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Introduction: Angiotensin converting enzyme (ACE) 2, is a co-receptor for the entry of SARS-CoV-2 into target cells. The impact of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on outcomes in patients with coronavirus disease 19 (COVID-19) is under investigation. Hypothesis: ACEIs/ARBs are associated with worse outcomes in patients hospitalized with COVID-19. Methods: We evaluated the in-hospital course of 469 adults admitted to Stony Brook University Hospital, NY, from March 1 to April 15, 2020 with severe COVID-19 pneumonia (need for high-flow O2). We excluded patients who required mechanical ventilation (MV) or died within 24h of admission. We used Cox regression models to examine the association of previous (home) use of ACEIs or ARBs with mortality and the composite of death or MV. Results: Table 1 summarizes the patient characteristics according to ACEI/ARB use (ACEI: 73; ARB: 73; 146/469 patients, 31.1%). After a median of 13 days (8-22), 123 patients (26.2%) died and 105 patients (22.4%) required MV and survived. In models adjusting for age, sex, race, body mass index, hypertension, diabetes, coronary artery disease, heart failure, atrial fibrillation, chronic lung disease, chronic kidney disease, and baseline 0 2 saturation, ACEIs/ARBs were not associated with mortality (HR 1.00; 95%CI 0.62-1.61; P=0.99). There was no difference between classes in mortality (ACEI vs. ARB: HR 1.14; 95%CI 0.61-2.15; P=0.68). However, there was a trend towards lower rates of death or MV with ACEI/ARB (HR 0.75; 95%CI 0.54-1.05; P=0.095), mainly because of lower MV rates. The protective effect of ARBs on the composite was significant (HR 0.66; 95%CI 0.44-0.99; P=0.046) whereas that of ACEIs was not (HR 0.87; 95%CI 0.57-1.31; P=0.50), albeit difference was not significant (P=0.28). Conclusions: In patients with severe COVID-19 pneumonia, ACEI/ARB use was not associated with mortality. Especially ARBs may reduce need for MV in this high-risk COVID-19 population.

Introduction: The value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in hospitalized patients with severe coronavirus disease 2019 (COVID-19) is unclear. Hypothesis: Elevated NT-proBNP is associated with worse prognosis in hospitalized COVID-19 patients regardless of history of HF. Methods: We evaluated the in-hospital course of 469 adults admitted to Stony Brook University Hospital, NY, from March 1 to April 15, 2020 with severe COVID-19 pneumonia (need for high-flow O 2 ). We excluded patients who required mechanical ventilation (MV) or died within 24h of admission. We used Cox regression models to examine the association of admission NT-proBNP with mortality and the composite of death or MV. Results: Admission NT-proBNP was available in 399 patients (85.1%) of this cohort. Table 1 summarizes the patient characteristics according to history of HF (41/399 [10.3%]). After a median of 13 days (8-22), 107 patients (26.8%) died and 86 additional patients (21.6%) required MV and survived. Both HF (HR 3.65; 95%CI 2.32-5.77; P2 saturation, every log-2 higher admission NT-proBNP was associated with 28% higher mortality in patients with HF (HR 1.28; 95%CI 1.02-1.61; P=0.037) and 26% higher mortality in patients without HF (HR 1.26; 95%CI 1.14-1.40; P Conclusions: In these high-risk COVID-19 patients, admission NT-proBNP was strongly predictive of mortality regardless of HF. Elevated NT-proBNP may thus identify patients in need of cardioprotective measures.

Background Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) can be serious complications of coronavirus disease 19 (COVID-19). Co-infections may worsen outcomes and prolong hospitalization. This risk may be exacerbated by systemic corticosteroids (steroids) and other adjunctive therapies. Methods We reviewed the records of all adults admitted to Stony Brook University Hospital, NY, from 3/1 to 4/15, 2020 with severe COVID-19 pneumonia, requiring high-flow O2 (non-rebreather mask, Venturi mask with FiO2 >50%, or high-flow nasal cannula). We excluded patients who received mechanical ventilation (MV) or died within 24h. Patients were followed until death or hospital discharge. We reviewed positive sputum cultures (PSC) for pathogenic microorganisms and calculated the incidence of HAP and VAP (nosocomial pneumonia, [NP]), rates of MV and impact on mortality. Fungi isolated from sputum, were considered colonization unless associated with fungemia. We also examined the impact of adjunctive therapies with immunosuppressive potential (steroids and tocilizumab), on HAP or VAP. Results A total of 469 patients were included (Table 1). Of these, 199 (42.4%) required intensive care and 172 (36.7%) MV. Median length of stay was 13 days (8–22) and 105 (22.4%) had PSC. Of these, 59 were considered true pathogens (HAP: 11, VAP: 48), with predominance of S. aureus (MSSA) 38.9%, Enterobacteriaceae 33.8% and Pseudomonas species 18.6%. 39 isolates were considered colonization (Table 2); Patients with PSC < 48h (N=7) from admission, were not considered NP. The incidence of NP was 7.0 per 1000 patient-days (95%CI 5.5–8.5). Of 11 patients with HAP, 9 needed MV. NP was more frequent among patients receiving steroids (9.0 vs 5.7 per 1000 patient-days; P=0.023). Use of tocilizumab was not associated with NP (6.2 vs 8.4 per 1000 patient-days; P=0.11). Mortality was nonsignificantly higher in patients with (20/59, 33.9%) vs. without (103/410, 25.1%) NP (P=0.16). Intubation and length of stay were the strongest predictors of NP in multivariable models. Cohort Characteristics of Patients with Severe COVID -19 Pneumonia on High Flow Oxygen (N= 469) All Microbes Isolated from Sputum Cultures Conclusion Among high risk COVID-19 patients, NP is a common complication. MSSA and Enterobacteriaceae were the most frequent isolates. The risk increases with intubation, longer hospital stay and use of steroids but not tocilizumab. Disclosures All Authors: No reported disclosures

