Role of Host Immune and Inflammatory Responses in COVID-19 Cases with Underlying Primary Immunodeficiency: A Review

J Interferon Cytokine Res. 2020 Dec;40(12):549-554. doi: 10.1089/jir.2020.0210.


Coronavirus disease 2019 (COVID-19) has spread rapidly and become a pandemic. Caused by a novel human coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), severe COVID-19 is characterized by cytokine storm syndromes due to innate immune activation. Primary immunodeficiency (PID) cases represent a special patient population whose impaired immune system might make them susceptible to severe infections, posing a higher risk to COVID-19, but this could also lead to suppressed inflammatory responses and cytokine storm. It remains an open question as to whether the impaired immune system constitutes a predisposing or protective factor for PID patients when facing SARS-CoV-2 infection. After literature review, it was found that, similar to other patient populations with different comorbidities, PID patients may be susceptible to SARS-CoV-2 infection. Their varied immune status, however, may lead to different disease severity and outcomes after SARS-CoV-2 infection. PID patients with deficiency in antiviral innate immune signaling [eg, Toll-like receptor (TLR)3, TLR7, or interferon regulatory factor 7 (IRF7)] or interferon signaling (IFNAR2) may be linked to severe COVID-19. Because of its anti-infection, anti-inflammatory, and immunomodulatory effects, routine intravenous immunoglobulin therapy may provide some protective effects to the PID patients.

Keywords: COVID-19; IVIG; SARS-CoV-2; cytokine release syndrome; innate immunity; primary immunodeficiency.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • COVID-19 / complications*
  • COVID-19 / immunology*
  • Comorbidity
  • Disease Susceptibility
  • Humans
  • Immune System*
  • Immunity, Innate
  • Immunoglobulins, Intravenous / metabolism
  • Inflammation*
  • Interferon Regulatory Factor-7 / metabolism
  • Pandemics
  • Primary Immunodeficiency Diseases / complications*
  • Primary Immunodeficiency Diseases / immunology*
  • Receptor, Interferon alpha-beta / metabolism
  • Risk
  • Toll-Like Receptor 3 / metabolism
  • Toll-Like Receptor 7 / metabolism


  • IFNAR2 protein, human
  • IRF7 protein, human
  • Immunoglobulins, Intravenous
  • Interferon Regulatory Factor-7
  • TLR3 protein, human
  • TLR7 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptor 7
  • Receptor, Interferon alpha-beta