Morphological and immunohistochemical changes in lymph nodes in COVID-19: features of BCL-6 and CD138 expression

Lymph node involvement in COVID-19 is accompanied by significant morphofunctional changes affecting both the structure and cellular composition of organs.

Objective: To conduct a comprehensive morphological and immunohistochemical study using BCL-6 and CD138 markers on lymph nodes of patients who died from laboratory-confirmed COVID-19.

Materials and methods: Autopsy specimens from 30 patients who died from laboratory-confirmed severe COVID-19 were analyzed. Autopsy specimens from the bronchopulmonary lymph nodes of patients whose death was not associated with SARS-CoV-2 infection served as a comparison group. Pathological examination was performed using standard hematoxylin and eosin staining, and monoclonal antibodies to BCL-6 and CD138 were used for immunohistochemistry. Statistical analysis of the data was performed using descriptive and analytical statistics methods with Prism 10.4.1 software (GraphPrad Software Inc., USA).

Results: Under the conditions of the COVID-19 viral infection, an increase in lymph nodes is observed macro- and microscopically, histologically, depletion of lymphoid tissue, loss or hypoplasia of germinal centers (≈90 %), sinus histiocytosis, and microthrombosis are noted. According to the results of immunohistochemical analysis, statistically significant differences were revealed in tissue samples, indicating a decrease in the proportion of large BCL-6⁺ zones and an increase in small BCL-6⁺ structures (p = 0.008) in the lymph nodes of patients with COVID-19 compared to the control group. An increase in the total area of large CD138⁺ clusters and the proportion of small CD138⁺ structures (p = 0.004) were also recorded.

Conclusion: Viral infection causes severe lymph node damage, characterized by destruction of follicular architecture and disruption of immune cell interactions. Lymph nodes in COVID-19 demonstrate a disruption of the germinal response (↓BCL-6) and pronounced plasma cell infiltration (↑CD138), indicating a shift toward an extrafollicular humoral response. These data are important for understanding the mechanisms of immune dysfunction in COVID-19 and may serve as a morphological basis for the development of new immunomodulatory treatment strategies.