Immune response to COVID-19 vaccination in adults and children with cancer: results from the prospective SerOzNET study

Background: Adults and childrenwith cancer are susceptible to severe SARS-CoV-2 disease. Vaccination is protective;data beyond initial response and regarding effect of booster doses are lacking in cancer patients. Method(s): The SerOzNET study assesses SARS-CoV-2 vaccine response in haematological and solid cancer patients aged 5 and older. Patients are recruited pre dose 1 and receive standard BNT162b2 (Pfizer) or ChadOx1-S (AstraZeneca) vaccine. Blood is taken at baseline and after each dose. Neutralizing antibody (NAb) titre, absolute antibody titre (Abbott), T cell response (IFN-gamma) and epigenetics are analysed. Clinical data are collected. Patients are followed for up to 3 months beyond dose 5. Result(s): 105 children (64% haem, 36% solid cancers) and 399 adults (35% haem, 65% solid cancers) were enrolled. In adults, NAb response rate increased after dose 3 (Post 2: 40% haem, 87%solid;Post 3:70%haem,97%solid). Post dose 2, predictors of nonresponse were ChadOx1-S vaccine (OR 3 p = .02), haem cancer (OR 14 p < .001), ECOG >=1 (OR 2.6 p = .01) and steroids (OR 5 p = .01). Post dose 3, only haem cancer predicted non-response (OR 16). IFN-gamma response is available for a subset, detectable in 41/90 (46%) postdose 1, 78/96 (81%) post-dose 2 and 35/42 (83%) post-dose 3;without significant difference between haem and solid cancer. In children, NAb response post dose 2 is available for 50 patients. Response rate between haem (19/31, 61%) and solid patients (13/19, 68%) was similar. IFN-gamma response post dose 2 was also similar: (14/22, 63%) vs solid patients (12/14, 85%) (p = .25). Analysis is ongoing. Conclusion(s): Response to two doses of SARS-CoV-2 vaccine is suboptimal in patients with cancer. The third priming dose is integral, with significantly higher response rates observed. 36% of children did not develop neutralizing antibodies post dose 2;subsequent doses are likely to be important for young patients.

Breakthrough COVID-19 infections in patients with cancer from a prospective study of COVID-19 vaccine response

Background: COVID-19 disease is more severe in unvaccinated cancer patients compared with the general population. There is limited data regarding clinical efficacy of vaccination in these patients. Method(s): SerOzNET (ACTRN12621001004853) is a prospective observational cohort study of adults and children with cancer receiving COVID-19 vaccination. The primary endpoint is serological response. An important secondary endpoint is outcome of COVID-19 infection after vaccination. We report self- and clinician reported COVID-19 infections. Result(s): Of 395 adults (20 years +), 74 (19%) reported COVID-19 infection over mean duration on study of 259 days. 71 (97%) had received 2 vaccine doses, 51 (69%) received 3+ doses. 21 (28%) had antiviral treatment. 62 (84%) had symptoms, 7 (9%) required hospitalisation, 0 required ICU admission or died due to COVID-19. Of 113 children/adolescents (5-19 years), 31 (27%) reported COVID-19 infection over mean duration on study of 215 days. 28 (90%) had received 2 vaccination doses, and 12 (39%) received 3+ doses. 23 (74%) had symptoms, 8 (25%) required hospitalisation, 2 (6%) had antiviral therapy, 0 required ICU admission or died due to COVID-19. Pediatric pts with COVID-19 infection had increased risk of hospitalisation compared with adults (p=0.03). Hematological cancer pts had non-significant but numerically higher rates of hospitalisation (Table). [Formula presented] Conclusion(s): Pts with cancer are likely to be exposed to COVID-19, with infection rates similar to the wider population. Vaccination appears to protect against ICU admission in cancer patients. However, 9% of adults and 25% of children with cancer required hospitalisation for COVID-19, demonstrating increased severity of symptoms compared to the general population. Higher rates of infection and hospitalisation in pediatric pts may be partly attributable to the lower proportion of children who had received a 3rd vaccination dose at the time of infection. Clinical trial identification: ACTRN12621001004853. Legal entity responsible for the study: Monash Health. Funding(s): Cancer Australia (Australian Federal Government) Victorian Cancer Agency (Victorian State Government, Australia) Leukaemia Foundation (Foundation, Australia). Disclosure: All authors have declared no conflicts of interest. Copyright © 2022

POLYMYOSITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE RESPONSIVE TO IV IMMUNOGLOBULIN THERAPY

SESSION TITLE: Critical Diffuse Lung Disease Cases 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Polymyositis (PM) and dermatomyositis (DM) are inflammatory syndromes that have been shown to be associated with interstitial lung disease in up to 64% of cases. Current management strategies for PM/DM-ILD are mostly derived from treatment of PM/DM and rely on the immunomodulatory effects of steroids and steroid sparing medications. Literature supports the use of intravenous immunoglobulins for the management of PM/DM-ILD. However, this stems from isolated case reports. CASE PRESENTATION: Our patient is a 43-year-old female, previously healthy, who was referred to our ILD clinic for evaluation of possible diffuse interstitial lung disease. Her symptoms began May of 2019 with dyspnea, cough, and muscle aches. Her initial workup was significant for reticular opacities in the mid to lower lung fields on x-ray, moderate restriction, and severe diffusion impairment on pulmonary function tests. High resolution CT scan (HRCT) of the lungs showed a radiological pattern suggestive of nonspecific interstitial pneumonitis (NSIP) with mid to lower lung predominant ground glass opacities, mild subpleural reticulation, traction bronchiectasis with no evidence of honeycombing or air trapping. Further workup showed a positive antinuclear antibody (ANA) in a speckled pattern with a titer of 1:320. Her other rheumatological workup was initially largely unremarkable and she denied significant drug/toxin exposure. She was treated with steroids with initial improvement, however had significant clinical deterioration requiring hospitalization and oxygen supplementation and was eventually started on Mycophenolate Mofetil in Aug 2020. Her pulmonary disease remained stable until she was admitted again in Jan 2021 with new hypoxemic respiratory failure requiring 6 L supplemental oxygen. During that admission, she was diagnosed with polymyositis and referred for a lung transplant evaluation, she also started on IVIG for the treatment of active myositis to wean her off steroids prior to transplant listing. She was discharged home and underwent a full transplant workup. She required readmission for worsening hypoxemia now requiring 12 L supplemental oxygen in May 2021, HRCT showed worsening ground glass opacities. She was again treated with IVIG and a steroid course and had near complete resolution of her hypoxia with a 2 L oxygen requirement only on ambulation. She continues to follow up with our interstitial lung disease team and the pulmonary transplant team. Her course has been complicated by multiple admissions with bacterial pneumonia as well as COVID-19 infection. DISCUSSION: Treatment of PM/DM associated ILD relies heavily on the use of steroids as well as steroids sparing agents such as Mycophenolate or Rituximab. IVIG has been implicated in improving underlying lung disease with data derived from case reports. CONCLUSIONS: Our case highlights the importance of further advanced research in this field. Reference #1: Peshbahar, S., & Bendstrup, E. (2020). Remarkable benefits of intravenous immunoglobulin (IVIG) in a patient with polymyositis-associated acute interstitial lung disease. European Clinical Respiratory Journal, 7(1), 1840706. Reference #2: Fathi, M. (2006). Interstitial lung disease in polymyositis and dermatomyositis. Karolinska Institutet (Sweden). DISCLOSURES: No relevant relationships by Hafsa Abdulla No relevant relationships by ALAA ABU SAYF

Humoral and cellular immune response to Sars-CoV-2 wild-type and variants of concern following 3-dose vaccination in a large cohort of adults with cancer: The SerOzNET study

