AN UNEXPECTED RECURRENCE: A CASE OF PNEUMOCYSTIS JIROVECI AND SARS-COV-2 IN AN IMMUNOCOMPROMISED PATIENT

SESSION TITLE: COVID-19 Co-Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Pneumocystis jirovecii pneumonia (PJP) remains a significant cause of morbidity and mortality in the immunocompromised population. It can be difficult to discern the radiographic imaging of COVID-19 from PJP. This case describes a noncompliant HIV positive male with remote history of PCP pneumonia and COVID-19 pneumonia who presents with simultaneous recurrence of both disease processes. CASE PRESENTATION: A 45-year-old male with PMH of HIV/AIDS noncompliant on ART (CD4+ 10) presented for evaluation of exertional dyspnea and productive cough for the past 2 weeks. Of note, patient had a history of covid-19 pneumonia about 15 months ago when he was treated with remdesivir and steroids and required supplemental oxygen support. He was also admitted about 8 months prior for PJP pneumonia and underwent treatment with steroids and TMP-SMX for 21 days also requiring supplemental oxygen support. During this presentation, initial vital signs showed: T 36.5 C HR 98 BP 112/63 RR 20 saturating 95% breathing ambient air. ABG on presentation showed PaO2 65 while breathing room air. Physical exam suggested bilateral crackles diffusely with chest radiography significant for increased interstitial markings bilaterally. CT chest showed bilateral groundglass changes suggestive of inflammatory process. He was initially started on antibiotic coverage with azithromycin, ceftriaxone, and TMP-SMX as the initial differential included PJP recurrence since he was noncompliant on secondary prophylaxis after recent infection. He was also started on steroids due to low PaO2. SARS-CoV-2 PCR returned positive however, the low CD4+ count, and a positive serum B-D-glucan assay prompted us to schedule a bronchoscopy to evaluate for PJP pneumonia. BAL showed positive silver stain along with bronchial wash was elevated PCR for PJP (5.6 million copies/mL). A diagnosis of concurrent COVID-19 pneumonia and PJP pneumonia was made. Patient did not receive remdesivir during this admission since his oxygenation began to improve during the hospitalization. Patient was discharged on appropriate regiment for PJP pneumonia and continued steroid taper. He was seen as a follow-up in outpatient clinic about 2 months later compliant on his ART regimen and secondary PJP prophylaxis (CD4 120). DISCUSSION: If it wasn't for the serum B-D-glucan, we likely would not have pursued further causes for hypoxia in an otherwise COVID-19 positive patient with characteristic radiographic findings. The sheer co-incidence and concurrent nature of presentation of these two disease processes make our case extremely unique. Going forward, it is reasonable to keep PJP in the differential when treating a hypoxic immunocompromised patient even if an alternative cause for hypoxia is present. CONCLUSIONS: Herein we present a case of a patient with remote history of COVID-19 pneumonia and PJP pneumonia now presenting with a simultaneous co-infection. Reference #1: Mouren, D., Goyard, C., Catherinot, E., Givel, C., Chabrol, A., Tcherakian, C., Longchampt, E., Vargaftig, J., Farfour, E., Legal, A., Couderc, L. J., & Salvator, H. (2021). COVID-19 and Pneumocystis jirovecii pneumonia: Back to the basics. Respiratory medicine and research, 79, 100814. https://doi.org/10.1016/j.resmer.2021.100814 Reference #2: Huang, L., Cattamanchi, A., Davis, J. L., Boon, S. d., Kovacs, J., Meshnick, S., Miller, R. F., Walzer, P. D., Worodria, W., & Masur, H. (2011). HIV-associated Pneumocystis pneumonia. Proceedings of the American Thoracic Society, 8(3), 294–300. https://doi.org/10.1513/pats.201009-062wr Reference #3: Tasaka, S. (2015). pneumocystis pneumonia in human immunodeficiency virus–infected adults and adolescents: Current concepts and Future Directions. Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine, 9s1. https://doi.org/10.4137/ccrpm.s23324 Group, T. R. C. (2020). Dexamethasone in hospitalized patients with covid-19. (2021). New England Journal of Medicine, 384(8), 693–704. https://doi.org/10.1056/nejmoa2021436 KOLDITZ, M., HALANK, M., BANDT, D., SPORNRAFT-RAGALLER, P., & HÖFFKEN, G. (2009). Early recurrence ofPneumocystis jirovecipneumonia in two HIV-infected patients: Linking infection relapse and immune reconstitution syndrome. Respirology, 14(6), 910–912. doi:10.1111/j.1440-1843.2009.01583.x Mussini C, Pezzotti P, Antinori A, Borghi V, Monforte Ad, Govoni A, De Luca A, Ammassari A, Mongiardo N, Cerri MC, Bedini A, Beltrami C, Ursitti MA, Bini T, Cossarizza A, Esposito R;Changes in Opportunistic Prophylaxis (CIOP) Study Group. Discontinuation of secondary prophylaxis for Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients: a randomized trial by the CIOP Study Group. Clin Infect Dis. 2003 Mar 1;36(5):645-51. doi: 10.1086/367659. Epub 2003 Feb 12. PMID: 12594647. DISCLOSURES: No relevant relationships by Mourad Ismail No relevant relationships by Carlos Palacios No relevant relationships by Rutwik Patel

