Clinical and Immunological Assessment of Patients with Sars-Cov-2 Infections

Abstract Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced coronavirus disease-2019 (COVID-19) has presented humanity with unprecedented challenges. Severe disease is associated with acute respiratory distress syndrome (ARDS), use of mechanical ventilation, ICU stay and prolonged hospitalization, The role of the immune system in the pathogenesis of COVID-19 disease is still unclear, which imposes limitations on identifying potential immunotherapy that can improve care for acute and chronic phases of COVID-19 in conjunction with current therapies. Research efforts are ongoing for more than 1 year to identify key immunological mechanisms involved in the disease process. While insightful, this knowledge is still incomplete and can be complemented with the assessment of immune response kinetics. Such assessment will help with the identification of early interventional modalities of immune cell regulation. With these considerations in mind, we aimed to assess several parameters of immune system regulation during the current medical care of patients with COVID-19. Methods: This is a pre-clinical prospective cohort study which involved laboratory-based assessments of blood samples obtained from COVID-19 patients and healthy volunteers. The study population was divided into three cohorts. Our first cohort included 18 years and older COVID-19 patients with respiratory complaints, oxygen (O2) saturations of less than or equal to 92 and pulmonary infiltrates on an imaging study or who were critically ill and required ventilatory support. Second cohort included 18 years and older COVID-19 patients who were hospitalized and did not require ventilatory support. Third cohort included participants with no prior diagnosis of COVID-19, or any recent viral respiratory symptoms including fever, cough or shortness of breath for the last 2 weeks. Patients with an established diagnosis of cancer or immunologic disorders were excluded. Blood specimens were collected over the period of hospitalization: specimen number 1 on day 1-3 of hospitalization, specimen number 2 on days 3-4 of hospitalization, specimen number 3 on days 5-7 of hospitalization, and specimen number 4 on 7-30 days after discharge. We performed capillary electrophoresis for serology and automated ELISA for cytokine measurement. We collected clinical data on patient demographic, clinical characteristics such as presence of any acute and chronic comorbidities and serum inflammatory markers C-Reactive Protein, D-Dimer and Ferritin. Results: We had 15 patients in cohort 1, 10 in cohort 2 and 15 in cohort 3. Patients in cohort 1 were older and had higher comorbidities. Males constituted a substantially high percentage of patients in cohort 1 and 2 (60% and 70% respectively). Patients had similar BMI in cohort 1 and 2. Total antibody levels were highest in cohort 1 but an upward trend over the course of hospitalization was noted in all cohorts. Most interesting pattern was noted in the context of antibodies against spike protein S1 receptor-binding domain (S1RBD) where patients in cohort 2 developed minimal S1RBD antibodies. Cohort 1 on average had higher levels of Interleukin 6(IL-6), Interleukin 8(IL-8), C-X-C motif chemokine ligand 10 (CXCL10) and other inflammatory cytokines except Interferon gamma (IFN-gamma) compared to Cohort 2. Remarkable difference in CXCL-10 levels was noted between the groups and healthy volunteers had the lowest levels. No significant difference in IFN-gamma was noted between cohorts and the levels quickly depleted over the course of the infection. Conclusion: Our analysis confirms that neutralizing antibodies do not correlate with lessened COVID-19 disease severity. Severe COVID-19 infection is secondary to ineffective innate immunity associated with immune overshoot. CXCL10 serves as a major component in triggering the cytokine storm that is a hallmark of SARS-CoV-2 infections. Our findings show an association between high levels of CXCL10 and more severe COVID-19 infection. There does not seem to be any significant correlation with disease severity and IFN-gamma levels. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Immunosuppressive Therapy with Antithymocyte Globulin and Cyclosporine for Fulminant Aplastic Anemia.

Blood ◽

10.1182/blood.v120.21.2364.2364 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2364-2364

Author(s):

Hiroshi Yagasaki ◽

Ken-ichiro Watanabe ◽

Kazuko Kudo ◽

Masahiro Tsuchida ◽

Hiroyuki Shichino ◽

...

