334. Impact of Overall Dexamethasone Exposure on Development of Invasive Pulmonary Aspergillosis in Hospitalized Patients with COVID-19

Background Abbreviated courses of corticosteroids, such as dexamethasone, have demonstrated significant improvements in clinical outcomes among patients infected with COVID-19, although chronic corticosteroid use can predispose patients to opportunistic infections. The RECOVERY trial investigators showed reduced 28-day mortality among patients treated with 6 mg/day dexamethasone for up to 10 days, however in clinical practice the dosage and duration of dexamethasone therapy can vary widely based on severity of disease and provider discretion. Upon observing an anecdotal increase in the number of patients presenting with potential invasive aspergillosis during the third wave of COVID-19, we sought to evaluate the impact of overall dexamethasone exposure on the development of invasive pulmonary aspergillosis. Methods Patients presenting to our institution from Dec. 2020 – Jan. 2021 with positive PCR for SARS-CoV-2 were screened for dexamethasone therapy. Assignment of high vs low dose dexamethasone groups were retrospectively made based on overall dexamethasone exposure. Low dose dexamethasone assignment was restricted to a total exposure of no more than 78 mg during a patient’s hospitalization. Adjudication of invasive pulmonary aspergillosis was made based on criteria that included host factors, radiologic findings, clinical factors, and mycological evidence. Results Dexamethasone therapy was provided to 202 patients admitted to the hospital with COVID-19. Invasive pulmonary aspergillosis was determined to be probable in n=7 patients based on European Organization for Research and Treatment of Cancer (EORTC) criteria, and in n=13 patients based on expanded criteria. Patients in the low dose dexamethasone group were less likely to be diagnosed with probable IPA based on EORTC criteria (n=0, 0% on low dose vs. n=7, 11% on high dose) as well as expanded criteria (n=9, 5% on low dose vs. n=11, 17% on high dose), p< 0.001. Conclusion Patients hospitalized with COVID-19 receiving high-dose dexamethasone may be at a higher risk of opportunistic infections such as invasive pulmonary aspergillosis compared to patients who receive low-dose dexamethasone therapy. Further investigation is needed to obtain higher certainty of IPA diagnosis. Disclosures All Authors: No reported disclosures

280. Burden of Hyperglycemia in Patients Receiving Dexamethasone for Severe COVID-19

Background Previous studies demonstrated the adverse impact corticosteroids can have on blood glucose homeostasis in both diabetics and non-diabetics. This raises concern for corticosteroid use in severe COVID-19 where the population is enriched for those at highest risk of severe disease, such as diabetics and patients with obesity. Previous studies of dexamethasone in COVID-19 were limited by the inability to assess steroid-induced hyperglycemia or the impact of hyperglycemia on hospital resources. Objective The study aimed to describe the clinical characteristics, management, and outcomes related to hyperglycemia, before and after dexamethasone therapy was used as the standard of care in patients with severe COVID-19. Methods We performed a pre/post retrospective study of patients with severe COVID-19 pneumonia admitted from May to July 2020 to Harbor-UCLA Medical Center. 126 patients were evaluated. 64 received dexamethasone and 62 did not. To quantify the effect of dexamethasone on diabetic vs. non-diabetic patients, we documented the average blood glucoses and frequency of correctional insulin doses required by each patient group (diabetic with and without dexamethasone, non-diabetic with and without dexamethasone). Results While dexamethasone was associated with higher median blood glucose and more frequent correctional insulin dosing in diabetic patients, there was minimal effect of dexamethasone on hyperglycemia in non-diabetic patients. Furthermore, while non-diabetic patients receiving dexamethasone required more doses of correctional insulin per day vs non-diabetic patients not receiving dexamethasone (0.3 doses per day vs 0.1 doses per day), the frequency of correctional insulin doses required by non-diabetics on dexamethasone remained low at 0.3 doses per day. Conclusion NIH COVID-19 guidelines recommend administering dexamethasone only if the patient is in a monitored setting. Our data support the NIH concerns that outpatients with diabetes receiving steroids are at risk for hyperglycemic complications. However, contrary to the NIH guidelines, our data suggest that patients without diabetes receiving steroids are at low risk for complications due to hyperglycemia and a majority do not require monitoring. Disclosures Eric Daar, MD, Gilead (Consultant)Gilead (Research Grant or Support)Merck (Research Grant or Support)Merck (Consultant)ViiV (Research Grant or Support)

Dexamethasone therapy and rates of secondary pulmonary and bloodstream infections in critically ill COVID-19 patients

