A Rapid Fatal Evolution of Coronavirus Disease-19 in a Patient With Advanced Lung Cancer With a Long-Time Response to Nivolumab

To the Editor:

Coronavirus disease-19 (COVID-19) is now a pandemic disease. In Italy, the first set of cases were documented at the end of January 2020 reporting a dramatic spread. Liang et al.¹ reported an increased risk of COVID-19 for patients with cancer, having poorer prognosis than those without cancer. We present a case of a rapid fatal evolution of COVID-19 in a patient with metastatic lung cancer in partial remission with immunotherapy since 2013.

On March 4, 2020, a 65-year-old male patient presented in the emergency department for shortness of breath, fever, and mental confusion. The hemogasanalysis revealed hypoxia; laboratory tests revealed normal leukocytes with lymphopenia, and elevation of C-reactive protein, transaminases, and lactate dehydrogenase. Chest radiograph showed reticular interstitial addensative findings (Fig. 1). Nasal swab was positive for COVID-19.

Figure 1.

March 4 2020 Chest X-ray.

His medical history was positive for emphysema and lung adenocarcinoma diagnosed in August 2012. At that time, the patient underwent cerebral metastasectomy, panencephalic radiotherapy, and chemotherapy (carboplatin and pemetrexed) until July 2013. After six cycles of chemotherapy, brain magnetic resonance imaging and computed tomography scan revealed progression of the disease. He was then enrolled in CA209-057 clinical trial and treated from August 2013 to February 14, 2020 with nivolumab, a programmed cell death protein-1 checkpoint inhibitor, in which there was partial response without adverse events reported. The last computed tomography scan was performed on February 2, 2020, which described stable disease (Fig. 2).

Figure 2.

February 4 2020 CT scan.

On March 5, 2020, he was admitted to the infectious disease unit and started empiric antibiotic treatment and oxygen therapy with a reservoir mask at 15 L/minute. He was sedated because of agitation; because of this, he never received prescribed lopinavir plus ritonavir and hydroxychloroquine. The patient had a rapid worsening of the condition and died on March 9, 2020.

There are no specific therapeutic agents for coronavirus infections. As per WHO’s guidelines in the management of severe COVID-19, our patient was treated with an empiric antimicrobial, oxygen therapy, and other symptomatic treatment.² Emerging evidence suggests that the same patient with a severe course may respond to the infection with a “cytokine storm.”³ Histologic examination of the biopsy samples at autopsy from a patient who died from severe COVID-19 revealed the presence of bilateral diffuse alveolar damage with cellular fibromyxoid exudates and mononuclear inflammatory lymphocytes in both lungs.⁴ Our patient had a history of long exposure to immunotherapy; and although a kind of paradoxical immunologic response to influenza infection or vaccination during the use of immune checkpoint inhibitors has been previously described,⁵ we have no data regarding immune checkpoint inhibitors and the risk of COVID-19. Our patient presented a rapid evolution of respiratory failure and was not treated with more invasive procedures, probably owing to his cancer and emphysema history. We do not know whether treatment with steroids, not routinely recommended in COVID-19 (but very useful against side effects of immunotherapy), could help to control pneumonitis in these patients.

This case emphasized the importance of a multidisciplinary approach, even in the presence of a severe outbreak like the pandemic COVID-19, because the knowledge of underlying disease and concomitant treatments is important to take the best individual therapeutic decision.