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Checkpoint inhibitor pneumonitis mimicking COVID-19 infection during the COVID-19 pandemic

2020; Elsevier BV; Volume: 146; Linguagem: Inglês

10.1016/j.lungcan.2020.06.013

1872-8332

Hsu-Liang Chang, Po-Ju Wei, Kuan‐Li Wu, Hung‐Ling Huang, Chih‐Jen Yang,

Pharmacological Receptor Mechanisms and Effects

As of May 27, 2020, 5,612,601 people have been diagnosed with COVID-19 and 349,060 deaths have been recorded, with a mortality rate of up to 6.22 % worldwide. Despite the current COVID-19 pandemic, many advanced lung cancer patients continue to receive regular immunotherapy, such as programmed cell death protein 1 (PD-1), programmed cell death protein 1 ligand (PDL-1) checkpoint inhibitors (CIs) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), as salvage therapies [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar]. Checkpoint inhibitor pneumonitis (CIP) is the most common fatal immune-related adverse event (irAE) in lung cancer patients receiving Cls and CIP related mortality may more than 20 %. During current COVID-19 pandemic, CIP is hard to distinguish from COVID-19 infection as they share similar clinical and radiographic presentations but different therapy strategies. Therefore, how to distinguish between the two diseases is an urgent issue. The overall incidence of CIP is 2.79−5.17% [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar,2Naidoo J. Wang X. Woo K.M. Iyriboz T. Halpenny D. Cunningham J. Chaft J.E. Segal N.H. Callahan M.K. Lesokhin A.M. Rosenberg J. Voss M.H. Rudin C.M. Rizvi H. Hou X. Rodriguez K. Albano M. Gordon R.A. Leduc C. Rekhtman N. Harris B. Menzies A.M. Guminski A.D. Carlino M.S. Kong B.Y. Wolchok J.D. Postow M.A. Long G.V. Hellmann M.D. Pneumonitis in patients treated with anti-programmed Death-1/Programmed death ligand 1 therapy.J. Clin. Oncol. 2017; 35: 709-717Crossref PubMed Scopus (799) Google Scholar], and PD-1 inhibitors have a higher incidence than PDL-1 inhibitors [3Pillai R.N. Behera M. Owonikoko T.K. Kamphorst A.O. Pakkala S. Belani C.P. Khuri F.R. Ahmed R. Ramalingam S.S. Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: a systematic analysis of the literature.Cancer. 2018; 124: 271-277Crossref PubMed Scopus (250) Google Scholar]. The incidence of CIP is also higher in patients receiving a combination of CIs and chemotherapy than in those receiving CI monotherapy [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar,3Pillai R.N. Behera M. Owonikoko T.K. Kamphorst A.O. Pakkala S. Belani C.P. Khuri F.R. Ahmed R. Ramalingam S.S. Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: a systematic analysis of the literature.Cancer. 2018; 124: 271-277Crossref PubMed Scopus (250) Google Scholar]. The mortality rate of all CI-associated irAEs is 0.45 %, among which CIP is the most common cause of death of irAEs [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar] and CIP related mortality may up to 22.7 % [4Tone M. Izumo T. Awano N. Kuse N. Inomata M. Jo T. Yoshimura H. Minami J. Takada K. Miyamoto S. Kunitoh H. High mortality and poor treatment efficacy of immune checkpoint inhibitors in patients with severe grade checkpoint inhibitor pneumonitis in non-small cell lung cancer.Thorac. Cancer. 