Comorbidities That Increase Risk for Severe Acute Covid-19 in Pediatric Population

Background: Little is understood about which comorbidities are associated with severe outcomes in children hospitalized with acute COVID-19. Some confusion lies especially for cancer or diabetes. Method(s): Data from 2 multicenter prospective cohort studies of hospitalized children (aged 0-18 years) with confirmed SARS-CoV-2 in Spain and Colombia were combined for this analysis. Data were obtained from 116 hospitals. Outcome was classified as (in decreasing order of severity): death, mechanical ventilation (MV), pediatric intensive care unit (PICU) admission, high flow/CPAP, oxygen therapy with nasal prong (NP) and hospitalization without respiratory support. Risk factors for severity, adjusting for age and gender, were identified using multinominal logistic regression and a backwards selection process. Result(s): A total of 1,753 patients were included, 734 (41.8%) in Spain and 1,019 (58.1%) in Colombia. The most frequent comorbidities were asthma (9.0%), chronic neurological disorder (NRL) (7.4%), immunosuppressive medication (7.2%), malignant neoplasms (5.4%) and chronic lung disease (not asthma) (CLD) (4.5%). Comorbidities associated with the different endpoints are summarized in Figure 1. Asthma was associated with a significantly increased risk of death (OR: 4.17;95%CI 1.34-12.97), MV (OR: 7.94 (3.59-17.56)), PICU admission (OR: 3.37 (1.91- 5.96)), high flow/CPAP (OR: 6.65 (2.69-16.46)), and NP (OR: 3.85 (2.57-5.77)) compared to hospitalization without respiratory support. NRL was associated with increased risk of death (OR: 7.34 (3.01-17.90)), MV (OR: 3.07 (1.20-7.82)) and high flow/CPAP (OR: 4.36 (1.68-11.29)). CLD was associated with increased risk of death (OR: 6.22 [2.28-16.94]) and NP (OR: 3.1 (1.74-5.58)) and in addition, chronic cardiac disease was associated with increased risk of MV (OR: 5.21 (1.76-15.41)) and PICU (OR: 2.78 (1.27-6.08)). Risks of death (OR: 4.49 (2.03-9.05)), MV (OR: 2.97 (1.52-5.81)), PICU (OR: 4.27 (2.89-6.33)), and NP (OR: 4.67 (3.64-5.99)) were higher in the Colombia Cohort. Conclusion(s): Asthma, chronic neurological, cardiac and lung disease;and belonging to the Colombia cohort were consistently associated with multiple severe outcomes of COVID-19. Cancer and diabetes association with selected endpoints rather than with most endpoints may be more related to the baseline disease than with the actual COVID-19.

[Risk of thrombosis recurrence among patients with COVID-19- and surgery-associated venous thromboembolism]. / Riesgo de recurrencia de la trombosis en pacientes con tromboembolia venosa asociada a COVID-19 y a cirugía.

Introduction: Recent surgery is a well-known major transient risk factor for venous thromboembolism (VTE) due to the low risk of VTE recurrence after anticoagulation is discontinued. On the other hand, the risk of VTE recurrence among patients with COVID-19-associated VTE is unknown. This study aimed to compare the risk of VTE recurrence between patients with COVID-19- and surgery-associated VTE. Methods: A prospective observational single-center study was performed including consecutive patients diagnosed with VTE in a tertiary hospital from January 2020 to May 2022 and followed up for at least 90 days. Baseline characteristics, clinical presentation, and outcomes were assessed. The incidence of VTE recurrence, bleeding, and death was compared between both groups. Results: A total of 344 patients were included in the study: 111 patients with surgery-associated VTE and 233 patients with COVID-19-associated VTE. Patients with COVID-19-associated VTE were more frequently men (65.7% vs 48.6%, p = 0.003). VTE recurrence was 3% among COVID-19 patients and 5.4% among surgical patients, with no significant differences (p = 0.364). The incidence rate of recurrent VTE was 1.25 per 1000 person-months in COVID-19 patients and 2.29 person-months in surgical patients, without significant differences (p = 0.29). In the multivariate analysis, COVID-19 was associated with higher mortality (HR 2.34; 95% CI 1.19-4.58), but not with a higher risk of recurrence (HR 0.52; 95% CI 0.17-1.61). No differences were found in recurrence in the multivariate competing risk analysis (SHR 0.82; 95% CI 0.40 - 2.05). Conclusions: In patients with COVID-19 and surgery-associated VTE, the risk of recurrence was low, with no differences between both groups.