Background: COVID-19 infection has poor outcomes for patients (pts) with cancer. Understanding vaccine response as a correlate of protection from severe infection is essential to advise pts regarding protective behaviours and optimal vaccine schedule. This Australian cohort is unique due to low rates of COVID-19 exposure at study entry (July-November 2021). and use of a 3 dose schedule. Pts initially received 2 doses of either BNT162b2 (Pf) at a 3 week interval, or ChadOx1-S (AZ) at a 6 week interval, all then received a 3rd dose, either mRNA-1273 (Mod) or Pf after 2-4 months, and finally a 4th dose at an interval of a further 3 months, for a subset. Methods: SerOzNET (ACTRN12621001004853) has enrolled pts with solid and haematological (haem) cancers prior to initial vaccination. Serial blood samples were processed for serum, PBMC and PMN at timepoints: 0, then 3-4 weeks post dose 1 then 2 then 3 then 4 (where administered). We report here neutralizing antibodies (nAb) against wild type (wt) and delta and omicron variants of concern (VOC);quantitative S-protein IgG antibody (Abbott);Tcell correlates measured by levels of interferon-g (IFN g), tumour necrosis factor-a, interleukins (IL-) 2/ 4/5/13;and epigenetic profiling of T cells. Results: The cohort consists of 401 pts with median age 58 (range 18-85);59% female;128 (32%) haem cancers. 377 (94%) are on current or recent (< 12 months) systemic therapy: 162 (43%) chemotherapy, 62 (16%) immunotherapy, 40 (10%) combined chemo/immunotherapy, 113 (29%) hormonal or targeted therapy. 42 (10%) received anti-CD20 therapy < 12 months, 6 (1.4%) had allogeneic stem cell transplant. NAb levels against wt are available for 256 pts post dose 1, 245 pts post dose 2 and 159 pts post dose 3 (will be updated). Response rates post dose were respectively 27%, 77% and 88%. Pts with haem cancer were less likely to respond to vaccination at any time compared to pts with solid cancer (p < 0.001, chi-squared test). After 3 doses, 3.8% of pts with solid cancer and 27.8% with haem cancer lacked NAb. NAb results to VOC delta are available for 92 pts post dose 2: 25/92 (27%) were negative, compared with a non-response rate to wt of 15% at same time in same pts. IFN-γ-Spike response was detectable in 18/31 (58%) and 24/30 (80%) pts post dose 1 and 2 respectively. 101 pts to date have received a 4th dose;data will be available at the meeting, as will epigenetic profiles and detailed clinicopathological correlations. Conclusions: This interim analysis shows that a significant proportion of pts with haem cancers (27.8%) lack protective Sars-CoV-2 antibodies following 3 vaccinations, whereas only 3.8% of solid cancer pts lack detectable response. Results from other B and T cell parameters may also be important in identifying pts less well protected by vaccination. Follow up is ongoing, response rate post 4th dose will be presented at the meeting.

Comprehensive humoral and cellular immune assessments to SARS-CoV-2 (wild type, delta and omicron) following two- and three-dose vaccination schedule in a large adult cancer population: SerOzNET study: placeholder abstract

Background: Defining cancer and treatment-related factors which influence protection against COVID-19 following vaccination are important given the worse outcomes following infection in this group. Sophisticated and detailed studies which go beyond a single measure are required particularly with correlation to multiple disease and treatment factors. This study cohort is unique due to (a) very low prior COVID-19 infection at time of sampling (July-Nov 2021), (b) vaccines studied were BNT162b2 (Pf) given 3 weeks apart or ChAdOx1 (AZ) spaced 12 weeks (dose 1, 2) (c) most participants then received a third dose 2 months later (heterologous for AZ). Methods: SerOzNET (ACTRN12621001004853) enrols Australian blood and solid cancer patients prior to vaccination, with serial blood analyses and qualitative measures. We measured neutralizing antibodies (nAb) against SARS-CoV-2 wild type (wt) and variants of concern delta and omicron, quantitative S-protein IgG antibody level (Abbott), and T-cell correlates (interferon-g, tumour necrosis factor-a, interleukins 2/4/5/13) and epigenetic profiling at baseline and 3-4 weeks post dose 1, 2 +/- 3.Results: 379 participants were included, median age 58 years (IQR 47-66) and 60% female. 30% participants had hematological malignancies with the remainder solid organ cancers. 90% patients were on current systemic cancer treatment (most commonly chemotherapy in 41%, chemoimmunotherapy or immunotherapy in 20%). In 331 patients where treatment intent was recorded, 47% was palliative. Only one patient had known prior COVID-19 infection. Of the initial 94 participants who received Pf vaccination, median (IQR) neutralizing antibody titre 4 weeks following dose 2 was 80 (40-160) for SARS-CoV-2 wt and 40 (0-80) for delta variant. Conclusion: Neutralizing antibody titres in this Australian cancer population following Pf vaccination appear lower than those reported elsewhere such as CAPTURE study (Fendler et al, 2021), possibly related to shorter interdose interval. Preliminary data highlights low nAb titres as expected in haematology patients but also in some cases with treatment not traditionally associated with immunosuppression such as hormonal therapy. These results will be updated in February 2022 with third dose, AZ and omicron variant data.

mSOFA Scores Associated with the Development of Pneumothorax, Pneumomediastinum and Subcutaneous Emphysema in Critically Ill Covid-19 Patient

