Acceptability and usability of a soft, flexible, wearable device for cough detection in children with cystic fibrosis

Background: Cough is a common symptom in cystic fibrosis (CF), and an increase in cough is an important sign of worsening lung disease and pulmonary exacerbation, the most common cause of hospitalization in people with CF. Objective monitoring of cough could be an important outcome measure for clinical trials, especially in children too young to perform pulmonary function tests. There are no accurate, objective methods of quantifying the frequency, severity, and duration of cough. Devices that have been tested to measure cough are neither highly reliable nor user friendly. We developed a mechano-acoustic sensor (MAS): a 4.8- cm- x 2.8-cm- (1 inch) long, thin, lightweight, stretchable, wireless device that adheres easily and securely to the skin surface and is worn at the base of the neck. The devicewas validated in adults being monitored for COVID- 19. This study evaluated usability and acceptability to children and their parents. Method(s): In Cohort 1, a small, flexible, fully wireless accelerometer-based MASwas applied to the suprasternal notch of children with CF using gentle adhesives. Participants were asked to perform activities that included forced coughs while sitting, lying down, and performing activities such as jumping or jogging and other pharyngolaryngeal activities such as swallowing, speaking, and throat clearing. The sessions were an average of about 30 minutes long. In Cohort 2, participants were asked to test the device for a longer period of wearable time (4-6 hours) in various settings, including outpatient clinics, inpatient rooms, and outside clinic and athome environments. Upon completion, all participants from both cohorts were asked to fill out the Acceptability and Usability Questionnaire, which consisted of six questions ranked on a 4-point Likert scale. Result(s): Cohort 1 included 21 children aged 3 to 18 (mean age 9.25 +/- 4.85), and Cohort 2 included 12 children aged 7 to 18 (mean age 12.15 +/- 4.42). On 31 (94%) questionnaires returned, 35.5% of participants strongly agreed and 61.3% agreed with the statement "I [or my child] like(s) wearing the cough sensor." Similarly, most participants found the cough sensor easy to use (74.2% strongly agreed, 25.8% agreed) and comfortable to wear (64.5% strongly agreed, 29.0% agreed), although they found the adhesive sticker difficult to take off and the device too obvious or large. Conclusion(s): Although qualitative and quantitative acceptability and usability data were overall positive, we have redesigned the cough sensor for comfort and are continuing enrollment. The new sensor, 3.5 x 1.6 x 0.8 cm, is smaller and sits lower on the neck so participants can better conceal it underneath clothing (Figure 1). We are providing universal adhesive remover wipes to all participants. Future work includes long-term monitoring (1-2 weeks) of pulmonary exacerbations using the new devices and further assessing usability and acceptability from participants.(Figure Presented) Figure 1. New cough sensor design with a longer neck and a smaller body, allowing it to be better concealed underneath a shirtCopyright © 2022, European Cystic Fibrosis Society. All rights reserved

Application of Neoaortoiliac System For Contained Rupture of Mycotic Infrarenal Aortic Aneurysm