Riesgo de recurrencia de la trombosis en pacientes con tromboembolia venosa asociada a COVID-19 y a cirugía Risk of thrombosis recurrence among patients with COVID-19- and surgery-associated venous thromboembolism

Introducción La cirugía reciente es un factor de riesgo transitorio mayor y conocido de tromboembolia venosa (TEV) debido al bajo riesgo de recurrencia de la TEV una vez suspendida la anticoagulación. Por otro lado, se desconoce el riesgo de recurrencia de la TEV en los pacientes con TEV asociada a COVID-19. El objetivo de este estudio consistió en comparar el riesgo de recurrencia de la TEV entre pacientes con TEV asociada a COVID-19 y a cirugía. Métodos Se realizó un estudio prospectivo, observacional y unicéntrico en el que participaron pacientes consecutivos diagnosticados de TEV en un hospital terciario entre enero de 2020 y mayo de 2022 y que fueron objeto de seguimiento durante un mínimo de 90 días. Se evaluaron las características iniciales, el cuadro clínico y los resultados clínicos. Se compararon las incidencias de recurrencia de la TEV, hemorragias y muertes entre ambos grupos. Resultados En el estudio se incluyó a un total de 344 pacientes: 111 con TEV asociada a cirugía y 233 con TEV asociada a COVID-19. Entre los pacientes con TEV asociada a COVID-19 hubo una mayor frecuencia de varones (65,7 vs. 48,6%, p = 0,003). La recurrencia de la TEV fue de 3% en los pacientes con COVID-19 y de 5,4% en los pacientes quirúrgicos, sin diferencias significativas (p = 0,364). La tasa de incidencia de TEV recurrente fue de 1,25 y 2,29 por 1.000 personas-meses en los pacientes con COVID-19 y quirúrgicos, respectivamente, sin diferencias significativas (p = 0,29). En el análisis multifactorial, la COVID-19 se asoció a una mayor mortalidad (HR = 2,34;IC 95%, 1,19-4,58), pero no a un mayor riesgo de recurrencia (HR = 0,52;IC 95%, 0,17-1,61). En el análisis multifactorial de riesgos competitivos no se observaron diferencias en cuanto a recurrencias (SHR = 0,82;IC 95%, 0,40-2,05). Conclusiones El riesgo de recurrencia fue bajo en los pacientes con TEV asociada a COVID-19 y a cirugía, sin diferencias entre ambos grupos.

A French single center experience on allogeneic stem cell transplant cryopreservation during SARS-CoV2 pandemic

Background Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for chemoresistant hematological malignancies. Because of transport restriction imposed by the COVID-19 pandemic, regulatory bodies and Societies recommended graft cryopreservation before recipient conditioning. However, the freezing and thawing processes, including washing steps, might impair CD34+ cell recovery and viability thereby impacting the recipient engraftment. Over one year (between March 2020 and May 2021), we aimed to analyse the results of frozen/thawed peripheral blood stem cell allografts in terms of stem cell quality and clinical outcomes. Material and Methods Transplant quality was evaluated by comparing Total Nucleated Cells (TNC), CD34+ cells and CFU-GM/kg numbers as well as TNC and CD34+ cell viabilities before and after thawing. Intrinsic biological parameters such as granulocyte, platelet and CD34+ cell concentrations were analysed as they might be responsible for a quality loss. The impact of the CD34+ cell richness of the graft on TNC and CD34 yields was evaluated by designing three groups of transplants based on their CD34 /kg value at collection: >8 × 10 6/kg, between 6 and 8 × 106/kg and <6 × 106/kg. The consequences of cryopreservation were compared in the fresh and thawed group by evaluating the main transplant outcomes. Results Over one year, 76 recipients were included in the study, 57 patients received a thawed and 19 patients a fresh allo-SCT. None received allo-SCT from a SARS-CoV2 positive donor. The freezing of 57 transplants led to the storage of 309 bags, for a mean storage time (between freezing and thawing) of 14 days. For the fresh transplant group, only 41 bags were stored for potential future donor lymphocyte infusions. Regarding the graft characteristics at collection, median number of cryopreserved TNC and CD34+ cells/kg were higher than those for fresh infusions. After thawing, median yields were 74.0%, 69.0% and 48.0% for TNC, CD34+ cells and CFU-GM respectively. The median TNC dose/kg obtained after thawing was 5.8 × 108 with a median viability of 76%. The median CD34+ cells/kg was 5 × 106 with a median viability of 87%. In the fresh transplant group, the median TNC/kg was 5.9 × 108/kg, and the median CD34+ cells/kg and CFU-GM/kg were 6 × 106/kg and 276.5 × 104/kg, respectively. Sixty-one percent of the thawed transplants were out of specifications regarding the CD34+cells/ kg requested cell dose (6 × 106/kg) and 85 % of them would have had this dose if their hematopoetic stem cell transplant (HSCT) had been infused fresh. Regarding fresh grafts, 15.8% contained less than 6 × 106 CD34+cells /kg and came from Peripheral Blood Stem Cells (PBSC) that did not reach 6 × 106 CD34+ cells /kg at collection. Regarding the factor that impaired CD34 and TNC yield after thawing, no significant impact of the granulocyte count, the platelet count or the CD34+ cells concentration / µL was observed. However, grafts containing more than 8 × 10 6/kg at collection showed a significantly lower TNC and CD34 yield. Transplant outcomes (engraftment, graft versus host disease (GvHD), infections, relapse or death) were not significantly different between the two groups.

