Potential Causative Association between Respiratory Viruses and Pneumococcus-Associated Disease in Young Children in Israel: Lessons from the COVID-19 Pandemic

Background. During the early Covid-19 pandemic, we observed a close-to-full disappearance of the activity of 4 respiratory viruses (RSV, hMPV, influenza, and parainfluenza), followed by an off-season sequential re-emergence in 2021. Surprisingly, a striking similarity between the dynamics of pneumococcus-associated disease (PAD;namely community-acquired alveolar pneumonia [CAAP;often considered pneumococcal] and bacteremic-pneumococcal pneumonia [IPD-Pneumonia]), was also observed. In contrast, adenovirus and rhinovirus activities did not change during COVID-19. We examined the association between PAD and RSV, hMPV, influenza, and parainfluenza (PAD-viruses). Methods. Surveillance of CAAP and IPD-Pneumonia incidences and viral activity in children < 5 years was described in detail previously [Danino D. et al. Clin Infect Dis. 2022, https://doi.org/10.1093/cid/ciab1014]. We extended the observations until December 2021, to capture the sequential re-emergence of the 4 PAD-viruses. A hierarchical linear regression model was used to quantify the association between PAD-viruses (each virus individually and combined), adenovirus and PAD. After fitting the models, the contribution of each virus was estimated. Results. The Figure shows striking similarities in the dynamics of CAAP, IPD-Pneumonia, and PAD-viruses both before and during the COVID-19 pandemic. During the expected peak season (Oct 2020 - Apr 2021) PAD episodes were extremely low. However, off-season peaks were seen during May - Dec 2021. Overall, 78% and 25% of all CAAP and IPD-Pneumonia episodes, respectively, were attributable to these viruses in children < 5 (Table). In CAAP, cases were attributable to each of the 4 PAD-viruses individually throughout the first 5 years of life: RSV and hMPV combined contributed 80%, 63%, and 42% of all CAAP episodes in children aged < 1, 1, and 2-4 years, respectively. The respective figures for influenza and parainfluenza combined were 13%, 21%, and 22%. Only RSV significantly contributed to IPD-Pneumonia (19%). Adenovirus did not contribute to PAD episodes. Conclusion. Our model suggests an important causative association between RSV, hMPV, influenza, and parainfluenza viruses and CAAP, and between RSV and IPD-Pneumonia. (Figure Presented).

Involvement of Respiratory Viruses in Community-Acquired Alveolar Pneumonia (CAAP) in Children < 5 Years in Southern Israel, Before and During the COVID-19 Pandemic

Background. Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) and to a lesser extent, parainfluenza and influenza viruses have been associated with pneumonia in young children. In contrast, adenovirus (AdV) and rhinovirus (RhV) are usually not associated with pneumonia. We aimed to evaluate the involvement of the four pneumonia associated viruses (grouped as PAV) in pediatric CAAP, before and during the COVID-19 pandemic. Methods. CAAP incidence and viral activity surveillance in southern Israel in children < 5y and virological detection methods were described previously (Danino. CID 2022, https://doi.org/10.1093/cid/ciab1014). We reviewed the period of Jan 2016 - Mar 2022. Most cases of COVID-19 in children < 5y occurred during Dec 2021 - Mar 2022 (Figure 1);Over 95% of children admitted for respiratory disease were tested for COVID-19 (PCR). Since AdV and RhV activity was previously not associated with CAAP and tended to be equally involved in mixed and single infections, the current analysis was done for the four PAV only. Results. CAAP incidence dynamics closely resembled the four PAV (grouped) activity dynamics (Figure 2A, 2B) with very low activity during the expected peak in winter 2020-2021, but with an off-season resurgence from spring 2021. Even though most CAAP episodes during the pandemic coincided with peak COVID-19 rates, only 9 CAAP episodes were COVID-19 positive (7 in 2022, of which 5 were RSV positive). Out of 3,430 CAAP episodes 55% were tested for PAV, of which 61% were positive, with similar rates before and during the pandemic. RSV was the most common involved virus, followed by hMPV. The virus distribution in CAAP during the entire period reflected their activity in the community (Figure 2C). Unlike pre-pandemic years where all four PAV appeared almost simultaneously, in 2021 PAV resurged sequentially, resulting in successive involvement in CAAP episodes, suggesting a causative association. Conclusion. 1. SARS-CoV-2 was only rarely involved in CAAP in young children. 2. PAV were involved in 61% of CAAP episodes in children < 5y with predominance of RSV and hMPV. 3. The atypical dynamics imposed by the COVID-19 pandemic suggests a causative association between PAV and CAAP. (Figure Presented).