Funding: None. Synopsis: 61-year-old male who initially presented to an outside facility with streptococcal pneumoniae meningitis and bacteremia. Of note, he had history of COVID-19 pneumonia a month prior. On hospital day 15, he reported sudden onset lower back pain prompting imaging which demonstrated a contained rupture of an infrarenal aortic aneurysm that had significantly evolved in comparison to admission imaging where his infrarenal aorta had the largest dimension measuring 2.9cm. We present the successful application of neoaortoiliac system (NAIS). Method(s): Proceeding with midline laparotomy we encountered dense adhesive disease due to his history of surgery for colon cancer. After adhesiolysis, we exposed the aorta and aneurysm with severe surrounding inflammatory changes. 20cm of femoral vein was harvested, reversed, and joined for a span of 4cm using an Endo GIA 45mm vascular load to create our neoaorta. Proximal and distal clamp zones were developed. Upon entering the aneurysm, a foul smell was encountered, revealing that the noxious process had destroyed the posterior wall of the aorta and paraspinal tissues. Our neoaorta was anastomosed in end-to-end fashion to the infrarenal aorta and subsequently to the common iliac arteries. Flow was initially restored to the hypogastric arteries and then the external iliac arteries. The retroperitoneum was closed over our repair and covered with omentum. Result(s): On post-operative day 2, he had hematochezia;intraoperatively, the IMA was noted to be 1mm in size, though had brisk back-bleeding and was ultimately ligated. A flexible sigmoidoscopy revealed ischemic sloughing of the sigmoid colon near his previous anastomosis from his colon cancer resection though no transmural necrosis. He remains on high-dose ceftriaxone to complete a 6-week course and metronidazole for 10 days due to his sigmoid mucosal ischemia per infectious disease recommendations. He is now post-operative day 10 and remains in the ICU. Conclusion(s): Mycotic aortic aneurysms constitute 1-1.8% of aortic aneurysms. The standard of treatment is aggressive debridement of involved aortic wall and periaortic tissue, in-situ or extra-anatomic reconstruction, coverage with an omental flap and long-term antibiotic therapy. NAIS is resistant to infection and aneurysmal dilation, however, is a time-consuming procedure with a mean completion time of 8 hours. Dorweiler et al. demonstrated that vascular reconstruction with femoral vein in infected aortoiliofemoral fields has a mortality of 9-10% with negligible rate of late complications (graft stenosis, thrombosis, and dilation) and that venous morbidity after femoral vein harvest is well tolerated. Clagett et al. demonstrated that NAIS fashioned from greater saphenous vein had a failure rate requiring intervention of 64% compared to 0% for those constructed with deep femoral vein. Lastly, it is important to note that our patient was previously COVID-19 positive. This case demonstrates that the sequela of COVID-19 may have been a significant factor in our patient's pathophysiology. As we continue to learn about the effects of COVID-19 on vascular pathology, we must keep a large repertoire of operative techniques at hand in order to treat complex presentations of vascular emergencies. [Formula presented] [Formula presented] [Formula presented] Institution: Orlando Health, Orlando, FLCopyright © 2022

Allergic contact dermatitis to the elastic bands of an N95 mask

Case report Introduction: In the wake of the COVID-19 pandemic, occupational contact dermatitis related to the use of personal protective equipment (PPE) has become increasingly prevalent. While most cases are irritant in nature, allergic contact dermatitis (ACD) remains an important cause of occupational dermatitis. We report a case of ACD to rubber accelerators in the elastic bands of an N95 mask. Informed consent was obtained from the patient for this report. Case Report: A 27-year-old healthcare worker presented with a progressive pruritic eruption over her face and neck, 1 week after she began wearing N95 masks at work. She had only worn disposable surgical masks. She had no medical history apart from hand dermatitis, which was well controlled with topical medications. Examination revealed linear eczematous plaques along her lateral cheeks and posterior neck, corresponding to contact areas between the mask bands and her skin. Patch tests revealed a positive reaction to several rubber accelerators, including Thimerosal, 2-Mercaptobenzothiazole (MBT), and Methylisothiazolinone. We performed another patch test to several N95 mask straps, to which the patient developed an eczematous reaction to the elastic bands of 2 N95 mask types with elastic bands. Clarification with the manufacturer confirmed the use of rubber accelerators similar in properties to MBT in the production of these masks. A diagnosis of allergic contact dermatitis to rubber accelerator was made. The patient's dermatitis resolved with topical corticosteroids and the avoidance of N95 masks with elastic bands. Discussion and Conclusion(s): The use of facial PPE such as masks is a recognised cause of occupational dermatitis among healthcare workers. A variety of dermatoses are associated with the use of facial PPE, with contact dermatitis being the most common. However, while the majority of contact dermatitis are irritant in nature, ACD remains an important and preventable cause of occupational dermatitis. Commonly implicated allergens associated with mask use include preservatives and adhesives used in their production, as well as metals in the nose clip. Although less common, mask elastic bands have also been reported to be a potential source of ACD, with rubber accelerators being identified as potential allergens. However, there is often a lack of declaration of such chemicals used in the production of PPE. Given the need for continued use in the occupational setting, early identification and avoidance of allergens are key. Failure to do so may result in the progression of skin lesions, ultimately affecting the patients' quality of life and work performance. With the ubiquitous use of masks in the current climate, we wish to highlight the need for greater awareness of rubber accelerators as potential allergens, and their presence in the elastic bands of frequently used PPE.