CROSS-SECTIONAL STUDY OF MOOD AND HEALTH OF THE HEALTH WORKERS FROM THE NAVARRE-OSASUNBIDEA HEALTH SERVICE AT LEAST 6 MONTHS AFTER SUFFERING SARS-COV-2 INFECTION.

Introduction: The group of workers in the health field is essential for dealing with the pandemic. Healthcare professionals experienced an unprecedented increase in patient deaths and at the same time, had to face difficult and exceptional working conditions. A quarter of the cases diagnosed in the first months of the epidemic in Spain corresponded to workers in the health sector. Material(s) and Method(s): Non-experimental, cross-sectional study of observational research that analyzes data of variables collected through a semi-structured interview, at least 6 months after having suffered SARS-CoV-2 infection. The 17 chosen items were grouped into 3 blocks: diagnosis and evolution;psychosocial aspects;attention, follow-up and actions. LIKERT-type numerical scales were used for the items (joy, anxiety, sadness and anger). Result(s): A total of 1,490 semi-structured surveys were analyzed. By occupations, the highest percentage corresponded to nurses (32.7%), doctors (19.7%) and nursing assistants (17.2%), while the lowest percentages were those related to Administrative (11.3 %), and Wardens (4.4%), and the remaining 14.5%, grouped as TECHNICIANS. Regarding the persistence of symptoms 6 months after infection, 28.1% of those surveyed answered affirmatively. The highest percentage of workers who reported persistence of symptoms at 6 months was nursing assistants (40.8%). Discussion(s): The risk of persisting with symptoms at 6 months increases correlatively as the professional's age increases. The result obtained is in agreement with the investigations published up to now.Copyright © 2022, Accion Medica S.A.. All rights reserved.

Risk of thrombosis recurrence among patients with COVID-19- and surgery-associated venous thromboembolism Riesgo de recurrencia de trombosis entre pacientes con COVID-19 y tromboembolismo venoso asociado a cirugía

Introduction Recent surgery is a well-known major transient risk factor for venous thromboembolism (VTE) due to the low risk of VTE recurrence after anticoagulation is discontinued. On the other hand, the risk of VTE recurrence among patients with COVID-19-associated VTE is unknown. This study aimed to compare the risk of VTE recurrence between patients with COVID-19- and surgery-associated VTE. Methods A prospective observational single-center study was performed including consecutive patients diagnosed with VTE in a tertiary hospital from January 2020 to May 2022 and followed up for at least 90 days. Baseline characteristics, clinical presentation, and outcomes were assessed. The incidence of VTE recurrence, bleeding, and death was compared between both groups. Results A total of 344 patients were included in the study: 111 patients with surgery-associated VTE and 233 patients with COVID-19-associated VTE. Patients with COVID-19-associated VTE were more frequently men (65.7% vs 48.6%, p =  0.003). VTE recurrence was 3% among COVID-19 patients and 5.4% among surgical patients, with no significant differences (p =  0.364). The incidence rate of recurrent VTE was 1.25 per 1000 person-months in COVID-19 patients and 2.29 person-months in surgical patients, without significant differences (p =  0.29). In the multivariate analysis, COVID-19 was associated with higher mortality (HR 2.34;95% CI 1.19–4.58), but not with a higher risk of recurrence (HR 0.52;95% CI 0.17–1.61). No differences were found in recurrence in the multivariate competing risk analysis (SHR 0.82;95% CI 0.40–2.05). Conclusions In patients with COVID-19 and surgery-associated VTE, the risk of recurrence was low, with no differences between both groups.

