Immune Responses in Pulmonary Sarcoidosis Following COVID-19

Anna Starshinova^1,2*Igor Vladimirovich Kudryavtsev^2,3Artem Rubinstein^2,3Tatiana Akisheva³Alexey Golovkin²Zoia Korobova³Anastasia Kulpina^1,2Dmitry Kudlay^4,5,6

• ¹Saint Petersburg State University, Saint Petersburg, Russia
• ²Almazov National Medical Research Centre, Saint Petersburg, Russia
• ³Institute of Experimental Medicine (RAS), Saint Petersburg, Russia
• ⁴I.M. Sechenov First Moscow State Medical University, Moscow, Moscow Oblast, Russia
• ⁵Lomonosov Moscow State University, Moscow, Moscow, Russia
• ⁶FSBI SSC Institute of Immunology, Moscow, Moscow Oblast, Russia

Background/Objectives: The complex interplay between sarcoidosis and COVID-19 remains an important area of research, since COVID-19 leads to long-term changes in the immune system. However, COVID-19 is often followed by autoimmune diseases, including newly manifesting sarcoidosis. The goal of this study is to characterize CD4+ T cell subsets, playing a pivotal role in the regulation of innate and adaptive immunity, in the peripheral blood of patients with sarcoidosis after COVID-19. Methods: The peripheral blood samples from patients with sarcoidosis (n = 61) were studied. We divided patients into two distinct groups: sarcoidosis patients with no history of COVID-19 (n= 30) and COVID-19 convalescent patients with sarcoidosis within 12–24 weeks after recovery (n = 31). Healthy controls (n = 40) were similar in terms of age and sex to patients with sarcoidosis. Immunophenotyping of peripheral blood cells was performed using a ten-color flow cytometry. Results: Sarcoidosis patients with COVID-19 history had higher levels of T-helper cells (Th) when compared to COVID-19 naïve patients with sarcoidosis, but lower levels when compared to healthy controls. In COVID-19 convalescent patients with sarcoidosis, we noted higher absolute numbers and percentages of CD45RA–CCR7– and CD45RA+CCR7– cells within Th subset. Among COVID-19 convalescent patients with sarcoidosis we also found higher levels of T helper 1 cells and T helper 2 cells (with CXCR5–CCR6–CXCR3+CCR4– and CXCR5–CCR6–CXCR3–CCR4+ phenotypes, respectively) when compared to other groups. We also noted a statistically significant increase in central memory CXCR5+CCR6–CXCR3– follicular Th cells, as wells as effector memory CXCR5+CCR6–CXCR3– and CXCR5+CCR6+CXCR3– follicular Th cells in both groups of patients with sarcoidosis vs. healthy controls. Conclusions: Our study demonstrated Th cells imbalance in patients with sarcoidosis and COVID-19 history. These findings suggest possible clinical and visual progression of chronic lung sarcoidosis in COVID-19 convalescent patients.