REMDESIVIR THERAPY AND ITS ASSOCIATION WITH SINUS BRADYCARDIA

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Various case reports have associated transient sinus bradycardia with Remdesivir (RDV) therapy for SARS-CoV2 infection. Pallotto et al., Gubitosa et al., and Touafchia et al. all reported the association of Remdesivir with increased risk of bradycardia in small samples of patients treated with RDV for COVID-19. To our knowledge, no large studies looked at this side effect of RDV therapy. We aimed to analyze the association between sinus bradycardia and Remdesivir therapy for COVID-19. METHODS: A retrospective case-control analysis was done for 1535 patients with SARS-CoV2 infection who were admitted to four teaching hospitals in an urban area in 2020. The mean age was 66 years (SD of 16.7, range 18-99), with 774 males (50.4%). Patients were divided into cases (treated with RDV) and controls (not treated with RDV). Multivariate logistic regression methods were used to analyze the associations between independent variables and outcomes. Pulse rate variables were recorded as pulse rate at day-0, day-3, day-7, and incidence of bradycardia on three consecutive days during admission. Other variables recorded were age, gender, comorbidities, prior history of cardiac disease/arrhythmias, concomitant medications (including AV nodal blockers, dexamethasone, Albuterol, and Lasix), and ICU admission. Survival analysis was run for 7-day and 30-day mortality, as well as survival to hospital discharge. RESULTS: 1415 patients were included in the final analysis, after the exclusion of 120 patients with previous heart blocks. 600 patients (39.1%) were in the Remdesivir group, and 935 patients (60.9%) were in the control group. Between both groups, a total of 454 patients (29.6%) had transient bradycardia on three consecutive days during hospitalization. A multivariate regression analysis was done after adjusting for all confounding variables (age, gender, history of cardiac diseases, AV-nodal blocking drugs, dexamethasone, furosemide, and albuterol therapy). It was seen that there was no statistically significant association between RDV therapy and persistent transient bradycardia (transient bradycardic events on three consecutive days) (Odds Ratio 0.823, 95% confidence interval (CI) 0.594-1.134, p=0.236). There was no statistically significant association of RDV therapy with patients having any bradycardia event during hospitalization in a sub-analysis (Odds Ratio 0.888, 95% confidence interval (CI) 0.665-1.184, p=0.419). Also, RDV failed to show any statistically significant mortality benefit (OR 1.1, CI 0.75-1.62, p=0.6). CONCLUSIONS: Our findings indicate that although transient sinus bradycardia in patients with COVID-19, can be triggered by severe hypoxia, inflammatory damage to AV-nodal cells, or exaggerated response to medications, there was no statistically significant association of RDV therapy with the risk of developing bradycardia. RDV therapy should not be withheld in patients at risk of developing bradycardia. CLINICAL IMPLICATIONS: Remdesivir therapy did not increase the risk of developing bradycardia in our patient population. RDV therapy should not be withheld in patients at risk of developing bradycardia. Larger RCTs are needed to validate these findings. DISCLOSURES: No relevant relationships by Rahul Bollam, source=Web Response No relevant relationships by Bhagat Kondaveeti, source=Web Response No relevant relationships by Florencio Mamauag, source=Web Response No relevant relationships by Kainat Saleem, source=Web Response No relevant relationships by Manasi Sejpal, source=Web Response No relevant relationships by Megha Sood, source=Web Response No relevant relationships by Morgan Stalder, source=Web Response No relevant relationships by Rosalie Traficante, source=Web Response No relevant relationships by Syed Arsalan Zaidi, source=Web Response

