Cellular and immune response in fatal COVID-19 pneumonia.

Abstract

Introduction: the severity of COVID-19, causing fatal pneumonia, acute respiratory distress syndrome (ARDS), and thrombotic complications, is linked to intense inflammation. Elevated CD4+ and CD8+ cells in the lungs indicate harmful inflammation in severe cases. This study investigates immune responses in lung tissues of deceased patients across different stages of COVID-19 pneumonia.

Methods: lung tissues from 160 fatal COVID-19 cases, diagnosed via Real-Time RT-PCR, were histologically analyzed to identify pneumonia stages. Inflammatory cell counts were assessed immunohistochemically. Non-parametric tests analyzed categorical variables, while regression analysis evaluated relationships between continuous variables.

Results: the average patient age was 68.1 years (± 12.6). Microscopic analysis identified four pneumonia stages. CD4+, CD68 (macrophages), and IgG4 levels peaked by day 14, with notable elevation within seven days of symptom onset. CD4+ levels were significantly lower in DAD pneumonia (49.4% ± 15.7%) compared to ARDS (66.4% ± 19.3%) and thrombosis (70.2% ± 28.9%) (p < 0.05). Male patients had higher CD4+ values (68.5% ± 21.1%) than females (56.9% ± 22.4%) (p < 0.05). B cells (CD20) and NK cells were depleted across all stages. IgG4 expression reached 80-90% in acute phases but was nearly absent during organization and fibrosis stages.

Conclusion: a sharp decline in CD4+ and CD8+ during acute pneumonia and sepsis reflects immune exhaustion, while their elevation in ARDS and thrombosis likely triggers cytokine storms, causing severe lung damage. Elevated IgG4 levels in acute lung tissue correlate with fatal outcomes in severe COVID-19.