Innate immune deficiencies are associated with severity and poor prognosis in patients with COVID-19

Abstract

COVID-19 can cause acute respiratory distress syndrome, leading to death in many individuals. Evidence of a deleterious role of the innate immune system is accumulating, but the precise mechanisms involved remain unclear. In this study, we investigated the links between circulating innate phagocytes and severity in COVID-19 patients. We performed in-depth phenotyping of neutrophil and monocyte subpopulations and measured soluble activation markers in plasma. Additionally, anti-microbial functions (phagocytosis, oxidative burst, and NETosis) were evaluated on fresh cells from patients. Neutrophils and monocytes had a strikingly disturbed phenotype, and elevated concentrations of activation markers (calprotectin, myeloperoxidase, and neutrophil extracellular traps) were measured in plasma. Critical patients had increased CD13low immature neutrophils, LOX-1 + and CCR5 + immunosuppressive neutrophils, and HLA-DRlow downregulated monocytes. Markers of immature and immunosuppressive neutrophils were strongly associated with severity. Moreover, neutrophils and monocytes of critical patients had impaired antimicrobial functions, which correlated with organ dysfunction, severe infections, and mortality. Together, our results strongly argue in favor of a pivotal role of innate immunity in COVID-19 severe infections and pleads for targeted therapeutic options.

The association of airborne particulate matter and benzo[a]pyrene with the clinical course of COVID-19 in patients hospitalized in Poland

“…During this period, the antiviral defense is based on the repertoire of the innate immune response, encompassing dendritic cells, natural killer cells, macrophages, monocytes, and neutrophils, that recognize pathogen-associated and damage-associated molecular patterns to induce inflammatory signaling associated with the production of multiple interferons and cytokines ( Diamond and Kanneganti, 2022 ; Kasuga et al, 2021 ). Studies indicate that dysregulation of these responses, manifested by overactivation and hyperinflammation, can significantly favor a more severe clinical course and worsen the prognosis ( Blot et al, 2020 ; Galani and Andreakos, 2021 ; Janssen et al, 2021 ; Kapała et al, 2022 ; Peyneau et al, 2022 ). Notably, air pollutants such as PM (and PM 2.5 in particular) and B(a)P are well documented to affect innate immune responses adversely.…”

Air pollution might affect the clinical course of COVID-19 in pediatric patients

“…The period of the week before hospitalization was chosen because it most likely represented a time of transition of SARS-CoV-2 infection from incubation phase to symptomatic one, a time during which the innate immune response constitutes an essential line of the antiviral defense ( Rzymski et al, 2022 )( Kasuga et al, 2021 , Diamond and Kanneganti, 2022 ). Its disruption can lead to cellular overactivation and hyper-inflammation, subsequently favoring a more severe clinical course of COVID-19 and worsening the prognosis ( Peyneau et al, 2022 , Galani and Andreakos, 2021 , Blot et al, 2020 , Janssen et al, 2021 ). In turn, air pollutants such as PM 2.5 and B(a)P have been evidenced to promote inflammation and adversely affect innate immune response ( Glencross et al, 2020 ).…”

Rationale of using the dual chemokine receptor CCR2/CCR5 inhibitor cenicriviroc for the treatment of COVID-19

“…For preexposure prophylaxis, the monoclonal antibody combinations of tixagevimab plus cilgavimab also have an EUA from the FDA for populations who are immunocompromised and with limited expected response to vaccination [13]. This is important because unvaccinated and immunocompromised patients are at most risk for severe COVID-19 including ARDS [14][15][16][17][18].…”