Finding the Signal in the Noise During COVID-19: A Survey on Multiple Sclerosis

With the abundance of information conveyed on Coronavirus disease 2019 (COVID-19), it is essential to isolate meaningful signal for the “4 P’s” (patients, providers, payers, and pharmaceutical companies) and data scientists working in the health care field. Given the global pandemic, we at Octave Bioscience thought it would be appropriate to take a step back from our normal Data Science for Health Care Professionals blog series to help in our local sphere, specifically in neurodegenerative chronic diseases like multiple sclerosis (MS). While this article focuses on the intersection of COVID-19 and MS, several of the topics we review will be applicable to health care at large. We believe that in order to facilitate access to the highest standard-of-care, accurate and up-to-date information is key for clinical pathways to guide evidence-based health care.

As a disclaimer, please follow the CDC Guidelines in order to protect yourself and take necessary action if you believe you are sick. These public health recommendations help slow the spread of COVID-19 and optimize the capacity of our healthcare system as we work to better understand this disease, giving the medical community valuable time to develop and test diagnostic capabilities, potential vaccines, and treatments.

How COVID-19 Has Affected Access to MS Care

COVID-19 is undoubtedly transforming health care delivery. With the increased risk of contracting and spreading COVID-19 by traveling to a clinic, many aspects of MS care management have transitioned to telehealth. In our partnering clinics, we have seen office visits, check-ins, consents/authorizations, prescriptions, billing, and scheduling transfer to virtual solutions in an expedited fashion. Some aspects of care currently cannot be conducted remotely, such as treatment delivery at infusion centers, diagnostic imaging (eg, MRI’s), blood draws, hands-on components of neurological evaluations, and in-person clinical trial requirements. Octave Bioscience is striving to make the continuum of MS care a feasible and seamless experience as it migrates to telehealth platforms.

The Wide Adoption of Telehealth Care Delivery

This year has brought about an unprecedented rise in the prevalence of telehealth for delivery of care. This is not the first time that remote medicine has been added to the suite of services offered by health care providers, but the rise of the COVID-19 pandemic has elevated the field, making it a more attractive option for health care delivery in many scenarios.

Providers and Payers. Health networks have been forced to provide virtual appointment alternatives for those opting out of in-person checkups. Telehealth reimbursement coding and billing is changing rapidly by state to enable care to continue remotely: the Center for Connected Health Policy put together a helpful resource for staying on top of billable procedures.

Surprisingly, there exists an unmet clinical need as no widely-available, MS-focused telehealth service is available regionally or nationally. The Veterans Administration system has utilized teleneurology for patients living with MS with promising signs of traction and improved outcomes (Block & Bove 2019). Simply making conversations between patients and providers easier with telehealth provides value to both parties. Additionally, this mode of communication is primed for remote monitoring, allowing for the extraction of features from video, sound, and other digital input that can inform the state and progression of a patient’s disease. Octave Bioscience has developed a MS telehealth platform to address the continuum of care that is currently being tested as part of the MOVING MS study.

Many of our partnering clinics and health networks have leaned heavily on their own telehealth and teleconferencing solutions to facilitate remote MS care management. In the absence of in-person evaluations, Moccia et al has suggested bringing together conventional examination, patient-reported outcome metrics (eg, Patient Determined Disease Steps, MS Impact Scale), and cognitive tests (eg, Symbol Digit Modalities Test) that can be delivered remotely and in multiple languages for assessing MS disability and relapses with teleneurology (2020).

Whether or not you have MS, some helpful telehealth resources include, but are not limited to, those in Table 1.

Table 1: A non-exhaustive list of available telehealth resources available to patients and providers (Octave 2020). Click on the name of the service to learn more about their offerings.

Payers and Providers. If your network of patients do not currently have access to telehealth alternatives and they feel uncomfortable traveling to a clinic, please consider partnering with an existing telehealth platform or connecting your patients to affordable non-covered options.

Emotional Well-Being and Coping During a Pandemic

One area in which telehealth tools have had a large impact is mental health. Depression, an often-described invisible symptom, exists in up to 70% of those with MS. The COVID-19 infection and associated socioeconomic effect and related social distancing guidelines have increased the feelings of anxiety, depression, and isolation. Achieving the right balance between infection control and mitigation of these negative consequences must be considered.

Patients. Life can be challenging getting back into your routine in the workplace and at home as shelter-in-place guidelines begin to ease restrictions. The National Multiple Sclerosis Society (NMSS) has a program called MS Navigators to help MS patients stay informed, find support networks, and handle financial challenges (including resources about MS COVID-19 en Español for Spanish-speaking populations). The Multiple Sclerosis Association of America (MSAA) is also providing expanded hours to their toll-free Helpline (800-532-7667, 8:30am-8pm ET, Monday-Friday) as well as a COVID-19 hardship waiver and live online webinars. The Global Healthy Living Foundation also provides free support, such as meditative practices and psychologist advice for taming anxiety, for chronic illness patients navigating COVID-19.

