VA research during the COVID-19 pandemic

VA COVID-19 research volunteer list As one of the nation's leaders in health research, VA is working to find ways to prevent and treat the coronavirus disease (COVID-19). Visit the website of VA's COVID-19 research volunteer list to learn how you can be part of these efforts and what to expect if you volunteer. Overview Active Research Clinical trials Observational studies Data analysis projects Other research activities COVID-19 work highlighted on HSR&D site Selected Studies of Note Selected Scientific Articles by VA Researchers Clinical Trials Laboratory Studies Data Analysis/Review Other Research Commentary Useful links

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Overview

In response to the COVID-19 pandemic, VA Research has undertaken a wide array of activities to support and advance VA’s clinical and research missions and help Veterans affected by the disease.

These efforts have focused on establishing and taking part in clinical trials and data analysis projects aimed at understanding and treating the disease. VA Research has coordinated closely with internal VA and external partners—such as other federal agencies, and pharmaceutical companies—to identify the areas in which VA’s nationwide research capacity, resources, and infrastructure could make the greatest contribution.

VA Research has taken these actions while working to ensure and promote the safety and well-being of all those involved in research. The program has also been enabling continuity of operations to the extent possible across the entire VA research portfolio, all of which is aimed at improving Veterans’ lives. 

On this web page, we summarize key COVID-19 research activities currently underway across the VA system, and provide background information on how the VA Office of Research and Development has rapidly mobilized the nationwide VA research community and resources to contribute to the national response to the pandemic. The information below is current as of March 1, 2021, and will be updated regularly.

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Active research

Below are examples of COVID-19 research underway in VA.

Clinical trials

As of mid-February 2021, more than 50 VA medical centers are involved in one or more COVID-19 clinical trials. Below are several examples. A full list of COVID-19 Clinical Trials in VA is also available.

• Testing prostate cancer drug—VA is funding a phase 2 clinical trial, the Hormonal Intervention for the Treatment in Veterans with COVID-19 Requiring Hospitalization (HITCH) trial, exploring whether degarelix, an androgen suppressor treatment used in prostate cancer, may be effective for men with COVID-19. The trial is active in 13 of 14 planned sites across the country.
• VA CURES—The wide-reaching “VA CURES” master protocol, launched in August 2020, enables a series of clinical trials across VA, the first one involving 702 Veterans who are hospitalized for COVID-19 from 25 VA sites. The study is examining the effects of convalescent plasma. VA CURES stands for “Coronavirus Research and Efficacy Studies.” The initiative aims to give Veterans faster access to potential COVID-19 treatments and to test their effectiveness. As a master protocol, VA CURES offers a standardized framework for studies on many potential treatments for COVID-19, without the need for a new study design and protocol each time.
• VA has been part of two major national research initiatives on COVID-19 vaccines and therapeutics:  Operation Warp Speed (OWS) and the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative.
  • Through OWS and other efforts, VA has been an active participant in several clinical trials designed to evaluate potential COVID-19 vaccines. These trials have included:
    • The Moderna/COVE trial, which took place at one VA site and is now closed to enrollment. In December 2020, Moderna obtained an emergency use authorization for its vaccine from the FDA.  
    • The AstraZeneca trial, for which one VA site continues to recruit on a limited basis.
    • The Janssen ENSEMBLE trial, which included 17 VA sites and is now closed to enrollment. The vaccine received FDA emergency use authorization in late February 2021.
    • The Pfizer trial, in which one VA site participated. In December 2020, Pfizer obtained an emergency use authorization for its vaccine from the FDA.  
    • The Novavax trial, which began in late December 2020 and for which two VA sites are currently recruiting.
• A few ACTIV protocols are in various stages at VA medical centers:
• ACTIV-2, an outpatient trial of monoclonal antibodies and antivirals, is now in its second phase, and several VA sites are registering for inclusion. The first phase, looking at the Lilly CoV555 monoclonal antibody, has been completed.
• ACTIV-3, an inpatient trial of a monoclonal antibody, is expected to involve about 25 VA medical centers.
• Trials with industry—VA is taking part in a number of industry-sponsored studies of promising medications for COVID-19. These include, for example, studies of the drug tocilizumab with Hoffman-La Roche, and sarilumab with Regeneron. Both drugs are used in arthritis care and block an inflammatory protein known as IL-6.
• Remdesivir trial with NIH—VA sites have been taking part in a randomized, placebo-controlled study of remdesivir and other medications for hospitalized patients with COVID-19, sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

