Teny M John1, Alexandre E Malek1, Victor E Mulanovich1, Javier A Adachi1, Issam I Raad1, Alexis Ruth Hamilton1, Elizabeth J Shpall2, Katayoun Rezvani2, Samuel L Aitken3, Nitin Jain4, Kimberly Klein5, Fernando Martinez5, Ceena N Jacob6, Sujith V Cherian7, Joanna-Grace M Manzano8, Mayoora Muthu8, Robert Wegner9. 1. Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX. 2. Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX. 3. Department of Infectious Disease, The University of Texas MD Anderson Cancer Center, Houston, TX. 4. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. 5. Department of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX. 6. Department of Internal Medicine, Cleveland Clinic, Cleveland, OH. 7. Division of Critical Care, Pulmonary and Sleep Medicine, University of Texas Health Science Center at Houston, Houston, TX. 8. Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX. 9. Division of Anesthesiology, Critical Care and Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
To the Editor:The emergence of novel coronavirus disease 2019 (COVID-19) has led to a global pandemic and has threatened the lives of millions of people. This disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in respiratory failure, multiple organ dysfunction, and death. Little is known about the spectrum of clinical presentations of COVID-19 in cancer patients. Herein, we present a patient with chronic lymphocytic leukemia (CLL) who developed organizing pneumonia (OP) as a late manifestation of COVID-19 after an initial improvement who was successfully treated with corticosteroids.
Report of Case
A 62-year-old woman with CLL, hypertension, and type 2 diabetes mellitus presented with low-grade fever, cough, and shortness of breath of 1-week duration. Her CLL was treated with rituximab initially that was switched to ibrutinib 3 months earlier but was discontinued a few days before her hospitalization due to palpitations and arthralgia. On admission, she was hypoxic, requiring supplemental oxygen at 2 L/min to maintain oxygen saturation, SpO2 > 93%, and in atrial fibrillation with no hemodynamic instability. Laboratory studies were significant only for elevated C-reactive protein at 74 mg/L (normal <10 mg/L). Nasopharyngeal swab specimen for reverse transcriptase-polymerase chain reaction for SARS-CoV-2 was positive, but negative for other respiratory viruses. Computed tomography scan of the chest showed bilateral ground-glass opacities (Figure A
). The patient was enrolled in the Mayo Clinic COVID-19 expanded access program for convalescent plasma (CCP) on day 9 of her illness and received one dose of CCP. The patient's respiratory status rapidly improved the day following CCP transfusion, maintaining SpO2 on room air. After 3 days, the patient developed daily low-grade fevers and increasing shortness of breath requiring supplemental oxygen via nasal cannula. Infectious disease workup including blood cultures and fungal serum markers were negative. A repeat chest computed tomography, on day 17 of illness (Figure B), revealed new and migratory ground-glass opacities in both lungs that were consistent with an OP pattern. The patient was started on intravenous methylprednisolone at 1 mg/kg/d, which resulted in improvement in oxygenation and resolution of fever. She was discharged in stable condition after 7 days of corticosteroids.
Figure
Axial computed tomography chest images on day 7 (day of admission, A) and day 17 after symptom onset (B), showing new and migratory lung infiltrates suggestive of organizing pneumonia.
Axial computed tomography chest images on day 7 (day of admission, A) and day 17 after symptom onset (B), showing new and migratory lung infiltrates suggestive of organizing pneumonia.
Discussion
Our case may present a rare clinical course of COVID-19. Given the radiological appearance of migratory lung infiltrates and rapid improvement with corticosteroids, we hypothesize that this is OP due to the associated hyper-inflammation phase commonly seen in the later stages of COVID-19. Moreover, acute fibrinous and OP (a subtype of OP) are described in COVID-19, which could be the case in our patient, although it cannot be confirmed without a tissue biopsy. Although we conjecture that this is likely the explanation in our case, other plausible mechanisms of OP in our patient are 1) an immune activation-like phenomenon following cessation of ibrutinib or 2) augmentation of immune response by convalescent plasma. Bruton’s tyrosine kinase inhibitors are involved in toll-like receptor–mediated signaling and triggering of inflammatory cytokine and chemokine release. Ibrutinib, a highly potent inhibitor of Bruton’s tyrosine kinase, is considered to protect against lung injury in COVID-19.Corticosteroids are not currently recommended in the management of hospitalized patients with COVID-19 unless there is a separate indication such as asthma or chronic obstructive pulmonary disease or in intubated patients with acute respiratory distress syndrome. Organizing pneumonia as a delayed presentation of COVID-19 for which corticosteroids have significant benefit should be considered. Moreover, given the increasing use of convalescent plasma, OP as a possible downstream consequence should be investigated.
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