Joint replacement surgery helps millions of people regain mobility and relieve pain every year. Like any surgery, however, there are risks—including prosthetic joint infection, which continues to be a challenge due to its diagnostic complexity.  “When a prosthetic joint infection is present, it can disrupt the recovery process and potentially risk the long-term benefits of joint replacement,” said Andy O. Miller, MD, Chief of Infectious Diseases at HSS. “Detecting and identifying prosthetic joint infection accurately and early is critical to timely intervention because it enables clinicians to potentially utilize less disruptive treatments. This can make all the difference in a patient's outcomes and restoration of their quality of life.”

“Prosthetic joint infections can result in significant patient health and economic burdens and can be challenging to diagnose,” said Niamh O’Hara, PhD, CEO and Co-Founder of Biotia. “Through this collaboration with HSS, we hope to advance the field of musculoskeletal disease diagnostics by bringing clinical metagenomics, a novel technology for diagnosing infections, to the frontlines of patient care.” 

Christopher E. Mason, PhD, Co-Founder of Biotia, emphasized the rigorous scientific foundation underpinning the collaboration, which “builds upon years of research in the field of prosthetic joint infection and developments in the field of clinical metagenomics. We’re proud to collaborate with HSS and to apply AI and advanced NGS methods with the goal of improving diagnostic capabilities, reducing the time to diagnosis, helping guide therapy, and improving patient care for those affected by complex infections.” 

Rooted in a shared commitment to improving patient outcomes, this collaboration unites Biotia’s cutting-edge sequencing platform and proprietary bioinformatics software with the clinical and surgical expertise of HSS physician-scientists from Adult Reconstruction and Joint Replacement, Infectious Disease, Pathology and Research.

“At HSS, we are constantly seeking innovative ways to improve care and enhance the lives of patients worldwide,” said Vijay Nair, Managing Director, Innovation at HSS. “Through this collaboration, we’re uniting a cross-disciplinary team across academia and industry to look at a complex clinical challenge from multiple angles. By combining our deep clinical expertise with Biotia’s diagnostic platform, our hope is to address a pressing need in the diagnosis and management of prosthetic joint infection so patients can get back to doing what they love following joint replacement surgery.” 

About Biotia 
Biotia is a health-tech company located in New York, NY, that leverages sequencing-based technology and proprietary AI-powered software to rapidly and accurately identify microorganisms and antimicrobial resistance. Biotia was spun out of Jacobs Technion-Cornell Institute at Cornell Tech and has a New York State CLIA lab for infectious disease diagnostics testing affiliated with SUNY Downstate Health Sciences University. 

To learn more about Biotia, visit www.biotia.io, or connect on X, Facebook, and LinkedIn. 

Biotia Media Contact: +1 (888) 685-2885, media@biotia.io 

HSS is the world’s largest academic medical center specialized in musculoskeletal health, spanning orthopedics, rheumatology and related disciplines. The HSS Research Institute maintains 20 laboratories dedicated to solving debilitating orthopedic and rheumatic conditions such as arthritis, bone and soft tissue injuries, autoimmune diseases, and musculoskeletal pain and deformities. There, more than 300 dedicated personnel focus on tissue repair, improving surgical outcomes, autoimmunity and inflammation, genomics, new treatments, and precision medicine.

“HSS has a long history of contributing to the collective base of clinical and basic science knowledge and finding healthcare solutions for complex conditions,” said Louis A. Shapiro, President and CEO, HSS. “We’re proud that through the joint efforts of our institution and philanthropic support, we will have the ability to make a strong impact on this growing and vital area of research.”