2019; 10: 2006-2012Crossref PubMed Scopus (53) Google Scholar]. The median interval between the first dose of CIs to the onset of CIP is 2.8 months (9 days to 19.2 months) [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar,2Naidoo J. Wang X. Woo K.M. Iyriboz T. Halpenny D. Cunningham J. Chaft J.E. Segal N.H. Callahan M.K. Lesokhin A.M. Rosenberg J. Voss M.H. Rudin C.M. Rizvi H. Hou X. Rodriguez K. Albano M. Gordon R.A. Leduc C. Rekhtman N. Harris B. Menzies A.M. Guminski A.D. Carlino M.S. Kong B.Y. Wolchok J.D. Postow M.A. Long G.V. Hellmann M.D. Pneumonitis in patients treated with anti-programmed Death-1/Programmed death ligand 1 therapy.J. Clin. Oncol. 2017; 35: 709-717Crossref PubMed Scopus (799) Google Scholar] and the median incubation period of COVID-19 infection is 5.1 days, with 97.5 % becoming symptomatic within 11.5 days [5Lauer S.A. Grantz K.H. Bi Q. Jones F.K. Zheng Q. Meredith H.R. Azman A.S. Reich N.G. Lessler J. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application.Ann. Intern. Med. 2020; 172 (Epub 2020 Mar 10): 577-582https://doi.org/10.7326/M20-0504Crossref PubMed Scopus (3791) Google Scholar]. The pathology of CIP often reveals different degrees of lymphocyte infiltration (mainly CD8+ T cells), and granuloma, interstitial pneumonitis, organized pneumonitis, diffuse alveolar injury or eosinophilic infiltration may also be present. Few studies have reported the pathology of COVID-19, however an autopsy report showed diffuse alveolar damage and airway inflammation [6Barton L.M. Duval E.J. Stroberg E. Ghosh S. Mukhopadhyay S. COVID-19 Autopsies, Oklahoma, USA.Am. J. Clin. Pathol. 2020; 153: 725-733Crossref PubMed Google Scholar]. Edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells in the early stage [7Tian S. Hu W. Niu L. Liu H. Xu H. Xiao S.Y. Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer.J. Thorac. Oncol. 2020; 15: 700-704Abstract Full Text Full Text PDF PubMed Scopus (1035) Google Scholar]. With regards to radiographic manifestations, bilateral distribution of ground glass opacities with or without consolidation in posterior and peripheral lungs is the cardinal hallmark of COVID-19. However, in CIP, the radiographic presentations are also ground glass opacities, reticular opacities, consolidations [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar, 2Naidoo J. Wang X. Woo K.M. Iyriboz T. Halpenny D. Cunningham J. Chaft J.E. Segal N.H. Callahan M.K. Lesokhin A.M. Rosenberg J. Voss M.H. Rudin C.M. Rizvi H. Hou X. Rodriguez K. Albano M. Gordon R.A. Leduc C. Rekhtman N. Harris B. Menzies A.M. Guminski A.D. Carlino M.S. Kong B.Y. Wolchok J.D. Postow M.A. Long G.V. Hellmann M.D. Pneumonitis in patients treated with anti-programmed Death-1/Programmed death ligand 1 therapy.J. Clin. Oncol. 2017; 35: 709-717Crossref PubMed Scopus (799) Google Scholar, 3Pillai R.N. Behera M. Owonikoko T.K. Kamphorst A.O. Pakkala S. Belani C.P. Khuri F.R. Ahmed R. Ramalingam S.S. Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: a systematic analysis of the literature.Cancer. 