Background: Coronavirus disease 2019 (COVID-19) has become a pandemic. Bacterial superinfections seem to be associated with higher mortality in COVID-19 patients in intensive care units (ICUs). However, details on the prevalence and species distribution of secondary infections are limited. Moreover, the increasing use of dexamethasone may pose an additional risk of superinfections.Methods: We performed a single-center retrospective study of the clinical and microbiological characteristics of 154 COVID-19 patients admitted to the ICU between March 2020 and January 2021, focusing on bacterial infections, use of antimicrobial agents and dexamethasone therapy.Results: The median age was 68 years; 67.5% of the patients were men. Critically ill COVID-19 patients were treated with dexamethasone since July 2020 (second wave), which was not common during the first wave of the pandemic. In the dexamethasone group (n=90, 58.4%), respiratory pathogens were detected more frequently, as were multidrug-resistant pathogens. The number of patients with polymicrobial detection of respiratory pathogens was significantly increased (p=0.013). The most frequently detected species were Enterobacterales, Staphylococcus aureus, and Aspergillus fumigatus. The rates of bloodstream infections did not differ between the groups. The use of dexamethasone in ICU COVID-19 patients was associated with higher rates of respiratory infectious complications.Conclusions: Secondary infections are present in a substantial fraction of critically ill COVID-19 patients. Respiratory pathogens were detectable in the majority of COVID-19 ICU patients. The use of dexamethasone poses a potential risk of secondary pulmonary infections. Infectious complications in patients with dexamethasone therapy could be associated with worse outcomes.

COVID-19 Advanced Care

The coronavirus disease 2019 (COVID-19) pandemic, related to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial burden in public health due to an enormous increase in hospitalizations for pneumonia with the multiorgan disease. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care, and ongoing trials are testing the efficacy of antiviral therapies, immune modulators and anticoagulants in the prevention of disease progression and complications, while monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Consensus suggestions can standardize care, thereby improving outcomes and facilitating future research. This review discusses current evidence regarding the pharmacotherapy of COVID-19.

Dexamethasone in Treatment of Comorbid SARS-CoV-2 Patients Aged over 50 Years with Lung Injury over 50 %

Aim. An efficacy assessment of steroid therapy in SARS-CoV-2 patients aged over 50 years with lung damage over 50 % (grade 3–4).Materials and methods. A retrospective study of 158 SARS-CoV-2 patients hospitalised in April—June 2020 was conducted under the inclusion criteria: age over 50 years, chest computed tomography (CT) for COVID-19-asso-ciated pneumonia, C-reactive protein (CRP) >50 mg/L, anticoagulant therapy, no contraindications to steroids, no biologic therapy. Cohort 1 patients (n = 96) received dexamethasone 4–12 mg/day, cohort 2 (n = 62) — a standard non-dexamethasone therapy.Results. Dexamethasone treatment associated with a significant alleviation of COVID-19-associated pneumonia in CT score (p = 0.001), reduced fibrinogen (p = 0.001), a trend to CRP reduction by day 8–10 and lower demand for oxygen therapy, including ventilatory support (p = 0.001). Mortality rate was 19.8 and 75.8 % in cohorts 1 and 2, respectively (p = 0.001).Conclusion. Dexamethasone therapy 4–12 mg/day in SARS-CoV-2 patients aged 50+ years with grade 3–4 CT changes receiving LMWH from start of hospitalisation significantly improved CT scores and reduced mortality.

A GRIN3A polymorphism may be associated with glucocorticoid-induced symptomatic osteonecrosis in children with acute lymphoblastic leukemia

Aim: To evaluate the association between candidate genetic polymorphisms and glucocorticoid-induced osteonecrosis in Arab children treated for acute lymphoblastic leukemia. Methods: A total of 189 children treated for acute lymphoblastic leukemia were genotyped for four SNPs with allele discrimination assays. The incidence and timing of radiologically confirmed symptomatic grade 4 osteonecrosis were classified based on the Ponte di Legno toxicity working group consensus definition. Results: Thirteen children developed grade 4 osteonecrosis (6.8%), of whom 12 received the intermediate/high-risk treatment protocol. GRIN3A variant allele carriers had to stop dexamethasone therapy earlier resulting in significantly shorter duration of dexamethasone treatment (mean [95% CI]: 75.17 [64.28–86.06] vs 85.90 [81.22–90.58] weeks; p = 0.054) and lower cumulative dose (mean [95% CI]: 1118.11 [954.94–1281.29] vs 1341.14 [1264.17–1418.11] mg/m2; p = 0.011). Conclusion: This is the first pharmacogenomics evaluation of the association between GRIN3A variants and glucocorticoid-induced osteonecrosis in Arab children.

Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma

This study sought to understand how the programmed death ligand 1 (PD-L1) inhibitor durvalumab and the immunomodulatory agent pomalidomide regulate immune cell activation and function in patients with relapsed/refractory (RR) multiple myeloma (MM). Immunologic changes in peripheral blood and bone marrow of patients treated with durvalumab as monotherapy or in combination with pomalidomide with/without dexamethasone were characterized by assessing subsets of immune cells and gene signatures to understand the immunomodulatory effect of the treatment. Soluble PD-L1 levels were elevated at screening in patients with RRMM but did not correlate with response to durvalumab combination therapy. Immune cell subsets were increased in peripheral blood during treatment with durvalumab and pomalidomide, and combination therapy induced significant gene expression changes in the MM tumor microenvironment versus durvalumab alone. Estimation of cell populations based on RNA sequencing data revealed increased monocytes, neutrophils, and natural killer cells with the combination therapy, but not with durvalumab alone. Additionally, multiplex immunofluorescence of bone marrow demonstrated that immune populations were different in responders versus nonresponders to durvalumab plus pomalidomide with dexamethasone therapy. Overall, durvalumab effectively blocked soluble PD-L1; however, durvalumab monotherapy was not associated with immunologic changes, which were observed with combination therapy.