Introduction: COVID-19 is a well-known cause of severe ARDS (acute respiratory distress syndrome), however recent data suggests that COVID-19 could represent a unique form of lung injury that places patients at increased risk of various uncommon complications such as pneumothorax, pneumomediastinum and subcutaneous emphysema. Studies so far have reported an increased incidence of barotrauma in intubated COVID-19 patients with unclear predictors. Our study aims to identify the different variables associated with development of pneumothorax, pneumomediastinum and subcutaneous emphysema in critically ill COVID-19 patients. Methods: We examined patients admitted to the intensive care unit from March 2020 to Feb 2021 at a large tertiary care center in Detroit, Michigan. We identified a total of 25 patients with COVID-19 ARDS requiring mechanical ventilation who developed pneumothorax, 12 who developed pneumomediastinum and 7 with subcutaneous emphysema. We compared those to 66 patients admitted with COVID-19 ARDS also requiring mechanical ventilation who did not develop any of these complications. The mean age of patients in our subject group was 61.81 years compared to a mean of 69.05 years in the control group. Male patients accounted for 58.33% of the subject group and 60.61% in the control group. Results: we detected a statistically significant difference in the modified Sequential Organ Failure Assessment Score (mSOFA) between the patients who developed these complications compared to those who did not (p<0.0001), with score being surprisingly lower in the group who developed the complication as opposed to those who did not (median mSOFA in subjects 3.5, n=32 vs median mSOFA in controls 11, n=66). Analysis of the subgroups of the mSOFA score revealed no statistically significant difference in the PF ratio (p=0.1995), platelet counts (p=0.065) and total bilirubin (p=0.4403). However, MAP was noted to be significantly lower in the control group than in the subject group accounting for a higher mSOFA score (p=0.0031). Similarly, creatinine was noted to be higher in the control group (p<0.0001) compared to the subject group. Discussion: In viewing our baseline patient characteristics we found a statistically significant difference (p<0.0001) in the rate of baseline chronic kidney disease between our subjects and control patients, with control patients having 100% baseline CKD and subjects having 19.4% baseline CKD. This could account for the higher mSOFA scores in controls. Conclusion: mSOFA did not predict the development of pneumothorax, pneumomediastinum or subcutaneous emphysema in patients admitted with COVID-19 ARDS requiring mechanical ventilation.

Do Managers Overreact When in Backlog? Evidence of Scope Neglect from a Supply Chain Experiment

Problem definition: We empirically examine a complementary behavioral source of the bullwhip effect that has been previously overlooked in the literature: that individuals order more aggressively (i.e., overreact) when they face shortages than when they hold inventory. Methodology/Results: We conduct a behavioral experiment using the beer distribution game. We estimate decision rules using multilevel modeling approaches that overcome several drawbacks of the estimation methods used in the earlier literature. We find robust evidence that, contrary to the overreaction when in backlog hypothesis and reports from popular press, decision makers order less aggressively and become insensitive to the scope of the problem when in backlog-a scope neglect phenomenon. Managerial implications: We propose a dual-process theoretical account predicated on affective reactions to explain this scope neglect. Our results suggest that affective reactions under novel operating conditions or dramatic events in supply chains, such as the COVID-19 pandemic, can overwhelm cognitive processing of managers and make them fail to recognize the full scope of the problems faced and update decision models accordingly. Understanding the cognitive-affective drivers of ordering behaviors that generate supply chain instability is important in designing interventions to mitigate their negative effects.

Risk factors, predictions, and progression of acute kidney injury in hospitalized COVID-19 patients: An observational retrospective cohort study.

