Both coronavirus disease 2019 (COVID-19) and mycobacterial immune reconstitution inflammatory syndrome (IRIS) in patients with HIV-1 infection result from immunopathology that is characterized by increased production of multiple pro-inflammatory chemokines and cytokines associated with activation of myeloid cells (monocytes, macrophages and neutrophils). We propose that both conditions arise because innate immune responses generated in the absence of effective adaptive immune responses lead to monocyte/macrophage activation that is amplified by the emergence of a pathogen-specific adaptive immune response skewed towards monocyte/macrophage activating activity by the immunomodulatory effects of cytokines produced during the innate response, particularly interleukin-18. In mycobacterial IRIS, that disease-enhancing immune response is dominated by a Th1 CD4 + T cell response against mycobacterial antigens. By analogy, it is proposed that in severe COVID-19, amplification of monocyte/macrophage activation results from the effects of a SARS-CoV-2 spike protein antibody response with pro-inflammatory characteristics, including high proportions of IgG3 and IgA2 antibodies and afucosylation of IgG1 antibodies, that arises from B cell differentiation in an extra-follicular pathway promoted by activation of mucosa-associated invariant T cells. We suggest that therapy for the hyperinflammation underlying both COVID-19 and mycobacterial IRIS might be improved by targeting the immunomodulatory as well as the pro-inflammatory effects of the ‘cytokine storm’.
【저자키워드】 COVID-19, SARS-CoV-2, human immunodeficiency virus type 1, Interleukin-18, immune reconstitution inflammatory syndrome, 【초록키워드】 coronavirus disease, Neutrophils, Monocytes, Macrophage, immune response, therapy, innate immune response, severe COVID-19, antibody, T cells, Antibody Response, Th1, cytokine, immunopathology, CD4, chemokine, immune, B cell, amplification, Characteristics, hyperinflammation, SARS-CoV-2 spike protein, immunomodulatory, Patient, pathway, antigens, IgG3, Adaptive immune response, T cell response, Inflammatory, innate response, Activation, syndrome, mycobacterial, HIV-1 infection, myeloid cell, IgA2, pro-inflammatory, immunomodulatory effect, Effect, effective, IgG1 antibodies, produced, amplified, proportion, characterized, condition, absence, activating, promoted, pathogen-specific, arise, skewed, 【제목키워드】 emergence, response, fire, fuel, Adding,