Postoperative Diffuse Peritonitis Causing Adhesive Bowel Obstruction Possibly Due to Sars-Cov-19 Infection: Report of a Case

Aim is to discuss diagnostic and therapeutic difficulties in COVID-19 related postoperative outcomes. A 5-year-old boy operated for jejunal atresia in neonatal period admitted with recurrent bilious vomiting. The upper GI series revealed dilated jejunum and absence of mechanical obstruction. The dilated jejunal segment was excised and anastomosis was performed. Later, he developed peritonitis without signs of anastomotic leaks. The second surgical exploration revealed diffuse peritonitis causing thickened and fibrous bowel loops causing hardly lysable adhesions. Then, his grandmother was learned to be COVID-PCR positive. Therefore, patients with atypical postoperative course should be investigated for possible COVID-19 during pandemics. Copyright © 2022 Ankara Pediatric Hematology Oncology Training and Research Hospital. All rights reserved.

Protecting Their Privacy: Teenagers & Telemedicine

Introduction: Telemedicine utilization has grown exponentially since the start of the COVID-19 pandemic. Virtual encounters provided a safe platform to continue patient care while mitigating the spread of COVID-19. However, we present a case that highlights the limitations and challenges of telemedicine, especially amongst sexually active teenagers. Case Description: A 15-year-old female presented to the ED with worsening abdominal pain and new onset bilious emesis. Six weeks earlier, she developed diarrhea and abdominal pain which was diagnosed as C. diff colitis. During this time, she had 10 virtual encounters between her pediatrician and GI team. Antibiotics were completed for C. diff with partial improvement, but were restarted after symptoms returned. She also reported vaginal discharge that was treated empirically with antifungals. Given the onset of bilious emesis and acute worsening abdominal pain, she was directed to the ED. She tested positive for COVID-19 and computed tomography of the abdomen/pelvis showed a partial small bowel obstruction (SBO). The first HEADSS exam during this illness was done on admission;she initially denied recent sexual activity. However, when expectations around confidentiality were clarified, she disclosed sexual intercourse ten weeks ago. Chlamydia trachomatis testing was positive and diagnostic laparoscopy for her SBO revealed diffuse adhesive disease consistent with pelvic inflammatory disease (PID) and Fitz-Hugh-Curtis syndrome. Adhesions were successfully lysed, she was started on appropriate antibiotics, her abdominal pain resolved and she was discharged home. Discussion: Telemedicine allows patients access to their physicians with the click of a button. It can prevent delays in diagnosis that would otherwise occur due to the inability to come into the clinic or hospital. However, managing patients through telemedicine can be challenging;this case highlights some of the difficulties. Firstly, there is no physical exam to aid diagnosis. It can also be difficult to discuss sensitive issues over video. Even during inperson visits, confidentiality remains an important yet challenging component for adolescents. With the added component of telemedicine and more family members at home, teen privacy may be at risk and needs to be confirmed during every encounter. Despite the ease, telemedicine must be carefully utilized to ensure adequate adolescent sexual healthcare and confidentiality. Conclusion: This case illustrates a rare presentation of SBO caused by PID in an adolescent female and should remind clinicians to approach abdominal pain in a sexually active adolescent with a broad differential. Moreover, the increased utilization of telemedicine during the COVID-19 pandemic creates opportunities for patient care, though comes with its imperfections. As telemedicine is here to stay, pediatricians must recognize these current limitations to avoid delays in diagnosis and care. (Figure Presented).