Towards a "Slowed Down” Pedagogy: An Emergent Youth-Led Practice of Politicized Care

We discuss how youth "slowed down” an online STEAM makerspace during the COVID-19 pandemic, opening up new ways of being and doing together. The practices youth enacted in slowing down arose from their politicized care for one another. Adult mentors, through moments of slowing down, were given an opportunity to rethink how to listen to youth's desired ways of doing STEAM. To discuss the implications of slowing down, this article features two instances in which Black youth "slowed down” in sessions to demonstrate their desired ways of being together/doing together within the STEAM context. Highlighting youths' moves has implications for how educators think about co-designing programs with youth and how to enact politicized care in the face of rapid social, environmental, and political change. © ISLS.

UTILITY OF RISK CALCULATORS AND INFLAMMATORY MARKERS IN THE ASSESSMENT OF OUTCOMES FOR PATIENTS WITH COVID-19 ON EXTRACORPOREAL MEMBRANE OXYGENATION

SESSION TITLE: ECMO and ARDS in COVID-19 Infections SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: Before the Coronavirus disease 2019 (COVID-19) pandemic, the use of extracorporeal membrane oxygenation (ECMO) specific scoring systems have been shown to predict survival better compared to general risk scores used in the intensive care unit (ICU). However, data is lacking on the utility of these scores in predicting mortality in COVID-19 patients managed with ECMO. Also, inflammatory markers have been reported to be predictors of mortality in patients with COVID-19 but have not been studied well in ECMO patients. Our study aims to assess the utility of standard ICU [Acute Physiology And Chronic Health Evaluation (APACHE-IV)] and ECMO specific [Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP)] risk calculators along with inflammatory markers in COVID-19 patients treated with ECMO. METHODS: This study is a retrospective analysis of all adult patients with COVID-related acute respiratory distress syndrome (ARDS) admitted to the ICUs of a quaternary care hospital between 03/01/2020 and 03/31/2022 who were managed with ECMO. Demographic and clinical characteristics, inflammatory markers at the time of hospital admission, and respiratory parameters at the time of ECMO cannulation of the patients who survived were compared and analyzed with patients who did not survive. RESULTS: Of the 36 COVID-19 patients managed with ECMO during the study period, 12 (33%) patients survived. Both groups were similar in terms of age, gender, and comorbidity burden (measured by Charlson Comorbidity Index). The severity of illness at the time of ICU admission (assessed by APACHE IV score) was not significantly different between two groups [Median (IQR) = 58 (50-67) vs. 60 (52-71), p= 0.627]. D-dimers at the time of ICU admission were significantly lower in the survivor group as compared to their counterpart [Median (IQR) ng/ml = 1238 (1021-1830) vs. 2990 (1298-16583), p= 0.031]. RESP score at the time of ECMO cannulation was significantly higher among the survivors as compared to non-survivors (Mean ± SD = 3.7 ± 2.2 vs. 1.3 ± 3.5, p= 0.042). CONCLUSIONS: Our study showed that higher D-dimers at the time of hospital admission and lower RESP score at the time of ECMO cannulation are associated with increased morality in patients with COVID-19 related ARDS placed on ECMO. Knowledge of these factors may assist with determining appropriate candidates for this limited resource as well as may enhance outcome predictions. Our study is limited by a relatively small sample size and therefore larger studies will be needed to validate our findings. CLINICAL IMPLICATIONS: This study shows that similar to pre-COVID studies, RESP score be useful in risk stratification of COVID-19 patients treated with ECMO. DISCLOSURES: No relevant relationships by ALEENA ARSHAD No relevant relationships by Dipak Chandy No relevant relationships by Oleg Epelbaum No relevant relationships by Daniel Greenberg No relevant relationships by Theresa Henson No relevant relationships by Areen Pitaktong No relevant relationships by Hamid Yaqoob