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Observational studies

• Natural history study—VA is collaborating with the Department of Defense on an observational, natural history study of COVID-19 illness titled “Epidemiology, Immunology and Clinical Characteristics of COVID-19” (EPIC³). Researchers will collect data and biospecimens from volunteers for up to two years to better understand the clinical course of COVID-19. Recruitment at up to 16 sites began in July 2020.
• COVID-19 and cancer—The National Cancer Institute COVID-19 in Cancer Patients Study, or NCCAPS, is a natural history study of COVID-19 in people with cancer. In a natural history study, researchers follow people and collect medical and other information about them over time to learn more about how a disease and its symptoms develop and change. Diagnosis and treatment of a disease are not part of natural history studies. The knowledge gained through this study will help doctors better manage treatment for people with cancer and COVID-19 in the future. As part of the NCCAPS study, researchers will collect blood samples, medical information, and medical images from 2,000 people with cancer who also have COVID-19. Each person will be followed for up to two years to help doctors understand how cancer affects COVID-19 and COVID-19 affects cancer. The study is recruiting volunteers nationwide, including at 11 VA locations.

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Data analysis projects

• COVID-19 Insights Partnership—VA is a key partner in the COVID-19 Insights Partnership, along with the departments of Energy (DOE) and Health and Human Services (HHS). The initiative aims to coordinate and share health data as well as research and expertise to aid in the fight against COVID-19.The Partnership creates a framework for VA and HHS to use DOE’s world-leading high-performance computing and artificial intelligence resources to conduct COVID-19 research and analyze health data.
• Million Veteran Program—VA’s Million Veteran Program (MVP) has deployed a COVID-19 questionnaire to participants to collect information about their experience with COVID-19. In addition, MVP has prioritized a series of research questions to examine the genetic basis of infection by SARS CoV-2; complications of infection; disease severity and outcomes; and response to various medications. MVP will also seek to identify disease mechanisms and new treatment targets for COVID-19. Given MVP’s racially and ethnically diverse participant population (~ 20% African American and 7% Hispanic), the influence of race and ethnicity on disease susceptibility, severity, and outcomes will be an integral part of the analyses.
• Synthesizing evidence from publications—Researchers from the HSR&D Evidence Synthesis Program are working to help synthesize publications about the novel coronavirus and COVID-19, and to translate that information quickly into usable guidance for clinicians. The ESP’s completed reports can be found here.
  Additional evidence reviews can be found at www.covid19reviews.org. The goal of this resource is to capture the work of evidence synthesis groups, like VA’s, around the US and the globe, and thereby avoid duplication of effort and maximize the contribution of these researchers. The catalog is maintained by the VA ESP Coordinating Center in Portland, Oregon. New evidence reviews and reviews in progress are identified through literature searching and correspondence with colleagues and content experts. The team has also set up a listserv to facilitate collaboration among systematic review researchers.
• International collaboration—Researchers with the VA Informatics and Computing Infrastructure team are participating in the Observational Health Data Sciences and Informatics (or OHDSI, pronounced "Odyssey") program, an international, interdisciplinary collaborative to maximize the value of health data through large-scale analytics.
• COVID Observational Research Collaboratory—A VA research initiative is bringing together VA experts to analyze the use and effects of COVID-19 drugs with clinical partners interested in the safety and efficiency of these therapies. VA’s Health Services Research and Development Service, Clinical Science Research and Development Service, and Cooperative Studies Program established the collaboratory soon after the pandemic took hold earlier this year.
• Dementia patients—VA researchers in Providence have funding from the National Institute on Aging to study COVID-19 risk factors and outcomes among Veterans with dementia who live in VA community living centers.