Keyword(s):

Aplastic Anemia ◽

Immunosuppressive Therapy ◽

Disease Severity ◽

Antithymocyte Globulin ◽

Conflicts Of Interest ◽

Clonal Evolution ◽

Unknown Etiology ◽

Acute Myelocytic Leukemia ◽

Late Response ◽

Significant Difference

Abstract Abstract 2364 Background: Survival after immunosuppressive therapy (IST) for aplastic anemia (AA) depends on disease severity, which is classified according to polymorphic neutrophil (PMN) count as follows: nonsevere AA (nSAA; PMN > 0.5 × 109/L); severe AA (SAA; PMN 0.2 – 0.5 × 109/L); and very severe AA (vSAA; PMN < 0.2 × 109/L). Although patients with fulminant AA, defined as PMN = 0 for > 2 weeks, generally have poor outcome, no data are available for a large cohort. Therefore, we evaluated the outcome of children with fulminant AA who were enrolled in an AA-97 study and received ATG, cyclosporine, and granulocyte colony-stimulating factor (G-CSF). Patients and Methods: A total of 288 children newly diagnosed with AA (median age, 8 years) were enrolled into an AA-97 study between 1997 and 2006 and treated with a combination of horse antithymocyte globulin (Lymphoglobulin®) and cyclosporine. For patients with PMN < 0.2 × 109/L, G-CSF was added. Patients were classified into 3 groups according to disease severity as follows: fulminant (PMN 0, n = 35); vSAA (PMN 0 – 0.2 × 109/L, n = 129); and SAA (PMN 0.2 – 0.5 × 109/L, n = 124). Of the 35 patients with fulminant AA, 8 had a history of acute hepatitis at the time of diagnosis. One case was considered to be drug-induced AA. The remaining 26 patients had unknown etiology. We evaluated the response rate (RR) at 6 months, 5-year overall survival (OS), and 5-year failure free survival (FFS). Treatment failure was defined as death due to any cause, a requirement for a secondary therapy, relapse, clonal evolution to myelodysplastic syndrome/acute myelocytic leukemia, and paroxysmal nocturnal hemoglobinuria. Results: The children with fulminant AA showed a significantly lower RR than those with vSAA and SAA (40.0%, 62.8%, and 64.5%, respectively; p =.023). Of the 20 non-responders in the fulminant AA group, 11 were rescued by alternative donor stem cell transplantation, and 5 achieved a late response after 6 months. As a result, no significant difference was noted in 5-year OS and 5-year FFS among the children with fulminant AA, vSAA, and SAA (88.5%/48.2%, 95.8%/65.1%, and 96.8%/68.1%, respectively). Conclusion: In consideration of favorable OS, the choice of IST is indicated in children with fluminant AA who lack an HLA-matched family donor. Disclosures: No relevant conflicts of interest to declare.

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Prolonged Thrombocytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation: Association with Reduced Ploidy and Immaturation of Megakaryocytes

Blood ◽

10.1182/blood.v116.21.4695.4695 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4695-4695

Author(s):

Xiao-hui Zhang ◽

Haixia Fu ◽

Lan-Ping Xu ◽

Dai-Hong Liu ◽

Kaiyan Liu ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Healthy Volunteers ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Conflicts Of Interest ◽

Significant Shift ◽

Hematopoietic Stem ◽

Significant Difference

Abstract Abstract 4695 Prolonged thrombocytopenia is a frequent complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its pathogenesis has remained obscure. In present study, by using a flow cytometry technique, we determined the frequency of bone marrow megakaryocytes (MKs) and MKs ploidy distributions in allo-HSCT recipients with or without prolonged thrombocytopenia (n=32 and 27, respectively) and in 13 healthy volunteers. Along with that, the expression of c-Mpl in MKs was measured. The result showed a significant difference in MKs ploidy distributions between the 3 groups. Both the allo-HSCT patients with or without prolonged thrombocytopenia showed a significant shift to low ploidy cells (left shift) with 55.63±18.62% and 44.63±19.38% of their MKs in ploidy classes 2N to 8N, respectively. In contrast, the healthy volunteers had only 25.97±10.70% of their MKs in ploidy classes 2N to 8N. And the patients with prolonged thrombocytopenia showed a marked increase in cells ≤8N, a significant decrease in the 16N and ≥32N cells comparing to patients without prolonged thombocytopenia, which told us there were more less mature MKs in the allo-HSCT recipients with prolonged thrombocytopenia. We concluded that prolonged thrombocytopenia and slow platelet engraftment after allo-HSCT may be related to reduced ploidy and immaturation of MKs. Disclosures: No relevant conflicts of interest to declare.