MS Therapeutic Decision-Making in the Time of COVID-19

Information communicated in this section has been echoed by the NMSS, MSIF, MSAA, and Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research. Octave Bioscience is not making any medical recommendations, but rather relaying advice from MS professionals.

While a MS diagnosis in itself does not indicate an increased risk of contracting COVID-19, certain factors (such as age, obesity, and limited mobility) may increase the risk for more severe illness (NMSS). MS patients are often prescribed medications that target different aspects of the immune system. This therapeutic strategy is widely adopted across multiple specialties including neurology, oncology, gastroenterology, dermatology and rheumatology. Risk of infection is a major concern for such patients and can exhibit a high degree of variability depending on the underlying etiology, disease stage, treatment response, and comorbidities (NMSS). The CDC provides a comprehensive guide on methods to mitigate this concern within immunocompromised populations.

Disease modifying therapies (DMTs) that are of an immune cell-depleting nature may pose a greater risk of infection among MS patients. The effect may be more variable with immunomodulatory drugs depending on their ability to restrict the immune response (NMSS).

Providers. Table 2 includes FDA-approved disease-modifying therapies frequently used by MS patients. The NMSS has provided detailed guidance on the selection of DMTs during the pandemic. Before starting a cell-depleting DMT or cessation of a DMT that carries warnings of a potentially severe increase in disability after stopping, providers should consider the associated risks and benefits. The general recommendation is to stay on your current DMT; caution should be taken before starting, switching, or stopping particular medications as this may increase the risk of hospitalization. These recommendations have been endorsed by the Consortium of Multiple Sclerosis Centers (CMSC) and members of the MS Coalition.

Table 2:Commonly prescribed DMTs which affect the immune system and their associated risks (Octave 2020). *Stopping fingolimod (FDA warning) and natalizumab (González‐Suarez et al. 2017, Papeix et al. 2016) without a plan introduces higher disability. Mitoxantrone is rarely used in the United States unless risks outweigh benefits. Monomethyl fumarate is FDA-approved but not readily-available at the time of publication.

Patients. People taking a DMT from the immunosuppressive categories living in a community with a COVID-19 outbreak should isolate as much as possible to reduce their risk of infection (see global advice from MSIF for more information). Consult your doctor with any concerns and before altering any course of treatment.

Pharma. Producers of these MS therapies should make concerted efforts to understand their relationship with COVID-19 and make said information transparent and readily-available to guide shared decision-making between physicians and patients.

Addressing Potential Ties Between MS and COVID-19

The search for a link between COVID-19 and autoimmune or neurodegenerative diseases, such as MS, is still in its infancy. There is a scarcity of evidence—mostly limited to anecdotal information from patients—linking MS and COVID-19. Progress has been temporarily curbed by the novelty of the coronavirus and the preeminent focus on rapid containment as to mitigate its uncontrolled and widespread transmission.

As a result, there continues to be an unmet need for research efforts that examine a) MS epidemiological and pharmacological factors influencing COVID-19 infection outcomes, and b) the direct and indirect impact of the novel coronavirus (SARS-CoV-2) on the MS disease course. By probing these topics highlighted in Table 3, the community is better equipped to address the guidelines for managing MS in the setting of the COVID-19 pandemic.

Table 3: We highlight some of the relevant research questions (inspired by the MS Data Alliance) as well as the corresponding pilot studies that are either recently completed, currently underway, or in the design-planning stages (Octave 2020).

Currently, there are six global results on ClinicalTrials.gov that match “Multiple Sclerosis” and “COVID-19”:

1. SUNLIGHT Study: Online Support Groups for MS to Address COVID-19 (New York City, USA)

    

2. The United Kingdom Multiple Sclerosis Register Covid-19 Substudy (Swansea, UK)

    

3. Epidemiological Characteristics of COVID-19 in Patients With MS or NMO (Paris, France)

    

4. COVID-19 Related Lockdown Effects On Chronic Diseases [active, no longer recruiting] (Dijon, France)

    

5. Fingolimod in COVID-19 (Fuzhou, China)

    

6. COVID-19 Ozanimod Intervention Study (COZI) [not yet recruiting] (Quebec City, Canada)

    

Providers. If you know of a patient that may be a good fit for one of these trials, please review the eligibility criteria and the trial contact information in the links above.

How to Contribute to Research: Overcoming the Data Scarcity in MS and COVID-19

Given the need for data to improve understanding of COVID-19, we invite you to contribute to the registries in Table 4 to help push forward the discovery of new treatments and methods for testing and controlling the spread.

Table 4: A list of data-collecting efforts around the world (Octave 2020). Please review the eligibility criteria linked to the initiative name if you believe that you are able to contribute.

We applaud these efforts and would like to highlight their importance in wrangling a rapidly evolving medical situation. Having a larger sample size of well-annotated reports to draw conclusions from will inherently increase the statistical power to push forward recommendations and guide decision-making amongst uncertainty.