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Other research activities

• Facilitating access to investigational drugs under the FDA’s expanded access, or “compassionate use,” program—VA Research has streamlined and organized a central assistance process for VA medical centers seeking expanded access (a.k.a. compassionate use) under FDA rules to investigational drugs for COVID-19 treatments. One treatment being used under this program is transfusions of blood plasma from patients who have recovered from COVID-19. This “convalescent” plasma contains antibodies that researchers believe may help other patients. Some 80 VA sites have treated more than 500 Veterans with convalescent plasma as part of the Mayo Clinic’s “expanded access” study of this therapy for COVID-19. The Mayo Clinic study is no longer enrolling participants, now focusing on data collection and analysis.
• COVID-19 and mental health—In addition to studying how to prevent or treat COVID-19, VA is examining the mental health impact of the pandemic. To date, ORD has funded nearly 30 studies looking at mental, behavioral, and social health and COVID-19. Some are new projects focused wholly on COVID-19, whereas others are supplements to existing projects that are broader in scope. The following study titles indicate some of the themes being explored:
  • Inflammatory and Mental Health Sequelae of COVID-19 in Veterans
  • An Integrative Technology Approach to Home-Based Conjoint Therapy for PTSD  
  • Impact of COVID-19 On Mental Health, Relationship Functioning and VA Telemental Health Service Use in a Longitudinal Cohort Study    
  • Impact of COVID-19 and Social Distancing on Mental Health and Suicide Risk in Veterans
  • Piloting a Self-Help Intervention to Improve Veteran Mental Health During the COVID-19 Pandemic
  • Mixed-Methods Pilot Study of the Impacts of Telemental Healthcare for High-Risk Veterans with Opioid Use Disorder During COVID-19
  • Adapting Caring Contacts to Counteract Adverse Effects of Social Distancing among High-Risk Veterans During the COVID-19 Pandemic
  • Virtual Pain Care for High-Risk Veterans on Opioids During COVID-19 (and Beyond)
  • Changes in the Delivery of Evidenced-Based Psychotherapies for Depression and PTSD as the Result of the COVID-19 Pandemic
  • Impacts of COVID-19 on African American Veterans with Chronic Pain
• Biomedical studies—VA biomedical researchers are part of the fight against COVID-19. The following project titles illustrate the scope of the VA lab studies already completed or being conducted to better understand how the virus works, and to identify new ways to keep it from spreading and causing disease.
  • 3D-Printed Respirator Mask Performance with and without Virus Inactivation 
  • A Safe Validation to Test the Efficacy of Disinfectants on Reusable 3D-Printed Face Masks During the COVID-19 Pandemic 
  • Leukocyte Rewiring as a Mechanism of COVID-19-ARDS 
  • Viral and Immune Dynamics of Sars-Cov-2 Infection in Moderate and Severe COVID-
  • Predictive Immune and Airway Monitoring in Healthcare Workers and Hospitalized COVID-19 Patients 
• Boosting the VA supply chain—Rehabilitation researchers are helping to build a more resilient supply chain for VA. Researchers from several centers are involved, such as the Human Engineering Research Laboratories (HERL) in Pittsburgh; the Center for Limb Loss and Mobility at the Puget Sound VA; the Minneapolis Adaptive Design and Engineering Program; and the Advanced Platform Technology Center in Cleveland. Partners in this effort include the VA Innovation Ecosystem, the U.S. Food and Drug Administration, the National Institutes of Health, and America Makes. These researchers and their colleagues have been designing, fabricating, and evaluating personal protective equipment (PPE) and other supplies to support VA’s response to this pandemic, such as masks, face shields, desk shields, nasal testing swabs. In many cases, 3D printing is involved.

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COVID-19 work highlighted on HSR&D site

For a concise overview of current VA Health Services Research and Development (HSR&D) efforts on COVID-19, visit COVID-19 Efforts.