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Acute Splenic Sequestration In a Newborn Cohort with Sickle Cell Anemia (SCA): Predictive Factors and Impact on Disease Severity

Blood ◽

10.1182/blood.v116.21.263.263 ◽

2010 ◽

Vol 116 (21) ◽

pp. 263-263 ◽

Cited By ~ 2

Author(s):

Cécile Arnaud ◽

Annie Kamdem ◽

Lena Coïc ◽

Nadia Médejel ◽

Emmanuelle Lesprit ◽

...

Keyword(s):

Risk Factors ◽

Disease Severity ◽

Predictive Factors ◽

G6pd Deficiency ◽

Conflicts Of Interest ◽

Blood Parameters ◽

Cox Regression Analysis ◽

Significant Difference ◽

The Impact

Abstract Abstract 263 Early occurrence of dactylitis, severe anemia and leukocytosis have been identified as risk factors for adverse outcome in children with SCA (Miller NEJM 2000), but the impact of acute splenic sequestrations (ASS) on disease severity has not yet been reported. The goal of this study was to define the predictive factors of ASS and to evaluate if this complication was a risk factor for disease severity. Methods. SS patients of the newborn cohort, seen at our SCA Center in Créteil before 3 months of age and older than 2 years at the last visit (n=197), were included in this study. Alpha and beta genotypes, and G6PD activity were determined. Blood parameters were recorded at steady state during the second year of life. ASS was defined as an Hb-decrease of ≥20% associated with a spleen-increase ≥2cm. Vaso-occlusive crises (VOC) requiring hospitalizations and acute chest syndromes (ACS) were recorded. The yearly rates of VOC and ACS were calculated for the entire follow-up and for the period before any intensification (transfusion program, hydroxyurea or SCT). Results. Median follow-up was 7.9 yr (range 2–24), providing 1820 patient-years. Alpha-Thal was present in 70/162 (43.2%); beta-haplotypes, available in 140 patients, were Car/Car in 62 (44.3%), Ben/Ben in 35 (25%), Sen/Sen in 7 (5%), and others in 34 (25.7%). G6PD deficiency was present in 24/171 (14%). At baseline, mean (SD) blood parameters were: Hb: 8g1/dL (1.2); Ht: 24.6% (3.9); MCV: 79.2 fL(8.3); HbF: 15.7% (8.2); LDH: 919 UI/L (369) and reticulocytes: 296 (114); WBC: 14.3 (5.2), neutrophils 5.8 (3.1) × 109/L. Among the 197 SS-patients, 64 (32%) experienced their first ASS at the median age of 2.0 yr (range 0.1–12.9) and 36/64 recurred. ASS occurred before 1 yr of age in 10 (5%) and before 2 yr in 33/197 (17%). Splenectomy was performed in 24 of them at the median age of 5.1 yr (range 2.7–12.9). The KM-estimated cumulative risk of ASS occurrence at age 7 was 32% (95%CI: 25–39%). The Cox-regression analysis showed that gender, G6PD deficiency, beta haplotypes were not risk factors whereas alpha-Thal significantly increased the risk of ASS occurrence (HR: 1.9, 95% CI:1.1-3.3, p=0.021). Among blood parameters, multivariate Cox analysis retained low platelet (HR: 1.4 per 1×107/L decrease; 95%CI:1.1-1.8, p=0.014) and high reticulocyte counts (HR=2.0 per 1×107/L increase; 95%CI:1.6-2.6) as independent significant predictive factors for ASS. Comparison of patients with or without ASS history showed no significant difference in the rate of ACS but significantly higher rates of VOC during the entire follow-up (0.68±0.58 vs 0.47±0.55; p=0.014) and in the number of hospitalizations (1.64±0.83 vs 1.29±0.92; p=0.01) in patients with ASS history. Rates of VOC before intensification were 1.1±0.7 and even 2.2±2.0 in those having experienced ASS before age 1 vs 0.6±0.7 (p=0.001) in those with no ASS history. Conclusion. Results from this study in a newborn cohort show that ASS are more frequent in patients with alpha-Thal and are associated with a higher rate of VOC. Splenectomy is usually recommended in case or recurrent ASS; however, our previous results show that geno-identical SCT can cure 95%SCA children and partly restore splenic function. We suggest that this procedure be proposed to those with available donor before considering total splenectomy. Disclosures: No relevant conflicts of interest to declare.

