COVID-19 pneumonia and immune-related pneumonitis: critical issues on differential diagnosis, potential interactions, and management

Abstract

Introduction: The COVID-19 pandemic occurred amid the cancer immunotherapy revolution. Immune checkpoint inhibitors (ICIs) have become the standard of care for several solid cancers and are associated with peculiar toxicities, including pneumonitis which has similar features to COVID-19 pneumonia. Areas covered: We summarize the main hallmarks of lung injury induced by ICIs and severe acute respiratory syndrome coronavirus 2 and discuss the critical aspects for differential diagnosis and management. Symptoms and radiological findings are often similar; conversely, treatments are quite different. Furthermore, we focus on potential interactions generating hypotheses that need confirmatory studies. Expert opinion: All cancer patients treated with immunotherapy should receive screening for SARS-CoV-2. This would improve the diagnosis and management of pneumonia and guide therapeutic choices. Furthermore, clinicians could estimate the risk/benefit of continuing ICI treatment in COVID-19 positive patients. Temporary withdrawal of the immunotherapy treatment pending resolution of viral infection may be a reasonable option in long-responders patients.

Unbiased Analysis of Temporal Changes in Immune Serum Markers in Acute COVID-19 Infection With Emphasis on Organ Failure, Anti-Viral Treatment, and Demographic Characteristics

“…Other analyses suffered from a small sample size (23). The large-scale proteomics analysis's primary goal is to deliver clues to potential mechanisms leading to disease pathology, especially if combined with longitudinal analysis of marker dynamics (1,11,23,24). However, such studies generate large amounts of data that are often difficult to put in the context of illness.…”

“…The treatments in COVID-19 should modulate the direct viral cytotoxicity and immune system response to infection (7,28,29). The ideal therapy for viral septicemia should reverse immune dysfunctions, normalize immunological mediators, and reverse organ failures (7,11,24). However, it is unclear how any proposed treatments for COVID-19 would alter the immunological reaction in the yet-to-be-described immunological landscape of the COVID-19 disease.…”

Deep Learning Algorithm Trained with COVID-19 Pneumonia Also Identifies Immune Checkpoint Inhibitor Therapy-Related Pneumonitis

“…Additionally, a “transfer learning” strategy, including some ICI patients’ CT data, should be tested and adapted for the partial training of algorithms. This is particularly important, as COVID-19 pneumonia cases are expected to decrease in the future and might become epidemiologically less relevant with the development and distribution of adequate vaccination therapies, whereas the number of ICI therapy-related pneumonitis is predicted to increase according to the increasing usage of ICI in cancer patients [ 34 ].…”

Immune checkpoint inhibitor does not increase risks of poor outcomes in cancer patients with COVID-19 infection: A systematic review and meta-analysis

“…First, recent reports have suggested that COVID-19 infection may mask ICI-related pneumonitis symptoms, thus potentially delaying essential treatments. [7,35] Although this might be detrimental considering that ICI-related pneumonitis accounts for about one-third of treatment-related deaths, their incidence is relatively rare. Furthermore, the risks of ICI pneumonitis tend to be augmented in early ICI recipients and super-responders [36], suggesting that a prompt and accurate risk strati cation, in addition to increased COVID-19 vigilance, may be able to mitigate this issue.…”