FORTUNATELY, NOT A TTP (THROMBOTIC THROMBOCYTOPENIC PURPURA). A CASE OF COVID INFECTION WITH EXTREME THROMBOCYTOPENIA (PLATELETS 5K/UL) AND SEVERE DEFICIENCY OF ADAMTS 13 (<2 %) WITHOUT TTP SYMPTOMS AND WITHOUT NEED FOR PLASMAPHERESIS

CASE: 54-year-old female presented with 1 week of generalized weakness, headache, congestion, cough with dark- colored phlegm, and several days of decreased smell and taste. She was unvaccinated and had positive sick contacts. Patient tested positive for Covid and found to have severe thrombocytopenia with platelets of 5K/uL, very rare schistocytes on smear, and no other notable abnormalities. She received platelet transfusion and was treated for presumed immune thrombocytopenia with IVIG and dexamethasone. The patient had no petechiae, bleeding, or other symptoms concerning for secondary TMA, notably TTP. The platelet count was 93 K/uL by day 5 and she was discharged home. Later that day her ADAMTS13 test resulted at <2% and the ADAMTS13 antibody was elevated. The patient was asked to return to the hospital for monitoring of TTP symptoms. She reported improvement in her weakness. Her thrombocytopenia and oxygen saturation remained normal. Bilateral lower extremity ultrasound showed no lower extremity VTE. On the day of discharge, 10 days after her original thrombocytopenia identified, she had a platelet count of 373 K/uL and repeated ADAMTS13 of 14.8%. IMPACT/DISCUSSION: ADAMTS13 is known as von Willebrand factor (VWF) protease as it cleaves prothrombotic and highly adhesive to platelets ultra-large multimers of VWF into smaller multimers, thus modulating VWF activity and regulating the adhesive function. A severe deficiency of ADAMTS13 characterizes TTP, a rare but potentially fatal disorder associated with thrombosis due to accumulation of prothrombotic ultra-large VWF multimers. There are literature reports of TTP and TTP-like syndromes in Covid-19. It is speculated that in COVID-19, the excess of VWF released in response to endothelial activation likely exhausts the available reserves of ADAMTS13, which may then propagate formation of microthrombi in different organs. We report an extreme thrombocytopenia, marked decrease of ADAMTS 13 and elevated ADAMTS13 antibodies, which would be confirmative evidence of TTP should our patient have clinical features of it. Our patient did not have fever, neurologic abnormalities, renal dysfunction, or active hemolysis. She was followed in outpatient clinic after the discharge. The platelet count recovered and ADAMTS 13 trended up without need for plasmapheresis. Our case is a good example of a fortunate outcome without any complications despite threatening presenting criteria. CONCLUSION: Covid-19 associated endothelial stimulation and damage could mimic a life-threatening disorder without expected fatal complications. On the other hand, it can ultimately lead to the most severe form of thrombotic microangiopathy, TTP, for which the mortality rate is close to 90%. It is hard to know which outcome to expect in different circumstances. Therefore, it is crucial for physicians to promptly recognize clinical picture of TTP as treatment is lifesaving.

Long-Term Results of a Novel, Externally-Powered, Spinal Cord Stimulator for Chronic Pain (AUS nPower study)

