Introduction

Enterovirus D68 (EV-D68) is gaining attention in the United States because of its association with large-scale outbreaks of severe respiratory disease and acute flaccid paralysis48 - 51. In children and people with compromised immune systems, however, this virus — a member of the non-polio enterovirus family, which typically causes cold-like symptoms at first but can progress to more serious illnesses — can sometimes lead to severe cases.

Historical Perspective and Outbreaks

EV-D68 — so named because it was first discovered in California in 1962 — until putting the virus on the map with a large outbreak in 2014, when severe cases of respiratory distress that required hospitalization began to be reported. Since that time, they have tracked frequent surges, typically occurring in conjunction with late summer and fall respiratory virus season. This virus is transmitted by people coming into contact with respiratory droplets from coughs and sneezes of those infected, as well as touching surfaces contaminated with the virus. In major outbreaks, such as that of 2014, the virus demonstrated an ability to spawn regional health crises of unparalleled magnitude; a reality which spawned significant research into understanding the origins and pathogenesis

Relation to Polio and Neurological Complications

Though EV-D68 is a non-polio enterovirus, its association with AFM—a disease of the spinal cord resulting in sudden-onset paralysis—has similarities to the dreaded poliovirus. But unlike the polio, EV-D68 has no known vaccine, heightening fears of even more outbreaks. While uncommon, EV-D68 can cause paralysis and extreme muscle weakness due to its neurotropic nature and when combined with a neurological syndrome called myelitis it has the potential to permanently paralyze young children.

Current Treatments and Management Strategies

No specific antiviral treatments are indicated for the treatment of EV-D68; management is largely supportive. In mild cases, we make sure that the patients stay hydrated and manage asthma symptoms while ensuring hospitalization for respiratory support in severe ones. This supportive care is also essential for avoiding complications from respiratory distress, particularly in the consequences of those with asthma​ who are at a higher risk of severe symptoms.
 

Research and Development of New Therapies for Enterovirus D68

Treatments for Enterovirus D68 (EV-D68) — which has been linked to severe respiratory and neurological illnesses including acute flaccid myelitis (AFM) — are advancing, though no antiviral or specific treatments yet exist for the illness that primarily impacts children. There are currently no FDA-approved treatments targeting EV-D68 or AFM, so supportive care is the mainstay of management. While recent breakthroughs have led to the launching of clinical trials with monoclonal antibodies for highly specific treatment.

Monoclonal Antibody Development

One promising approach to further studies is the monoclonal antibody EV68-228-N which has been derived using blood from recipients recovered from EV-D68 infections. This antibody has demonstrated the ability to potently neutralize multiple EV-D68 strains in preclinical research.

• Clinical Trials: Mining and refining EV68-228-N began with a phase I clinical trial that was sponsored by the National Institutes of Health (NIH) to evaluate safety, dosing recommendations, and pharmacokinetics. The trial studies are ongoing and recruiting healthy adult volunteers, 18-49 years of age. People are given the antibody in different doses to see how well it is tolerated and how long it sticks around in the body.
• Trial Design: This is a double-blinded, placebo-controlled study taking place at key sites such as the Vanderbilt University Medical Center and the University of Maryland. This includes close watch on the participants, especially as they receive treatments initially, both to monitor safety and gain an early hint of how effective a treatment may be.
• Manufacturing and Innovation: KBio and ZabBio have developed a plant-based platform for the antibody using Advanced Technology in Biopharmaceutical production from plants, a quick, lower-cost way to make biopharmaceuticals. The platform is a major advancement in monoclonal antibody development, which could lead to significantly reduced response times during public health crises.

Implications and Future Directions

The research through clinical trials is critical in the management strategy of EV-D68 infections and its complications. Success in developing EV68-228-N could enable a transformational therapy for this virus and have great utility to public health since the disease emerges on an irregular basis, and frequently leads to severe outcomes. Ongoing research and cooperation among scientists are needed to more fully understand the claims of EV-D68 or related pathogens.

Preventive Measures

Because EV-D68 is a respiratory pathogen associated with severe manifestations and has the potential to cause outbreaks, especially in children and individuals with certain medical conditions (e.g., asthma), strategies for prevention are needed. The measures that have been recommendation according to the current health guidelines are essentially preventive in nature and are specified as follows:

• Basic Hygiene Practices

• Handwashing: Wash hands often and thoroughly with soap and water for at least 20 seconds, especially after coughing, sneezing or visiting public places, as well as touching surfaces in those areas.
• Hand Sanitizers: It can reduce the possibility of passing germs in situations where soap is not available by using a 60% alcohol-based hand sanitizer.
• Respiratory Etiquette

• Cover Your Coughs and Sneezes: Cover your mouth and nose with a tissue or use the inside of your elbow when you cough or sneeze.
• Avoid Touching Your Face: Advise Each and every one You Know (especially children ) Not to touch their eyes, nose, or mouth with unwashed hands.
• Social Distancing and Mask-Wearing

• Avoid Close Contact: Stay away from people who are sick. If EV-D68 is widespread, try to avoid crowded locations like those mentioned above.
• Use of Masks: Wearing a mask, such as in crowded or high-risk spaces, to help contain respiratory droplets, particularly when physical distancing is difficult.
• Clean and Disinfect Frequently Touched Surfaces

• Regular Cleaning: Routinely clean and disinfect frequently touched surfaces such as doorknobs, light switches, electronics, toys, and other things.
• Vaccinations and Health Monitoring

• Flu Vaccine: There are no vaccines for preventing EV-D68 infections, but the flu shot can protect against influenza and help reduce the overall burden of respiratory illness.
• Monitor Health: Watch for respiratory symptoms, particularly in children and those with underlying health conditions. Early detection and medical consultation can prevent severe outcomes.
• Special Considerations for High-Risk Groups

• Asthma Management: Individuals with asthma should have an up-to-date asthma action plan and should use it for this EV-D68 outbreak period. This can involve daily reliance on preventative inhalers and the ability to take a rescue inhaler as needed.
• Public Awareness and Education

• Community Education: Health regulators should educate the public about EV-D68, its clinical symptoms, mode of transmission, and preventive measures. It can enable communities to proactively respond to mitigate the spread of the virus.
• Travel Considerations

• Stay Informed: Find out any travel advisories or EV-D68 outbreak reports before traveling; consider delaying travel to areas of high transmission.

By adhering to these preventive measures, individuals and communities can significantly reduce the risk of transmission of EV-D68 and protect those most vulnerable to severe diseases. These strategies are also effective against other respiratory viruses, making them valuable practices beyond just EV-D68 outbreaks.

Conclusion

The sustained nature of EV-D68, which has affected several children, demonstrates the importance of continued surveillance and investigation. Although no vaccine or specific antiviral for EV-D68 is available at present, progress in research and public health interventions are essential to help address the lifecycle of this virus, leading to a future where these viral infections will have a lesser burden. Implications for Public Health Prevention practices can ensure proper diagnosis and management of EV-D68, improve outcomes, and decrease the community burden of disease through public and healthcare provider awareness.