COVID-IRIS: Immune reconstitution after G-CSF administration for neutropenia during acute COVID-19 infection

Background: Immune reconstitution inflammatory syndrome (IRIS) is a rapid inflammatory response with immune recovery, most commonly observed following antiretroviral therapy initiation in people with HIV and underlying opportunistic infections. To date there is one reported case of COVID-associated IRIS in a neutropenic patient treated with granulocyte colony-stimulating factor (G-CSF). Here we describe a second case of COVID-associated IRIS in a patient with history of follicular lymphoma who received G-CSF during acute COVID-19 infection. Case: A 64-year-old woman with history of follicular lymphoma and autologous stem cell transplant one year prior presented with dyspnea, diarrhea, and fever, and tested positive for SARS-CoV-2. She had received three doses of the Pfizer BioNTech vaccine. She was admitted to the hospital for acute hypoxic respiratory failure and treated with remdesivir 100mg, dexamethasone 6mg, and 2 L/min supplemental oxygen via nasal cannula for five days. Twelve days after discharge, the patient returned with persistent diarrhea, fatigue, fever, and an oxygen saturation of 87% on room air. She again tested positive for SARS-CoV-2 by PCR. She was admitted to the intensive care unit for high-flow nasal cannula (HFNC) with oxygen at 30 L/min and 50% FiO2 and treated with methylprednisolone 1 mg/kg daily. On admission, her D-dimer was 3943 ng/mL, C-reactive protein 136 mg/L, absolute neutrophil count (ANC) 767/mcL, platelets 84/mcL. Her chest CT scan was negative for pulmonary embolism but demonstrated bilateral ground glass opacities characteristic of COVID-19 pneumonia. Her ANC reached a nadir of 186 on day 3 at which point G-CSF (filgrastim 300 mcg/day) was administered for three days with subsequent neutrophil recovery. On day 6, in light of a negative test for COVID antibodies, she received high-dose monoclonal antibodies through a compassionate use program. At that time, her oxygen requirements were stable and inflammatory markers had decreased to CRP 25 and D-Dimer 940. However, her oxygen requirements and inflammatory markers rapidly increased thereafter, with HFNC settings up to 60L/80%, D-dimer 27754, and CRP 135. After a repeat chest CT on day 8 showed worsened ground glass opacities throughout all lung fields, her steroid dose was increased to methylprednisolone 2 mg/kg daily out of concern for COVID-associated IRIS following G-CSF administration. Her oxygen requirement and inflammatory markers declined over the following 2-3 days and she was transferred out of the ICU. Discussion: We present here an unusual case of COVID-associated IRIS after G-CSF administration in a transplant patient with COVID-19 pneumonia. Given the increased risk of infection and severe illness in immunosuppressed patients despite vaccination, it is important for providers to be aware of complications associated with adjunct therapies such as G-CSF in this vulnerable population.