Introduction: A novel spinal cord stimulation (SCS) system with a battery-free micro-implantable pulse generator (mIPG;Nalu Medical, Inc. CA, USA) is available for the treatment of intractable chronic pain. The system utilizes an external power source that bi-directionally communicates with the mIPG (∼1.5 cc volume). Methods: A prospective, multi-center clinical study was initiated to confirm the safety and performance of this novel system, in the treatment of trunk and limb intractable chronic pain. Specifically, subjects with leg(s) and/or back pain, meeting eligibility criteria were recruited and consented into the study. Subjects underwent a SCS trial utilizing a menu of therapy options, including tonic and the novel pulsed stimulation pattern (PSP) therapy. Eligible subjects received the permanent implant and were followed-up for up to 12-months from activation. Due to global COVID-19 restrictions, subjects were moved into a long-term follow-up (LTFU) phase, with study visits planned every 6-months, for an additional 2-years from their last visit. This reports on the long-term clinical and functional (depression, activities of daily living, overall change in quality of life) outcomes. The study was approved by an independent Ethics Committee and conducted in compliance with local regulations. Results: Twenty-five (25) intractable chronic back and/or leg pain subjects, using the PSP therapy, passed a screening and trial phase with ≥50% pain reduction in leg(s) and/or back and moved into the long-term implant phase of the study. Of these 25 subjects, 13 subjects have currently completed an average of 22-months follow-up;the average pain reduction was 73% (n=12) in the leg and 64% (n=11) in the back, from baseline to this time point. The responder rate (≥50% pain relief) was 92% in the leg (11/12) and 64% (7/11) in the back. In addition, all subjects wore the external power source via an adhesive clip and rated both its average comfort and ease of use as <1 on an 11-point scale (0=Very Comfortable, 10=Very Uncomfortable;0=Very Easy, 10=Very Difficult). The average percent improvement on the Beck’s Depression Inventory (BDI) was 40% (n=13) from screening to 22-months;the average improvement in Oswestry Disability Index (ODI) was 34% (n=13) at this time point. Sixty-nine percent (69%;9/13) of subjects indicated “very much improved” on the Patient Global Impression of Change. Conclusion: These results continue to demonstrate the favorable performance of this novel, battery-free, externally-powered micro-implantable SCS through 22-months post implantation. Further investigation is warranted to confirm these preliminary findings. Disclosure: Paul Verrills, FAFMM GDMM (Hons) MM (Pain Medicine) FIPP AMA: Abbott: Consulting Fee: Self, Abbott: Speakers Bureau: Self, Nalu: Ownership Interest - Future Stock Options: Self, Nalu: Contracted Research: Self, Nevro: Contracted Research: Self, Saluda: Contracted Research: Self, Nalu: Speakers Bureau: Self, Biotronik: Consulting Fee: Self, Presidio: Contracted Research: Self, John Salmon, MBBS: None, Dan Bates, MBBS: None, James Yu, MD: None, Bruce Mitchell, MD: None, Neels Du Toit, MBChB: None, Matthew Green, MD: None, Murray Taverner, MBBS: None, Vahid Mohabbati, MD: None, Peter Staats, MBA,MD: Saluda Medical: Consulting Fee: Self, Grunenthal: Royalty:, Medtronic: Fees for Non-CME/CE Services (e.g. advisor):, electroCore: Employee:, SPR therapeutics: Ownership Interest:, Nalu: Fees for Non-CME/CE Services (e.g. advisor):, Gary Heit, MD, PhD: Nalu Medical Inc: Consultant: Self, Robert Levy, MD, PhD: Nalu: Ownership Interest:, Saluda: Ownership Interest:, James Makous, PhD: Nalu Medical: Consulting Fee:, Nalu Medical: Ownership Interest:

Enhancing The Development Of Engineered Wood Products From Planted Timber Species In Sarawak

