key: cord-1012021-jx849j2b
authors: Pandian, Elizabeth; D'Souza, Gretel
title: COVID-19 PNEUMONIA COMPLICATED BY CMV PNEUMONITIS FOLLOWING TREATMENT WITH AN IL-6 INHIBITOR
date: 2021-10-31
journal: Chest
DOI: 10.1016/j.chest.2021.07.341
sha: 76f3cd8516b21d880801deab6bd4a92e678bd9c2
doc_id: 1012021
cord_uid: jx849j2b

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: IL-6 inhibitors have emerged as a treatment option for moderate to severe COVID-19 infections. A hyperinflammatory state has been theorized to be the driving factor for acute respiratory distress syndrome in COVID-19. We discuss the case of a patient who received sarilumab for severe Covid infection and later developed CMV pneumonitis. IL- 6 inhibitors have been associated with secondary bacterial infections;however, the data on secondary viral and atypical infections are limited. CASE PRESENTATION: A 55-year-old male with no known past medical history presented to the hospital with complaints of worsening cough and shortness of breath. The patient was found to be COVID positive 3 days prior to presentation. CT chest on admission showed extensive peripheral ground-glass and consolidative lung opacities. Treatment with Decadron and Remdesivir was initiated.On hospital day 9, the patient had worsening respiratory status requiring up to 40 liters of vapotherm at 100% FiO2. After ruling out superimposed bacterial infection, he was treated with Sarilumab 400mg for worsening acute hypoxemic respiratory failure felt to be due to a hyperimmune syndrome from COVID-19. 10 days following treatment with Sarilumab, the patient's CRP normalized and his oxygen requirement decreased, he eventually weaned down to 5L nasal cannula.On hospital day 27, the patient again developed acute respiratory distress requiring intubation. A repeat chest CT showed evolving ground-glass and consolidative opacities with new basilar predominant traction bronchiectasis and architectural distortion. Additional lab testing revealed, CMV IgG >10 ( 0.00-0.59 U/ml) CMV IgM of 37.2 (0.0-29.9 AU/ml), CMV PCR DNA of 325000 ( not detected), and negative fungitell. Samples from bronchoalveolar lavage showed a CMV PCR of 46500 IU/ml ( not detected). Treatment with ganciclovir 5mg/kg q12h was initiated. Following treatment, the patient had progressive improvement in respiratory status, was weaned from the ventilator, and eventually discharged from the hospital. DISCUSSION: Cytokine storm is thought to play a key role in the lung injury seen in COVID 19 and IL-6 is essential in the propagation of cytokine Storm. There is an ongoing concern for bacterial infections in the setting of IL-6 inhibitors but the data on viral infections in this setting is limited. Van Duin et al describes a case of CMV reactivation in the setting of treatment with tocilizumab for rheumatoid arthritis. The patient developed fever and shortness of breath following the 2nd infusion of tocilizumab. A CT scan of the chest showed pneumonitis. Labs were significant for viremia on CMV PCR and positive CMV IgG. The patient had improvement after treatment with ganciclovir, similar to our case. CONCLUSIONS: The adverse effects of IL-6 inhibitors are not fully understood. Based on our limited experience we recommend checking CMV IgG before initiation of IL-6 inhibitors. REFERENCE #1: Han, Q., Guo, M., Zheng, Y., Zhang, Y., De, Y., & Xu, C. et al. (2020). Current Evidence of Interleukin-6 Signaling Inhibitors in Patients With COVID-19: A Systematic Review and Meta-Analysis. Frontiers In Pharmacology, 11. doi: 10.3389/fphar.2020.615972 REFERENCE #2: Tleyjeh, I., Kashour, Z., Damlaj, M., Riaz, M., Tlayjeh, H., & Altannir, M. et al. (2021). Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis. Clinical Microbiology And Infection, 27(2), 215-227. doi: 10.1016/j.cmi.2020.10.036 REFERENCE #3: van Duin D, Miranda C, Husni E. Cytomegalovirus viremia, pneumonitis, and tocilizumab therapy. Emerg Infect Dis. 2011;17(4):754-756. doi:10.3201/eid1706.101057 DISCLOSURES: No relevant relationships by Gretel D'Souza, source=Web Response No relevant relationships by Elizabeth Pandian, source=Web Response

INTRODUCTION: IL-6 inhibitors have emerged as a treatment option for moderate to severe COVID-19 infections. A hyperinflammatory state has been theorized to be the driving factor for acute respiratory distress syndrome in COVID-19. We discuss the case of a patient who received sarilumab for severe Covid infection and later developed CMV pneumonitis. IL-6 inhibitors have been associated with secondary bacterial infections; however, the data on secondary viral and atypical infections are limited.

A 55-year-old male with no known past medical history presented to the hospital with complaints of worsening cough and shortness of breath. The patient was found to be COVID positive 3 days prior to presentation. CT chest on admission showed extensive peripheral ground-glass and consolidative lung opacities. Treatment with Decadron and Remdesivir was initiated.On hospital day 9, the patient had worsening respiratory status requiring up to 40 liters of vapotherm at 100% FiO2. After ruling out superimposed bacterial infection, he was treated with Sarilumab 400mg for worsening acute hypoxemic respiratory failure felt to be due to a hyperimmune syndrome from COVID-19. 10 days following treatment with Sarilumab, the patient's CRP normalized and his oxygen requirement decreased, he eventually weaned down to 5L nasal cannula.On hospital day 27, the patient again developed acute respiratory distress requiring intubation. A repeat chest CT showed evolving ground-glass and consolidative opacities with new basilar predominant traction bronchiectasis and architectural distortion. Additional lab testing revealed, CMV IgG >10 ( 0.00-0.59 U/ml) CMV IgM of 37.2 (0.0-29.9 AU/ml), CMV PCR DNA of 325000 ( not detected), and negative fungitell. Samples from bronchoalveolar lavage showed a CMV PCR of 46500 IU/ml ( not detected). Treatment with ganciclovir 5mg/kg q12h was initiated. Following treatment, the patient had progressive improvement in respiratory status, was weaned from the ventilator, and eventually discharged from the hospital.

DISCUSSION: Cytokine storm is thought to play a key role in the lung injury seen in COVID 19 and IL-6 is essential in the propagation of cytokine Storm. There is an ongoing concern for bacterial infections in the setting of IL-6 inhibitors but the data on viral infections in this setting is limited. Van Duin et al describes a case of CMV reactivation in the setting of treatment with tocilizumab for rheumatoid arthritis. The patient developed fever and shortness of breath following the 2nd infusion of tocilizumab. A CT scan of the chest showed pneumonitis. Labs were significant for viremia on CMV PCR and positive CMV IgG. The patient had improvement after treatment with ganciclovir, similar to our case.

The adverse effects of IL-6 inhibitors are not fully understood. Based on our limited experience we recommend checking CMV IgG before initiation of IL-6 inhibitors.

Signaling Inhibitors in Patients With COVID-19: A Systematic Review and Meta-Analysis

Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis

Cytomegalovirus viremia, pneumonitis, and tocilizumab therapy