Differentiation of COVID-19 Pneumonitis and ICI Induced Pneumonitis

Abstract

Immune checkpoint inhibitors (ICI) have become the standard of care treatment for several tumor types. ICI-induced pneumonitis is a serious complication seen with treatment with these agents. Cancer has been reported to be one of the risk factors for severe coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that has engulfed the world in the last couple of months. In patients with cancer treated with ICI who present at the emergency department with respiratory symptoms during the COVID-19 pandemic, correct diagnosis can be challenging. Symptoms and radiological features of ICI pneumonitis can be overlapping with those of COVID-19 related pneumonia. For the latter, dexamethasone and remdesivir have shown encouraging results, while vaccines are currently being evaluated in phase III trials. The mainstay of treatment in ICI pneumonitis is immunosuppressive therapy, as this is a potentially fatal adverse event. It has been speculated that immunosuppression may be associated with increased risk of progression to severe COVID-19, especially during the early stage of infection with SARS-CoV-2. Therefore, distinction between these two entities is warranted. We summarize the clinical, radiological features as well as additional investigations of both entities, and suggest a diagnostic algorithm for distinction between the two. This algorithm may be a supportive tool for clinicians to diagnose the underlying cause of the pneumonitis in patients treated with ICI during this COVID-19 pandemic.

Keywords: COVID-19; SARS-CoV-2; co-rads; immune check inhibitor (ICI); pneumonitis.

Figure 1

(A,B) A patient with ICI pneumonitis. Although ground glass opacities are present (A), consolidations outside the areas of ground glass opacities are the dominant feature (B), corresponding to a pattern of organizing pneumonia. (C,D) Two cases of RT-PCR proven COVID-19. One patient with typical well-demarcated slightly rounded subpleural ground glass opacities with thickened inter- and intralobular septa within this area (crazy paving): CO-RADS 5 (C). The second patient shows well-demarcated, but not rounded, bilateral subpleural ground glass opacities with early thickening inter- and intralobular septa (D). During the COVID-19 pandemic this case was judged as very highly suspicious (CO-RADS 5), but this case lacks confirmatory features.

Figure 2

Diagnostic algorithm for discrimination between COVID-19 and ICI pneumonitis. CRP, C-reactive protein; ERS, erythrocyte sedimentation rate; PT, prothrombin time; S-IL-2-R, soluble interleukin 2 receptor; IL-6, interleukin 6; BAL, bronchoalveolar lavage; GGO, ground-glass opacity; OP, organizing pneumonia; NSIP, non-specific interstitial pneumonia; HP, hypersensitivity pneumonitis. For features of OP, NSIP, and HP we refer to the accompanying text.