2018; 124: 271-277Crossref PubMed Scopus (250) Google Scholar], including the following patterns: cryptogenic organizing pneumonia, ground glass opacities, interstitial pneumonitis, hypersensitive pneumonitis and pneumonitis not otherwise specified. The lower lobe is the most commonly involved lobe and the most common distribution is mixed and multifocal. The diagnosis of CIP is made after the exclusion of other diseases, and COVID-19 infection needs to be confirmed by RT-PCR, isothermal amplification assay or serology test. The most common symptoms in CIP are dyspnea, followed by cough, fever and 33 % of cases are asymptomatic. In COVID-19 infection, the most common symptom is fever, followed by cough, fatigue, sputum production, and shortness of breath [8Ye Z. Zhang Y. Wang Y. Huang Z. Song B. Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review.Eur. Radiol. 2020; 19: 1-9https://doi.org/10.1007/s00330-020-06801-0Crossref Scopus (901) Google Scholar]. Early detection and discontinuing CIs if CIP develops is the most reliable management, and steroids are the standard treatment for CIP [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar, 2Naidoo J. Wang X. Woo K.M. Iyriboz T. Halpenny D. Cunningham J. Chaft J.E. Segal N.H. Callahan M.K. Lesokhin A.M. Rosenberg J. Voss M.H. Rudin C.M. Rizvi H. Hou X. Rodriguez K. Albano M. Gordon R.A. Leduc C. Rekhtman N. Harris B. Menzies A.M. Guminski A.D. Carlino M.S. Kong B.Y. Wolchok J.D. Postow M.A. Long G.V. Hellmann M.D. Pneumonitis in patients treated with anti-programmed Death-1/Programmed death ligand 1 therapy.J. Clin. Oncol. 2017; 35: 709-717Crossref PubMed Scopus (799) Google Scholar, 3Pillai R.N. Behera M. Owonikoko T.K. Kamphorst A.O. Pakkala S. Belani C.P. Khuri F.R. Ahmed R. Ramalingam S.S. Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: a systematic analysis of the literature.Cancer. 2018; 124: 271-277Crossref PubMed Scopus (250) Google Scholar]. In contrast, steroids may be harmful for COVID-19 patients and not indicated in current management [9Russell C.D. Millar J.E. Baillie J.K. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury.Lancet. 2020; 395: 473-475Abstract Full Text Full Text PDF PubMed Scopus (1536) Google Scholar]. Several drugs have been used by the beginning of COVID-19 outbreak and a great number of clinical trials have been launched to investigate the therapeutic effect. Though No U.S. Food and Drug Administration (FDA)-approved drugs for COVID-19 infection as yet, the FDA has authorized the emergency use of remdesivir to treat hospitalized adult and pediatric patients with suspected or laboratory-confirmed SARS-CoV-2 infection and severe COVID-19. Recently, Beigel et al. reported a global trial of remdesivir therapy for COVID-19 infection and successfully achieved the primary endpoint. The rate ratio for recovery was 1.32 (95 % confidence interval, 1.12–1.55; P < 0.001) and the median recovery time was 11 days compared to 15 days in those who received placebo [10Beigel J.H. Tomashek K.M. Dodd L.E. Mehta A.K. Zingman B.S. Kalil A.C. Hohmann E. Chu H.Y. Luetkemeyer A. Kline S. Lopez de Castilla D. Finberg R.W. Dierberg K. Tapson V. Hsieh L. Patterson T.F. Paredes R. Sweeney D.A. Short W.R. Touloumi G. Lye D.C. Ohmagari N. Oh M.D. Ruiz-Palacios G.M. Benfield T. Fatkenheuer G. Kortepeter M.G. Atmar R.L. Creech C.B. Lundgren J. Babiker A.G. Pett S. Neaton J.D. Burgess T.H. Bonnett T. Green M. Makowski M. Osinusi A. Nayak S. Lane H.C. Members A.