Background Coronavirus disease 19 (COVID-19) leading to acute respiratory distress syndrome is associated with need for intensive care (IC), mechanical ventilation (MV), and prolonged recovery. These patients are thus predisposed to blood stream infections which can worsen outcomes. This risk may be aggravated by adjunctive therapies. Methods We reviewed the medical records of all adults admitted to Stony Brook University Hospital, NY, from March 1 to April 15, 2020 with severe COVID-19 pneumonia (requiring high-flow O2). Patients who received MV or died within 24h were excluded. Patients were followed until death or hospital discharge. We reviewed positive blood cultures (PBC) for pathogenic microorganisms, and calculated the incidence of bacteremia, rates of infective endocarditis (IE), and impact on mortality. Microbes isolated only once and belonging to groups defined as commensal skin microbiota were labelled as contaminants. We also examined the impact of adjunctive therapies with immunosuppressive potential (steroids and tocilizumab), on bacteremia. Results A total of 469 patients with severe COVID-19 pneumonia were included (Table 1). Of these, 199 (42.4%) required IC and 172 (36.7%) MV. Median length of stay was 13 days (8–22) and 94 (20.0%) had PBC. Of these, 43 were considered true pathogens (bacteremia), with predominance of E. faecalis and S. epidermidis, and 51 were considered contaminants (Table 2). The incidence of bacteremia (43/469, 9.2%) was 5.1 per 1000 patient-days (95%CI 3.8–6.4). An echocardiogram was performed in 21 patients, 1 had an aortic valve vegetation (IE) by methicillin sensitive S. aureus. Bacteremia rates were nonsignificantly higher with steroids (5.9 vs 3.7 per 1000 patient-days; P=0.057). Use of tocilizumab was not associated with bacteremia (5.8 vs 4.8 per 1000 patient-days; P=0.28). Mortality was nonsignificantly higher in patients with (15/43, 34.9%) vs. without (108/426, 25.4%) bacteremia (P=0.20). Length of stay was the strongest predictor of bacteremia, with risk increasing by 7% (95%CI 6%-9%, P< 0.001) per additional day. Cohort Characteristics of Patients with Severe COVID-19 Pneumonia on High-Flow O2 (N= 469) All Microorganisms Isolated from Blood Cultures Conclusion The incidence of bacteremia was relatively low and IE was uncommon in this study of severe COVID-19 patients. Risk of bacteremia increased with longer hospital stay and with steroids use, but not with tocilizumab. Disclosures All Authors: No reported disclosures

Bruton tyrosine kinase (BTK) is a critical effector molecule for B cell development and plays a major role in lymphoma genesis. Ibrutinib is the first-generation BTK inhibitor. Ibrutinib has off-target effects on EGFR, ITK, and Tec family kinases, which explains the untoward effects of ibrutinib. Resistance to ibrutinib was also reported. The C481S mutation in the BTK kinase domain was reported to be a major mechanism of resistance to ibrutinib. This review summarizes the clinical development of novel BTK inhibitors, ACP-196 (acalabrutinib), ONO/GS-4059, and BGB-3111.

T790M mutation is the most common mechanism for resistance to first- and second-generation tyrosine kinase inhibitors (TKI) for epidermal growth factor receptor (EGFR). Several third-generation EGFR mutant selective TKIs are being explored to conquer this resistance. AZD9291 (osimertinib, tagrisso) has been approved for treatment of the metastatic EGFR T790M mutation-positive non-small cell lung cancer. Resistance to AZD9291 has been described. C797S mutation was reported to be a major mechanism for resistance to T790M-targeting EGFR inhibitors. This review summarizes the latest development in identifying the C797S mutation and EAI045, the novel selective inhibitor overcoming the C797S mutant.