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Immunologic Effects of An Oral BRAF Inhibitor in a BRAF Wild-Type Murine Model

Blood ◽

10.1182/blood.v118.21.4935.4935 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4935-4935

Author(s):

Gregory S. Vosganian ◽

Rinke Bos ◽

Linda Sherman

Keyword(s):

Immune Response ◽

Immune System ◽

Cytokine Production ◽

Serum Glucose ◽

Tnf Alpha ◽

Splenic Lymphocytes ◽

Wild Type ◽

Ifn Gamma ◽

Glucose Levels ◽

Significant Difference

Abstract Abstract 4935 Introduction: Metastatic melanoma represents a clinical challenge as aggressive therapy often results in unacceptable toxicity and less intensive therapy results in suboptimal clinical outcomes. PLX-4032 is an orally available small molecule which targets constitutively activated BRAFV600E in melanoma cells. BRAF is an important regulator of cell growth, proliferation and migration. We examined the effect of PLX-4032 on the immune system in two BRAF wild type murine systems: the first to determine the effect of PLX-4032 on cytokine production and the second to determine any functional immune effect of PLX-4032 in an insulinoma model. Methods: Effect of PLX-4032 on cytokine production: B10.D2 BRAF WT mice were injected with CD8 lymphocytes expressing a TCR specific for HA518-526 peptide (clone 1) and CD4 lymphocytes expressing a TCR specific for HA110-119 peptide (SFE) on Day 0 and concurrently simulated with appropriate peptide, incomplete Freund's adjuvant, and poly IC. Mice received PLX-4032 200mg/kg or placebo daily for 5 days. On day 6, splenic lymphocytes were harvested and flow cytometry performed to determine CD4 and CD8 IL2, IFN gamma, and TNF alpha production. Effect of PLX-4032 on functional immune response: B10.D2 BRAF WT rat insulin promoter (RIP)-Tag2-hemagglutinin mice bearing insulinoma were injected with clone 1 and SFE lymphocytes on Day 0 and received concurrent stimulation as above. Mice received PLX-4032 200mg/kg or placebo daily for 30 days and serum glucose levels were monitored weekly. Results: Effect of PLX-4032 on cytokine production: We noted no significant difference in the absolute number of splenic lymphocytes recovered in the two groups. There was no significant difference in the percent of CD8+ clone 1 cells producing TNF alpha, IL2 or IFN gamma. There was similarly no significant difference in the percent of CD4+/SFE lymphocytes recovered between the treatment and control groups, nor was there a significant difference in the percent of cells producing IFN gamma. Effect of PLX-4032 on functional immune response: Treatment with PLX-4032 resulted in no significant inhibition of the immune response of transferred lymphocytes against insulinoma. Mice in both groups developed significantly elevated serum glucose levels at the same time and remained diabetic for a similar duration. Discussion: Our data demonstrate that PLX-4032 does not appear to exert a quantitative or functional effect on the immune system in BRAF WT mice. Melanoma therapies often include medications which augment patient immune function or specifically target immune regulation; these data suggest that PLX-4032 does not inhibit normal immune function and therefore may have a role in combination with immunologically directed therapy, possibly resulting in synergistic anti-tumor effect by targeting multiple pathways involved in tumor survival. Disclosures: No relevant conflicts of interest to declare.

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Poly [ADP-Ribose] Polymerase 1 (PARP-1) Expression Before and After Immunochemotherapy In Patients With B Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v122.21.5293.5293 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5293-5293

Author(s):

Panagiotis Theodorou Diamantopoulos ◽

Maria Sofotasiou ◽

Vasiliki Papadopoulou ◽

Katerina Polonyfi ◽

Theodoros Iliakis ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Healthy Volunteers ◽

