ABSTRACT
BACKGROUND: Multiple myeloma (MM) and Waldenström macroglobulinemia (WM) are associated with significant immunoparesis. Based on the ongoing COVID-19 pandemic, there is an urgent need to understand whether patients are able to mount a sufficient response to COVID-19 vaccines. METHODS: MM and WM patients are vaccinated with mRNA-1273 (Moderna), BNT162b2 mRNA (Pfizer/BioNTech), or JNJ-78436735 (Johnson & Johnson) in a prospective clinical trial. Primary endpoint is SARS-CoV-2 spike protein (S) antibody (Ab) detection 28 days after final vaccination. Secondary endpoints include functional serologic assessments and T-cell responses at 28 days, 6 months, 9 months, and 12 months following vaccination. S Abs were detected by Elecsys assay (Roche Diagnostics), with 3 0.80 U/mL defined as positive and titers > 250 U/mL considered stronger correlates of neutralization. SARS-CoV-2 wildtype and variant S-specific Ab isotypes and FcγR binding profiles were quantified by custom Luminex assay. Antibody-dependent neutrophil and cellular phagocytosis (ADNP and ADCP) were assessed using flow cytometry. RESULTS: To date 141 patients have been enrolled, 137 (91 MM and 46 WM) of whom had an S Ab assessment. Median Ab titer was 178.0 (IQR, 16.10-1166.0) for MM and 3.92 (IQR, 0-278.9) for WM. S Ab response rate was 91% (83/91) in MM and 56% (27/46) in WM. However, responses achieving S Ab >250 U/mL were 47.3% (43/91) in MM and 26.1% (12/46) in WM. In patients 375 years, responses >250 u/mL were 13.3% (2/15;p<0.05). Vaccine-specific S Ab responses >250 u/mL following mRNA-1273, BNT162b2, and JNJ-78436735 were 67.6% (23/34;p<0.05), 38.3% (18/47;p=NS), and 20% (2/10;p=NS) in MM and 50.0% (8/16;p<0.05), 14.8% (4/27;p<0.05), and 0% (0/3;p=NS) in WM. Among MM patients with progressive disease, S Ab response >250 u/mL occurred in 30% (6/20) as opposed to 55.6% (30/54) for VGPR+ (p<0.05). MM patients having autologous stem cell transplant within 12 months demonstrated 100% (5/5;p<0.05) S Ab responses. For MM patients actively receiving an anti-CD38 monoclonal Ab or an immunomodulatory drug, S Ab response occurred in 38.9% (14/36;p=NS) and 50.9% (28/55;p<0.05). Among WM patients, S Ab responses >250 U/mL occurred in 63.6% (7/11;p<0.05) previously untreated;0% (0/9;p<0.05) who received rituximab within 12 months;10% (2/20);p<0.05) on an active Bruton Tyrosine Kinase (BTK) inhibitor;and 20% (3/15;p=NS) who received other therapies. Functional Ab studies were performed on 14 MM patients, 14 WM, patients, and 14 healthy donors (HD) (Figure 1). All patients were assessed 28 days following their final vaccination and myeloma patients had an additional assessment 28 days following initial vaccination. MM and WM patients demonstrated less IGG1 and IGG3 S Ab production than HD. MM patients showed increased IgA and IgM S Ab production as well as increased FcgR2A binding following a second vaccine in contrast to HD. Both ADNP and ADCP were reduced in MM and WM patients. MM patients demonstrated improved ADCP in SARS-CoV-2 variants B.1.351, B.1.117, and P.1 versus wildtype (p<0.05). CONCLUSIONS: We report the first known evidence of impaired functional humoral responses following COVID-19 vaccines in patients with MM and WM. Overall, WM patients showed more severe impairment of COVID-19 S Ab responses. Most previously untreated WM patients achieved S Ab responses, however the most significant reduction in S Ab responses were seen in WM patients who received rituximab within 12 months or active BTK inhibitors. For MM patients, being in disease remission associated with improved S Ab response. Among MM and WM patients, age 375 years associated with significantly lower rates and vaccination with MRNA-1273 (Moderna) elicited significantly higher S Ab response rates than other vaccines. A defect in ADNP and more profound defect in ADCP suggests overall compromised opsinophagocytic activity among MM and WM patients. Data comparing first and second vaccine responses in MM patients, suggest less efficient class switching to IGG as well as incomple e maturation of their FcgR2A binding profiles but normal maturation of FcgR3A. Interestingly, ADCP was improved in several emerging SARS-CoV-2 variants. T-cell studies are pending and will be updated. Further understanding of the immunological response to COVID19 vaccination is needed to clarify patients risks, and necessity for booster or alternative protective measures against COVID-19. (Figure Presented).
