiving an impressive—almost overwhelming—number of COVID-19 research submissions, Houston Methodist established the Retrospective Research Task Force (RRTF), led by Bita A. Kash, PhD, MBA, FACHE, Occidental Petroleum Centennial Chair in Quality and Outcomes Research and director of the Center for Outcomes Research. The RRTF began meeting weekly to review study protocols, focus institutional resources on high priority projects and advise on next steps.

Farhaan S. Vahidy, PhD

To track projects and share data resulting from completed projects, a digital repository was developed: COVID-19 Surveillance and Outcomes Registry, or CURATOR. The project was led by Farhaan S. Vahidy, PhD, MBBS, MPH.

After considering the unique needs of Houston Methodist and the Houston community, Vahidy observed that clinical and administrative systems, such as EPIC, were not conducive to fulfilling COVID-19 research needs. To address this, he led the CURATOR team to develop a new resource that reduces the lag time in generating evidence. CURATOR’s design is scalable and replicable to other clinical domains.

Creating CURATOR took a truly collaborative effort. Staff from the Center for Outcomes Research, including Stephen L. Jones, MD, MSHI, John F., Jr. and Carolyn Bookout Distinguished Professor in Surgical Quality and Outcomes Science, Department of Surgery, and associate research professor of outcomes research, Charlie Nicholas, senior application analyst, Osman Khan, data analyst, and Khurram Nasir, MD, MPH, co-director, Center for Outcomes Research, Department of Cardiology and DeBakey Heart & Vascular Center, worked closely with Billy Askary, director, System Analytics, and Jonathan Raines, senior applications analyst, Research Technology.

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Surveillance Study Assesses Asymptomatic Workers Houston Methodist is among the first health care systems in the U.S. to complete a large-scale employee surveillance program for asymptomatic SARS-CoV-2 infection. Led by Vahidy and Dirk Sostman, MD, Houston Methodist chief academic officer, the study has tested almost 3,000 volunteers to date. Leaders across the Houston Methodist system cooperated in the initiative, which included our academic medical center and six satellite hospitals.

The goal was to assess the prevalence of SARS-CoV-2 infection among asymptomatic COVID-19 facing and nonH. Dirk Sostman, MD, FACR

COVID-19 facing health care workers, as well as non-clinical staff and community residents. A total of 2,872 asymptomatic participants were administered a reverse transcriptase polymerized chain reaction (RT-PCR) test for SARS-CoV-2.

Results of the study were published on medRxiv on May 21, indicating that those with COVID-19 patient exposure had a higher rate of SARS-CoV-2 positivity than those not routinely exposed or engaged in COVID-19 patient care. Among COVID-19 facing health care workers, 5.4% were positive. Among non-COVID-19 facing health care workers, 0.6% were positive. None of the non-clinical health care workers or community volunteers tested positive. This suggests that general environmental exposure within hospitals is not a significant source of asymptomatic SARS-CoV-2 infection across Houston Methodist.

The ability to rapidly set up the study, obtain and analyze data, and turn it into a published report was one offshoot of the Center for Outcomes Research's streamlined process. And planning ahead to allow the possibility of additional studies, the surveillance trial included taking blood samples to compare results between RT-PCR and blood tests.

Vahidy F, Sostman HD, Bernard D, Boom ML, Drews AL, Christensen PA, Finkelstein J, Kash BA, Phillips RA, Schwartz RL. Prevalence of SARS-CoV-2 infection among asymptomatic healthcare workers in greater Houston: a cross-sectional analysis of surveillance data from a large healthcare system. medRxiv 2020 May 21. DOI: 10.1101/2020.05.21.20107581 [Note: This publication has not yet been evaluated and so should not be used to guide clinical practice.]

“

In the face of the COVID-19 pandemic, we have found a great opportunity to propel Houston Methodist towards a learning health care system. This system enables rapid access to validated data that are iteratively incorporated into clinical and business operational decision making and are simultaneously and continually evaluated for validity.

”

– Farhaan S. Vahidy, PhD, MBBS, MPH Coneway Family Centennial Endowed Directorship in Quality and Outcomes Associate Director Center for Outcomes Research Houston Methodist

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NEWS BRIEFS 1

Provider Burnout During Pandemic “Provider Burnout and Fatigue during the COVID-19 Pandemic: Lessons Learned from a High-Volume Intensive Care Unit” is the title of a timely paper published in Anesthesia & Analgesia on April 9, 2020. Lead author Farzan Sasangohar, PhD, assistant professor of outcomes research, Department of Surgery, and Bita A. Kash, PhD, MBA, FACHE, Occidental Petroleum Centennial Chair in Quality and Outcomes Research, director of the Center for Outcomes Research, and co-director of the Center for Health & Nature, collaborated with the ICU research team, led by Faisal Masud, MD. The paper has garnered attention on social media and press, including Science Daily, MedicalXpress and Psych Central.

