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June 28, 2022
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COVID-19 vaccination recommended for patients with inborn errors of immunity

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People with inborn errors of immunity can receive COVID-19 vaccines with no greater risk for adverse events, according to a review published in Annals of Allergy, Asthma & Immunology.

Vaccination is essential for patients with inborn errors of immunity (IEI) who face elevated morbidity and mortality with COVID-19, according to the researchers, who also found these patients experienced stronger responses with messenger RNA (mRNA) vaccines.

Risks for poor antibody response with COVID-19 vaccination among patients with IEI include diagnosis of common variable immunodeficiency, IEI with presence of autoimmune complications, agammaglobulinemia, and other causes of B cell aplasia including recent rituximab treatment.
Data were derived from Durkee-Shock J, et al. Ann Allergy Asthma Immunol. 2022;doi:10.1016/j.anai.2022.06.009.

“Patients with inborn errors of immunity often have poor vaccine responses, and this population has been disproportionately impacted by the COVID-19 pandemic,” Michael D. Keller, MD, director of the translational research laboratory in the CETI (Cell Enhancement and Technologies for Immunotherapy) Program and director of the Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiency Disorders at Children’s National Hospital in Washington, D.C., told Healio.

Michael D. Keller

“We sought to analyze all current studies on COVID-19 vaccine efficacy in this vulnerable population,” said Keller, who also is an associate professor in the division of allergy and immunology at Children’s National Hospital.

The review of 26 studies involved 1,439 patients with IEI who received the Moderna mRNA-1273, Pfizer-BioNTech BNT162B2 or Johnson & Johnson Ad26.COV2.S COVID-19 vaccines, with results showing all three vaccines were immunogenic and effective.

Also, the researchers found antibody responses to COVID-19 vaccination in 72% of these patients, with stronger responses among those patients who received the Moderna and Pfizer mRNA vaccines.

However, the patients with IEI consistently had lower levels of neutralizing antibodies compared with healthy controls, according to the researchers. The researchers also found gradual decreases in titers with breakthrough infections in the months following vaccination.

Diagnosis of common variable immunodeficiency, presence of autoimmune comorbidities, agammaglobulinemia and other causes of B-cell aplasia including recent treatment with rituximab were among the risk factors for poor antibody responses.

Patients with IEI appear to experience more reactogenicity in response to mRNA vaccines compared with the general population. Although common symptoms include fever, myalgias and fatigue, their severity does not appear to be greater among patients with IEI.

Flaring of autoinflammatory disorders appears limited to insignificant as well. Further, the researchers found no evidence that patients with IEI have higher risks for adverse events with COVID-19 vaccination.

Many of these patients use immunosuppressive therapy to manage their autoimmune or autoinflammatory disease, the researchers continued, which could impact the safety and efficacy of vaccines.

Different studies in the review found various effects of these therapies on antibody responses to the COVID-19 vaccines, ranging from failures to generate antibodies to responses that were less robust than healthy controls to no impact at all.

Patients with IEI also may receive immunoglobulin replacement therapy (IGRT), which can adversely affect vaccination as well. However, the researchers did not find IGRT to have a negative impact on COVID-19 vaccination, with a varied but increasing trend in titers over time and no difference when compared with patients not receiving IGRT therapy.

The researchers additionally found that preventive therapy including monoclonal antibodies for patients who are not expected to mount adequate responses to active vaccination would be appropriate for patients with IEI as well, with case reports supporting active immunization against COVID-19 at least 2 weeks before therapy.

“There was general consensus in studies showing that many patients with IEI have some response to mRNA COVID-19 vaccines, though generally not as robust as healthy individuals,” Keller said. “There is also strong consensus that additional boosters are beneficial for protecting this population.”

Still, the researchers said, ideal vaccine regimens, booster timing and protection duration following vaccination remain unclear among patients with IEI, yet they added that they are encouraged by preliminary data on uptake of COVID-19 vaccination in this population.

Despite mild compromises in efficacy and immunogenicity among patients with IEI, the researchers said, COVID-19 vaccines seem to be safe even when autoimmune and autoinflammatory diseases are present.

“The current data strongly supports COVID-19 vaccination in patients with IEI and that mRNA vaccines are safe in this population,” Keller said.

Benefits may be limited, the researchers said, but risks are minimal for non-live vaccination platforms, with strong recommendations for mRNA vaccines when they are available for most if not all patients with IEI.

“Additional large longitudinal studies are ongoing to look at the longevity of protection against COVID-19 in IEI patients who are vaccinated,” Keller said.

These studies may provide further guidance for clinicians and patients, the researchers said.

For more information:

Michael D. Keller, MD, can be reached at mkeller@childrensnational.org.