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Selected Studies of Note

Using genetics, researchers identify potential drugs for early treatment of COVID-19
A study using genetics suggests researchers should prioritize clinical trials of existing drugs that target two proteins to manage COVID-19 in its early stages. Researchers studied the genomes of more than 7,500 patients hospitalized with COVID-19 and more than a million controls. They found that two proteins, ACE2 and IFNAR2, are likely involved in COVID-19 hospitalization. IFNAR2 is the target for approved drugs used to treat multiple sclerosis. A drug developed prior to the pandemic to treat severe respiratory illness targets ACE2. The researchers suggest that clinical trials should examine existing drugs such as these known to act on these two proteins for possible new treatments for COVID-19. (Nature Medicine, April 9, 2021)

COVIDVax risk model could save lives with vaccination prioritization
Researchers with the VA Puget Sound Healthcare System developed a model called COVIDVax to estimate COVID-19 risk and guide vaccine prioritization. To develop the model, the researchers used data from more than 7.5 million VA patients to predict COVID-19-related death. COVIDVax was highly accurate at predicting which patients were at greatest risk of dying from COVID-19. Using this model to prioritize vaccination was estimated to be able to prevent 64% of deaths that would occur by the time 50% of all VA enrollees are vaccinated. Prioritizing vaccination based on COVIDVax should prevent a large number of deaths, concluded the researchers. (JAMA Network Open, April 1, 2021)

Veteran suicide risk during the pandemic
Researchers from several VA offices studied the COVID-19-related factors that protected against and increased risk of suicidal thoughts of Veterans during the pandemic. They studied data on more than 3,000 Veterans with pre-existing psychiatric conditions before and after the pandemic began. Pre-pandemic purpose in life and higher income appeared to be protective against suicidal thoughts.COVID-19 infection, pre-pandemic psychosocial difficulties, and increased psychiatric symptoms increased risk of suicidal thoughts during the pandemic. Among Veterans infected with COVID-19, older Veterans and those with low feelings of purpose in life were at greatest risk of suicidal thoughts. Interventions to help enhance purpose in life may help lower suicide risk during the pandemic, according to the researchers. (Journal of Psychiatric Research, March 16, 2021)

Review: Most adults develop antibodies after virus infection
A review by VA Portland researchers summarized the available evidence of the body’s antibody response to SARS-CoV-2 infection. Studies show that most adults who contract the virus develop detectable levels of antibodies. Antibody levels peak around 20 to 25 days after infection, and may remain detectable for at least 120 days. Some evidence suggests that older age, greater disease severity, and presence of symptoms are linked to higher antibody levels. The review showed that some adults do not develop antibodies after SARS-CoV-2 infection, and the reasons for this are unclear. While the evidence available will help scientists understand how the body reacts to the virus, most studies available were small, highlighting the need for more research. (Annals of Internal Medicine, March 16, 2021)

Increasing physical distance in schools not linked to fewer COVID-19 cases
Maintaining three feet versus six feet of physical distance between students did not affect COVID-19 cases, found a study by VA Boston researchers and colleagues. Researchers looked at COVID-19 infection data for nearly 540,000 students and more than 99,000 staff attending in-person school in the Massachusetts public school system. They found that infection rate was similar in districts with policies requiring three feet of physical distance, compared with districts requiring six feet. Increasing physical distance is not necessary to prevent COVID-19 cases in schools, concluded the researchers, provided that universal mask mandates and other precautions are implemented. (Clinical Infectious Diseases, March 10, 2021)

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Selected Scientific Articles by VA Researchers

Clinical Trials

A neutralizing monoclonal antibody for hospitalized patients with Covid-19. ACTIV-3/TICO LY-CoV555 Study group, Lundgren JD, et al. Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had COVID-19. N Engl J Med. 2020 Dec 22. Online ahead of print.