“As experts in inflammatory disorders and in the development of interventions for overactive immune responses, the clinicians and researchers at HSS are well-positioned to investigate many of the adverse effects of COVID-19,” says Lionel B. Ivashkiv, MD, Chief Scientific Officer at the HSS Research Institute. “This includes studying the causes of these adverse effects as well as how to prevent and treat them.”What follows are descriptions of the first group of funded projects in basic/translational research:

Activation of pDCs by SARS-CoV-2 and Its Impact on Macrophage Response

Principal Investigator: Franck Barrat, PhD

Co-Investigator: Marie-Dominique Ah Kioon, PhD

This project will study cell types that are responsible for cytokine storm syndrome — the hyperactive immune response seen in people with COVID-19 — by looking at how certain immune cells are activated by SARS-CoV-2. Research in mice infected with SARS-CoV, a coronavirus similar to the one that causes COVID-19, has suggested that plasmacytoid dendritic cell precursors (pDCs) are key to the immune response to infection. These pDCs activate macrophages, which in turn secrete cytokines. In the SARS-CoV research, depletion of pDCs appeared to protect the mice from lethal lung injury. Using blood samples from donors, the investigators will study the pathway by which pDCs activate macrophages and look at ways to therapeutically block that process.

Inhibiting RNA Polymerase II Transcription Complexes in Macrophages to Target COVID-19–Associated Cytokine Storm

Principal Investigator: Inez Rogatsky, PhD

Co-Investigators: Steven Josefowicz, PhD, and Robert P. Fisher, MD, PhD

This pilot project will dissect the role of macrophages in SARS-CoV-2-induced acute respiratory distress syndrome (ARDS), the main driver of COVID-19-associated mortality. We will test small-molecule inhibitors of RNA Polymerase II (Pol II) transcription complexes for their ability to modulate type I interferon and inflammatory pathways in monocytes/macrophages. This research will be done using cultured macrophages as well as donor blood and blood from COVID-19 patients.

Mechanisms of Cytokine Storm in Patients with COVID-19

Principal Investigator: Mary K. Crow, MD

Co-Investigators: Mikhail Olferiev, MD, and Lionel B. Ivashkiv, MD

The objectives of this study are to describe the process of the cytokine storm in people with COVID-19 and to identify biologic predictors of a favorable outcome in patients with severe cases of the disease. The project aims to characterize immune cell populations seen in COVID-19 patients who experience cytokine storm and compare them to those patients who do not, to compare the immune response before and after patients are given the anti-inflammatory drug anakinra, and to identify measures that suggest patients are more likely to decline and eventually require mechanical ventilation. The research will employ blood samples from HSS patients who are being treated for COVID-19 at New York–Presbyterian Hospital and who meet certain other qualifications.

What follows are descriptions of the first group of funded projects in the areas of clinical and health outcomes research:

Response to and Recovery from TKA in Patients with Antibodies to SARS-CoV-2

Principal Investigator: Miguel Otero, PhD

Co-Investigators: Meghan Kirksey, MD, PhD, and Peter K. Sculco, MD

It is unknown if people who have been exposed to COVID-19 may be at higher risk of experiencing an abnormal immune response following surgery, resulting in poor outcomes. This study will evaluate the response to and recovery from total knee arthroplasty (TKA) in people who have antibodies to COVID-19 — a marker of exposure. This study will include both patients who have COVID-19 antibodies and those who don’t, to act as controls. Patients will be followed for six weeks after surgery and evaluated for the presence of certain immune markers in the blood, as well as symptoms of inflammation including pain and stiffness in the joint.

SARS-CoV-2 Exposure and the Role of Vitamin D Among Hospital Employees

Principal Investigator: Emily M. Stein, MD, MS

Co-Investigators: Theresa T. Lu, MD, PhD; Andy O. Miller, MD; Jeri Nieves, PhD; and Alana Serota, MD

It is unknown if people with vitamin D deficiency may be more likely to become infected with COVID-19. This study will investigate vitamin D status and associated immune markers as risk factors for COVID-19 infection in a cohort of healthcare workers. Healthcare workers are at higher risk of contracting COVID-19 than the general population, making them a good group to study. Vitamin D is critical for immune function and is known to be protective against respiratory-tract infection and tuberculosis. This prospective, observational study will follow healthcare workers at HSS and at other healthcare facilities for one year, to determine whether levels of vitamin D and certain immune cells in the blood make someone more susceptible to COVID-19 infection.