ASSOCIATION BETWEEN ETHNICITY AND COVID-19 PATIENTS TREATED WITH EXTRACORPOREAL MEMBRANE OXYGENATION

SESSION TITLE: Impact of Health Disparities and Differences SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: As of March 25, 2022, age-standardized data reported by the Centers for Disease Control and Prevention showed that Hispanic, Black and American Indian or Alaska Native are about twice as likely to die from coronavirus disease 2019 (COVID-19) as their White and Asian counterparts. However, there is paucity of data regarding the effect of race on outcomes in COVID-19 related acute respiratory distress syndrome (ARDS) patients managed with extracorporeal membrane oxygenation (ECMO). Our study aims to understand the differences in the outcome between White/Asian and other ethnically minority COVID-19 patients treated with ECMO in our intensive care unit (ICU). METHODS: Retrospective analysis of adult patients with COVID-19 related ARDS treated with ECMO in the ICUs of a quaternary care hospital between 03/01/2020 and 03/31/2022. Patients were divided into two groups: White/Asian (WA) and Other Minorities (OM). Demographics, clinical characteristics, and outcomes of the two groups were compared. RESULTS: Of the 36 COVID-19 patients managed with ECMO during the study period, 18 (50%) patients belonged to the WA group while 18 (50%) patients belonged to the OM group. In the WA group, 16 (89%) were white and 2 (11%) were Asians whereas in the OM group, 16 (89%) patients were Hispanics and 2 (11%) patients were African-American. Both groups were similar in terms of age, gender, comorbidity burden (measured by Charlson Comorbidity Index), and severity of illness at the time of ICU admission (assessed by APACHE-IV score). Mean RESP score was lower in the OM group but was not statistically significant (1.3 ± 3.9 vs 2.9 ± 2.3, p= 0.157). This was reflected in the higher hospital mortality in the OM group compared to the WA group [n= 9 (50%) vs. 15 (83%), p=0.075]. There was no significant difference between the groups in the rate of ECMO-related complications, including major bleeding requiring transfusion, transaminitis (alanine transaminase greater than 5 times of upper normal limit), stroke, myocardial dysfunction (defined as an ejection fraction < 30%), acute kidney injury requiring dialysis and positive sterile fluid cultures. CONCLUSIONS: Our study showed higher mortality in ethnically minority patients compared to the white and Asian population but the difference was not statistically significant. It is possible that the relatively small number of patients in our study led to a beta error. Higher mortality rates among people of color have been attributed to low socio-economic status, structural inequities in health care and differences in vaccination rates. CLINICAL IMPLICATIONS: Larger studies are needed to further explore differences in clinical characteristics and outcomes of COVID-19 patients of different races and ethnicities treated with ECMO. DISCLOSURES: No relevant relationships by ALEENA ARSHAD No relevant relationships by Dipak Chandy No relevant relationships by Subo Dey No relevant relationships by Oleg Epelbaum No relevant relationships by Daniel Greenberg No relevant relationships by Theresa Henson No relevant relationships by Lawrence Huang No relevant relationships by Daniel Peneyra No relevant relationships by Areen Pitaktong No relevant relationships by Hamid Yaqoob

EXTRACORPOREAL MEMBRANE OXYGENATION: A HOPE FOR THE SICKEST PATIENTS WITH COVID-19

SESSION TITLE: ECMO and ARDS in COVID-19 Infections SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: The role of extracorporeal membrane oxygenation (ECMO) for patients with coronavirus disease 2019 (COVID-19) related acute respiratory distress syndrome (ARDS) is evolving. Data from different waves of the pandemic has shown that mortality of COVID-19 patients treated with ECMO ranges from 40-94%. Pre-COVID studies have shown that ECMO is associated with bleeding in 30-50% of patients, thrombotic complications in about 10% and secondary infections in 40% of patients. However, there is a paucity of data regarding complications with the use of ECMO in COVID-19 patients. In this study, we describe the hospital course and complications seen in the COVID-19 patients admitted to our Intensive Care Unit (ICU) treated with ECMO. METHODS: Retrospective cohort analysis of adult patients with COVID-19 related ARDS admitted to the ICUs of a quaternary care hospital between 03/01/2020 and 03/31/2022 who were managed with ECMO. RESULTS: Of the 36 COVID-19 patients treated with ECMO, 23 (64%) patients were male. Median age was 48 years (IQR 36-59). Patients had a mean BMI of 36 ± 12. Median Charlson Comorbidity Index (assesses comorbidities) was 1 (0-2) and median APACHE-IV score (assesses severity of illness at the time of ICU admission) was 60 (51-72). Prior to initiation of ECMO, 14 (39%) patients were proned and 29 (81%) patients received a trial of neuromuscular blockade. Patients had high plateau pressures (mean 31 ± 8 cm H20) with pO2/FiO2 ratios consistent with severe ARDS (mean 63 ± 17) at the time of ECMO cannulation. Mean Respiratory ECMO Survival Prediction (RESP) score was 2.1 ± 3.3. The most common complications were bleeding requiring transfusion seen in 94% of patients and positive sterile fluid cultures (53% patients). Hemorrhagic stroke was seen in 3 patients (8%). None of the patients had limb ischemia or clotting of the cannula requiring catheter exchange. Withdrawal of care occurred in 3 patients (8%). 13 (35%) patients were successfully decannulated from ECMO;however only 12 (33%) patients were discharged alive. CONCLUSIONS: Our study shows a survival rate in COVID-19 patients treated with ECMO that is comparable to previously reported studies. High bleeding and infection rates can possibly be explained by steroid use and COVID-19 disease specific characteristics. CLINICAL IMPLICATIONS: Our study describes the hospital course of the COVID-19 patients treated with ECMO and can be used to evaluate it's role in the management of severe COVID-19 patients refractory to conventional ventilatory management. DISCLOSURES: No relevant relationships by ALEENA ARSHAD No relevant relationships by Dipak Chandy No relevant relationships by Oleg Epelbaum No relevant relationships by Daniel Greenberg No relevant relationships by Theresa Henson No relevant relationships by Lawrence Huang No relevant relationships by Daniel Peneyra No relevant relationships by Areen Pitaktong No relevant relationships by Hamid Yaqoob

