Pediatric Hepatitis of Unknown Origin: Are Viruses to Blame?

Navigating new and especially concerning developments can be challenging in the day and age of the Internet being the foremost platform for receiving up to date information…and misinformation. Navigating emerging evidence and opinions, prioritizing what “voices” hold prominence in your own formation of ideas can be difficult. I need to emphasize, the most reliable sources of information are official sources, those associated with government and institutions of positive reputation. Even if you have personal distaste for the approach or conclusions of these entities or personalities, their base facts are indeed facts, not conflation or cherry picking. Internet literacy is a critical skill set in navigating the most expedient tool of information. These details are particularly important as medical personnel and public health professionals turn their eyes to the developing issue of pediatric patients presenting with acute hepatitis “of unknown origin”.

At the time of this writing, more than 300 cases had been identified across more than 20 countries and at least 5 children have died. None of the cases being investigated have uncovered typical hepatitis viruses. According to a Centers for Disease Control and Prevention (CDC) brief, many of the cases in the United States have found active adenovirus infections. The CDC’s brief also “ruled out” COVID-19 as a cause. In the United Kingdom however, about 20% have uncovered active SARS-CoV-2 (the virus that causes COVID-19) infections. Other potential causes are being investigated as public health officials at the WHO and across are requesting providers share case data with local health departments in order to aggregate sufficient information.

Using the official CDC Director’s Twitter account, Dr. Rachel Walensky shared recently issued guidance to providers. The responses from users claiming a variety of expertise expressed concern at the CDC’s declaration that COVID-19 is not a potential cause for these cases. For these users, and likely parents watching the issue hit various news outlets, the omission of a potential for post-COVID responses seems odd and without an explanation and clarity as to investigative processes taken, doesn’t do a whole lot for repairing already deeply damaged public trust. Indeed, all of the readily available links on the issue from the CDC’s website exclusively point toward adenovirus, undermining the nature of investigative efforts to explore multiple potential causes. In contrast, the UK’s governmental updates outline why the COVID vaccine has been ruled out: most children affected are too young to have received the shots (the CDC’s briefing does not include this statement). The United Kingdom Health Security Agency’s latest update on this issue can be found here.

Part of why COVID is suspected is because of some of the unique features of the virus. A growing body of evidence is finding “pieces” of SARS-CoV-2 in a variety of body tissue, not just the lungs or brain as has been readily covered in other reports. One of the most persistent theories being tossed around includes hepatitis (generally, inflammation of the liver) as an issue of “long COVID” or a type of “post-viral” syndrome as a result of COVID infection. Part of the reason for that leap is SARS-CoV-2 has a special propensity for causing cell-to-cell fusion, resulting in “giant” cells with multiple nuclei and allowing the virus to spread in a body in an unusual fashion, evading the immune system. An additional concern is the issue of SARS-CoV-2 “superantigens” or a pathogen that “hyper-stimulates” immune responses. In one theory, currently being investigated, the super-antigenic effects of a COVID infection are being looked at as to the potential causation of multisystem inflammatory syndrome in children (MIS-C). Indeed, the issue is of such concern researchers have submitted to the Lancet (a leading scientific journal regarding infectious disease) an article urging providers to appropriately test tissue samples beyond blood in order to rule out potential long-lasting but harder to detect impacts of a SARS-CoV-2 infection.

Regardless of particular cause, at this stage, parents concerned about their children’s health should be aware that acute hepatitis tends to present similarly to most gastrointestinal bugs; abdominal pain, fever, vomiting, and nausea are common. Jaundice of the skin and eyes and darkening of urine are very key indicators something severe is occurring and needs immediate medical attention. Parents should contact their child’s provider if their children are expressing concerning symptoms.

One Shot or Two? Necessity of COVID-19 Vaccination Among People Living with HIV and/or Chronic Liver Disease

At the time of this writing, the United States’ Food and Drug Administration (FDA) has provided Emergency Use Authorizations (EUAs) to 3 COVID-19 vaccines, with Novavax’s product potentially leading the race to become the fourth. While some have fretted over “which vaccine” is “the best”, governors and clinicians have resoundingly adopted a simple answer: “which ever vaccine you can get”. While President Biden has pushed to expand eligibility to all adults in the US by May 1st, as we’re all too familiar with in patient advocacy, eligibility does not necessarily equate to access and, in this respect, demand still vastly outstrips vaccine supply domestically.

The debate on who should get a vaccine and when began well before the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations in December 2020. ACIP’s recommendations focused primarily on constructing an ethical model based on hospitalizations and mortality, with an eye toward those performing duties most necessary to meet the health care demands of the moment. Ultimately, outside of this job-based prioritization, ACIP gave top priority via age-based allocation and then ascertaining those at-risk for these outcomes based on pre-existing conditions. Most states adopted some version of these prioritized populations. The debate on the efficacy of this model continues to rage on – what about those in marginalized communities more impacted by COVID-19 than more affluent communities? What about younger people with comorbidities? Which health conditions should be prioritized?