Conflicts Of Interest ◽

Lymphocytic Leukemia ◽

Response To Treatment ◽

Mrna Levels ◽

Protein Levels ◽

Significant Difference ◽

Before And After ◽

Parp 1

Abstract Introduction Poly [ADP-ribose] polymerase 1 (PARP-1) has a central role in the repair of single-stranded DNA (ssDNA) breaks, thus protecting the cell from genomic instability. This enzyme is a promising target in anticancer treatment. The aim of the present study is to investigate the role of PARP1 in B chronic lymphocytic leukemia (B-CLL) patients pre- and post- treatment. Patients and Methods Blood samples were collected from B-CLL patients before treatment and following 3 cycles of immunochemotherapy (chosen by the treating physician according to common clinical practice). Quantification of PARP1-mRNA levels was performed by a SYBR-green based PCR performed on BIORADCFX96 (BIORAD). The results were expressed in correlation to the mRNA levels of the endogenous housekeeping gene of beta actin (ACTB). The detection of the gene product was performed by Western Blot using anti-PARP1 antibody (clone 47-258; Calbiochem). We detected the 70 KD protein segment that results from the in vivo fractionation of PARP1 by caspase-3. The protein bands were visualized using an enhanced chemiluminescence detection system (Amersham Biosciences) and quantitated by densitometry using the gel analysis software ImageJ. We correlated the PARP1 protein levels to those of a group of healthy volunteers. We also studied the differences between PARP1-mRNA and protein levels before and after treatment and correlated them to clinical response. The related samples Wilcoxon Signed Rank test (IBM SPSS statistics, version 19.0) was used for the statistical analysis of the results. Results Samples were obtained from 24 B-CLL patients before treatment and from 15/24 following 3 cycles of immunochemotherapy. The patients' characteristics are shown in Table 1. Pre-treatment PARP1 protein levels were similar to those of 15 healthy volunteers (p=0.426). No statistically significant difference was noted between the PARP1-mRNA and protein levels following treatment (p=0.507 and 0.650 respectively) (Table 1). Multivariate analysis did not reveal statistically significant differences in the mRNA and protein levels in correlation to the stage of disease, the peripheral blood lymphocyte count, the LDH levels, the response to treatment and the overall prognosis of the patients. Conclusions The expression of PARP1 in patients with B-CLL seems to be comparable to that of healthy persons. We could not distinguish patients displaying reduced levels of PARP1, as previously reported by others. Moreover, PARP1 expression is not affected by immunochemotherapy, irrespective of stage and response to treatment. Thus, this molecule seems not to participate in the mechanisms involved in DNA repair and apoptosis that are impaired in B-CLL. The study is still ongoing with the addition of more subjects. Disclosures: No relevant conflicts of interest to declare.

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Expression Of Cancer-Testis Antigen In Multiple Myeloma

Blood ◽

10.1182/blood.v122.21.5341.5341 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5341-5341

Author(s):

Jingna Ji ◽

Shangqin Liu ◽

Li He ◽

Chaoping Xu ◽

Guiying Hu ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Healthy Volunteers ◽

Cell Lines ◽

Plasma Cells ◽

Conflicts Of Interest ◽

Clinical Stage ◽

Disease Stage ◽

Significant Difference ◽

Expression Frequency

Abstract In order to detect the CTAs expression in the cell lines and in patients with multiple myeloma (MM). Reverse transcriptase polymerase chain reaction (RT-PCR) detects the mRNA expression of MAGE-C1/CT7, SSX1, SSX2 and SSX4 in MM cell lines RPMI8226 and U266 and patients. Collect clinical MM patients with bone marrow specimens of 25 cases,18 cases of healthy volunteers as a control, The expression frequency in MM patients of CTA gene is parametric statistical analysis with age,gender,the amount of plasma cells,clinical stage and MM type. The CTA members we detected all express in RPMI8226 and U266 cell lines, the expression frequencies of MAGE-C1/CT7 of SSX1, SSX2 and SSX4 in 25 cases bone marrow of MM patients are as follows: 28%（7/25）、80%（20/25）、40%（10/25）、68%（17/25）. 18 cases of healthy volunteers with bone marrow does not express the gene. Four kinds of genes in the bone marrow of patients with simultaneous expression of two or more frequency 80%（20/25）, at least have an expression of the frequency 88%（22/25）. Expression of SSX1 and SSX4 in different disease stage was statistically significant(P <0.05), expression frequency was mainly for patients in the phase Ⅲhigher thanⅠand Ⅱ. Expression of MAGE-C1/CT7 and SSX2 in the period of disease was not statistically significant(P﹥0.05), Detected by the four CTA with age, gender, MM type and the volume of plasma cells was no significant difference(P﹥0.05). It was suggested MAGE-C1/CT7, SSX1, SSX2 and SSX4 gene in MM cell lines RPMI8226 and U266 and MM patients can co-express, while do not express in healthy people. In the expression frequency, SSX1 and SSX4 relate with MM clinical stage,MAGE-C1/CT7 and SSX2 do not relate with clinical stage,the 4 CTAs do not relate with gender,age,clinical type and volume of plasma cells. it provides theoretical support for the CTA vaccine in multiple myeloma immunotherapy. Disclosures: No relevant conflicts of interest to declare.