Comparison of Extracorporeal Membrane Oxygenation Survivors with Non-Survivors;A Retrospective Analysis at a Quaternary Center

Rationale: International organizations, including the World Health Organization and Extracorporeal Life Support Organization have recommended the use of extracorporeal membrane oxygenation (ECMO) in the management of patients with Coronavirus Disease-19 (COVID-19) related acute respiratory distress syndrome (ARDS) based on favorable outcomes shown by some studies from earlier parts of the pandemic. Mortality rates of COVID-19 patients with the use of ECMO has ranged from 40-94%. Some reports suggest early initiation of ECMO leads to better outcomes before refractory hypoxemia leads to multi-organ failure. However, the predictors of mortality among COVID-19 patients treated with ECMO remain unclear. Also, ECMO has been associated with potentially life-threatening bleeding and thromboembolic complications. This study aims to identify the risk factors associated with the mortality in COVID-19 patients managed with ECMO and to assess the effect of ECMO related complications on mortality. Methods: Retrospective analysis of adult patients with COVID-related ARDS treated with ECMO at the ICUs of a quaternary care hospital between 03/01/2020 and 08/31/2021. Demographics, clinical characteristics, and outcomes of the patients who survived were compared with those who did not survive. Hemorrhagic complications were defined as bleeding requiring transfusion, hemorrhagic stroke and coagulopathy with International Normalized Ratio (INR) > 3. Thrombotic complications were defined as limb ischemia and ischemic stroke. Myocardial dysfunction was defined as a drop in ejection fraction to less than 30%, liver dysfunction as alanine transaminase (ALT) greater than 5 times of upper normal limit (ULN), and kidney involvement as acute kidney injury (AKI) requiring dialysis. Results: Of the 31 COVID-19 patients managed with ECMO during the study period, 11 (36%) patients survived. Both groups were similar in terms of age, gender, comorbidity burden (measured by Charlson Comorbidity Index), and severity of illness at the time of ICU admission (assessed by APACHE-IV score). Days spent on mechanical ventilation (MV) before ECMO cannulation were lower in survivors as compared to non-survivors but the difference was not statistically different. The incidence of complications was not statistically different between two groups. Conclusion: Our study shows a survival rate in COVID-19 patients treated with ECMO that is similar to previously reported studies. Our study did not reveal any significant predictive differences between survivors and nonsurvivors, thereby continuing to make the process of patient selection for ECMO challenging during this pandemic. Our study is limited by a relatively small sample size and therefore larger studies will be needed to confirm our findings.

Association Between Urban Greenspace and Mental Wellbeing During the COVID-19 Pandemic in a US Cohort

The Coronavirus Disease 2019 (COVID-19) pandemic brought unprecedented socially isolating measures to mitigate the spread of disease, heightening the importance of public outdoor urban greenspace. Here, we investigated the association between tree-rich greenspace and mental health in a large opportunity sample surveyed using a crowdsourcing research website (www.covid19resilience.org) between April 6th and October 12th, 2020 during the pandemic in the United States. Participants living in the U.S. (N = 2,089, 83.1% females, mean age 42 years, age range 18-90 years) were mapped to 1,080 unique ZIP Codes and mean tree canopy density was calculated with a 250m buffer around each ZIP Code grouped by quartile as a proxy for nearby greenspace. Four mental health parameters were assessed: (1) COVID-19-related worries;(2) anxiety symptoms;(3) depression symptoms;and (4) a standardized and weighted composite mental health score of all three parameters. Multivariate regression analyses with multilevel models were used to study the association between nearby greenspace and the four mental health outcomes, controlling for participant demographics and ZIP Code urbanicity. In the entire cohort, increased nearby greenspace showed a significant protective effect for depression (Coef. = -0.27;p = 0.0499), and composite mental health scores (Coef. = -0.19;p = 0.038) when comparing ZIP Codes with the most greenspace to ZIP Codes with the least, with no observed effects on COVID-19 related worries or anxiety individually. Stratifying by age suggested protective trends of greenspace on mental health in older subsets of the population (top age quartile, over 51 years old) experiencing less depression (Coef. = -0.45;p = 0.048) and lower composite mental health scores (Coef. = -0.34;- = 0.032) as a function of nearby greenspace. Additionally, younger subsets of the population (second youngest age quartile, 31-38 years) experienced lower COVID-19 related worries (Coef. = -1.34;p = 0.022) as a function of greenspace. These findings may indicate that tree-rich greenspace plays a protective role on mental health during the COVID-19 pandemic, specifically in certain age groups, supporting the use of greenspace-related strategies to help mitigate mental health burden during this challenging and isolating time.

