Long-Term Pulmonary Sequelae and Immunological Markers in Patients Recovering from Severe and Critical COVID-19 Pneumonia: A Comprehensive Follow-Up Study
Authors: Strumiliene Edita , Urbonienė Jurgita , Jurgauskiene Laimute , Zeleckiene Ingrida , Bliudzius Rytis , Malinauskiene Laura , Zablockiene Birutė , Samuilis Arturas , Jancoriene Ligita 
Published: November 2024

Background and Objectives: Severe and critical COVID-19 pneumonia can lead to long-term complications, especially affecting pulmonary function and immune health. However, the extent and progression of these complications over time are not well understood. This study aimed to assess lung function, radiological changes, and some immune parameters in survivors of severe and critical COVID-19 up to 12 months after hospital discharge. Materials and Methods: This prospective observational cohort study followed 85 adult patients who were hospitalized with severe or critical COVID-19 pneumonia at a tertiary care hospital in Vilnius, Lithuania, for 12 months post-discharge. Pulmonary function tests (PFTs), including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and diffusion capacity for carbon monoxide (DLCO), were conducted at 3, 6, and 12 months. High-resolution chest computed tomography (CT) scans assessed residual inflammatory and profibrotic/fibrotic abnormalities. Lymphocyte subpopulations were evaluated via flow cytometry during follow-up visits to monitor immune status. Results: The median age of the cohort was 59 years (IQR: 51–64). Fifty-three (62.4%) patients had critical COVID-19 disease. Pulmonary function improved significantly over time, with increases in FVC, FEV1, VC, TLC, and DLCO. Residual volume (RV) did not change significantly over time, suggesting that some aspects of lung function, such as air trapping, remained stable and may require attention in follow-up care. The percentage of patients with restrictive spirometry patterns decreased from 24.71% at 3 months to 14.8% at 12 months (p < 0.05). Residual inflammatory changes on CT were present in 77.63% at 6 months, decreasing to 69.62% at 12 months (p < 0.001). Profibrotic changes remained prevalent, affecting 82.89% of patients at 6 months and 73.08% at 12 months. Lymphocyte counts declined significantly from 3 to 12 months (2077 cells/µL vs. 1845 cells/µL, p = 0.034), with notable reductions in CD3+ (p = 0.040), CD8+ (p = 0.007), and activated CD3HLA-DR+ cells (p < 0.001). This study found that higher CD4+ T cell counts were associated with worse lung function, particularly reduced total lung capacity (TLC), while higher CD8+ T cell levels were linked to improved pulmonary outcomes, such as increased forced vital capacity (FVC) and vital capacity (VC). Multivariable regression analyses revealed that increased levels of CD4+/CD28+/CD192+ T cells were associated with worsening lung function, while higher CD8+/CD28+/CD192+ T cell counts were linked to better pulmonary outcomes, indicating that immune dysregulation plays a critical role in long-term respiratory recovery. Conclusions: Survivors of severe and critical COVID-19 pneumonia continue to experience significant long-term impairments in lung function and immune system health. Regular monitoring of pulmonary function, radiological changes, and immune parameters is essential for guiding personalized post-COVID-19 care and improving long-term outcomes. Further research is needed to explore the mechanisms behind these complications and to develop targeted interventions for long COVID-19.