Patients. One immediate way for both healthy and recovered patients to help is by donating blood or plasma. Not only is the world in constant need of transfusions (especially during a global pandemic), but there is also ongoing research and hope that COVID-19 antibodies in plasma of recovered donors will 1) directly help those with COVID-19 better fight the disease, and 2) aid in clinical research for testing and treatments. If you are willing and able to donate blood, please consult the organizations and screeners below to find the nearest blood donation center to advance our collective ability to combat COVID-19:

• COVIg-19 Plasma Alliance

   

• National COVID-19 Convalescent Plasma Project

   

• American Red Cross

   

Resources for Data Scientists

There are countless ways that data scientists can contribute their skills to ongoing research and dissemination of information. We will highlight a few efforts as a way to inspire and think about how you can make a difference in your local sphere:

• Several competitions have been set up to crowdsource intellectual efforts. One popular choice among data scientists for building the best classification, clustering, or regression model on public datasets is Kaggle. To help with the COVID-19 crisis, they invite all problem-solvers to help leverage NLP on scientific literature, forecast the spread of cases and fatalities, and contribute to an exploratory data analysis for frontline responders.

   

• There are several national electronic health record data sharing and interoperability initiatives underway including:
  • The National COVID-19 Cohort Collaborative (N3C), which is led by the National Center for Data to Health (CD2H) and the National Center for Advancing Translational Science (NCATS) for creating a centralized, secure portal of COVID-19 clinical data including a COVID-19 phenotype data in a secure online enclave that payers, providers, and pharma can use to gain insights into patients across the US. This initiative is a partnership among several Health and Human Services (HHS) agencies whose partner sites’ data have been ingested into this platform: the NCATS Clinical and Translational Science (CTSA) program and the Patient Centered Outcomes Research Network or PCORnet (see below), the Observational Health Data Science Initiative (OHDSI), the Accrual to Clinical Trials (ACT) network, and TriNetX.

     

  • A Harvard-led initiative Consortium for Clinical Characterization of COVID-19 by EHR (4CE) which is based on the Integrating Informatics for Biology to the Bedside (i2b2) TranSMART Foundation platform.

     

  • PCORnet’s Common Data Model provides demographics, diagnoses, vital signs, laboratories, prescriptions, dispensed medications, medications administered (multiple settings), procedures, and facility and patient geographic information, as well as patient reported outcomes. PCORnet has developed a COVID ontology and phenotype which it is sharing with the research community.

     

• Many epidemiological dashboards and visualizations have been pivotal to communities understanding the appropriate guidelines as COVID-19 swept across the globe (and are just as important in understanding how we phase back into our ways of life). Here are a few of our favorite visualizations which give most value to viewers:

   

  • Johns Hopkins University’s Center for Systems Science and Engineering built this dashboard to map geographical spread and have since expanded case-reporting to include metrics on testing, hospitalization, and fatality rates.
  • The Institute for Health Metrics and Evaluation built a dashboard which examines the hospital capacity (in terms of beds, intensive care units, and ventilators) to accommodate the number of COVID-19 cases in a given region, as well as forecast the spread over time in response to social distancing protocols.

     

  • Worldometer has put together this intuitive and well-sourced interface for a by-region census of COVID-19 cases.

     

• Contact tracing is a means of tracking down anyone who might have been infected by a person who was recently diagnosed so those contacts can quarantine themselves and prevent further spread. This, when applied thoughtfully, is an important tool in mitigating infections. Kineviz has introduced GraphXR for Contact Tracing in order to protect the safety of an organization’s team members while preserving their privacy.

   

For all of these efforts, there should be an emphasis on actionability (ie, enabling users to do something with said information) and inclusivity to all demographics and identities. Despite the urgency with a lot of these matters, please remember to use the best data science practices—as Octave Bioscience has described in previous blog entries to date: Data Science, Data Engineering, and ETL—to save time and ensure highest quality analysis in the long run.

Next Post

Our next blog entry will return to technical features of data science with an exploration of the regulatory aspects of clinical data science at large.

About David Hughes

David Hughes is the Principal Machine Learning Data Engineer for Octave Bioscience. He develops cloud-based architectures and solutions for surfacing clinical intelligence from complex medical data. He leverages his interest in graph based data and population analytics to support data science efforts. David is using his experience leading clinical pathways initiatives in oncology to facilitate stakeholder engagement in the development of pathways in neurodegenerative diseases. With Octave, he is building a data driven platform for improving patient experience, mitigating cost, and advancing health care delivery for patients and families.

About Octave Bioscience

The challenges for MS are significant, the issues are overwhelming, and the needs are mostly unmet. That is why Octave is creating a comprehensive, measurement driven Care Management Platform for MS. Our team is developing novel measurement tools that feed into structured analytical data models to improve patient management decisions, create better outcomes and lower costs. We are focused on neurodegenerative diseases starting with MS.