Risk of thrombosis recurrence among patients with COVID-19 and surgery-associated venous thromboembolism.

INTRODUCTION: Recent surgery is a well-known major transient risk factor for venous thromboembolism (VTE) due to the low risk of VTE recurrence after anticoagulation is discontinued. On the other hand, the risk of VTE recurrence among patients with COVID-19-associated VTE is unknown. This study aimed to compare the risk of VTE recurrence between patients with COVID-19- and surgery-associated VTE. METHODS: A prospective observational single-center study was performed including consecutive patients diagnosed with VTE in a tertiary hospital from January 2020 to May 2022 and followed up for at least 90 days. Baseline characteristics, clinical presentation, and outcomes were assessed. The incidence of VTE recurrence, bleeding, and death was compared between both groups. RESULTS: A total of 344 patients were included in the study: 111 patients with surgery-associated VTE and 233 patients with COVID-19-associated VTE. Patients with COVID-19-associated VTE were more frequently men (65.7% vs 48.6%, p =  0.003). VTE recurrence was 3% among COVID-19 patients and 5.4% among surgical patients, with no significant differences (p =  0.364). The incidence rate of recurrent VTE was 1.25 per 1000 person-months in COVID-19 patients and 2.29 person-months in surgical patients, without significant differences (p =  0.29). In the multivariate analysis, COVID-19 was associated with higher mortality (HR 2.34; 95% CI 1.19-4.58), but not with a higher risk of recurrence (HR 0.52; 95% CI 0.17-1.61). No differences were found in recurrence in the multivariate competing risk analysis (SHR 0.82; 95% CI 0.40-2.05). CONCLUSIONS: In patients with COVID-19 and surgery-associated VTE, the risk of recurrence was low, with no differences between both groups.

Patients Admitted to Pediatric Intensive Care with Sars-Cov2: Results from a Nationwide Multicentre Study

BACKGROUND AND AIM: Admission to PICU due to SARS-CoV2 infection in children is unfrequent. However there are few pediatric patients who may require intensive care management. The aim of our study was to describe characteristics and evolution of those patients admitted to Spanish PICUs due to SARS-CoV2 infection. METHOD(S): A multicentre nationwide prospective registry involving all Spanish PICUs was carried out between 1st of march 2020 and 30 November 2021. RESULT(S): During the study period 299 patients where admitted to the participating units. Median age was 8.9 years (IQR 4.4 -12.2). 208 patients (69,6%) where diagnosed of Multisystem Inflamatory Syndrome associated to SARS-CoV2 (MIS-C). 225 patients (75.3%) where previously healthy. Main reason for admission was shock (which was present in 55.9% of patients). Respiratory difficulty was present only in 40.8% of patients. 50.5% of patients required vasoactive drugs, which was more frequent among those presenting with MIS-C (66.5% vs 20.9%, p<0.001). Only 17.4% of patients required mechanical ventilation, which was less frequent in patients with MIS-C (11.1% vs 34.1% p<0.001). 9 patients (3%) included in the registry died. Death was more frequent among patients with previous diseases (9.6% vs 0.9%, p<0.001) and less frequent in those admitted due to MIS-C (0.5% vs 9.3%, p<0.001). CONCLUSION(S): MIS-C was the most frequent cause of admission to PICU in Spain related to SARS-CoV2 infection. Most patients were admitted presenting shock and required vasoactive drugs, but only a few mechanical ventilation. Mortality rate was low. Prognosis was more favourable in those admitted due to MIS-C.