SINUS BRADYCARDIA AS A PREDICTOR OF SEVERITY OF COVID-19 INFECTION: TRANQUILITY BEFORE CHAOS

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Various cardiac manifestations of the COVID-19 virus have been reported since early 2020, including a range of arrhythmias, but to our knowledge, only 2 case reports exist describing new bradycardia in patients with COVID-19 infection. We aimed to analyze the association between sinus bradycardia and severity of covid-19 infection, including survival outcomes. METHODS: A retrospective analysis was done for 1535 patients with SARS-CoV2 infection who were admitted to four teaching hospitals in an urban area in 2020. The mean age was 66 years (SD of 16.7, range 18-99), with 774 males (50.4%). Multivariate logistic regression methods were used to analyze the associations between independent variables and outcomes. Pulse rate variables were recorded as pulse rate at day-0, day-3, day-7, and incidence of bradycardia on 3 consecutive days during admission. Other variables recorded were age, gender, comorbidities, prior history of cardiac disease/arrhythmias, concomitant medications (including AV nodal blockers, dexamethasone, Remdesivir, Albuterol, and Lasix), and ICU admission. The severity of COVID-19 infection was graded by the need for ICU admission vs. no ICU admission. Survival analysis was run for 7-day and 30-day mortality, as well as survival to hospital discharge. RESULTS: 1415 patients were included in the final analysis, as 120 patients with prior heart block were excluded. 508 patients (33.1%) required ICU admission due to severe hypoxia, 708 patients (46.2%) had at least one episode of significant bradycardia. Our sample population had an inpatient all-cause mortality of 18.1%. After adjusting for confounding variables, it was seen that patients with incident bradycardia on 3 consecutive days were more likely to require ICU admission than patients without these bradycardia events (Odds Ratio 1.58, p=0.001). There was no significant association of bradycardia with survival to hospital discharge (p=0.761). It was also seen in a sub-analysis that tachycardia on day-3 is statistically significantly associated with 7-day mortality, such that patients with tachycardia on day 3 had 2.9 (p<0.001) times the odds of 7-day mortality compared to those with normal heart rate. We also tested the overall significance of pulse rate at day-0, day 3, day 7, and persistent bradycardia and found that pulse at day 3 was a statistically significant predictor of 7-day mortality (p=0.001). CONCLUSIONS: Our findings suggest a possible correlation between bradycardia and the severity of COVID-19 symptoms;more severe COVID-19 cases were associated with a higher incidence of new bradycardia events. Transient sinus bradycardia can be triggered by severe hypoxia, inflammatory damage to AV-nodal cells, or exaggerated response to medications, but the exact etiology is still unknown. Bradycardia might be a warning sign of possible acute worsening of symptoms and should be monitored closely. Further studies are warranted to confirm these findings. CLINICAL IMPLICATIONS: Transient sinus bradycardia is possibly associated with a higher likelihood of ICU admission due to the severity of COVID-19 symptoms, and these patients should be monitored closely. DISCLOSURES: No relevant relationships by Firas Abdulmajeed, source=Web Response No relevant relationships by Abasin Amanzai, source=Web Response No relevant relationships by Rahul Bollam, source=Web Response No relevant relationships by Florencio Mamauag, source=Web Response No relevant relationships by Kainat Saleem, source=Web Response No relevant relationships by Morgan Stalder, source=Web Response No relevant relationships by Syed Arsalan Zaidi, source=Web Response

DID WE NEED THOSE ANTIBIOTICS? OUTCOMES OF PATIENTS WITH COVID-19 TREATED FOR BACTERIAL SUPERINFECTION OF THE LUNGS

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: The COVID-19 pandemic has affected over half a billion people worldwide. Series report that up to 75% of hospitalized patients with COVID-19 receive broad-spectrum antibiotics;however, the incidence of bacterial coinfection is consistently reported to be low. The diagnosis of bacterial superinfection of the lungs (BSL) is clinical, which presents the possibility of overdiagnosis and overutilization of antibiotics. The aim of this study was to describe the outcomes of patients who were treated for a bacterial superinfection of the lungs (BSL) compared to those who were not. METHODS: We conducted a retrospective chart review of all consecutive patients with a diagnosis of COVID-19 hospitalized at our center. We defined BSL as a documented episode of pneumonia treated with antibiotics. We collected information on demographics, comorbidities, and microbiological markers. We compared patients with and without a diagnosis of BSL in terms of intensive care unit (ICU) stay, intubation, length on mechanical ventilation, length of hospital stay (LOS) and 7-day and 30-day mortality. RESULTS: Five hundred eighty-two patients had a diagnosis of COVID-19, of which 105 had BSL. Patients with BSL were older compared to those without BSL (mean age 74 vs 70 years) and more likely to be male (57% vs 47%), but they were similar in proportion of White patients (64 vs 63.6) and Charlson comorbidity index (5 vs 4). Patients with BSL had a higher likelihood of admission to the ICU (63% vs 19%) and higher intubation rates (31% vs 9%). BSL patients had longer mechanical ventilation (9 vs 3 days) and greater length of stay (13 vs 7). Only 17 BSL patients had sputum cultures, of which 10 were positive. None of the BSL patients had a positive Legionella urinary antigen or Streptococcus pneumoniae urinary antigen, and only 6/57 (10.5%) had a positive MRSA nasal screen. Seven-day and 30-day mortality were not statistically different between BSL and non-BSL patients (p=0.18, p=0.65 respectively). Interestingly, Cox proportional hazard analysis adjusted for age, sex, race, CCI and ICU stay yielded a significantly reduced mortality at 7 and 30-day among BSL patients (HR=0.2 CI [.1-0.7], p=.0106, HR=0.5 [CI.3-0.8], p=0.0101, respectively). CONCLUSIONS: Patients with BSL received more intense supportive care, and had a longer ICU stay, yet did not have a greater mortality. When adjusting for age, sex, race, CCI and ICU, there was a significant reduction in mortality. It is tempting to interpret these finding as an effect of antibiotics;however, we did not record COVID-19-specific treatments such as steroids, tocilizumab and remdesivir. It is likely that the BSL patients received more steroids, which have been associated with reduced mortality. In our population, microbiological testing was performed in a minority of patients, and it was therefore not a reliable marker of true infection. It is possible that many patients in the BSL group did not truly have a bacterial infection. CLINICAL IMPLICATIONS: Patients with a diagnosis of BSL were sicker, but we observed no difference in unadjusted mortality. Studies on the outcomes of the BSL among COVID-19 patients should account for the effect of concurrent COVID-19 specific therapy. DISCLOSURES: No relevant relationships by Abdelrhman Abo-zed, source=Web Response No relevant relationships by Abasin Amanzai, source=Web Response No relevant relationships by Ricardo Arbulu Guerra, source=Web Response No relevant relationships by NIRZARI PANDYA, source=Web Response No relevant relationships by Morgan Stalder, source=Web Response No relevant relationships by Rosalie Traficante, source=Web Response No relevant relationships by Mohamed Yassin, source=Web Response