The Centre of Excellence in Wood Engineered Products (CeWEP) established in early 2017 aimed in making Sarawak the hup of the down-stream industry especially for the planted timber species. Wood engineered products generally produced by binding the strands, particles, fibres, veneers or boards of wood, together with adhesives to form composite materials. They are products precisely design with specifications and tested to meet national or international standards. Sarawak with land areas of 124,500 sq km, generated wood and timber products of more than 5 million metric tons since 2012 onward. These forest products catered mostly for the upstream industries such as sawn timbers, plywood, veneer, wood moulding, laminated boards, particleboards, MDF, woodchip, charcoal/briquette, laminated flooring and wood pellets. Advanced timber products have not been fully emphasized yet. It is high time for the Sarawak state to shift gear in the timber downstream industries focusing in wood engineered products from planted timber species. The state has for the past decade involved in timber plantation activities. Seven (7) timber species namely the Acacia mangium, Azadirachta excelsa, Kyaya ivorensis Neolamarckia cadamba, Octomeles sumatrana, Paraserianthes falcataria, and Tectona grandis have been planted in various location in the state. With an area of 2.8 million ha of planted forest, the state is seriously intended to increase the production of the downstream timber industry which is equivalent to the existing industry in Peninsular Malaysia. Timber downstream industries, such as laminated/composited furniture & construction materials that generate high income, are expected to be actively produce in 2030. The CeWEP is still at an early stage of its establishment. The occurrence of the Covid-19, especially from 2020 to 2022, has slowdown the progress pace of the centre. As of now, CeWEP has managed to reach stage 2 in the ten years of strategic planning. The repercussion progress will somehow be made to ensure the planning is completed successfully in 2030. With efforts being currently made by those involved in the University of Technology Sarawak (UTS) and with close cooperation and support by other internal and external agencies/networking, the CeWEP will play an important in utilizing the planted timber species in generating income for the rural people and Sarawak state government

Abstracts for the American Vein and Lymphatic Society, AVLS 35th Annual Congress

The proceedings contain 35 papers. The topics discussed include: ambulatory phlebectomy in the treatment of superficial venous disease;artificial intelligence in the research of vein valve damage;associated factors, natural history and management of venous leg ulceration from the UK Biobank cohort;biomatrix sclerofoam in large recurrent varices with three year follow-up;comparison of the effects of detergent and osmotic sclerosants in an ex-vivo human vein study using histology and immunohistochemistry;COVID-19 and VTE: institution of an aggressive anticoagulation policy decreased venous thromboembolism (VTE) in surgical patients;cyanoacrylate adhesive closure of incompetent perforator veins;and efficiency of non-drug complex rehabilitation of patients with chronic venous diseases of the lower limbs and obesity.

Use of Defibrotide in Patients with COVID-19 Pneumonia;Results of the Defi-VID19 Phase 2 Trial

