The Immunogenicity and Safety of COVID-19 and Influenza Vaccine Co-administration and Interval in Immunocompromised Hosts

Background:

People living with immunocompromising conditions (PLIC) are more susceptible to complications related to respiratory infections. According to Statistics Canada data, in 2020 approximately 14% of Canadians aged 15 years or older suffered from a compromised immune system. PLIC (e.g., solid organ transplant (SOT) recipients, people living with human immunodeficiency viruses (PLWH), inflammatory bowel disease (IBD), or systemic autoimmune rheumatic diseases (RD) are at risk for experiencing a wide range of respiratory infections. A recent North American study assessed the socioeconomic burden associated with immunocompromising conditions. MarketScan datasets from 2017-2021 showed that PLIC accounted for 32% of hospitalizations for acute respiratory infections (representing a 5-8-fold higher risk than in non-immunocompromised hosts).

PLIC are at elevated risk of severe infection and death from COVID-19 increasing burden to patients and healthcare systems. Often including members of diverse ethnocultural origin, PLIC have also been among the most significantly affected by the COVID-19 pandemic. Vaccination is the most effective way to reduce the severity respiratory disease and infection-associated complications in the general population. Yet, suboptimal immune status results in a higher risk for COVID-19-related hospitalization (up to 13-fold) and death (up to 19-fold) compared with the general population in many PLIC, with substantial implications for healthcare burden and costs, despite PLIC comprising but a minority of the overall population.

Immunogenicity and protection from severe disease can be improved in PLIC with COVID-19 booster doses. A systematic review by the COVID-19 evidence network found that PLIC were more susceptible to severe infections and hospitalizations with emerging variants when compared with the general public. This was attributed to immunomodulatory agents (e.g., calcineurin inhibitors, antimetabolites, steroids, cytotoxic therapy, biological response modifiers) impairing the formation of memory T cells, decreasing cellular-mediated immune responses, and limiting capacity to seroconvert and sustain protective immune memory responses. For example, a meta-analysis in SOT found seroconversion and cellular response rates of 39.2% (95% confidence interval [CI], 33.3%-45.3%) and 41.6% (95% CI, 30.0%-53.6%), respectively, after the primary series in solid organ transplant (SOT).

As the pandemic progressed, it was observed that three or four doses of COVID-19 vaccines increased immunogenicity and protected against severe disease requiring hospitalization, with antibody response being most pronounced in the presence of hybrid immunity, arising when SARS-CoV-2 infection was paired with multiple vaccinations. Importantly, decreased immunogenicity has been observed in PLIC in relation to other vaccines, such as the Inactivated Influenza Vaccine (IIV), warranting high-dose (HD) IIV administration to accomplish seroconversion.