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Background/Objectives: SARS-CoV2 causes the COVID-19 disease, capable of producing a severe acute respiratory syndrome. Several clinical variables and genetic variants have been related to a worse prognosis. The aim of this study is to measure if difference in the gene expression are associated with COVID-19 severity. Method(s): We performed RNA-seq Transcriptome in RNA extracted from lymphoblastoid cell line in 20 patients who require hospitalization (10 from the intensive care unit) in a GeneStudio S5 Plus Sequencer (Ion Torrent Technology). FASTQ files were obtained and trimmed using BBtools, BBduk for cutting, filtering and masking the data, and Dedupe for the elimination of duplicates. Mapping and counting matrix was done in bash using the Salmon program. Differential expression analysis and subsequent functional enrichment was performed using Rstudio (DESeq2, ClusterProfiler, GO and KEGG). Result(s): We observed that 2042 differentially expressed genes (1996 overexpressed, LFC>0 and 406 underexpressed, LFC<0) were obtained between patients who require hospitalization versus those in the intensive care unit. We found some genes previously SARS-CoV-2 associated (PGLYRP1, HDAC9 and FUT4). Furthermore, genes involved in the activity of the immune system and in inflammatory processes showed significant differences between cohorts (ABCF1 (LFC = -25.14, padj = 1.05e-13), ABHD16A (LFC = 25.00, padj = 1.05e-13) and IER3 (LFC = -24.45, padj = 2.43e-13)). Conclusion(s): We described differential expression in genes of the immune system and inflammatory processes that might be have a role in the risk of develop severe symptoms of COVID-19, including admission in the intensive care unit. This results should be validated by additional functional studies.
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Background: Breats cancer is a major health problem in elderly ( >= 70 years) women. Increase incidence with age and the progressive increase in life expectancy mean that the numbers in elderly breast cancer diagnosis are increasing. These patients do not always receive the proper treatment and despite this the survival of this population is not always depends on cancer, there are other competing causes of death typical of the aging population. Method(s): A retrospective observational analysis of women >= age 70 diagnosed with breast carcinoma in HUPHM between 2014 and 2020 was made. Clinical, pathological data and stages at diagnosis were analyzed. We checked our patients with the national death center (official national registry) thus obtaining an exact date of death and the cause of death. Data updated in January 2023 , ensuring a minimum follow-up of 24 months. We excluded deaths from Covid or of unknown cause to avoid bias. Result(s): A total of 421 patients were analyzed, mean age of 78.6 years and median follow-up of 48 months. 28% of patients had died at the time of analysis, 11% due to cancer and 17% from other causes. If we analyze the population deceased by cancer, no deaths are detected in patients diagnosed with carcinoma in situ (4% of the population), in stage I (30% of the population) the cumulative incidence of cancer death at 5 years is 3%, 7% In stage II (30% of the population), 15% in stage III (16%) and 70% in stage IV (12%). Death by other causes are more frequent in early breast cancer, the cumulative incidence at 5 years are 10% in stage I, 22% in stage II, 44% in satge III and just 10% in stage IV. The most frequent causes of death in this population were caridovascular events and infections. There are no differences in 5-year mortality according to histological subtypes 20%, 12%, 25% and 12% for triple negative, Rh+/HER2-, RH+/her2+ and RH-/HER2+ respectively. Conclusion(s): Although elderly patients do not receive optical treatments, mortality from cancer in early stages is incidental at 5 years, a different scenario is seen in metastatic disease in which the patient's prognosis depends mainly on the oncological disease, Therefore, an effort should be made in the treatment of these patients with metastatic breast cancer since adequate treatments can have a clearly positive impact on the survival of patients. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest.Copyright © 2023
ABSTRACT
Heat shock proteins of 90 kDa (HSP90) have been proposed as adjuvants in the design of new vaccine formulations. In our laboratory, two cytosolic isoforms of plant HSP90 (AtHsp81.2 from Arabidopsis thaliana and NbHsp90.3 from Nicotiana benthamiana) demonstrate to have adjuvant properties against parasitic infections such as Toxoplasmosis and Neosporosis. We showed that plant HSP90 fused or mixed with the antigen of interest can enhance and modulate the immune response. To evaluate the adjuvant properties of plant HSP90 in other infectious diseases poorly characterized, we proposed to use the receptor binding domain (RBD) of the Spike protein of SARS-CoV2, and the main candidate in the design of subunit vaccines. Initially, we evaluated the humoral response against RBD using the strategy protein mixture (Adjuvant + Antigen). Thirty C57 mice (male and female) were randomly separated into 7 groups and intramuscularly immunized with AtHsp81.2, NbHsp90.3 or RBD as control groups, rRBD + rAtHsp81.2, rRBD + rNbHsp90.3 or rRBD + Alum as vaccinated groups. A PBS group immunized with PBS 1x buffer was also included. Mice received a two-dose schedule delivered in 21-day intervals, and the sera were obtained at 0, 21-, 42-, 63-and 84-days post-immunization (dpi). The analysis of the humoral response showed a significant increase in anti-RBD IgGt, which persisted between 21 and 42 dpi. In addition, the RBD + AtHsp81.2 group showed a Th2 profile with a significant increase of anti-RBD IgG1 like the control RBD + Alum group. By contrast, the RBD + NbHsp90.3 group showed a significant increase in anti-RBD IgG2b towards a Th1 profile. Finally, we evaluated the capacity of the sera to neutralize lentiviral vectors pseudotyped with Spike glycoprotein. Serum-neutralizing antibody titers were determined by the 50% inhibitory dilution. The sera obtained at 42 dpi from mice immunized with rRBD + rAtHsp81.2 and rRBD + rNbHsp90.3 showed the potential to neutralize viral infection. In addition, the differential profile of both isoforms in the triggered humoral response offers an advantage of rapid and safe response in pandemic situations such as those experienced by SARS-CoV2. Neurosciences.