Background: The clinical spectrum of COVID-19 ranges from pauci-symptomatic forms to severe disease characterized by respiratory failure requiring mechanical ventilation and intensive care unit (ICU) management, as well as multisystem involvement characterized by sepsis, organ dysfunction and death. Treatment of COVID-19 is not standardized, and respiratory failure from ARDS is the leading cause of mortality;in-hospital mortality at 28-days in our tertiary care center in Lombardia, northern Italy was 23% during the first wave in 2020(Ciceri et al. 2020). Endothelial damage and thrombo-inflammation have been identified as common to both COVID-19 pathophysiology and veno-occlusive disease (VOD/SOS). Defibrotide (DF) has endothelial-protective properties, with pro-fibrinolytic, anti-thrombotic, anti-ischemic, anti-inflammatory, and anti-adhesive activity, but no significant systemic anticoagulant effects and is approved for the treatment of severe VOD/SOS. Aim: A prospective, multicenter, phase II, single-arm, open label trial (DEFI-VID19, NCT04335201) was conducted in patients (pts) with COVID-19 ARDS to evaluate the efficacy of DF in addition to best available therapy per institutional guidelines. The primary endpoint was respiratory-failure rate (RFR) defined as progression of respiratory failure, i.e. severe gas transfer deficit (PaO2/FiO2<200 mmHg), need of ICU or death at day+14 from treatment start. Secondary endpoints included overall survival (OS) at 28 days, duration of hospitalization and safety. A sample size of 50 pts was calculated to detect an absolute reduction of 20% in RFR at day+14, assuming a failure rate in non-treated pts of 70% (alpha=5%, power=90%, two-sided test). Pts received DF intravenously at 6.25 mg/kg/dose by 2-hour infusion repeated every 6 hours. Expected treatment duration was 14 days, with earlier discontinuation if clinical improvement occurred. LMWH at prophylactic dose was allowed. Approval was provided by the National IRB for COVID-19 trials at Institute Spallanzani (Rome) and by the Italian Agency for Drug (AIFA). All patients provided written informed consent. Results: Overall, 52 pts were enrolled from September 2020 to April 2021;48 were evaluated for efficacy and safety;4 pts were excluded due to screen failure (n=2) or withdrawal of informed consent at day 2 after defibrotide was initiated (n=2). Median age was 60.5 years (range 53-71);35 pts (73%) were male and 65% had comorbidities, with high blood pressure, obesity and COPD most common. Two pts had pre-existing diagnoses of non-Hodgkin lymphoma. Median time from onset of COVID-19 symptoms and from Sars-COV2 PCR by nasal swab to enrollment were 8 (range 7-10) and 3 days (range 1-6), respectively. All pts were hospitalized and scale 5 of 8-category ordinal scale by WHO criteria, requiring noninvasive ventilation with CPAP or high-flow oxygen, with a median P/F ratio of 211 (range 134-275) mmHg. At treatment start, the median and (range) lymphocyte counts, LDH, CRP, ferritin, D-dimer and IL-6 were 0.7 (0.5-0.9) x 10e9/L;404 (291-491) U/L;49 (22-97) mg/L;823 (363-1088) ng/ml;0.44 (0.28-1.29) µg/mL and 20 (11-32), respectively. Median treatment duration was 8.5 days (range 6-11). Overall, 13/48 pts (27%) discontinued the treatment due to clinical worsening and/or need of further therapies: 9 pts experienced progressive respiratory failure and 6 of those were transferred to ICU for IOT (one pt required ECMO), and 4 required full anticoagulation due to pulmonary embolism (n=1), ischemic stroke (n=1), and femoral deep venous thrombosis (n=2). All pts who completed the treatment 35/48 (73%) were discharged with no need of oxygen support. Overall, 14 SAEs have been reported in a median time of 6 days (range 2-10): all unrelated to DF. No pts experienced hemorrhagic events. The incidence of RFR at day 14 was 25 (+/- 6)%, and at day 28, 27 (+/- 6) %. Probability of OS at day 28 was 89 (+/-4) %, at day 60 83 (+/- 5)%. Overall, 8 pts died from COVID-19 -related complications. No pts required re-admission after hospital discha ge (median 14 days) or died after discharge. Conclusion: Treatment with DF in pts with grade 5 WHO COVID 19 ARDS does not induce bleeding, and is associated with rapid restoration of respiratory function (73% of pts). Notably, no oxygen support was needed at discharge and a 1-month OS rate of 89% was observed, which is higher than historical controls (77%) treated in the same setting. Disclosures: Richardson: Takeda: Consultancy, Research Funding;AbbVie: Consultancy;Karyopharm: Consultancy, Research Funding;AstraZeneca: Consultancy;Oncopeptides: Consultancy, Research Funding;Jazz Pharmaceuticals: Consultancy, Research Funding;Protocol Intelligence: Consultancy;Secura Bio: Consultancy;Regeneron: Consultancy;Celgene/BMS: Consultancy, Research Funding;GlaxoSmithKline: Consultancy;Janssen: Consultancy;Sanofi: Consultancy. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Carlo-Stella: Incyte: Honoraria;Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;Sanofi: Consultancy, Research Funding;AstraZeneca: Honoraria;Celgene: Membership on an entity's Board of Directors or advisory committees;ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding;Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen Oncology: Honoraria;Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Whole Blood Adhesion to VCAM-1 and P-Selectin and RBC Mechanical Fragility Can be Compromised in Long COVID-19 Patients with Sickle Cell Disease