PREDICTORS AND OUTCOMES OF BACTERIAL AND FUNGAL SUPERINFECTIONS IN CRITICALLY ILL PATIENTS WITH COVID-19

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Secondary infections are well-described complications in patients with viral pneumonia and are associated with increased mortality and morbidity (1). A recent meta-analysis reported that secondary infections in critically ill Coronavirus Disease 19 (COVID-19) patients in intensive care unit (ICU) are around 14% (2). Most of the studies are limited by false-positive cultures in non-sterile body fluids (2). Our study aims to assess the burden of secondary infections by focusing on the positive rate of sterile body fluid cultures in ICU patients, to examine associated risk factors and to assess their impact on outcome. METHODS: Retrospective analysis of all adult patients with COVID-related acute respiratory distress syndrome (ARDS) admitted to the ICUs of a quaternary care hospital between 03/01/2020 and 05/31/2020. Patients who had positive sterile body fluid (blood, peritoneal, pleural or cerebrospinal fluid) cultures for bacteria or fungi, were compared with those without positive cultures. RESULTS: Of the 210 patients admitted to our ICU with COVID-19 related ARDS, 55 patients (26%) had positive sterile body fluid cultures, of which 37 grew bacteria, 7 fungi and 11 both. Patients with positive cultures were similar in terms of baseline demographics, comorbidities and severity of illness at ICU admission to those patients without positive cultures. Peak inflammatory markers were significantly higher in the positive culture group. In the positive culture group, the rates of receipt of steroids (78% vs. 61%, p=0.02) and convalescent plasma (64% vs. 45%, p=0.03) were significantly higher. The prevalence of acute kidney injury (AKI) requiring dialysis was significantly greater in the positive culture group (55% vs. 28%, p<0.001). There was no difference in terms of mortality between the two groups. However, mechanical ventilation (MV) free days at day 28 were significantly lower in the positive culture group (Mean ± S.D: 2.7 ± 5.7 vs. 6 ± 9.9, p=0.004). CONCLUSIONS: Our study shows that the incidence of superinfections in COVID-19 patients admitted to ICUs is higher than previously reported. The higher incidence is comparable to the rate of superinfections in the H1N1 influenza pandemic of 2009 (2). However, the high rates of steroid and plasma administration in our positive culture group may also have contributed to the high incidence of secondary infections. Our results have also shown that these infections may prolong ventilatory support as well as increase the likelihood of developing AKI requiring dialysis. Therefore, intensivists need to be vigilant about not missing superinfections in patients with COVID-19 which can negatively impact patient outcomes. CLINICAL IMPLICATIONS: This study will help to identify the risk factors associated with higher incidence of secondary infections in patients with COVID-19, and will assist physicians to identify and treat them early in the course of disease. 1. I. Martín-Loeches, A. Sanchez-Corral, E. Diaz, R.M. Granada, et al., H1N1 SEMICYUC Working Group Community-acquired respiratory coinfection in critically ill patients with pandemic 2009 influenza A(H1N1) virus. Chest, 139 (2011), pp. 555-562. 2. Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect. 2020;81(2):266-275. DISCLOSURES: No relevant relationships by ALEENA ARSHAD, source=Web Response No relevant relationships by Dipak Chandy, source=Web Response No relevant relationships by Oleg Epelbaum, source=Web Response No relevant relationships by Daniel Greenberg, source=Web Response No relevant relationships by Muhammad Rizwan, source=Web Response No relevant relationships by Hamid Yaqoob, source=Web Response

Youth Critical Data Practices in the COVID-19 Multipandemic

This study investigates how youth from two cities in the United States engage in critical data practices as they learn about and take action in their lives and communities in relation to COVID-19 and its intersections with justice-related concerns. Guided by theories of critical data literacies and data justice, a historicized and future-oriented participatory methodological approach is used to center the lived lives and communities of participants through dialogic interviews and experience sampling method. Data were co-analyzed with participants using critical grounded theory. Findings illustrate how youth not only aimed to reveal the dynamic and human aspects of and relationships with data as they engage with/in the world as people who matter but also offered alternative infrastructures for counter data production and aggregation toward justice in the here and now and desired possible futures. Implications for studies of learning with/through data practices in everyday life in relation to issues of justice are discussed.

Inhaled nitric oxide for the treatment of COVID-19 and other viral pneumonias in adults