COUGHING UP A LUNG

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: The novel coronavirus SARS-CoV-2 is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as adult respiratory syndrome, sepsis, coagulopathy, and death. The increase in the vasoconstrictor angiotensin II, the decrease in the vasodilator angiotensin, and the sepsis-induced release of cytokines can trigger a coagulopathy in COVID-19 [1]. In extreme cases of pulmonary embolism, pulmonary infarction can occur but is relatively rare given the dual blood supply to the lungs. We present a unique case of COVID-19 associated pulmonary embolism complicated by infarction, hydropneumothorax, and loss of the left lower lobe in a previously healthy young man. CASE PRESENTATION: A 42-year-old male presents with acute shortness of breath and chest pain. He has a history of Factor 5 Leiden. Vital signs included sinus tachycardia and a 95% oxygen saturation on 3L nasal cannula. Physical exam was notable for crackles in the left lung base with diminished breath sounds compared to the right. Computed tomography with angiogram (CTA) of the chest revealed an acute saddle pulmonary embolism with occlusive clots in left segmental branches and he was treated with heparin. Two days later, he developed leukocytosis and a severe, productive cough with thick, brown sputum. Repeat CTA chest revealed extensive, multiloculated cavitation throughout the left lung, with air fluid levels and wall thickening suggesting lung necrosis and a new hydropneumothorax. With regards to his pleural effusion, he was managed conservatively with piperacillin-tazobactam. Neither surgical intervention nor chest tube placement was performed. His sputum production and clinical condition slowly recovered, and he was discharged home on oral antibiotics with plan for serial imaging. DISCUSSION: We were faced with multiple competing issues including COVID-19 infection, pulmonary embolism with lung necrosis, and hydropneumothorax. In just one week, pulmonary necrosis developed followed by a severe cough productive of first bloody, then dark tan sputum. We had concerns for empyema and so our thoughts were to immediately drain the pleural effusion. However, the degree of lung destruction and evidence of direct communication between the left lower lobe bronchus and pleural space gave us concerns for creating a bronchopleural fistula, if any surgical interventions were to occur. Surprisingly, after 2 weeks of heavy coughing, his cough abated which correlated with decreased size of patient's left lower lobe. At discharge, his left lower lobe was nearly gone and hydropneumothorax was slightly improved. The "sputum" he had been coughing up for weeks was actually necrotic lung. CONCLUSIONS: We present a case of a COVID-19 infection complicated by pulmonary embolism with significant lung necrosis and hydropneumothorax, which was managed conservatively due to concerns of producing a bronchopleural fistula. REFERENCE #1: M;MWM. COVID-19: Coagulopathy, Risk of Thrombosis, and the Rationale for Anticoagulation. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. REFERENCE #2: Chengsupanimit T;Sundaram B;Lau WB;Keith SW;Kane GC;Clinical characteristics of patients with pulmonary infarction - A retrospective review. Respiratory medicine. DISCLOSURES: No relevant relationships by Abdelrhman Abo-zed, source=Web Response No relevant relationships by Amitha Avasarala, source=Web Response No relevant relationships by Daniel Dunlap, source=Web Response No relevant relationships by Syed Hussain, source=Web Response No relevant relationships by Morgan Stalder, source=Web Response