Regardless of where one’s local government falls on this debate, evidence catalogued by the CDC indicates a very real need for people living with HIV and those with chronic liver diseases to seek a vaccine as readily as possible as these cohorts are at increased risk for complications related to a COVID-19 infection. Studies have found PLWH experiencing an acute COVID-19 infection may see as much as 50% drop in CD4 T-cells compared to their historical levels, a condition known as lymphopenia – of which, is also an indicator for severe COVID-19 and protracted recovery or death. Additionally, the same study found key clinical metrics used to measure inflammation were similarly increased among PLWH. Another study out of Wuhan, examining people with chronic, yet controlled Hepatitis B infections may see a reactivation of viral activity and/or potentially face significant progression of liver cirrhosis during and after a COVID-19 diagnosis. Another study found SARS-CoV-2 may target certain cells in the bile tract and cause focused damage to the systems serving a person’s liver, with another study suggesting the need for health care providers to emphasize liver repair post COVID diagnosis.

While Janssen ensured PLWH were enrolled in phase 3 clinical trials for their product, none of the currently authorized products included solid organ transplant recipients in their trials. While the American Society of Transplantation notes COVID-19 vaccine administration recommendations for solid organ transplant recipients remains the same as other vaccines (either completed at least 2 weeks prior to transplant or initiated at least 1 month after transplant). Which may pose a problem according to a study published in March showing transplant recipients having received the first shot in the series mounted an antibody response just 17% of the time. While antibody responses are not necessary to confer immunity, they are the leading indication of an immune response. The authors of this study will be seeking to answer that question later this year.

Furthermore, additional research is needed in assessing post-acute COVID-19 infections and the implications of “long COVID”. Most research at this moment on long-COVID is tied to assessing symptom presentation and frequency of health care needs. However, there is a minor bit of information regarding organ function post-hospitalization with COVID-19 – none of it is “good news”. In particular, people experiencing chronic liver diseases were almost 2 times as likely to experience “major adverse events” after being released from the hospital due to COVID-19.

All of this information culminates with a sense of urgency some states are heeding in expanding vaccine access “ahead of schedule” to include people living with HIV or specific programming targeted to provide vaccines to these communities.

Brandon Macsata, CEO of ADAP Advocacy Association, recently penned a blog addressing any hesitancy among people living with HIV around getting their vaccines: “Vaccines are an important element of the journey, along with proven public health strategies (i.e., wearing masks, remaining social distant, washing hands). For the HIV-positive community, it is even more important for us to do our collective part to protect ourselves, as well as the people around us. Get your Covid-19 vaccine!”

With the CDC’s guidance on prioritizing our communities in vaccination schemes, I couldn’t agree more.

Modeling Navigation: Hepatitis C Toolkit for Improving Care for People Who Use Drugs

In September 2020, our friends at the National Association of State and Territorial AIDS Directors announced the launch of a new hepatitis C toolkit and navigation model to improve care for people who use drugs (PWUD) and other impacted populations. NASTAD, in partnership with the New York City Health Department, spent 8 years developing this model of care navigation and the associated toolkit and has made an informational training video available to preview the program for interested health departments, providers, and community-based organizations.

The model builds upon what’s now common knowledge: clients often need help navigating complex systems of care, an influx of information, and available support. NASTAD’s training video walks viewers (and prospective partners) through nearly every aspect of the model, from staffing needs to potential funding sources. While standard roles are as expected, including program managers and data personnel, rather than strictly relying on peers, the toolkit specifically delineates between “peer navigators” and “patient navigators”, including suggested job descriptions and distinctions on educational requirements. Notably, the peer role works to support the activities of the patient navigator role (as opposed to supporting case management work directly, as seen in many HIV peer programs). Entities considering the model should note: combining these roles may weaken the efficacy of the program and, given role descriptions, overburden staff assigned to the task. Further, for these roles to be effective, providers will need to be comfortable with an active navigator advocating for and with a client. Those same providers should also note, both navigators are designed to support positive health outcomes for clients and to work in tandem with a client’s provider, including medication adherence support, follow up with provider instructions, and to ensure appointments are attended.

NASTAD’s model envisions a comprehensive approach of assessment beginning at the time of contact (either during outreach or testing activities) and throughout the care continuum. From education to treatment preparedness, the model’s training curriculum and suggested documents prompt both types of navigators to consider their language, a client’s needs in housing, stress management, co-occurring health issues, and encourage actively linking clients to resources that are not necessarily medically based. The model supports this approach from the very design of the program – highlighting the success of (and need for) syringe services programs (SSPs), medication assisted treatment (MAT), addressing maintenance of contact with a client regardless of housing status, and instructing administrators on the necessity of a robust referral network.

The virtual training includes recognition of barriers and evaluation of a case study during COVID. NASTAD notes stigma, access to care, language access, and medication prior authorization are the most common barriers to engagement, retention, and success in care. Challenges include, as we previously noted, a COVID-associated plummet in HCV testing, changes in working hours, the need to access facilities with ever changing rules of access, and technology barriers, especially for homeless clients. Successes include easier access to treatment thanks to flexibilities in insurance approvals, more easily tracking down and following up with clients thanks to “stay-at-home” orders, and easier contact tracing.

Resources at the end of the training materials are either national or based in/from New York City and prospective partners will need to consider adding to or substituting this resource list with their own, more local resources. NASTAD encourages accessing the program’s technical assistance and capacity building assistance teams and those of partners involved in developing program materials (also found in the resources section of the materials).

This model poses an opportunity that may only be limited by the will power of funders and willingness to collaborate in an environment where community-based organizations are encouraged to be everything to everyone. Funders should take note of the extraordinary potential NASTAD’s model offers and support both entities seeking to implement it and those entities implementing partners would need to rely on in order to fulfill the wrap around nature of care and navigation the model envisions.