RATIONALE: There is a growing population at increased risk of viral pneumonia;over 50,000 people in the United States died from pneumonia in 2015. RSV, influenza, and other viruses are common causes of severe viral lower respiratory tract infection (LRTI), and COVID-19 pneumonia is associated with high mortality rates. With limited treatment options currently available, viral COVID-19 LRTI in particular represents a significant unmet medical need. Inhaled nitric oxide (iNO) is a highly promising treatment option, given its documented antimicrobial and anti-inflammatory effects as well as beneficial effects on pulmonary vasculature. In particular, the antiviral effect of iNO on SARS-CoV-2 has been attributed to covalent binding to SARS-CoV-2 protease. In multiple clinical trials and compassionate use cases, intermittent exposure to 150 - 250 ppm iNO was well tolerated, resulted in improved physical and lung function, reduced bacterial load in patients with cystic fibrosis , and shortened time to improvement of clinical signs and time to fit for discharge in patients with acute bronchiolitis. Based on these data, we have initiated a prospective, randomized, open label, multi-center pilot clinical trial to evaluate the safety and efficacy of iNO for the treatment of viral pneumonia in adult patients. METHODS: In the current study, subjects (ages 18-80) with COVID-19 (COVID group) or other acute viral pneumonias (Viral LRTI group) requiring inpatient hospitalization are being randomized 1:1 to be treated with intermittent inhalations of 150 ppm iNO, given for 40 minutes 4 times daily for up to 7 days in addition to standard supportive treatment (SST), or to receive SST alone. iNO is being delivered by the LungFitTM, an innovative portable device under development (Beyond Air, NY, USA) that generates NO from room air. Study endpoints include safety, ICU admission, O2 supplementation requirement, and time to resolution of fever. RESULTS: The study will be conducted in up to 10 centers in Israel. To date, 6 subjects have been enrolled (COVID group), three have been randomized to iNO + SST and three to SST alone. All treatments have been well tolerated. CONCLUSIONS: Based on current data demonstrating the antiviral and anti-inflammatory effects of NO, in addition to its complex beneficial effect on oxygenation, iNO delivered by the LungFit system has the potential to treat viral pneumonias including COVID-19, thereby providing therapy for this currently unmet medical need.

The effect of chronic immunosuppression on the severity and outcomes of COVID-19 icu patients

Rationale: There is currently limited and conflicting data regarding the effect of immunosuppression on severity and outcomes of Coronavirus Disease 2019 (COVID-19). Mortality rates of solid organ transplant recipients hospitalized with COVID-19 range as widely as 5-67%. Some of these reports therefore seem to suggest that immunosuppressed patients have a similar mortality when compared to non-immunosuppressed patients. Also, there is limited data on the incidence of bacterial and fungal superinfections in these critically ill COVID-19 patients who are immunosuppressed. Our study aims to understand the impact of immunosuppression on the clinical course and outcomes of COVID-19 patients admitted to our intensive care units (ICUs). Methods: This study is a retrospective analysis of all adult patients with COVID-related acute respiratory distress syndrome (ARDS) admitted to the ICUs of a quaternary care hospital between 03/01/2020 and 05/31/2020. Patients on chronic immunosuppressive medications were identified. Demographic and clinical characteristics, inflammatory markers at the time of ICU admission and clinical outcomes of these patients were compared and analyzed with patients who were not immunosuppressed. Means, medians and categorical variables were compared using t-test, Mann-Whitney U-test and Fisher's exact test, respectively. P-value of <0.05 was taken to be statistically significant. Results:Of the 210 patients admitted to our ICUs with COVID-related Acute Respiratory Distress Syndrome, 23 (11%) were taking immunosuppressant medications before they were admitted to our unit. 11 patients had a history of organ transplantation (Liver: 4, Kidney: 4, Heart: 2 and Stem cell transplantation: 1). There was no statistically significant difference between the two groups in terms of demographics, comorbidities, severity as indicated by inflammatory markers and outcomes such as death, acute kidney injury (AKI) requiring dialysis, and bacterial or fungal superinfection. Conclusion: Our study seems to imply that there is no significant difference in the severity and outcomes of the immunosuppressed patients who were admitted to our ICUs. Our study did show an increased incidence of mortality (52.17% vs. 44.02%) and an increased rate of positive sterile fluid cultures (34.78% vs. 25.13%) in these immunosuppressed patients but the difference was not statistically significant. It is possible that an increased sample size may have revealed statistically significant differences. Therefore, larger studies are needed to determine if immunosuppression impacts the outcome of critically ill COVID-19 patients.

Impact of elevated troponins on mortality of ICU patients

Introduction: Myocardial injury as evidenced by elevated cardiac troponin levels may occur in 7-36% of hospitalized patients with coronavirus 2019 (COVID-19). Studies have shown that COVID-19 patients with elevated cardiac troponin are more likely to require the intensive care unit (ICU) and mechanical ventilation and have a higher risk of death. However, studies on the impact of elevated troponins at the time of hospital admission on mortality of ICU patients are limited. Here we aim to characterize, compare, and analyze COVID-19 patients in our institution's ICUs who had elevated troponins. Methods:This study is a retrospective analysis of adult patients with COVID-19 admitted to the ICUs of a tertiary care hospital between 03/01/2020 and 05/31/2020. Myocardial injury was defined as troponin ≥ 0.04 ng/mL. Only patients who had troponins measured within 24 hours of hospital admission were included. We excluded patients with a past medical history of chronic kidney disease (CKD) or end-stage renal disease (ESRD). We also excluded those patients who were transferred to our ICU from another hospital and where admission labs from the transferring institution were not available for our review. We compared the clinical characteristics and outcomes of critically ill COVID-19 patients who had elevated troponins with those who did not.Results: Of the 210 patients admitted with COVID-related Acute Respiratory Distress Syndrome, 178 had troponin measured within 24 hours of hospital admission. 25 patients had a past medical history of CKD or ESRD and 11 patients were transferred from another hospital with no labs available from their day of admission. Of the 142 remaining patients, 72 (50.7%) had an elevated troponin while 70 (49.9%) had a normal troponin at presentation. Patients with elevated troponins were older (67.5 ± 15.1 vs 60.2 ± 14.2), and predominantly male (72.2% vs. 54.3%). Inflammatory markers were significantly elevated in both groups but not statistically different. Therapies provided were similar in both groups. Most importantly, patients with an elevated troponin had significantly increased risk of mortality compared to those with a normal troponin at admission (55.6% vs. 34.3%).Conclusion: Our results suggest that myocardial injury is a common occurrence in COVID-19 patients requiring ICU admission. Additionally, mortality in this population is significantly higher further indicating myocardial injury as a predictor of mortality. To determine if elevated troponin levels are independent of other risk factors for mortality in COVID-19 such as age, and gender will need to be determined in future studies.

