Major Decrease of HLA-DR on CD14 Monocytes Is Associated with SRF
Immunoparalysis of sepsis is characterized by significant decrease of the number of HLA-DR molecules on CD14 monocytes. This also happens in immune dysregulation caused by SARS-CoV-2 (Figures 1A and 1B). Although patients with bacterial-CAP-associated MAS also have decreased HLA-DR molecules on CD14 monocytes, their circulating ferritin is significantly higher than normal. This is a feature found only in a few patients with SARS-CoV-2 and MAS (Figure 1C). The absence of traits of MAS among cases of SARS-CoV-2 with immune dysregulation is further proven by the low scores of hemophagocytosis (HS). HScore is proposed as a classification tool for secondary MAS, and values more than 169 are highly diagnostic (Fardet et al., 2014). Seven patients with SARS-CoV-2 had HS above this cut-off, and all were properly classified by using ferritin (Figure 1D). Among patients with bacterial CAP at an intermediate immune state, the number of molecules of HLA-DR on their CD14 monocytes was lower than in healthy patients. However, patients with pneumonia caused by SARS-CoV-2 at an intermediate immune state maintained their number of molecules of HLA-DR on CD14 monocytes much closer to the healthy condition. When this number suddenly dropped, SRF supervened (Figures 1A and 1B). Moreover, the absolute counts of neutrophils and monocytes were higher among patients with immune dysregulation than patients with MAS (Figures 1E and 1F).
Figure 1 Characteristics of Immune Dysregulation of COVID-19
(A) Absolute numbers of the molecules of the human leukocyte antigen (mHLA-DR) on CD14 monocytes. Patients with bacterial CAP and CAP caused by SARS-CoV-2 are classified into three states of immune activation: intermediate, immunoparalysis for bacterial CAP and dysregulation for COVID-19, and MAS.
(B) Mean fluorescence intensity (MFI) of HLA-DR on CD14 monocytes of healthy volunteers and of patients with CAP caused by SARS-CoV-2 classified according to their state of immune activation.
(C) Ferritin concentrations in the serum of patients with bacterial CAP and sepsis and CAP caused by SAR-CoV-2 according to their state of immune activation.
(D) Hemophagocytosis score among patients with CAP caused by SARS-CoV-2 classified according to their state of immune activation.
(E) Absolute neutrophil counts among patients with CAP caused by SARS-CoV-2 classified according to their state of immune activation.
(F) Absolute monocyte counts among patients with CAP caused by SARS-CoV-2 classified according to their state of immune activation.
Bars in each graphic represent mean values and standard errors. Statistical comparisons are indicated by the arrows; ns: non-significant; ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001. Comparisons were done by the Mann-Whitney U test followed by correction for multiple comparisons.