OBJECTIVES: Studies have shown that acute kidney injury (AKI) occurrence post SARS-CoV-2 infection is complex and has a poor prognosis. Therefore, more studies are needed to understand the rate and the predications of AKI involvement among hospitalized COVID-19 patients and AKI's impact on prognosis while under different types of medications. PATIENTS AND METHODS: This study is a retrospective observational cohort study conducted at Bahrain Defence Force (BDF) Royal Medical Services. Medical records of COVID-19 patients admitted to BDF hospital, treated, and followed up from April 2020 to October 2020 were retrieved. Data were analyzed using univariate and multivariate logistic regression with covariate adjustment, and the odds ratio (OR) and 95% confidence (95% CI) interval were reported. RESULTS: Among 353 patients admitted with COVID-19, 47.6% developed AKI. Overall, 51.8% of patients with AKI died compared to 2.2% of patients who did not develop AKI (p< 0.001 with OR 48.6 and 95% CI 17.2-136.9). Besides, deaths in patients classified with AKI staging were positively correlated and multivariate regression analysis revealed that moderate to severe hypoalbuminemia (<32 g/L) was independently correlated to death in AKI patients with an OR of 10.99 (CI 95% 4.1-29.3, p<0.001). In addition, 78.2% of the dead patients were on mechanical ventilation. Besides age as a predictor of AKI development, diabetes and hypertension were the major risk factors of AKI development (OR 2.04, p<0.01, and 0.05 for diabetes and hypertension, respectively). Also, two or more comorbidities substantially increased the risk of AKI development in COVID-19 patients. Furthermore, high levels upon hospital admission of D-Dimer, Troponin I, and ProBNP and low serum albumin were associated with AKI development. Lastly, patients taking ACEI/ARBs had less chance to develop AKI stage II/III with OR of 0.19-0.27 (p<0.05-0.01). CONCLUSIONS: The incidence of AKI in hospitalized COVID-19 patients and the mortality rate among AKI patients were high and correlated with AKI staging. Furthermore, laboratory testing for serum albumin, hypercoagulability and cardiac injury markers maybe indicative for AKI development. Therefore, clinicians should be mandated to perform such tests on admission and follow-up in hospitalized patients.

CNN-based Transfer Learning for Covid-19 Diagnosis

CNN-based transfer learning method plays a significant role in the detection of various objects such as cars, dogs, motorcycles, face and human detection in nighttime images by using visible light camera sensors. This method mainly depends on the images captured by cameras in order to detect the mentioned objects in a variety of environments based on convolutional neural networks (CNNs). In this study, we utilized the same method to detect coronavirus phenomena by using chest X-ray images that have been collected from three different open-source datasets with the aim of rapid detection of the infected patients and speed up the diagnostic process. We used one of the deep learning architectures in a Transfer Learning mode and modified its final layers to adapt to the number of classes in our investigation. The deep learning architecture that we used for the purpose of COVID-19 detection from X-ray images is a CNN designed to detect human in nighttime. We also modified the CNN architecture in three different scenarios named (Model 1, Model 2 and Model 3) in order to improve the classification results. Compared to model one and two, the result improved in model three and the number of misclassified cases reduced particularly in detecting Abnormal and COVID-19 cases. Although our CNN-based method shows high performance in COVID-19 detection, CNN decisions should not to be taken into consideration until clinical tests confirms symptoms of the infected patients. © 2021 IEEE.

SAARSNet: A Deep Neural Network for COVID-19 Cases Diagnosis

The global spread of the COVID-19 is a continuously evolving situation and it is still a major risk on the health of people around the world. A huge number of people are infected by this deadly virus and the number is still getting increased day by day. At this time, no specific vaccines or treatments of COVID-19 are found. Numerous ways are offered to detect COVID-19 such as swab test, CDC and RT-PCR tests. All of them can detect corona virus in different ways but they are not recommended by the reason of their limited availability, inaccurate results, high false-negative rate predicates, high cost and time consuming. Hence, medical radiography and Computer Tomography (CT) images were suggested as the next best alternative of RT -PCR and other tests for detecting Covid-19 cases. Recent studies found that patients with COVID-19 cases are present abnormalities in chest X-Ray images. Motivated by this, many researchers propose deep learning systems for COVID-19 detection. Although, these developed AI systems have shown quite promising results in terms of accuracy, they are closed source and unavailable to the research community. Therefore, in the present work, we introduced a deep convolutional neural network design (SAARSNet) designed to detect COVID-19 cases from chest X-Ray images. 1292 X-Ray images have been used to train and test the proposed model. the images have been collected from two open-source datasets. The input images are progressively resized into (220 by 150 by 3) in order to decrease the training time of the system and improve the performance of the SAARSNet architecture. Furthermore, we also investigate how SAARSNet makes predictions under three different scenarios with the aim of distinguishing COVID-19 class from both Normal and Abnormal classes as well as gaining deeper perceptions into critical factors related to COVID-19 cases. We also used the confusion metrics for evaluating the performance of SAARSNet CNN in an attempt to measure the true and false identifications of the classes from the tested images. With the proposed architecture promising results has been achieved in all of the three different scenarios. Although, there are some misclassified cases of COVID-19, the corresponding performance was best in detecting both Normal and Abnormal cases correctly. Furthermore, in the three classes scenario, normal class has been achieved 100% positive predictive value while optimistic results have been investigated in detecting COVID-19 and abnormal classes. © 2020 IEEE.