ABSTRACT
SESSION TITLE: COVID-19 Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Much has been learned about the immune dysregulation and release of pro-inflammatory cytokines since the emergence of the COVID-19 pandemic.1 Patients with interstitial lung disease are often on immunosuppressive agents, such as rituximab, which is a B-cell depleting agent. There has been a large retrospective cohort study showing that rituximab therapy was the only immunosuppressive medication with a trend towards in-hospital death.2 We present a case of COVID-19 in a patient on rituximab with ANCA vasculitis. CASE PRESENTATION: A 51-year-old male, never smoker, with ANCA positive vasculitis (positive MPO and PR3) and interstitial lung disease (on 4-5L of oxygen) presented to the hospital with nausea and fever for 2 days and was found to have a positive SARS-CoV-2 PCR. At the time of presentation, he was on rituximab 1000 mg x 2 doses every 6 months with last infusion one month prior to presentation, azathioprine 150 mg daily, prednisone 15 mg daily, nintedanib 100 mg BID, and IVIG monthly. Spirometry showed FVC of 1.60L/37% predicted and an FEV1 1.28L/39% predicted. Patient had 2 COVID vaccinations and one booster (all Pfizer mRNA), the latter 3 months prior to presentation. On admission, he was saturating at 55% on 4L and placed on 15L non-rebreather;he was afebrile, normotensive, and with a pulse of 110 BPM. Exam was notable for a cough, wheezing, and tachypnea. Lab work was notable for positive SARS-COV-2 PCR, a total white blood cell count of 5.3x103 uL, and a normal hemoglobin and platelet count. He had a CO2 of 34, normal creatinine, and no transaminitis. Lactate dehydrogenase (LDH) was elevated at 318 U/L, and lactate was elevated at 3.5 mmol/L. His chest x-ray on admission demonstrated patchy filling opacities and low lung volumes. He received dexamethasone, remdesivir, and the monoclonal antibodies casirivimab and imdevimab (REGEN-COV) on the first day of admission. Patient also received his monthly IVIG dose inpatient. After a week, he was weaned back to his home oxygen and symptomatically back to baseline. Most recent PFTs on the same outpatient immunosuppressive regimen as prior to admission are unchanged. Patient received two doses of preventative monoclonal antibodies (EVUSHELD) 3 months after admission. DISCUSSION: Here we discuss a case of a patient with severe COVID-19 pneumonia requiring inpatient hospitalization despite three COVID mRNA vaccinations, likely secondary to difficulty in mounting an immune response to the vaccinations given his use of immunosuppressive medications. This is also an example of the early use of monoclonal antibodies in an inpatient with long term preservation of his underlying lung function.3 CONCLUSIONS: We recommend counseling and close observation of patients on rituximab due to risk of severe COVID-19 infection as well the use of preventative monoclonal antibodies (EVUSHELD). Reference #1: Jamal M, Bangash HI, Habiba M, Lei Y, Xie T, Sun J, Wei Z, Hong Z, Shao L, Zhang Q. Immune dysregulation and system pathology in COVID-19. Virulence. 2021 Dec;12(1):918-936. doi: 10.1080/21505594.2021.1898790. PMID: 33757410;PMCID: PMC7993139. Reference #2: Andersen, K. M., Bates, B. A., Rashidi, E. S., Olex, A. L., Mannon, R. B., Patel, R. C., Singh, J., Sun, J., Auwaerter, P. G., Ng, D. K., Segal, J. B., Garibaldi, B. T., Mehta, H. B., Alexander, G. C., Haendel, M. A., & Chute, C. G. (2022). Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: A retrospective cohort study using data from the National COVID Cohort Collaborative. The Lancet Rheumatology, 4(1), e33–e41. https://doi.org/10.1016/S2665-9913(21)00325-8 Reference #3: Weinreich, D. M., Sivapalasingam, S., Norton, T., Ali, S., Gao, H., Bhore, R., Xiao, J., Hooper, A. T., Hamilton, J. D., Musser, B. J., Rofail, D., Hussein, M., Im, J., Atmodjo, D. Y., Perry, C., Pan, C., Mahmood, A., Hosain, R., Davis, J. D., Yancopoulos, G. D. (2021). Regen-cov antibody combination and outcomes in outpatients with covid-19. New England Journal of Medicine, 385(23), e81. https://doi.org/10.1056/NEJMoa2108163 DISCLOSURES: Advisory Committee Member relationship with Genentech Please note: 2019-2022 Added 06/06/2022 by Ayodeji Adegunsoye, value=Consulting fee Advisory Committee Member relationship with Boehringer Ingelheim Please note: 2018-2022 Added 06/06/2022 by Ayodeji Adegunsoye, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2018-2022 Added 06/06/2022 by Ayodeji Adegunsoye, value=Honoraria Consultant relationship with Genentech Please note: 2018-2020 by Ayodeji Adegunsoye, value=Consulting fee Removed 06/06/2022 by Ayodeji Adegunsoye No relevant relationships by Cathryn Lee No relevant relationships by Kavitha Selvan PI relationship with Boehringer-Ingelheim Please note: >$100000 by Mary Strek, value=Grant/Research Support PI relationship with Galapagos Please note: $70,000-100,00 by Mary Strek, value=Grant/Research Support Endpoint Adjudication Committee Member relationship with Fibrogen Please note: $1-$1000 by Mary Strek, value=Honoraria No relevant relationships by Rachel Strykowski