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause severe vascular complications associated with endothelial dysfunction and systemic inflammation. COVID19-specific IgG are detectable within a week of infection. Long COVID-19 has been described in patients continuing to exhibit symptoms after the virus is no longer detectable in the respiratory secretions, including fatigue, dyspnea, headache, and brain fog. The recent FAIR Health study reviewed a total of 1,959,982 COVID-19 patients for the prevalence of long COVID symptoms and reported that 23.2% had at least one post-COVID symptom [1]. The underlying biologic mechanisms of long COVID remain unclear, thus treatments are limited to symptomatic relief and supportive care. Many long COVID symptoms are consistent with systemic inflammation and impaired oxygen delivery observed in individuals with sickle cell disease (SCD), in turn associated with elevated blood cell adhesion and decreased red blood cell (RBC) stability. The aim of this study was to determine if deleterious changes in in blood cell properties related to adhesion and membrane stability under stress can be associated with the symptoms of long COVID-19. In this work we evaluated 7 SCD patients that were diagnosed with SARS-Cov-2 and tracked their recovery using semiquantitative IgG and blood cell function assays. Methods: Blood samples were collected by the Foundation for Sickle Cell Disease (SCD) Research from SCD (homozygous SS, n=6) patients coming for regular or urgent clinic visit with SARS-CoV-2 serological and blood cell functions tests performed per the standard of care. Semiquantitative IgG assay was performed using DXi-80 (Beckman Coulter). Flow adhesion of whole blood to VCAM-1 (FA-WB-VCAM)and P-Selectin (FA-WB-Psel) substrates were determined by counting the cells that remain adherent in a microfluidics channel after perfusion with whole blood 1:1 diluted with HBSS buffer and washed by reversed flow at 1 dyne/cm 2. Red blood cell mechanical fragility (RBC MF) was measured as hemolysis induced by an oscillating cylindrical magnet with periodic non-invasive probing of cell-free hemoglobin fraction. Six individuals with SCD recovering from SARS-Cov-2 with biomarker data available both before and for more than 3 months after the infection (179±62 days) were included in the study. Results: IgG levels varied from less than 0.1 to 37, with positive values being defined as IgG > 1. The median estimated half-life of IgG decline was 53 days ranging from 25 to 90 days (the last, for the hospitalized patient). Averaged for IgG positive (IgG+) and IgG negative (IgG-) conditions, combining pre- and post-infection IgG- conditions, values of patient hemoglobin (Hb), FA-WB-VCAM, FA-WB-Psel, and RBC MF cell properties lacked statistical significance (under both a paired t-test and population statistics). Hb levels remained essentially unchanged regardless of the time from infection or IgG status. However, FA-WB-VCAM, FA-WB-Psel, and RBC MF were all significantly elevated after SARS-Cov-2 seroconversion and remained elevated despite declining IgG levels (e.g., Fig. 1). These increases in biomarker values were statistically significant for both FA-WB-VCAM and RBC MF, and were approaching significance for FA-WB-Psel (p<0065). These increases were highly patient-specific with potential return to pe-infection values observed in some cases at about 5-6 months after the infection. A qualitative review of the medical records indicated a new subjective report of fatigue in 5 of 6 patients. Longer observations are required to determine if abnormal blood cell adhesive properties and RBC membrane instability are mechanisms of long-COVID-19 pathophysiology. Conclusions: Whole blood adhesion to both p-selectin and VCAM-1 as well as RBC membrane stability can be significantly impaired in convalescent SARS-Cov-2 patients suggesting an association with long COVID-19. New and emerging treatments that modify whole blood adhesive properties and RBC membrane stability should be investigated for t eir potential to accelerated recovery from long COVID-19. Health F. A Detailed Study of Patients with Long-Haul COVID: An Analysis of Private Healthcare Claims;White Paper. June 15, 2021 Disclosures: Tarasev: Functional Fluidics: Current holder of stock options in a privately-held company. Ferranti: Functional Fluidics: Current holder of stock options in a privately-held company. Allen: Functional Fluidics: Current Employment. Gao: Functional Fluidics: Current Employment. Topping: Functional Fluidics: Current Employment. Ferranti: Functional Fluidics: Current Employment. Makinde-Odesola: Functional Fluidics: Other: conduct research for academic program. Hines: Functional Fluidics: Current holder of stock options in a privately-held company.