Association of Immunomodulatory Medication Use and Social Determinants of Health with COVID-19 Infection in Systemic Rheumatic Disease Patients in New York City

Principal Investigator: Medha Barbhaiya, MD, MPH

Co-Investigators from HSS: Lisa Mandl, MD, MPH; Catherine MacLean, MD, PhD; Vinicius Antao, MD, PhD; Jane Salmon, MD; and Mayu Sasaki, MPH

Other Co-Investigators: Candace Feldman, MD, MPH (of Brigham and Women’s Hospital); Debra D’Angelo, MS (of Weill Cornell Medicine)

Using data from the INSIGHT Clinical Research Network, a central repository containing longitudinal electronic health data for residents of New York City, investigators will assemble a cohort of patients being treated with immunomodulatory medications for rheumatic disease. This patient population will then be used to study the effect of these medications on COVID-19 incidence and outcomes. Retrospective data will be used to evaluate the incidence and severity of COVID-19 in these patients. Patients will also be studied prospectively to determine whether there’s a relationship between COVID-19 infection and future rheumatic disease as well as to study connections between infection and future psycho-social issues.

Assessment of Surgical Outcomes in the COVID-19 Pandemic Era

Principal Investigator: Andy O. Miller, MD

Co-Investigators: Scott A. Rodeo, MD, and Mark Fontana, PhD

Investigators will implement a patient registry to evaluate how COVID-19 affects outcomes and complication rates after orthopedic surgery. This registry, along with COVID-19 screening procedures, will provide the tools to address specific research questions. Among these questions are determining the incidence of current and prior infection among the HSS surgical population, the clinical features associated with current and prior infections in this patient population, and whether COVID-19 status affects short-term complication rates.

What follows is a description of an integrated multidisciplinary study being undertaken jointly by the Adult Reconstruction and Joint Replacement (ARJR) Perioperative Research Group, Anesthesiology and Rheumatology:

Prediction and Prevention of Postoperative Blood Clots in COVID-19 Patients

Principal Investigators: Friedrich Boettner, MD; Kethy M. Jules-Elysee, MD; Lisa A. Mandl, MD, MPH

Co-Investigators: ARJR surgeons: Alejandro Gonzalez Della Valle, MD; Jason Blevins, MD; David J. Mayman, MD; Peter K. Sculco, MD; Geoffrey H. Westrich, MD and Thomas P. Sculco, MD

Medicine/Rheumatology: Medha Barbhaiya, MD, MPH; Doruk Erkan, MD, MPH; Deanna Jannat-Khah, DrPH

Pathology: Thomas W. Bauer, MD, PhD

Anesthesiology: Stavros G. Memtsoudis, MD, PhD, MBA; Alexandra Sideris, PhD

ARJR: Amethia Joseph, MHA; Ethan Krell, MS

Weill Cornell Medicine: Raymond David Pastore, MD

Recent literature suggests that one of the major complications seen in people with COVID-19 is thrombosis (the formation of blood clots) due to endothelial dysfunction, persistent inflammation and potentially antiphospholipid antibodies. As elective surgeries resume, those with prior exposure to SARS-CoV-2 will inevitably present for treatment, and some may have perioperative management considerations related to their risk of deep-vein thrombosis. This project will use, a noninvasive device that can determine clotting risks, to investigate whether people who have had COVID-19 have a more dysfunctional endothelium preoperatively and at 24 hours after surgery. The investigators will measure antiphospholipid antibodies and inflammatory markers, and evaluate the prevalence of asymptomatic post-operative deep-vein thrombosis in people who undergo TKR and have SARS-CoV-2 antibodies.

COVID-19 Translational Research Core at HSS

Principal Investigator: Theresa Lu, MD, PhD

Co-Investigators: Jessica Andrés-Bergós, PhD; Miguel Otero, PhD and Emily M. Stein, MD, MS

The COVID-19 Translational Research Core (TRC) was designed to fill critical gaps in the resources needed to promote the broad range of COVID-19–related clinical and translational research at HSS. The TRC will provide consultation on the design and implementation of COVID-19 research in the areas of orthopedics, rheumatology and metabolic bone disease; support for a COVID-19 biobank; and technical expertise and facilities required for clinical and translational researchers working on COVID-19–related projects. The TRC staff will help to acquire, house, and track biospecimens from investigator-initiated COVID-19–related research studies.