Prompt Hematological Recovery in Response to a Combination of Pegylated Interferon α-2a and Rituximab in a Profoundly Immuno-Suppressed Hairy Cell Leukemia Patient with a Mycobacterial Infection at Onset: Benefits and Drawbacks of Rapid Immune Reconstitution.

The present paper reports, to the best of our knowledge for the first time, the efficacy and tolerability of the combination of interferon (IFN)α-2a in pegylated formulation and rituximab after a "priming" phase with IFN in the frontline treatment of hairy cell leukemia (HCL) in a profoundly immunosuppressed patient with a Mycobacterium abscessus infection at onset. This immunotherapy combination may represent a potential therapeutic option in patients with active severe infection and for whom the use of purine nucleoside analogues (PNA) is contraindicated. The benefits and drawbacks of remarkably rapid immune reconstitution in the context of opportunistic infections are highlighted as well, as the potentially paradoxical effects of immune recovery as a result of effective immunotherapy strategies, known as immune reconstitution inflammatory syndrome (IRIS), have to be taken into account when dealing with patients with opportunistic infections.

Delayed Immune Reconstitution Inflammatory Syndrome in an Immunosuppressed Patient With SARS-CoV-2.

Both immune reconstitution inflammatory syndrome (IRIS) and severe coronavirus disease 2019 (COVID-19) are marked by hyperinflammation as a consequence of dysfunction in myeloid cells and increased production of proinflammatory cytokines. Although these features are common to both diseases, their physiopathology remains unclear. Here we report the case of a 63-year-old woman admitted for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In her clinical course, she developed acute respiratory distress syndrome, probably triggered by the use of granulocyte colony-stimulating factor (G-CSF). We hypothesize that G-CSF unmasked IRIS.

COVID-19 and HIV-Associated Immune Reconstitution Inflammatory Syndrome: Emergence of Pathogen-Specific Immune Responses Adding Fuel to the Fire.

Both coronavirus disease 2019 (COVID-19) and mycobacterial immune reconstitution inflammatory syndrome (IRIS) in patients with HIV-1 infection result from immunopathology that is characterized by increased production of multiple pro-inflammatory chemokines and cytokines associated with activation of myeloid cells (monocytes, macrophages and neutrophils). We propose that both conditions arise because innate immune responses generated in the absence of effective adaptive immune responses lead to monocyte/macrophage activation that is amplified by the emergence of a pathogen-specific adaptive immune response skewed towards monocyte/macrophage activating activity by the immunomodulatory effects of cytokines produced during the innate response, particularly interleukin-18. In mycobacterial IRIS, that disease-enhancing immune response is dominated by a Th1 CD4+ T cell response against mycobacterial antigens. By analogy, it is proposed that in severe COVID-19, amplification of monocyte/macrophage activation results from the effects of a SARS-CoV-2 spike protein antibody response with pro-inflammatory characteristics, including high proportions of IgG3 and IgA2 antibodies and afucosylation of IgG1 antibodies, that arises from B cell differentiation in an extra-follicular pathway promoted by activation of mucosa-associated invariant T cells. We suggest that therapy for the hyperinflammation underlying both COVID-19 and mycobacterial IRIS might be improved by targeting the immunomodulatory as well as the pro-inflammatory effects of the 'cytokine storm'.

A Case of Steroid-Responsive, COVID-19 Immune Reconstitution Inflammatory Syndrome Following the Use of Granulocyte Colony-Stimulating Factor.

We present a case report of a 54-year-old male with metastasized nasopharyngeal carcinoma presenting to the hospital with dyspnea, anorexia and fever. Examination revealed chemotherapy-induced pancytopenia. The patient tested positive for SARSCoV-2, but respiratory complications were mild. The patient was treated with granulocyte-colony stimulating factor (G-CSF) leading to amelioration of the neutropenia. However, severe acute respiratory distress syndrome (ARDS) occurred, prompting the diagnosis of immune reconstitution inflammatory syndrome (IRIS). GCSF is currently investigated as additional therapy in ARDS, but this case report emphasizes that risks and benefits must be carefully assessed. To our knowledge, this is the first case report of IRIS-induced ARDS in a COVID-19 patient.