Understanding Evolving Variants, Vaccines, and Treatment for COVID-19

As COVID-19 continues to evolve as a worldwide pandemic, research on its health-related impacts, novel variants, and vaccines have presented growing challenges for at-risk patients and health care stakeholders, according to researchers of a session presented at CHEST 2021, titled, “Viruses, Variants, Vaccines, and Virulence: The Present and Future of COVID-19.”

Presenters Shazia Jamil, MD, specialist, Pulmonary Medicine, Critical Care Medicine, and Sleep medicine, Scripps Memorial Hospital La Jolla, and Ryan Maves, MD, FCCP, professor, Infectious Diseases, Wake Forest School of Medicine, began the discussion with an overview of currently-identified COVID-19 variants and their respective effects regarding transmissibility and patient outcomes:

• Alpha variant, firstly identified in Great Britain, is 40% to 83% more transmissible and approximately 35% more deadly than original coronavirus, with no significant impact on vaccine effectiveness.
• Beta variant, firstly identified in South Africa, is highly transmissible but with no increased risk of severity or death compared with original coronavirus. Vaccine efficacy is compromised with Beta variant vs with Alpha variant.
• Lambda variant, firstly identified in Peru, has not yet outcompeted any of the other more dominant variants. Associated with 2-fold increase in virus shedding and 2-fold decrease in neutralizing antibodies of vaccinated donors.
• Delta variant, firstly identified in India, is the predominant variant in the United States. Associated with a 5.8-fold decrease in neutralizing antibody titers compared with other variants, greater incidence of infection in unvaccinated individuals vs vaccinated (73% vs 3.7%), and greater risk of hospitalization vs those infected with other variants

“In simple terms, the virus is becoming more and more efficient, it wants to mutate, it wants to survive,” said Jamil. “Viruses need hosts to mutate–host gene editing accounts for almost 65% of reported mutations. This is not a random genetic drift, and therefore the first and foremost step to curb mutation is inhibition of replication. It is critical to continue to implement strict public health measures by all that are vaccinated or nonvaccinated.”

Continuing the discussion on preventive measures, Maves focused on at-risk populations, particularly the efficacy of current vaccine and monoclonal antibody treatment strategies.

As the latest wave of COVID-19 infections begin to level off after the significant surge associated with the Delta variant, deaths have also decreased, but remain markedly high with approximately 1500 Americans dying each day from the virus, said Maves.

“Thankfully this appears to be coming down at least in some parts of the country, but certainly not all of them, with heavy ongoing surges in northern Idaho, Utah, Eastern Washington, and Montana, particularly in areas with limited hospital resources and limited access to advanced critical care due to geographic distance,” he added.

Despite 77% of eligible Americans having received at least 1 dose of a COVID-19 vaccine, the “pandemic of the unvaccinated” continues to increase the risk of developing more infectious and deadly virus mutations, but most notably, poses a growing threat for at-risk populations whose risk of infection and serious disease are significantly greater than the general population.

Including those who are immunocompromised, pregnant, obese, and elderly (≥ 65 years), as well as people with diabetes and end-stage renal disease, current preventive measures against COVID-19 in these populations, even those fully vaccinated, may warrant increased investigation and action due to declining vaccine efficacy over time and risk of breakthrough infections associated with the Delta variant.

Addressing current preventive measures, Maves highlighted 4 key areas:

• Nonpharmacologic interventions (eg, mask wearing, social distancing, avoiding large crowds)
• 3-dose primary series of mRNA COVID-19 vaccination for at-risk populations
• Booster shots
• Immunotherapy with monoclonal antibodies

With recent evidence reported in JAMA finding that immunocompromised individuals who underwent solid organ transplants remained at risk for COVID-19 following 2 doses of mRNA vaccine, the potential of a 3-dose primary series of mRNA COVID-19 vaccines may improve protection for these populations.

In fact, another study in the New England Journal of Medicine finds that transplant recipients who were given a third dose of mRNA vaccine were associated with 71% virus neutralization vs 13% of those who received solely 2 doses.

“One of the beauties of the mRNA, technology is that it provides a way to provide not just a humoral response in terms of antibodies, but also a cell mediated immune response without having to give a live virus vaccine which is the historical way that we've been able to produce cell mediated immunity,” said Maves.

“It's a bit of a semantic trick but it's useful to consider that the third dose in the immunocompromised is not a booster, that is a third dose of their primary series–their primary series is not complete until they receive that third dose,” he further explained. “Boosters, on the other hand, are an opportunity to enhance immunity in someone who has already been completely vaccinated, and that is 6 months after they've completed their second dose.”

Regarding investigational monoclonal antibody therapies, currently available products include bamlanivimab plus etesevimab, casirivimab plus imdevimab (REGEN-COV), and sotrovimab.

In findings of 2 NEJM studies, REGEN-COV was firstly associated with a 71.3% reduction in hospitalization and death and 4-day reduction in symptom duration in patients with COVID-19 who had risk factors for severe disease. Findings of the other study highlighted the potential of REGEN-COV as a preventive measure for COVID-19, with an 83% reduction found in the risk of progressing to symptomatic disease after being exposed to COVID-19.

Ultimately, there remains a high degree of resource availability for at-risk populations, noted Maves, but these added resources may also raise concerns for equity, both in different regions and populations of the United States and globally.