 

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Laboratory Studies

Blockade of SARS-CoV-2 spike protein-mediated cell-cell fusion using COVID-19 convalescent plasma. Wang L, Zhao J, Nguyen LNT, Adkins JL, Schank M, Khanal S, Nguyen LN, Dang X, Cao D, Thakuri BK, Lu Z, Zhang J, Zhang Y, Wu XY, El Gazzar M, Ning S, Moorman JP, Yao ZQ. COVID-19 convalescent plasma may not only inhibit SARS-CoV-2 spike proteins, but also neutralize the virus’s ability to cross cell membranes. Sci Rep. 2021 Mar 10;11(1):5558.

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery. McClain MT, et al. Blood tests revealed both diverse and conserved components of the immune response in COVID-19 and provide for potential biomarker-based approaches to diagnosis. Nature Commun. 2021 Feb 17;12(1):1079.

Quantifying absolute neutralization titers against SARS-CoV-2 by a standardized virus neutralization assay allows for cross-cohort comparisons of COVID-19 sera. Oguntuyo KY, et al. Researchers developed a test of the efficacy of COVID-19 vaccines and other treatments that avoids using the live virus. mBio. 2021 Feb 16;12(1):e02492-20.

Severe COVID-19 pneumonia is associated with increased plasma immunoglobulin G agonist autoantibodies targeting the 5-hydroxytryptamine 2A receptor. Zimering MB. A specific cell receptor is prevalent in acute, severe COVID-19 infection and may help explain the biological processes of more severe cases. Endocrinol Diabetes Metab J. 2021 Feb 2;5(1):1-9.

A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease. Baker JD, Uhrich RL, Kraemer GC, Love JE, Kraemer BC. Hepatitis C drugs have potential to be repurposed as a treatment for COVID-19. PLoS One. 2021 Feb 1;16(2):e0245962.

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Data Analysis/Review

Mental health treatment and the role of tele-mental health at the Veterans Health Administration during the COVID-19 pandemic. Zhang J, Boden M, Trafton J. VA and other large health care systems will need to expand outreach and continue to develop tele-mental health services to maintain care continuity and initiate care for existing and new patients during COVID-19 and future large-scale outbreaks. Psychol Serv. 2021 Apr 8. Online ahead of print.

Differences in COVID-19 testing and test positivity among Veterans, United States, 2020. Differences in COVID-19 testing and test positivity among Veterans, United States, 2020. Ferguson JM, Abdel Magrid HS, Purnell AL, Kiang MV, Osborne TF. Despite receiving more tests than White Veterans, Black and Hispanic/Latino Veterans were at increased risk of receiving a positive COVID-19 test result, suggesting social inequities are driving disparities in COVID-19 prevalence. Public Health Rep. 2021 Apr 7. Online ahead of print.

Universal masking to control healthcare-associated transmission of SARS-CoV-2. Thompson ER, Williams FS, Giacin PA, Drummond S, Brown E, Nalick M, Wang Q, McDOnald JR, Carlson AL. Universal masking was effective in preventing further spread of SARS-CoV-2 in a medical facility. Infect Control Hosp Epidemiol. 2021 Mar 29:1-24.

Clinical evidence of an interferon-glucocorticoid therapeutic synergy in COVID-19. Lu Y, Liu F, Tong G, Qiu F, Song P, Wang X, Zou X, Wan D, Cui M, Xu Y, Zheng Z, Hong P. Early interferon therapy in patients being treated with glucocorticoids for COVID-19 was associated with earlier hospital discharge, better symptom relief, and lower viral shedding. Interferon did not have these effects in patients not receiving glucocorticoids. Signal Transduct Target Ther. 2021 Mar 3;6(1):107.

Virtual care expansion in the Veterans Health Administration during the COVID-19 pandemic: Clinical services and patient characteristics associated with utilization. Ferguson JM, Jacobs J, Yefimova M, Greene L, Heyworth L, Zulman DM. While virtual care may expand access, access barriers must be addressed to avoid exacerbating disparities. J AM Med Inform Assoc. 2021 Mar 1;28(3):453-462.