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Multiple Myeloma Vaccination Patterns from a Large Health System: An Example of Cancer Care Delivery Research (CCDR)

Blood ◽

10.1182/blood.v124.21.5677.5677 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5677-5677

Author(s):

Andinet W Alemu ◽

John O Richards ◽

Maharaj Singh ◽

Jenna K Mandler ◽

Martin K Oaks ◽

...

Keyword(s):

Health Care ◽

Multiple Myeloma ◽

Immune System ◽

Cancer Care ◽

Conflicts Of Interest ◽

Care Delivery ◽

Initial Step ◽

Vaccination Status ◽

Average Charge ◽

Significant Difference

Abstract Background We have a poor understanding of the vaccination immune response and outcomes in multiple myeloma (MM). As MM patients (Pts) are living longer and therapies are immunomodulatory there is an unmet medical need to further characterize the role of the immune system. A common reason for hospitalization or death in MM Pts is infection. As an initial step in MM Cancer Care Delivery Research (CCDR), we evaluated the current vaccination practice patterns in MM Pts at Aurora Health Care using the EMR and data analytics. Methods An IRB approved study reviewed MM Pts from 5/15/2012 to 5/15/2014. Data collected included demographics, influenza (FV) and pneumonia vaccination (PV) history, hospitalization episodes, cost associated with hospitalization, and admission and discharge diagnoses. Pts were considered PV positive if vaccinated within 5 years prior to study with any PV type. FV was none (no FV in 2012-2014), optimal [FV in 2012 and (2013 or 2014)], or suboptimal [FV in 2012 or (2013 or 2014)]. Data was analyzed using SAS and STATA 12. Results A total of 1131 MM Pts were identified. Race included 70% white, 13% black, and 17% mixed, other or information not available. MM median age at diagnosis was 71 and only 4% (47) had prior autologous stem cell transplantation. PV rate was 30%. FV was 55% none, 24% suboptimal and 20% optimal. There was no statistically significant difference in the rate of PV and FV when stratified vs age, gender, and race. Over two years there were a total of 662 hospitalization events involving 317 MM Pts. The total cost of hospitalization was approx $35M. The average charge per hospitalized patient was $110K (range: $2K -1.3M) with an average $52K per hospitalization encounter (range: 2K – 648K). The rate of PV and FV vaccination among Pts with index hospitalization is significantly higher than non-hospitalized patients. There was no difference in hospitalization cost based on vaccination status. (See Table 1) Discussion Vaccination rates were low and did not correlate with hospital outcomes. This may be explained as a limitation for a retrospective EMR analysis without accounting for temporal relationship of vaccines – i.e. possible vaccination after admission. Alternatively, this may indicate that our current methods of vaccination in MM are not effective. Other limitations include need for a more granular review of treatment regimens and infectious complications. Additional surrogate markers are needed to understand the effect of vaccines and the immune system on health care outcomes such as hospitalizations, cost, and survival. This will be addressed in prospective registries and immunologic studies at our center and may be queried at other health systems. Table 1 – Vaccination Status and Hospitalizations Vaccination Status % Hospitalization Events, % Hospitalization Charge, $ PV – No 70% 20% $16M PV – Yes 30% 52% $18M FV – None 55% 16% $9M FV – Suboptimal 24% 42% $13M FV - Optimal 20% 43% $12M Disclosures No relevant conflicts of interest to declare.

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Rapid COVID-19 Prognostic Blood Test for Disease Severity Using Epigenetic Immune System Biomarkers

Delaware Journal of Public Health ◽

10.32481/djph.2020.07.008 ◽

2020 ◽

Vol 6 (2) ◽

pp. 26-29

Author(s):

Adam G. Marsh ◽

G. Mark Anderson ◽

Erich J. Izdepski

Keyword(s):

Immune System ◽

Disease Severity ◽

Blood Test

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THU0296 PROTEIN PROFILING IN INDIVIDUALS BEFORE ONSET OF ANCA-ASSOCIATED VASCULITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3033 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 376.2-376

Author(s):

E. Berglin ◽

A. Esberg ◽

J. Dahlqvist ◽

J. Sjöwall ◽

A. Lundquist ◽

...