ABSTRACT
Currently, we are in a situation of transition in the way of teaching, caused by COVID-19. In a very short time, students have been forced to introduce in their teaching-learning process the use of digital resources that allow them to continue learning. Faced with this situation, an adequate digital competence is required, understood not as a single skill, but as a set of skills that facilitate the use of educational technology, teamwork, critical thinking, creativity and communication. The objective of this work is to propose a causal structural model of the dimensions that configure digital competence in technical-professional students. The study was carried out with a non-probabilistic sample of 17301 students from AIEP of the Andres Bello University in Chile. The validity of this instrument was carried out by applying the partial least squares (PLS) method of structural equation modeling. The main result was that the model explained 32.90% of the true variance of the students' digital competence. In addition, the reliability, convergent and discriminant validity of the established causal relationships were verified, determining a model with an acceptable goodness of fit.
ABSTRACT
Updated analysis confirms sustained poor prognosis of COVID-19 in patients with lymphoma in Latin America: A cohort of 160 patients from GELL. Introduction: Ongoing SARS-COV-2 pandemic has impacted the management of cancer patients worldwide. Several reports have demonstrated inferior outcomes of patients with hematological malignancies, including higher rates of intensive care unit admission, need for mechanical ventilation and death. The impact of COVID-19 is profound in resource-restricted countries, including Latin America. Most cohorts reported have not included patients from Latin America, and there is paucity of data of the outcome of cancer patients with COVID-19 in low- and middle-income countries. Grupo de Estudio De Linfoproliferativos En Latino-America (GELL )is a collaborative network of hematological centers in 13 countries in Latin America. We report updated outcomes of lymphoma patients diagnosed with COVID-19 in Latin America. Methods: We conducted a retrospective study including patients with a diagnosis of lymphoma and COVID-19 infection. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma were excluded from the analysis We defined active disease as follow: (1) patients with detectable disease either prior to initiating therapy or upon relapse, and/or (2) patients undergoing active cancer treatment. The primary outcome was overall survival at 100 days. Survival curves were estimated using the Kaplan Meier method. Uni and multivariable analysis were carried out with Cox model. Results: A total of 160 patients were available for analysis. Median age was 60 years old. Hypertension was the most common comorbidity (33%). Most patients had aggressive lymphomas (62%), including 43% of patients with diffuse large B-Cell lymphoma (DLBCL). Follicular lymphomas were observed in 13% of patients and Hodgkin lymphoma in 12.5% of patients. With a median follow-up of 37 days, the 100-day OS was 64% (95CI 56-74%, fig. 1). In univariate analysis, age (HR 1.03, p=0.0025), hypertension (HR 2.01, p=0.017), >1 number of prior lines (HR 2.78, p=0.011), patients currently on treatment (HR 1.83, p=0.043), ferritin >2000 ng/mL (HR 4.74 p=0.00047) were associated with inferior OS. In multivariate analysis, age (HR 1.03, p=0.0026) and patients currently on treatment (HR 1.82, p=0.04) had inferior OS. There was a trend towards inferior outcomes in patients receiving monoclonal antibodies in univariate analysis (HR 1.82, p=0.081) but not in multivariable analysis (HR=1.29, p=0.48). Use of steroids was not statistically related to mortality (HR 1.79, p=0.074). Finally, contrary to other cohorts, no improvement in OS was observed in patients diagnosed later on the pandemic (fig. 2). Conclusion: In this large cohort of Latin American patients with lymphoma malignancies, our updated analysis showed a maintained dismal prognosis with COVID-19 infection. With a median follow up of 37 days, the 100-day OS was 64%. Older age and ongoing active cancer treatment were significantly associated with mortality. The use of monoclonal antibodies and systemic corticosteroids were not statistically associated to poor survival. Current efforts are focused on improving immunization in the Latin American population. There is an unmet need for improving survival in patients with hematologic malignancies and COVID-19 infection. [Formula presented] Disclosures: Perini: Janssen: Honoraria, Speakers Bureau;Takeda: Honoraria, Speakers Bureau;Astra Zeneca: Honoraria, Speakers Bureau;MSD: Honoraria, Speakers Bureau. Otero: ASTRA ZENECA: Current Employment. Abello: Dr Reddy's: Research Funding;Amgen: Honoraria;Janssen: Honoraria. Castillo: Abbvie: Consultancy, Research Funding;BeiGene: Consultancy, Research Funding;Pharmacyclics: Consultancy, Research Funding;Janssen: Consultancy;Roche: Consultancy;TG Therapeutics: Research Funding.