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Other Research

Association of symptoms of posttraumatic stress disorder with posttraumatic psychological growth among US Veterans during the COVID-19 pandemic. Pietrzak RH, Tsai J, Southwick SM. Many Veterans reported positive post-traumatic growth related to dealing with the pandemic, with this effect highest in those who screened positive for COVID-19-associated PTSD symptoms. JAMA Netw Open. 2021 Apr 1;4(4):e214972.

Association between risk factors for complications from COVID-19, perceived chances of infection and complications, and protective behavior in the US. Schoeni RF, Wiemers EE, Seltzer JA, Langa KM. Adults with risk factors for COVID-19 complications reported higher perceived susceptibility to complications. During common activities, the majority of adults, including the highly susceptible, did not consistently wear masks. JAMA Netw Open. 2021 Mar 1;4(3):e213984.

Why couldn’t I go in to see him? Bereaved families’ perceptions of end-of-life communication during COVID-19. Feder S, Smith D, Griffin H, Shreve ST, Kinder D, Kutney-Lee A, Ersek M. Communication between patients, families, and health care teams at the end of life remains critically important during times of limited in-person visitation. J Am Geriatr Soc. 2021 Mar;69(3):587-592.

Emergency physicians and personal narratives improve the perceived effectiveness of COVID-19 public health recommendations on social media: A randomized experiment. Solnick RE, Chao G, Ross RD, Kraft-Todd GT, Kocher KE. Emergency physicians sharing personal narratives on Twitter are perceived to be more effective at communicating COVID-19 health recommendations compared to federal officials sharing impersonal guidance. Acad Emerg Med. 2021 Feb;28(2):172-183.

Characterization of hospital airborne SARS-CoV-2. Stern RA, Koutrakis P, Martins MAG, Lemos B, Dowd SE, Sunderland EM, Garshick E. Results show that COVID-ward hospital controls are effective at controlling disease spread, and that the virus can possibly be spread through airborne transmission over distances greater than six feet. Respir Res. 2021 Feb 26;22(1):73.

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Commentary

COVID-19 Insights Partnership: Leveraging big data from the Department of Veterans Affairs and supercomputers at the Department of Energy under the Public Health Authority. Ramoni R, Klote M, Muralidhar S, Brandt C, Bernstein MA, McMahon BH, Jacobson DA, Justice AC. Investigators from multiple federal agencies will be able to combine DOE’s high-performance computing and artificial intelligence expertise with health information from Veterans and non-Veterans diagnosed with COVID-19 to bolster the nation’s ability to understand, prevent, and treat the disease. J Am Med Inform Assoc. 2021 Mar 29. Online ahead of print.

The Veterans Health Administration approach to COVID-19 vaccine allocation—Balancing utility and equity. Tarzian AJ, Geppert CMA. VHA was able to mobilize early to identify vaccine allocation guidelines and proactively prepare facilities to vaccinate VHA staff and Veterans as soon as vaccines were approved. Fed Pract. 2021 Feb;38(2):52-54.

An issue of trust—Vaccinating Black patients against COVID-19. Okorodudu DO, Okorodudu DE. Trust needs to be built through transparency and partnership to further COVID-19 vaccination in the Black community and other vulnerable populations. Lancel Respir Med. 2021 Jan 19. Online ahead of print.

Does universal testing for COVID-19 work for everyone? Dumyati G, Gaur S, Nace DA, Jump RLP. The authors propose a structured approach for facility-wide testing of nursing home residents and staff. J AM Med Dir Assoc. 2020 Nov;21(11):1525-1532.

Implementation of infection control measures to prevent healthcare-associated transmission of SARS-CoV-2. Lepak AJ, Shirley DK, Buys A, Stevens L, Safdar N. Adoption of the infection control bundle described may be helpful to prevent SARS-CoV-2 spread within health care institutions. Infect Control Hosp Epidemiol. 2020 Oct 12:1-13.

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Useful links

• VA COVID-19 Research Volunteer List
• Department of Veterans Affairs Public Health
• Centers for Disease Control and Prevention
• COVID-19 Reviews [maintained by VA ESP]

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Any health information on this website is strictly for informational purposes and is not intended as medical advice. It should not be used to diagnose or treat any condition.