Immunomodulation for Severe COVID-19 Pneumonia: The State of the Art

Abstract

COVID-19 has become a worldwide pandemic caused by the novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe cases of COVID-19 have accounted for 10-20% of all infections, leading to more than 500,000 deaths. Increasing evidence has suggested that the inflammatory cytokine storm originating from the anti-SARS-CoV-2 immune response plays an important role in the pathogenesis of critically ill patients with COVID-19, which leads to mixed antagonistic response syndrome (MARS). In the early stage of severe COVID-19, systemic inflammatory response syndrome causes acute respiratory distress syndrome, multiple organ dysfunction syndrome, and even multiple organ failure. In the late stage of severe disease, increased production of anti-inflammatory cytokines drives the immune response to become dominated by compensatory anti-inflammatory response syndrome, which leads to immune exhaustion and susceptibility to secondary infections. Therefore, precise immunomodulation will be beneficial for patients with severe COVID-19, and immunosuppressive or immune enhancement therapy will depend on the disease course and immune status. This review summarizes the current understanding of the immunopathogenesis of severe COVID-19, especially the role of the inflammatory cytokine storm in disease progression. Immune indicators and immunotherapy strategies for severe COVID-19 are reviewed and the potential implications discussed.

Keywords: coronavirus disease 2019; critical illness; immunomodulation; pneumonia; severe acute respiratory syndrome coronavirus 2.

Figure 1

Profile of the immune response of severe COVID-19 and potential immunotherapeutic approaches. IL, interleukin; NLR, neutrophil-to-lymphocyte ratio; LY, lymphocyte; IFN-γ, interferon-γ; IP-10, IFN-γ-inducible protein-10; TCMs, traditional Chinese medicines; IVIG, intravenous immunoglobulin; PD-1, programmed cell death-1; PD-L1, programmed death ligand 1.