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Background: Immune checkpoint inhibitors (ICIs) are increasingly included in management guidelines for various types of cancer. However, immune-related adverse events (irAEs) are an inevitable consequence of these therapies. Some of these side effects, such as pneumonitis, can be particularly serious. Additionally, the combination of ICIs with radiotherapy (RT) may further increase the risk of pneumonitis. Objective: The aim of this systematic review is to examine all available studies on pneumonitis following the use of ICIs and RT to assess its appearance and severity. Methods: We systematically searched four different databases (PubMed, Scopus, Cochrane, and DOAJ) to identify all relevant studies within our scope. Additionally, we reviewed the references of the studies we found, as well as those of other systematic reviews and meta-analyses. We assessed the risk of bias using the Cochrane Risk of Bias Tool version 2 for randomized controlled trials and the RTI Risk of Bias Item Bank for non-randomized trials. Finally, we extracted relevant data into an Excel file and presented them in tables throughout this study. Results: A total of 58 articles met our inclusion criteria, comprising 4889 patients across multiple studies and nine case reports. Due to significant heterogeneity in study methodologies and data reporting, a cumulative statistical analysis was not performed. The included studies were published between 2017 and 2025. The incidence of pneumonitis varied, with retrospective studies showing higher rates compared to randomized and non-randomized controlled trials. Case reports described a range of pneumonitis presentations, treatments, and outcomes, with corticosteroids being the primary treatment. Conclusions: The incidence of pneumonitis varied, with retrospective studies showing the highest rates compared to other study designs. Early detection and management of pneumonitis in patients receiving RT and/or ICIs are crucial for improving outcomes. Identifying high-risk patients through predictive models, radiomics, and biomarkers may help tailor treatment strategies and minimize toxicity. Further research is needed to establish the most appropriate diagnostic criteria, optimize management approaches, and refine advanced imaging and biomarker-based risk stratification to improve patient care. Interdisciplinary collaboration is essential for reducing the risk of pneumonitis and improving patient outcomes.

Background: Dysregulation of the immune response in the course of COVID-19 has been implicated in critical outcomes. Lymphopenia is evident in severe cases and has been associated with worse outcomes since the early phases of the pandemic. In addition, cytokine storm has been associated with excessive lung injury and concomitant respiratory failure. However, it has also been hypothesized that specific lymphocyte subpopulations (CD4 and CD8 T cells, B cells, and NK cells) may serve as prognostic markers for disease severity. The aim of this study was to investigate possible associations of lymphocyte subpopulations alterations with markers of disease severity and outcomes in patients hospitalized with COVID-19. Materials/Methods: A total of 42 adult hospitalized patients were included in this study, from June to July 2021. Flow-cytometry was used to calculate specific lymphocyte subpopulations on day 1 (admission) and on day 5 of hospitalization (CD45, CD3, CD3CD8, CD3CD4, CD3CD4CD8, CD19, CD16CD56, CD34RA, CD45RO). Markers of disease severity and outcomes included: burden of disease on CT (% of affected lung parenchyma injury), C-reactive protein and interleukin-6 levels. PO2/FiO2 ratio and differences in lymphocytes subsets between two timepoints were also calculated. Logistic and linear regressions were used for the analyses. All analyses were performed using Stata (version 13.1; Stata Corp, College Station, TX, USA). Results: Higher levels of CD16CD56 cells (Natural Killer cells) were associated with higher risk of lung injury (>50% of lung parenchyma). An increase in CD3CD4 and CD4RO cell count difference between day 5 and day 1 resulted in a decrease of CRP difference between these timepoints. On the other hand, CD45RARO difference was associated with an increase in the difference of CRP levels between the two timepoints. No other significant differences were found in the rest of the lymphocyte subpopulations. Conclusions: Despite a low patient number, this study showed that alterations in lymphocyte subpopulations are associated with COVID-19 severity markers. It was observed that an increase in lymphocytes (CD4 and transiently CD45RARO) resulted in lower CRP levels, perhaps leading to COVID-19 recovery and immune response homeostasis. However, these findings need further evaluation in larger scale trials.