The incidence of stroke in critically ill COVID-19 patients and its association with elevated D-Dimers

Introduction:Ischemic and hemorrhagic strokes appear to be complications of Coronavirus Disease 2019 (COVID-19). Implicated mechanisms include severity of inflammation in these patients that leads to endothelial injury and a more severe prothrombotic state. Patients with a more severe presentation appear to be at higher risk. Based on observational data, intracranial hemorrhage occurs in 0.2-0.9% of hospitalized COVID-19 patients, while ischemic stroke occurs in 0.9-2.5%. Small reports have indicated that d-dimer levels preceding the stroke are higher than in COVID-19 patients without strokes. In our study we aimed to determine the incidence of stroke in our intensive care unit (ICU) patients with COVID-19, and further assess the association between ddimer levels at the time of ICU admission and ischemic/hemorrhagic stroke.Methods: This study is retrospective analysis of all adult patients with COVID-related acute respiratory distress syndrome (ARDS) admitted to the ICUs of a tertiary care hospital between 03/01/2020 and 05/31/2020. We identified patients who had a stroke based on CT head findings. Demographic and clinical characteristics, inflammatory markers at the time of ICU admission and clinical outcomes of patients with stroke were compared and analyzed with patients who did not have stroke. Means, Medians and categorical variables were compared using t-test, Mann-Whitney U-test and Fisher's exact test, respectively. P-value of <0.05 was taken to be statistically significant.Results:Of the 210 patients admitted to our ICUs with COVID related ARDS, 20 (9.5%) had strokes (18 ischemic, 2 hemorrhagic) at some point in their hospitalization. There was no statistically significant difference between the groups in terms of demographics, comorbidities, and outcomes such as death. Therapies provided, including steroids and therapeutic anticoagulation, were similar in both groups. D-dimer levels at the time of ICU admission in the patients with stroke were significantly higher than in patients without stroke (p= 0.025). Conclusion: Our study shows that the incidence of stroke in COVID-19 patients admitted to ICUs is higher than previously reported, despite most being on anticoagulation. Our study also demonstrated that COVID-19 ICU patients who developed stroke during their hospitalization had significantly higher d-dimer levels at the time of ICU admission. Our findings suggest that intensivists need to be constantly vigilant about not missing strokes in critically ill COVID-19 patients. The findings also suggest that the magnitude of d-dimer elevation at the time of ICU admission may be a useful predictor of developing strokes during the hospitalization. Larger studies are needed to confirm our findings.