-S.G. Remdesivir for the treatment of Covid-19 - preliminary report.N. Engl. J. Med. 2020; https://doi.org/10.1056/NEJMoa2007764Crossref PubMed Scopus (4986) Google Scholar]. We summarize the differences between CIP and COVID-19 infection in Table 1 and wish the summary could help clinicians to distinguish CIP from COVID-19 infection in current horrible COVID-19 pandemic.Table 1The differences between checkpoint inhibitor pneumonitis (CIP) and COVID-19 infection.Checkpoint inhibitor pneumonitis (CIP)COVID-19 infectionIncidenceOverall 2.79−5.17 % [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar,2Naidoo J. Wang X. Woo K.M. Iyriboz T. Halpenny D. Cunningham J. Chaft J.E. Segal N.H. Callahan M.K. Lesokhin A.M. Rosenberg J. Voss M.H. Rudin C.M. Rizvi H. Hou X. Rodriguez K. Albano M. Gordon R.A. Leduc C. Rekhtman N. Harris B. Menzies A.M. Guminski A.D. Carlino M.S. Kong B.Y. Wolchok J.D. Postow M.A. Long G.V. Hellmann M.D. Pneumonitis in patients treated with anti-programmed Death-1/Programmed death ligand 1 therapy.J. Clin. Oncol. 2017; 35: 709-717Crossref PubMed Scopus (799) Google Scholar,3Pillai R.N. Behera M. Owonikoko T.K. Kamphorst A.O. Pakkala S. Belani C.P. Khuri F.R. Ahmed R. Ramalingam S.S. Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: a systematic analysis of the literature.Cancer. 2018; 124: 271-277Crossref PubMed Scopus (250) Google Scholar] PD-1 inhibitors/ PDL-1 inhibitors = 4 % / 2 % # The incidence of CIP is higher in those receiving CI and chemotherapy than with CI monotherapy–Interval to onsetMedian time 2.8months, with a wide range (9 days to 19.2 months)[1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar,2Naidoo J. Wang X. Woo K.M. Iyriboz T. Halpenny D. Cunningham J. Chaft J.E. Segal N.H. Callahan M.K. Lesokhin A.M. Rosenberg J. Voss M.H. Rudin C.M. Rizvi H. Hou X. Rodriguez K. Albano M. Gordon R.A. Leduc C. Rekhtman N. Harris B. Menzies A.M. Guminski A.D. Carlino M.S. Kong B.Y. Wolchok J.D. Postow M.A. Long G.V. Hellmann M.D. Pneumonitis in patients treated with anti-programmed Death-1/Programmed death ligand 1 therapy.J. Clin. Oncol. 2017; 35: 709-717Crossref PubMed Scopus (799) Google Scholar]Median incubation period of 5.1 days, with 97.5 % becoming symptomatic within 11.5 days [5Lauer S.A. Grantz K.H. Bi Q. Jones F.K. Zheng Q. Meredith H.R. Azman A.S. Reich N.G. Lessler J. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application.Ann. Intern. Med. 2020; 172 (Epub 2020 Mar 10): 577-582https://doi.org/10.7326/M20-0504Crossref PubMed Scopus (3791) Google Scholar].Pathology findingDifferent degrees of lymphocyte infiltration, mainly CD8+ T cells, including granuloma, interstitial pneumonitis, organized pneumonitis, diffuse alveolar injury or eosinophilic infiltration [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar]Diffuse alveolar damage and airway inflammation in an autopsy report [6Barton L.M. Duval E.J. Stroberg E. Ghosh S. Mukhopadhyay S. COVID-19 Autopsies, Oklahoma, USA.Am. J. Clin. Pathol. 2020; 153: 725-733Crossref PubMed Google Scholar]. Edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells in the early stage [7Tian S. Hu W. Niu L. Liu H. Xu H. Xiao S.Y. Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer.J. Thorac. Oncol. 2020; 15: 700-704Abstract Full Text Full Text PDF PubMed Scopus (1035) Google Scholar]MortalityCIP is the most common cause of death in all CI- associated irAEs, and CIP related mortality may up to 22.7 % [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar,4Tone M. Izumo T. Awano N. Kuse N. Inomata M. Jo T. Yoshimura H. Minami J. Takada K. Miyamoto S. Kunitoh H. High mortality and poor treatment efficacy of immune checkpoint inhibitors in patients with severe grade checkpoint inhibitor pneumonitis in non-small cell lung cancer.Thorac. Cancer. 