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Introduction: Cancer healthcare has been affected by Coronavirus disease 2019 (COVID-19) pandemic, interfering the normal function of oncology units and increasing diagnostic delay. Nevertheless, the rising incidence of respiratory infections led to an increase in medical consultations and chest imaging explorations. The aim of the study was to assess whether the increase in medical evaluations in the context of the pandemic led to an increase in the detection of early-stage thoracic tumours. Methods: We performed a retrospective single-institution study, collecting data from patients diagnosed with thoracic tumours between March, 1, 2020 and December, 31, 2021. We analysed their demographic and clinical data, symptoms at diagnosis and those who were diagnosed due to SARS-CoV-2 infection. Results: A total of 378 patients were analysed. Main results are shown in Table-1. Only 5.3% of newly diagnosed thoracic tumours were related to a suspected or confirmed SARS-CoV-2 infection. However, these patients were not diagnosed at earlier stages (p = 0.414). When we evaluated symptoms at diagnosis, we found that asymptomatic patients presented in earlier stages (p <0.000, Figure-1), being the majority incidental findings during the follow-up of oncological and non-oncological pathologies. Regarding symptomatic patients, most presented as locally advanced or metastatic diseases and no changes have been observed in the pattern of presentation compared to studies prior to the pandemic. [Formula presented] Conclusions: COVID-19 pandemic did not seem to increase thoracic tumours diagnosis in our study. Lung cancer diagnosed in patients due to SARS-CoV-2 infection was not detected in earlier stages. Clinical presentation was similar to previous reported outside COVID-19 pandemic. Nevertheless, we find that asymptomatic patients diagnosed incidentally presented more frequently in localized stages in comparison with symptomatic patients. [Formula presented] Keywords: COVID19, Lung Cancer, Diagnosis
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Background: Madrid has been the epicenter of the SARS-CoV2 pandemic in Spain. We analyzed the experience at our hospital with SARS-CoV2 infection and cancer patients (p). Method(s): We analyzed our experience from March 1 to April 30 at the Puerta de Hierro University Hospital in Madrid. Diagnosis of SARS-CoV2 infection was made by RT-PCR, suspected cases not confirmed were excluded. Result(s): Overall in-hospital mortality cancer p with COVID-19 was 15.2% (95%CI, 6.3;5.2), similar to 12.7% (95%CI,11.1;4.4) with p=0.615 of the global COVID-19 hospitalised population and greater than that of patients admitted without SARS-CoV-2 infection during the same period 4.3% (95%CI;3.6;5.2) p0.001. Among 653 patients receiving active cancer therapy during this period, 24 (3.7%) developed COVID-19 and required admission, 4.2% of were receiving chemotherapy, 9.5% immunotherapy and 2.1% targeted therapies. Lung and breast cancer were the most frequent (26.1%), followed by colorectal (19.6%) and breast cancer. No significant differences due to the cancer treatment received were observed. Mortality in lung cancer patients was the highest (25%). The univariate analysis (between p who developed serious event vs. those who did not), showed that higher Brescia, CURB-65 scale, lactate dehydrogenase (LDH) or C-reactive protein (CRP) levels at admission, the greater risk of developing severe complications (p0.05) [Formula presented]. Conclusion(s): Patients with cancer, especially lung cancer, and SARS-CoV2 infection have a worse overall prognosis than the general population. Objective parameters such as LDH, CRP at admission, Brescia index or CURB-65 should alert us to a more serious evolution and suggest early an early intensive care unit (ICU) admission. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Copyright © 2020
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Objectives. The effect of COVID-19 infection in pregnant women and her neonate is not well-understood, with no clear evidence for vertical transmission. This study aims to determine the maternal and neonatal clinical characteristics and the dyad’s outcomes among those infected with COVID-19 infection. Methods. An ambispective cross-sectional study involving pregnant women with confirmed COVID-19 infection was conducted at the Philippine General Hospital from April to August 2020. Two hundred nine obstetric patients were included, 14 of whom consented to specimen collection to determine vertical transmission. Results. The majority of pregnant women with COVID-19 infection and their neonates had good outcomes. Labor, delivery, and the immediate postpartum course were generally uneventful. The all-cause maternal morbidity rate was high at 75.6 per 100 cases during the five-month study period. COVID-19 related morbidities included the development of Guillain-Barré Syndrome. The in-hospital all-cause maternal mortality rate was 1.91 per 100 cases. The causes of maternal death were acute respiratory failure, septic shock, and congenital heart disease (atrial septal defect with Eisenmengerization). The in-hospital, all-cause neonatal mortality rate was 1.04 per 100 neonates of cases. The lone mother and infant deaths were in a postmortem rt-PCR swab negative mother with an rt-PCR swab positive live neonate who eventually succumbed after nine days of life. All 14 dyads with collected specimens that included amniotic fluid, placental tissue, umbilical cord, and neonate nasopharyngeal swab tested negative for SARS-CoV-2 rt-PCR. Conclusion. The prognosis for COVID-19 infected pregnant patients was generally good, with most of the patients discharged improved. Almost all of the neonates born to COVID-19-infected mothers were stable-term infants. There was no evidence for vertical transmission, as shown by negative rt-PCR results for all the additional specimens obtained. In general, the prognosis for COVID-19 infected dyads was good. The majority of the mothers were discharged well with their term infants. All possible maternal sources of COVID-19 infection to the neonate tested negative. This study provided no evidence for vertical transmission. © 2021 University of the Philippines Manila. All rights reserved.