Omicron’s more mild nature may ease challenges for patients with immunodeficiencies

The omicron variant of the SARS-CoV-2 virus presents unique challenges for patients with immunodeficiencies and their health care providers, according to a paper published in The Journal of Allergy and Clinical Immunology: In Practice.

However, the comparatively mild nature of the omicron variant also may herald the end of the challenges created by the pandemic for these patients, Rohan Ameratunga, BHBB, MBChB, PhD, immunologist in the department of clinical immunology at Auckland Hospital in Auckland, New Zealand, and colleagues wrote.

Predicted susceptibility

Patients with innate immune system defects and those with T-cell defects generally have worse outcomes with COVID-19, the authors wrote, although most patients who have X-linked agammaglobulinemia (XLA) without comorbidities appear protected against severe disease.

Omicron is more transmissible than previous variants, but has been associated with lower rates of acute respiratory distress syndrome (ARDS), hospitalization and death, the authors wrote. Anosmia also appears to be less common with omicron, although gastrointestinal symptoms are more prominent.

According to the authors, omicron is less prone to provoking severe cytokine storms that lead to ARDS and multiple organ dysfunctions than previous variants of the virus. It also potentially is less likely to cause severe T-cell dysregulation.

As a result, the authors wrote, omicron likely will impact the disease severity and prognosis of patients with immunodeficiencies, who often have pre-existing chronic lung disease such as bronchiectasis.

Older patients with immunodeficiencies and other comorbidities such as chronic lung disease may be less susceptible to severe outcomes from omicron than previous variants, with lower fatality rates as well.

Whether patients with innate immunity and T-cell defects will have increased susceptibility to COVID-19 with omicron, as they did with previous variants, will need to be determined, the authors continued.

Diagnostic challenges, potential solutions

Patients with immunodeficiencies may face challenges in diagnosing infection with omicron, according to the authors. For example, patients with XLA do not generate antibodies, but they do have preserved cellular immune responses to vaccination for COVID-19.

There also are high titers of SARS-CoV-2 antibodies in subcutaneous and IV immunoglobulin preparations, prompting an urgent need for diagnostic T-cell assays for patients with immunodeficiencies, the authors wrote.

Because the rapid evolution of the virus may make commercial T-cell assays for SARS-CoV-2 obsolete, new assays using the omicron receptor binding domain should be developed quickly to identify breakthrough infections, the authors added.

Such assays could indicate vaccine efficacy in patients with immunodeficiencies and indicate the need for prophylactic drugs, monoclonal antibodies or other treatments, the authors wrote, while enabling personalized approaches for treating these patients.

The greater effectiveness that remdesivir (Veklury, Gilead) and molnupiravir (Lagevrio, Merck) have against omicron compared with previous variants likely will have a disproportionate benefit for patients with immunodeficiencies, the authors continued, with combinations of such drugs proving very effective in mitigating severe outcomes.

Early omicron variants appeared sensitive to sotrovimab (GSK and Vir Biotechnology) — although, as Healio previously reported, the agent lost its FDA authorization for treatment in areas of high BA.2 frequency based on a lack of efficacy — and bebtelovimab (Lilly), which can be used as prophylaxis or in the infection’s early stages to reduce the risk for progression to the pulmonary and systemic phases of the disease.

However, new monoclonal antibodies likely will need to be developed from convalescent individuals infected with omicron, the authors added.

Further, the authors were optimistic that the NZACE2-Patari project — which aims to reduce the burden of the virus in the lungs by intercepting it in the nose — would be an effective prophylactic against omicron because it is based on modified ACE2 receptors.

Patients with immunodeficiencies who have been vaccinated and have early access to effective antiviral therapeutics may be less likely to contract chronic COVID-19 as well, which the authors called a public health emergency that must be prevented at all costs.

Convalescent plasma infusions have led to vaccine and monoclonal antibody resistant clades among patients with immunodeficiencies who had chronic COVID-19 from previous virus variants.

Omicron may make chronic COVID-19 less likely, the authors wrote, but patients with immunodeficiencies who contract it may see more efficacy with convalescent plasma infusions from omicron survivors.

Vaccine strategy

The authors cautioned that many patients with immunodeficiencies have suboptimal responses to vaccines, although studies have shown that patients with common variable immunodeficiency disorders do experience partial responses to COVID-19 vaccines.

The authors suggested that three or four primary doses of the COVID-19 vaccine may adequately protect patients with immunodeficiencies against severe outcomes. Providers also should consider using heterologous vaccination with an mRNA vaccine followed by an adenovirus-based or subunit vaccine.

Healthy patients and patients with immunodeficiencies alike with hybrid immunity from infection followed by vaccination experience robust, long-term protection, the authors wrote. Omicron itself could then be considered an effective live attenuated virus vaccine in patients with immunodeficiencies who have been vaccinated.

As a result of this protection, the authors said that omicron itself may protect patients against more virulent strains of SARS-CoV-2 in the future and indicate the beginning of the end of the pandemic, providing relief for patients with immunodeficiencies.