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Introduction: The impact of the SARS-CoV-2 virus on patients with interstitial lung disease (ILD) remains poorly understood. As patients with ILD often have severe underlying lung parenchymal involvement, and immunosuppressive therapy is common in this population, they are presumed to be at high risk for severe COVID-19 pneumonitis. We investigated clinical differences between those with ILD who tested positive for the SARS-CoV-2 virus compared to those with ILD who did not, and explored the relationship with use of immunosuppressive therapy. Methods: In this retrospective cohort study, we identified patients evaluated at the University of Chicagoin 2020 who were enrolled in the ILD registry, and stratified by SARS-CoV-2 seropositive status. We then compared baseline clinical characteristics between SARSCoV- 2 seropositive and SARS-CoV-2 seronegative patients and assessed immunosuppressive therapy at time of COVID diagnosis. C-reactive protein (CRP) and leukocyte subsets were evaluated at COVID diagnosis compared to time of baseline ILD evaluation. Variable comparisons were determined by two-sided t-tests, or chi-square tests as appropriate, and logistic regression models were fitted to assess the odds of death from COVID-19 using generalized linear models with maximum-likelihood estimation.Results: 309 subjects with ILD were included in this analysis, of which 21 patients had a confirmed SARS-CoV-2 infection (6.8%). Patients with SARS-CoV-2 were younger (55 yrs vs. 66 yrs;P=0.006) , had similar baseline leukocyte counts (9.4 vs 8.6;P=0.569) and demonstrated a trend towards a lower CRP (4.9 vs9.3;P=0.068) when compared to those without. Subjects with SARS-CoV-2 and ILD were more likely to have a diagnosis of autoimmune related-ILD (CTD-ILD or IPAF) (71% vs 39%;P=0.004), higher baseline lymphocyte fraction of circulating leukocytes (29% vs. 21%;P=0.025);greater prevalence of honeycomb fibrosis (43 vs. 21%;P=0.044), and were more frequently hypoxemic [SpO2<92%] (20% vs. 4%;P=0.009) at ILD diagnosis. The majority (62%) of patients with SARS-CoV-2 virus were on immunosuppressive therapy at time of diagnosis. Although, CRP titers were higher at diagnosis of COVID pneumonitis than at ILD diagnosis (52mg/L vs. 5mg/L;P=0.006), the lymphocyte fraction of circulating leukocytes did not differ (24% vs 28%;P=0.52)(Fig.1). Further, subjects with ILD and SARS-CoV-2 had higher odds of death than those without SARS-CoV-2 (OR=24, 95% CI-4-152;P<0.001). Conclusion: SARS-CoV-2 is prevalent in ILD, and may put those who are younger, with autoimmune ILD, and on immunosuppressive therapy at higher risk. Larger studies are needed to fully explore the relationship between ILD and immunosuppressive therapy in COVID-19. .
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Background: Morbidity and mortality due to coronavirus disease 2019 (COVID-19) may in part be due tointerleukin-6 (IL-6)-mediated hyperinflammation. The IL-6 receptor-targeted monoclonal antibody tocilizumab (TCZ)has been repurposed to treat COVID-19-related hyperinflammation, but prospective data are lacking. Given TCZ'srisks of secondary infection and potential blunting of the adaptive immune response and its finite supply, study of theefficacy, safety, and dose response of TCZ for the treatment of COVID-19-related hyperinflammation is needed. Methods: We conducted an adaptive phase 2 study of low-dose (LD) TCZ in hospitalized, non-mechanicallyventilated adult patients with COVID-19 pneumonitis and evidence of hyperinflammatory syndrome, with C-reactiveprotein (CRP) ≥ 40 micrograms per milliliter. Dose cohorts were determined by a trial Operations Committee, withthe initial doses of 80 or 200 milligrams, depending on the magnitude of CRP elevation and epidemiologic riskfactors. Doses were decreased to 40 mg and 120 mg after interim assessment. The primary objective was to assessthe relationship of dose to clinical improvement in temperature and oxygen requirement and biochemical responseby CRP. Results: 32 patients received LD TCZ. 25 of 32 (78%) patients receiving LD TCZ at any dose achieved feverresolution. In terms of dose-response, fever resolution in 24 hours was observed in 6 of 8 (75%) who received 200milligrams, 3 of 4 (75%) who received 120 milligrams, 11 of 15 (73%) who received 80 milligrams, and 5 of 5 (100%)who received 40 milligrams (p = 0.80 for response rate difference). Biochemical response consistent withinterleukin-6 pathway inhibition, corresponding to a ≥ 25% CRP decline, after a single dose of LD TCZ wasobserved in 5 of 8 (63%) who received 200 milligrams, 4 of 4 (100%) who received 120 milligrams, 10 of 15 (67%)who received 80 milligrams, and 5 of 5 (100%) who received 40 milligrams (p = 0.34 for response rate difference).100% of patients achieved CRP response within two doses of LD TCZ. Within the 28-day follow-up period, 5 (16%)patients died. For patients who recovered, median time to clinical recovery was 4 days (interquartile range, 2-5).Clinically presumed and/or cultured bacterial superinfections were reported in 4 (12.5%) patients. Correlativebiologic studies examining anti-SARS-CoV-2 antibody production across a range of TCZ doses are presentedseparately (abstract A-22514927). Conclusions: LD TCZ, in addition to standard of care, was associated with improvement of clinicalhyperinflammation parameters in hospitalized adult patients with COVID-19 pneumonitis. No relationship betweenTCZ dose and clinical or biochemical response relationship was identified. Results of the COVIDOSE trial provide arationale for a randomized, controlled trial of LD TCZ versus standard of care in those patients with COVID-19pneumonitis who have evidence of hyperinflammation. (COVIDOSE, ClinicalTrials.gov number, NCT04331795 .).