“The HERO-HCQ trial is more than an important opportunity to evaluate the effectiveness of hydroxychloroquine as a preventative measure against COVID-19. We also hope to learn a lot more about the disease and how it affects healthcare workers and their families,” said Andy O. Miller, MD, an infectious disease specialist at HSS who is part of the leadership team responding to the COVID-19 pandemic and spearheading the trial. “We’re calling on HSS healthcare workers to share their perspectives so that we can understand and provide answers to the problems they face in real time — and over time.”

Hydroxychloroquine (Plaquenil®) is an oral prescription medication approved by the US Food & Drug Administration for the treatment of malaria and autoimmune diseases such as lupus and arthritis. “There is a lot of interest in testing this drug as a preventative agent for COVID-19 because it appeared to block SARS-CoV-2 from entering cells in lab studies,” explained Emily Margaret Stein, MD, MS, an internal medicine specialist and clinical researcher at HSS who is collaborating with Dr. Miller on the HERO-HCQ trial. “But like all medications, there are potential risks as well as benefits. Before we make recommendations on who should or should not be taking hydroxychloroquine, we need solid evidence.”

Researchers at the Duke University Clinical Research Institute designed and are leading the nationwide HERO-HCQ trial. The Patient-Centered Outcomes Research Institute is providing up to $50 million in funding. As partners of the INSIGHT Clinical Research Network, the PCORnet affiliate organization in New York City, HSS, along with New-York Presbyterian/Weill Cornell Medical Center, Columbia University Medical Center and Mount Sinai Hospital are collaborating on the trial since they are caring for large numbers of patients with COVID-19. “HSS has long been working with PCORnet to answer big healthcare questions,” said Dr. Stein. “COVID-19 is the challenge we are facing today.”

All healthcare workers who provide care, supplies or services to patients at HSS —including doctors, nurses, registrars, housekeepers, food delivery staff and janitors — can register to see if they are eligible to participate in the study. People with existing conditions, such as renal disease or heart conditions that put them at risk for known adverse effects associated with the drug, will not be eligible to participate.

Dr. Miller and Dr. Stein hope to recruit at least 350 study volunteers at HSS. As a double-blind, randomized, placebo-controlled study, participants will take either hydroxychloroquine or a placebo tablet once daily for 30 days. Clinical assessments will involve nasopharyngeal swab tests for COVID-19 and blood tests to detect the presence of antibodies at the beginning of the study and after four weeks. Researchers will also collect information about participants’ health and ask them to fill out quality-of-life surveys.

The target completion date for the HERO-HCQ trial is July 2020. Different from typical studies that take months to collect and analyze data, researchers will analyze data from the study every two weeks. “As soon as there is clear evidence of an effect, either way, the lead investigators will stop the trial and make a recommendation,” said Dr. Stein. “If the evidence shows the drug provides no benefit in preventing COVID-19, that will still be a useful result — we will save time and resources and look for other ways to help healthcare workers. If there is clear evidence of a benefit, they will recommend using the drug as preventative therapy.”

“It’s difficult to think that by doing our daily jobs, we could get sick, and we could also infect our loved ones at home,” said Dr. Miller. “This is the time to be proactive, to develop ways to stay safe on the front lines. I encourage all HSS healthcare workers to be a part of HERO-HCQ—and to be part of the solution.”

Learn more about the HERO Registry here.

Dr. Miller explained that Staphylococcus aureus is the leading cause of surgical site infections, and conducted a study to identify groups who are most at risk.

After comparing cotton swab samples from patients in orthopedic and rheumatologic waiting rooms, Dr. Miller found that "patients who are on biologic agents for rheumatoid arthritis are substantially and significantly more likely to have staphylococcus skin carriage and therefore more likely to be at risk for surgical site infections".

"We think it's significant because now we can identify that group as a group that may be at higher risk of getting surgical site infections and we can do things to try to minimize that risk," Dr. Miller added.

Watch the full interview at healio.com [registration required].