NITRIC OXIDE IS A POWERFUL ANTI-CORONAVIRUS-INHALED AGENT THAT ACTS WITHIN HOURS

SESSION TITLE: Late-breaking Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Nitric oxide (NO) is a small endogenous messenger molecule with free radical characteristics that plays a key role in the pathophysiological processes in the lung, including host defense against airway pathogens. NO donors have been reported to inhibit replication of severe acute respiratory syndrome coronavirus (SARS-CoV-1) in vitro, and exogenous gaseous NO (gNO) at concentrations = 150ppm has been shown to act as a potent antimicrobial agent. In multiple clinical trials, administration of high dose (150 to 250ppm) intermittent gNO (30-40 min cycles, 2-5 cycles a day) was safe and well-tolerated, with promising antimicrobial efficacy potential. Beyond Air™ has developed the LungFit™ platform system, which produces and delivers up to 400 ppm gNO from ambient air to the human lung, eliminating the need for cylinders. Given its safety and antimicrobial activity, inhaled gNO is a potential treatment for patients with COVID-19. The objective of this in vitro study is to evaluate the use of gNO as a method of treating human coronavirus infection as a proof of concept for the treatment of SARS-CoV-2. METHODS: OC43 human coronavirus was exposed to 150-250ppm gNO, for up to 8 hours intermittently (1-hour alternating) both before and after infection of human HCT-8 cells. Host cell viability was assessed by an XTT cell proliferation-based assay 3-7 days post exposure to NO. The coronavirus viability was assessed by TCID50 (Median Tissue Culture Infectious Dose) 3-7 days post exposure. RESULTS: When coronavirus was exposed to 250ppm NO prior to infection, a significant reduction in infectivity was achieved as viral load was reduced by 24-fold compared to untreated sample and host cell viability was higher by more than 85% (p<0.05). Post infection exposure of OC43 coronavirus to 250ppm NO resulted in 45% increase in host cell viability (p<0.05). Upon exposure of coronavirus infected cells to 150ppm NO. While coronavirus lost 50% of its infectivity after 4 hours of treatment with 150ppm NO, complete inhibition of infectivity was achieved after 8 hours of treatment. CONCLUSIONS: These results indicate the potential of inhaled gNO as a novel treatment for COVID-19. According to our data, 150-250ppm gaseous NO shows anti-coronavirus properties against OC43 human coronavirus in vitro, when administered either prior to or post infection. CLINICAL IMPLICATIONS: The data presented shows that the use of NO and the LungFit™ system may be effective for usage in both prevention and treatment of the SARS-CoV-2 infection. DISCLOSURES: No relevant relationships by Amir Avniel, source=Web Response No relevant relationships Added 07/15/2020 by Hila Confino, source=Web Response, value=Salary Removed 07/15/2020 by Hila Confino, source=Web Response No relevant relationships Added 07/15/2020 by Hila Confino, source=Web Response, value=Salary Removed 07/16/2020 by Hila Confino, source=Web Response No relevant relationships Added 07/15/2020 by Elya Dekel, source=Web Response, value=Salary Removed 07/16/2020 by Elya Dekel, source=Web Response No relevant relationships by Pam Golden, source=Web Response No relevant relationships Added 07/15/2020 by Matan Goldshtein, source=Web Response, value=Salary Removed 07/16/2020 by Matan Goldshtein, source=Web Response Owner/Founder relationship with Beyond air company Please note: $20001 - $100000 Added 06/11/2020 by David Greenberg, source=Web Response, value=Consulting fee No relevant relationships Added 05/26/2020 by Rinat Kalaora, source=Web Response, value=Salary Removed 07/16/2020 by Rinat Kalaora, source=Web Response No relevant relationships Added 05/26/2020 by Rinat Kalaora, source=Web Response, value=stocks Removed 07/16/2020 by Rinat Kalaora, source=Web Response No relevant relationships Added 07/16/2020 by Rinat Kalaora, source=Web Response, value=Salary Removed 07/16/2020 by Rinat Kalaora, source=Web Response No relevant relationships Added 07/16/2020 by Rinat Kalaora, source=Web Response, value=Shares Removed 07/16/2020 by Rinat Kalaora, source=Web Response No relevant relationships Added 07/15/2020 by Omer Lerner, source=Web Response, value=Salary Removed 07/16/2020 by Omer Lerner, source=Web Response No relevant relationships by Steve Lisi, source=Web Response No relevant relationships by Yonat Shemer-Avni, source=Web Response No relevant relationships Added 07/16/2020 by Shay Yarkoni, source=Web Response, value=Salary Removed 07/16/2020 by Shay Yarkoni, source=Web Response No relevant relationships Added 07/16/2020 by Shay Yarkoni, source=Web Response, value=Shares Removed 07/16/2020 by Shay Yarkoni, source=Web Response

Association among income loss, financial strain and depressive symptoms during COVID-19: evidence from two longitudinal studies.

BACKGROUND: The COVID-19 pandemic has major ramifications for global health and the economy, with growing concerns about economic recession and implications for mental health. Here we investigated the associations between COVID-19 pandemic-related income loss with financial strain and mental health trajectories over a 1-month course. METHODS: Two independent studies were conducted in the U.S and in Israel at the beginning of the outbreak (March-April 2020, T1; N = 4 171) and at a 1-month follow-up (T2; N = 1 559). Mixed-effects models were applied to assess associations among COVID-19-related income loss, financial strain, and pandemic-related worries about health, with anxiety and depression, controlling for multiple covariates including pre-COVID-19 income. FINDINGS: In both studies, income loss and financial strain were associated with greater depressive symptoms at T1, above and beyond T1 anxiety, worries about health, and pre-COVID-19 income. Worsening of income loss was associated with exacerbation of depression at T2 in both studies. Worsening of subjective financial strain was associated with exacerbation of depression at T2 in one study (US). INTERPRETATION: Income loss and financial strain were uniquely associated with depressive symptoms and the exacerbation of symptoms over time, above and beyond pandemic-related anxiety. Considering the painful dilemma of lockdown versus reopening, with the tradeoff between public health and economic wellbeing, our findings provide evidence that the economic impact of COVID-19 has negative implications for mental health. FUNDING: This study was supported by grants from the National Institute of Mental Health, the US-Israel Binational Science Foundation, Foundation Dora and Kirsh Foundation.