Keyword(s):

Immune System ◽

Growth Factor ◽

Random Forest ◽

Symptom Onset ◽

Partial Least Square ◽

Protein Profiling ◽

Serum Samples ◽

Anca Associated Vasculitis ◽

Significant Difference ◽

Novel Biomarkers

Background:Etiology and pathogenesis of ANCA-associated vasculitis (AAV) is multifactorial and understanding of the processes leading from a healthy immune system to autoimmunity and on to debut of symptoms in AAV is rudimentary.Objectives:To identify inflammatory proteins related to the early processes preceding AAV development, and potential novel biomarkers, using large-scale protein analysesMethods:The Swedish National Patient Register of in-patient carevand the Swedish Cause of Death Register with discharge diagnosis from ICD-9 and-10 for AAV were co-analysed with the registers of 4 different blood biobanks to identify AAV individuals with available samples predating onset of symptom. Of the pre-AAV cases 86 (36 male, 50 female; mean age (SD); 51.9 (16.9) years) were identified with at least one plasma or serum sample (28 plasma, and 100 serum) pre-dating symptom onset (mean (SD); -4.3 (3.1) years), and 14 had 2-3 samples. Serum and plasma control samples matched for sex, age and sampling date were identified (n=198; 82 male, 116 female; mean age (SD); 51.9±15.9 years). The samples were analysed for levels of 92 proteins using proximity extension assay (OLINK inflammation panel, SciLifeLab, Uppsala, Sweden). Data were analysed using routine statistical methods, random forest and Partial Least square-discriminant analysis (PLS-DA).Results:As previously described for the assay significant difference between plasma and serum samples were observed both in pre-AAV individuals and controls. In pre-AAV plasma samples significantly increased concentrations of interleukin (IL)-2, chemokine ligand (CCL)-4, fibroblast growth factor (FGF)21, IL-4 and CCL20 were found closer to symptom onset, (<5 years) than later (> 5 years) and compared with controls. In serum tumor necrosis factor receptor superfamily member (TNFRSF)9, CXCL9, osteoprotegerin and vascular endothelial growth factor-A were significantly increased <5 years before onset vs. later (>5 years) and compared with controls. PLS-DA score scattered plot separated the pre-AAV individuals from healthy controls (R2=0.26), with significantly increased levels of CCL23, CXCL5, and matrix metalloproteinases-1 (MMP-1),transforming growth factor-ß, orosomucoid, en-rage (S100A12) and IL-7 and decreased FGF-19 level in serum. Binary logistic regression analyses comparing tertiles for these proteins confirmed significantly increased odds ratios for disease development of CCL23, CXCL5 and MMP-1. The findings were confirmed in random forest analysis where these factors were among the 20 most discriminatory factors between pre-symptomatic AAV and controls.Conclusion:In serum samples collected years before symptom onset of AAV, proteins involved in immune system activation were increased, suggesting that the inflammatory process is initiated long before clinical manifestations of the disease appear. These findings propose the elevated proteins as novel biomarkers for disease progression.References:[1]Watts et al. Ann Rheum Dis 2007;66:222-22Acknowledgments:Vasculitis Foundation, USADisclosure of Interests:Ewa Berglin: None declared, Anders Esberg: None declared, Johanna Dahlqvist: None declared, Johanna Sjöwall: None declared, Anders Lundquist: None declared, Kristina Lejon: None declared, Ingegerd Johansson: None declared, Aladdin J Mohammad Speakers bureau: lecture fees from Roche and Elli Lilly Sweden, PI (GiACTA study), Solbritt Rantapää Dahlqvist: None declared

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Impact of Face Masks on 6-Minute Walk Test in Healthy Volunteers

Pulmonary Circulation ◽

10.1177/2045894020988437 ◽

2021 ◽

Vol 11 (1) ◽

pp. 204589402098843

Author(s):

Kevin M. Swiatek ◽

Charnetta Lester ◽

Nicole Ng ◽

Saahil Golia ◽

Janet Pinson ◽

...

Keyword(s):

Healthy Volunteers ◽

Face Mask ◽

Walk Test ◽

Six Minute Walk Test ◽

Significant Difference ◽

6 Minute Walk Test ◽

The Impact ◽

Minute Walk

Our objective was to establish the impact of wearing a face mask on the outcome of six-minute walk test in healthy volunteers. In a study of 20 healthy volunteers who each completed two 6MWTs, one with a mask and one without, there was no difference in distance walked. However, there was a significant difference in perception of dyspnea between the two groups.

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