2019; 10: 2006-2012Crossref PubMed Scopus (53) Google Scholar]6.22 % (349,060 deaths /5,612,601 confirmed cases) to May 27, 2020Chest CTThe basic imaging signs of CIP include ground-glass opacity(GGO), consolidation, interlobular septal thickening, distraction branch expansion, nodules, and reticular shadow [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar,2Naidoo J. Wang X. Woo K.M. Iyriboz T. Halpenny D. Cunningham J. Chaft J.E. Segal N.H. Callahan M.K. Lesokhin A.M. Rosenberg J. Voss M.H. Rudin C.M. Rizvi H. Hou X. Rodriguez K. Albano M. Gordon R.A. Leduc C. Rekhtman N. Harris B. Menzies A.M. Guminski A.D. Carlino M.S. Kong B.Y. Wolchok J.D. Postow M.A. Long G.V. Hellmann M.D. Pneumonitis in patients treated with anti-programmed Death-1/Programmed death ligand 1 therapy.J. Clin. Oncol. 2017; 35: 709-717Crossref PubMed Scopus (799) Google Scholar] and some studies divided CIP into five patterns, included cryptogenic organizing pneumonia; ground glass opacities, Interstitial pattern, hypersensitive pneumonitis and pneumonitis not otherwise specified. # Involvement: Lower > middle > upper lungs # Distribution: Mixed and multifocal > peripheral and lower and diffuseBilateral distribution of GGO with or without consolidation in posterior and peripheral lungs is the cardinal hallmark of COVID-19 [8Ye Z. Zhang Y. Wang Y. Huang Z. Song B. Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review.Eur. Radiol. 2020; 19: 1-9https://doi.org/10.1007/s00330-020-06801-0Crossref Scopus (901) Google Scholar]. COVID-19 images included GGOs 14−98 %; consolidation 2−64 %; GGO and consolidation 19−59 %; interlobular septum thickening 1−75 %; reticular pattern 1−22 %; crazy paving 5−36 %; air bronchogram 21−80 %; bronchial wall thickening 11−23 %; pleural thickening 32 %, subpleural line 20 %, nodules 3−13%, reversed halo sign 2−3%, pleural effusion or pericardial effusion 1−8%; lymphadenopathy 4−8%DiagnosisThe diagnosis of CIP should be made after excluding other interstitial lung diseases and infection [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar,2Naidoo J. Wang X. Woo K.M. Iyriboz T. Halpenny D. Cunningham J. Chaft J.E. Segal N.H. Callahan M.K. Lesokhin A.M. Rosenberg J. Voss M.H. Rudin C.M. Rizvi H. Hou X. Rodriguez K. Albano M. Gordon R.A. Leduc C. Rekhtman N. Harris B. Menzies A.M. Guminski A.D. Carlino M.S. Kong B.Y. Wolchok J.D. Postow M.A. Long G.V. Hellmann M.D. Pneumonitis in patients treated with anti-programmed Death-1/Programmed death ligand 1 therapy.J. Clin. Oncol. 2017; 35: 709-717Crossref PubMed Scopus (799) Google Scholar,3Pillai R.N. Behera M. Owonikoko T.K. Kamphorst A.O. Pakkala S. Belani C.P. Khuri F.R. Ahmed R. Ramalingam S.S. Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: a systematic analysis of the literature.Cancer. 2018; 124: 271-277Crossref PubMed Scopus (250) Google Scholar].RT-PCR, isothermal amplification assays, serology testsSymptomsDyspnea, cough 35 %, fever 12 %, chest pain 7 %. asymptomatic 33 % [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar,2Naidoo J. Wang X. Woo K.M. Iyriboz T. Halpenny D. Cunningham J. Chaft J.E. Segal N.H. Callahan M.K. Lesokhin A.M. Rosenberg J. Voss M.H. Rudin C.M. Rizvi H. Hou X. Rodriguez K. Albano M. Gordon R.A. Leduc C. Rekhtman N. Harris B. Menzies A.M. Guminski A.D. Carlino M.S. Kong B.Y. Wolchok J.D. Postow M.A. Long G.V. Hellmann M.D. Pneumonitis in patients treated with anti-programmed Death-1/Programmed death ligand 1 therapy.J. Clin. Oncol. 