key: cord-0725875-uo78tsir authors: Souza, Ive Lima; Fernandes, Ítalo; Taranto, Patrícia; Buzaid, Antonio Carlos; Schvartsman, Gustavo title: Immune-related pneumonitis with nivolumab and ipilimumab during the COVID-19 pandemic date: 2020-06-17 journal: Eur J Cancer DOI: 10.1016/j.ejca.2020.06.004 sha: 2e138fdffc3298a12a117e5fc668262d68cf20a5 doc_id: 725875 cord_uid: uo78tsir nan The city of São Paulo is the epicenter of the COVID-19 pandemic in South America. Until May 24 th , 2020, a total 49,306 confirmed cases and 3,550 deaths were attributed to the new coronavirus (Sars-Cov-2) in the city.(1) As such, patients with acute respiratory symptoms with hospitalization criteria are usually admitted under the presumed diagnosis of COVID-19, until at least one negative reverse transcriptase polymerase chain reaction (RT-PCR) test. However, patients undergoing immune checkpoint inhibitors are at risk for immune-related pneumonitis. This currently poses a diagnostic challenge, as symptoms and computerized tomography (CT) findings often overlap. (2) (3) (4) (5) Steroids, the main treatment modality for immune-related adverse events, are cautioned against for COVID-19, potentially causing delay in proper management of a severe condition. (6) We present two cases of metastatic melanoma patients treated with standard dose of ipilimumab at 3 mg/kg and nivolumab at 1mg/kg. The first patient is an 83-year-old man with a melanoma of unknown primary origin metastatic to lymph nodes and brain. The second is a 74-year-old woman with uveal melanoma metastatic to the liver. Both patients developed acute respiratory symptoms following the first dose of therapy, with low-grade fever Figure 1C) . A second RT-PCR test was collected for both, but intravenous methylprednisolone was initiated only for the male patient at that time, with dramatic clinical and radiologic improvement within 24 hours ( Figure 1E ). For the female patient, steroids were further withheld until a second negative RT-PCR was released, four days following admission. A third CT scan was obtained, again with worsening of previous findings ( Figure 1D ). At this point, immune-related pneumonitis was finally favored and she was started intravenous methylprednisolone. Her symptoms also markedly improved within one day. After three days, a repeat chest CT showed a marked improvement in GGO and consolidations ( Figure 1F ). The patients were discharged from the hospital between two to five days after steroid initiation on an oral prednisone taper, without oxygen support and in a good clinical condition. A third RT-PCR and serologic testing (IgM and IgG) were obtained at discharge, negative for both patients. A mean delay of 3 days in steroid initiation was attributed to the COVID-19 pandemic. The current pandemic is imposing a presumed diagnosis of COVID-19 in patients with respiratory symptoms in epidemic regions. However, it is important to consider differential diagnosis. For patients undergoing chemo or immunotherapy, pneumonitis is an adverse event that may be present in up to and is the gold-standard diagnostic method. The test, however, may present as a false-negative in 11-29% of cases, warranting a new test if clinical and radiographic features are highly suggestive of the condition. (7) In this report, the mean delay of corticosteroid administration was 3 days, which may have led to a clinical and radiologic deterioration, increased patient exposure to Sars-Cov-2 in the wards reserved for suspected cases and to a longer hospitalization. Though routine corticosteroids should be avoided due to the possible impairment in viral clearance, its role in the current pandemic remains unclear. (6, 8) It seems unlikely that a short course of steroids (24-48h) may irreversibly affect both the clinical outcome of an unconfirmed COVID-19 infection or compromise immunotherapy efficacy. Conversely, symptoms may rapidly improve if the pneumonitis is from immune-mediated etiology, as occurred in our patients within 24h. In conclusion, we warrant caution with the utilization of immune checkpoint inhibitors during the COVID-19 pandemic, particularly when combining two agents. We recommend always considering immune-related pneumonitis among differential diagnosis when respiratory signs and symptoms overlap with treatment timing. Based on our experience, we consider one negative RT-PCR sufficient to initiate steroids, in the absence of other likely diagnosis, while a second sample is collected and analyzed. Clinical Characteristics of Coronavirus Disease 2019 in China Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy Radiological Society of North America Expert Consensus Statement on Reporting Chest CT Findings Related to COVID-19. Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA Immune-Related Adverse Events: Pneumonitis Pharmacologic Treatments for Coronavirus Disease Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome No funding was required for the letter. Not applicable. All authors wrote, proofread, participated in the care of the patient and approved the final manuscript. The authors declare that they have no competing interests with the present work.