Stuck in Pandemic Uncertainty: A Review of the Persistent Effects of COVID-19 Infection in Immune Deficient People

Background: Immune-deficient/disordered people (IDP) are underrepresented in COVID-19 studies. Specifically, there is limited research on post-SARS-CoV-2 infection outcomes, including viral persistence and long-term sequelae in these populations. <br><br>Objectives: This review aimed to examine the published literature on the occurrence of persistent SARS-CoV-2 positivity, relapse, reinfections, variant coinfection, and post-acute sequelae of COVID-19 in IDP, especially those with inborn errors of immunity. <br><br>Sources: PubMed was searched using Medical Subject Headings (MeSH) terms to identify relevant articles from the last four years. Articles on primary and secondary immunodeficiencies were chosen and a special emphasis was placed on including articles that studied people with inborn errors of immunity. The absence of extensive cohort studies including these individuals has limited most articles in this review to case reports, whereas the articles focusing on secondary immunodeficiencies include larger cohort, case-control, and cross-sectional studies. Articles discussing HIV/AIDS were excluded. <br><br>Content: Scientific literature suggests that IDP of any age are more likely to experience persistent SARS-CoV-2 infections. While adult IDP exhibit a higher rate of post-acute sequelae of COVID-19 (PASC), milder COVID-19 infections in children may reduce their risk of experiencing PASC. Reinfections and coinfections may occur at a slightly higher rate in IDP than the general population. <br><br>Implications: While IDP experience increased viral persistence and inter-host evolution, it is unlikely that enough evidence can be generated at the population-level to support or refute the hypothesis that infections in IDP are significantly more likely to result in variants of concern than infections in the general population. Additional research on the relationship between viral persistence and the rate of long-term sequelae in IDP could inform the understanding of the immune response to SARS-CoV-2 in IDP and the general population.