2017; 35: 709-717Crossref PubMed Scopus (799) Google Scholar,3Pillai R.N. Behera M. Owonikoko T.K. Kamphorst A.O. Pakkala S. Belani C.P. Khuri F.R. Ahmed R. Ramalingam S.S. Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: a systematic analysis of the literature.Cancer. 2018; 124: 271-277Crossref PubMed Scopus (250) Google Scholar].Fever 85−90 %, cough 65−70 %, fatigue 35−40 %, sputum production 30−35 %, shortness of breath 15−20 %, myalgia/arthralgia 10−15 %, headaches 10−36 %, sore throat 10−15 %, chills 10−12 % [5Lauer S.A. Grantz K.H. Bi Q. Jones F.K. Zheng Q. Meredith H.R. Azman A.S. Reich N.G. Lessler J. The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application.Ann. Intern. Med. 2020; 172 (Epub 2020 Mar 10): 577-582https://doi.org/10.7326/M20-0504Crossref PubMed Scopus (3791) Google Scholar,8Ye Z. Zhang Y. Wang Y. Huang Z. Song B. Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review.Eur. Radiol. 2020; 19: 1-9https://doi.org/10.1007/s00330-020-06801-0Crossref Scopus (901) Google Scholar].TreatmentEarly detection and discontinue CIs. Steroids are the standard treatment for CIP. For grade 2–3 CIP, an equivalent dose of prednisolone of 1–2 mg/kg/day is recommended. The overall course of steroid treatment is approximately 6–8 weeks [1Wang H. Guo X. Zhou J. Li Y. Duan L. Si X. Zhang L. Liu X. Wang M. Shi J. Zhang L. Clinical diagnosis and treatment of immune checkpoint inhibitor-associated pneumonitis.Thorac. Cancer. 2020; 11: 191-197Crossref PubMed Scopus (53) Google Scholar,2Naidoo J. Wang X. Woo K.M. Iyriboz T. Halpenny D. Cunningham J. Chaft J.E. Segal N.H. Callahan M.K. Lesokhin A.M. Rosenberg J. Voss M.H. Rudin C.M. Rizvi H. Hou X. Rodriguez K. Albano M. Gordon R.A. Leduc C. Rekhtman N. Harris B. Menzies A.M. Guminski A.D. Carlino M.S. Kong B.Y. Wolchok J.D. Postow M.A. Long G.V. Hellmann M.D. Pneumonitis in patients treated with anti-programmed Death-1/Programmed death ligand 1 therapy.J. Clin. Oncol. 2017; 35: 709-717Crossref PubMed Scopus (799) Google Scholar].No FDA-approved drugs as yet, but in the United States, the FDA has authorized the emergency use of remdesivir to treat hospitalized adult and pediatric patients with suspected or laboratory-confirmed SARS-CoV-2 infection and severe COVID-19. Steroids may be harmful [9Russell C.D. Millar J.E. Baillie J.K. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury.Lancet. 2020; 395: 473-475Abstract Full Text Full Text PDF PubMed Scopus (1536) Google Scholar]# immune-related adverse events, irAE; checkpoint inhibitor, CI; checkpoint inhibitor pneumonitis, CIP; ground glass opacities, GGO; Food and Drug Administration, FDA; programmed cell death protein 1, PD-1; programmed cell death protein 1 ligand, PDL-1. Open table in a new tab # immune-related adverse events, irAE; checkpoint inhibitor, CI; checkpoint inhibitor pneumonitis, CIP; ground glass opacities, GGO; Food and Drug Administration, FDA; programmed cell death protein 1, PD-1; programmed cell death protein 1 ligand, PDL-1. No funding.