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Background: Some studies have suggested a higher risk of respiratory complications related to COVID-19 (C-19) in cancer patients (pts), but there is a lack of knowledge concerning the outcomes and prognostic factors. We evaluated whether various factors can predict a more serious C-19 infection. Methods: We conducted a retrospective study including 51 pts diagnosed of C-19 between March 10 and April 7, 2020. All pts present tumor disease at diagnosis of C-19: advanced disease, neoadjuvant treatment (ttm) or maintenance ttm after definitive chemoradiotherapy. It has been evaluated whether certain factors may present an increased risk for the development of a SCE, defined as death, the need of high oxygen flow (FiO2≥50%), non-invasive or invasive mechanical ventilation or Intensive Care Unit admission. These factors have been age, ECOG, ttm line, type of ttm, time from last ttm to C-19 diagnosis, smoke, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, cardiopathy, body mass index, fever, cough, dyspnea, myalgia, gastrointestinal symptoms, infiltrates in chest radiography, CURB65 ≥1, creatine phosphokinase, lactate dehydrogenase and D-Dimer elevated, lymphopenia and PaO2/FiO2 <300 mmHg. Results: At the time of the data cut-off on May 16 2020, we have collected 51 cancer pts. Most of them were men (61%) with a median age of 68 years (range 19-86). Lung cancer was the most frequent type of cancer (22%), and the most common ttm was chemotherapy (51%). Eighteen pts (35%) developed a SCE, with 13 deaths (25%). Only dyspnea and PaO2/FiO2 <300 mmHg showed an increased risk to develop a SCE. [Formula presented]. Conclusions: Despite our retrospective analysis and the limited number of pts, we conclude that advanced cancer pts receiving antitumoral ttm have a higher risk for the development of SCE when considering the presence of PaO2/FiO2 <300 mmHg and dyspnea on admission. Therefore, it is crucial to screen for C-19 infection in any cancer patient who reports dyspnea, given the potential risk of poor evolution. Legal entity responsible for the study: Oncology Department, Hospital Universitario Ramon y Cajal, Madrid. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
ABSTRACT
Introduction COVID- 19 is a disease that has claimed the lives of many people. However, alterations in labo-ratory profiles in the city of Tacna have not been accurately established in association with its severity to support diagnosis and treatment.Objective To determine biomarkers related to the severity of COVID- 19 in patients treated at the social security hospital in Tacna during 2020.Methods We performed an observational, cross-sectional, and analytical study that included 308 patients with COVID- 19 from the social security hospital in Tacna, Peru, during the "first wave" of the pandemic (from July to August 2020). Immunological, hematological, arterial gas, hemostasis, and biochemical markers were collected. Patients were categorized into mild, moderate, and severe based on the clinical criteria found on clinical records. Correlation strength was per-formed according to Spearman's Rho coefficient. The performance of the biomarkers associat-ed with severity was analyzed with the Receiver Operating Characteristic curve.Results Regarding hematological markers there was a positive correlation with monocyte count (correla-tion coefficient: 0.841;area under the curve 97.0 degrees/o;p < 0.05) and a negative correlation with lymphocyte count (correlation coefficient:-0.622;area under the curve 82.7 degrees/o;p < 0.05). Regarding biochemical markers, arterial gases and hemostasis, no significant correlations were found. In immunological markers, we found positive correlation with ferritin (correlation coef-ficient: 0.805;area under the curve 94.0 degrees/o;p < 0.05), and C-reactive protein (correlation coeffi-cient: 0.587;area under the curve 87.4 degrees/o;p < 0.05).Conclusions The biomarkers that can be considered as parameters associated with the severity of COVID- 19 are the absolute blood count of monocytes and serum ferritin concentration.