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SARS-CoV-2 Genome Sequencing Studies James M. Musser, MD, PhD, Fondren Foundation Distinguished Presidential Endowed Chair, and Chair, Department of Pathology & Genomic Medicine, and S. Wesley Long, MD, PhD, assistant professor of pathology and genomic medicine, unveiled the first of several SARS-CoV-2 gene sequencing studies. Studying the virus since the earliest days of the pandemic entering Houston has allowed the researchers to look for viral mutations that might impact antiviral resistance, vaccine development and other novel therapies. “Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas,” was published May 3, 2020, in bioRxiv. DOI: 10.1101/2020.05.01.072652

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Plasma Donations Sought Houston Methodist is seeking patients who have recovered from proven COVID-19 infection to donate their blood plasma. Plasma from a healthy, recovered patient contains antibodies that kill the virus and have the potential to heal and potentially save the life of a hospitalized COVID-19 patient. Eligible donors include both Houston Methodist patients and patients treated at other locations with proven COVID-19 infection. Interested donors, please call 346.238.4360.

Find details at houstonmethodist.org/research/covid19/plasma-therapy.

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Reliant Donation for COVID-19 Innovation In late May, Reliant made a $130,000 donation to Houston Methodist to create the “Reliant Innovation Fund,” enabling critical care innovations that drive the future of health care in a post COVID-19 world. The fund designates $100,000 to empower EnMed students to create groundbreaking solutions for critically ill patients. The remaining $30,000 is intended to support and expand the mobile app, CareSense. The digital platform allows continued care for COVID-19 patients after they leave the hospital.

Reliant’s donation is part of the company’s continued COVID-19 support across Texas and parent company, NRG Energy, Inc.’s, $2 million donation to pandemic relief efforts.

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A Tribute to Our Nurses & Health Care Team Nurses Week began on May 6 with a special tribute by the Blue Angels, the U.S. Navy's flight demonstration squadron.

They flew a special loop above the Texas Medical Center as an added acknowledgement of the value of health care workers and first responders. Appropriately, their show also coincided closely with National Hospital Week, which began May 10.

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Pathology Labs Find Innovative Solutions The pathology labs worked around the clock to get SARS-CoV-2 tests turned around in record speed. The teams constantly innovated better ways to test and solve high-level problems as they arose. The Department of Pathology & Genomic Medicine leaders include Randall J. Olsen, MD, PhD, professor of clinical pathology and genomic medicine, Center for Molecular & Translational Human Infectious Diseases Research, S. Wesley Long, MD, PhD, assistant professor of pathology and genomic medicine, and Jessica S. Thomas, MD, PhD, MPH, assistant professor of clinical pathology and genomic medicine.

Additionally, the directors of the pathology labs at the community hospitals moved mountains to implement testing and plasma trials at each location. Our pathology leaders and their teams went above and beyond during the coronavirus crisis.

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Concept to Commercialization Series A 12-week series, focused on how to take an idea to the market, is helping faculty researchers lay the foundation for translating key laboratory discoveries to clinical uses that improve patient lives. Those who seek a practical and efficient process for making that happen will benefit from this course, taught by experts in related specialties. Those who attend consistently will have a written project proposal ready for a panel review on the final day. Held every other Wednesday, June 17 – Nov. 18, attendance is free with registration at events.houstonmethodist.org/commercialization-series.

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Methodology Launches Digital Edition Methodology, the source for research and education news at Houston Methodist, is now a digital-first publication. Previously produced in print only, our award-winning magazine highlights the groundbreaking research and innovative tools developed by our scientists and clinicians. The digital-first approach offers a responsive design that allows individuals to share the articles directly to their social media accounts and also includes interactive features such as video and motion graphics. Visit the site at read.houstonmethodist.org/methodology, and sign up for a monthly enewsletter.

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UPCOMING EVENTS

UPCOMING EVENTS Activities are tentative, subject to cancellation or change in date, location and format.

Visit attend.houstonmethodist.org for updates.

June 17 - November 18, 2020

October 26-28, 2020

Concept to Commercialization: How to Take an Idea to the Market*

August 7, 2020

Second Annual ISEVS Symposium*

November 7, 2020 6th Annual Adult Congenital Heart Symposium*

8 Annual Houston Methodist Cancer Symposium* th

November 16-20, 2020

August 7-9, 2020 12th Annual Cardiovascular Fellows’ Boot Camp: Laying the Foundation

September 10, 2020

2020 Sepsis Symposium*

September 11-12, 2020 13th Annual Advances in Neurology*

September 19, 2020

CVD Prevention Symposium*

October 10, 2020

December 7, 2020

Pumps & Pipes 14: 20|20 Vision

December 19, 2020 9th Annual Symposium on Enhancing Geriatric Understanding and Education (SEGUE): Geriatric Ophthalmology for Non-Geriatricians*

2020 Emerging Topics in Liver Disease Conference*

October 2-3, 2020

Houston Methodist J.C. Walter Jr. Transplant Center Educational Series*

Thyroid Eye Disease Symposium*

METHODOLOGY The Research and Education Magazine of Houston Methodist

Editor-in-Chief Rebecca M. Hall, PhD Managing Editor LaVonne Carlson Design & Creative Lead Doris T. Huang Photographers Khalil Abusharekh Trevor Burt, EdD Fernando Castaldi George Kovacik Contributing Writers LaVonne Carlson Lisa Merkl Patti Muck Laura Niles

Public Relations Contact Gale Smith 832.667.5843 gsmith@houstonmethodist.org Find more online: read.houstonmethodist.org/methodology Office of Communications and External Relations Houston Methodist Academic Institute Houston Methodist news@houstonmethodist.org HMAINEWS-015 | 06.2020 | 1300

* These activities have been approved for AMA PRA Category 1 CreditTM. Houston Methodist is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.