Assessment of the COVID-19 pandemic and its impact on a children's hospital: The point of view of patients and families

The coronavirus pandemic has affected our health, social behavior, and quality of life. In addition to the deaths and morbidity, the crisis also affects all spheres in society. The objective of this study was to assess the perception of hospital patients and families regarding the pandemic. This is a descriptive study conducted May-July 2020 in the Sant Joan de Déu children’s hospital, Barcelona, Spain. We developed a mix-method approach. It included online semi-structured interviews and photo voice. Seventeen patients’ representatives were interviewed. In their opinion, the pandemic has affected the health of patients and families at the physical and psychological areas. The pandemic also made them to adapt to the new technologies. Participants expressed the impact the pandemic had at the social level and in the sustainability of patients’ associations. Members of the Infant and Youth Councils expressed their feelings about the pandemic through pictures. It is necessary to carry out social research that helps to interpret the impact that the pandemic is having on patients, families and society. © The Author(s), 2022.

A randomized multicentre clinical trial to evaluate the efficacy of melatonin in the prophylaxis of SARS-COV-2 infection in high-risk contacts (MECOVID trial): Preliminary data

Objective: To evaluate the efficacy of melatonin as a prophylactic treatment on prevention of symptomatic SARSCoV- 2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Material and/or methods: In April 2020 we designed a two-arm parallel randomized double-blind controlled trial. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomized 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. Study visits: Screening (D1), Week 4, 8 and 12. A follow-up phone call was performed 4 weeks after the last intake of the study drug. The main outcome was the number of SARS-CoV-2 symptomatic infections (COVID-19) confirmed by polymerase chain reaction (PCR) or serologic test or according to each centre diagnosis protocol. During the study, participants should daily enter in an online application data concerning treatment administration, adverse events, food intake, exercise, sleeping hours and other data related to the effects of melatonin. Also, participants were asked to fulfil the Pittsburgh Sleep Quality Index (PSQI) at screening and at the 12 week visit. Results: A total of 344 volunteers were screened, mean age was 40.1 (10.8) years and most of them were females (80.8%). Three hundred fourteen were randomized (151 placebo;163 melatonin) and 308 received the study treatment (148 placebo;160 melatonin). We detected 13 SARS-CoV-2 symptomatic infections during the follow-up, 2.6% in the placebo arm (n = 4/151) and 5.5% in the melatonin arm (n = 9/163) (p = 0.2). A total of 124 participants had at least one adverse event. A total of 304 adverse events were detected. No severe adverse events related to treatment were reported. Conclusions: We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in high-risk contacts (hospital staff). Other safety and efficacy data, PSQI data and data obtained from the online application fulfilled by the participants will be soon analysed.

THE PROTECTION OF HEALTH & SOCIAL-HEALTH WORKERS IN THE SPANISH CRIMINAL CODE AGAINST THE COVID-19 PANDEMIC (CONSIDERATIONS ON OMISSIVE BEHAVIOR IN ARTS. 316 AND 317 SCC)

Since the beginning of the Covid-19 pandemic, one of the most affected professional groups, at different levels, are the health and social-health workers. On the one hand, this work shows the situation of vulnerability of this group of workers, especially during the first months of the pandemic, observing the high rates of contagion, illness and death, and the lack of protection as a result of insufficient personal protective equipment (PPE). On the other hand, this paper analyzes if this lack of protection can generate criminal responsibility for crimes against the safety of workers (art. 316 & 317 Spanish Criminal Code), with special focus of the normative omission in such precepts, and explaining some of the most controversial elements of these criminal offenses.

Adverse events reported after administration of BNT162B2 and mRNA-1273 COVID-19 vaccines among healthcare workers

Background and importanceSince December 2019, the world has faced a new disease known as COVID-19. On 11 March 2020, the World Health Organization officially declared the COVID-19 pandemic. Given the health emergency, vaccine development progressed rapidly, but with limited safety data under real-world conditions.Aim and objectivesTo describe and compare the incidence of adverse events with the BNT162b2 and mRNA-1273 COVID-19 vaccines, taking into account the number of doses and subjects previously positive for SARS-CoV-2 infection.Material and methodsA retrospective observational study was conducted in a tertiary hospital between March and April 2021. Data were collected through a questionnaire sent by email to hospital staff. Demographics and data regarding the occurrence of adverse events were collected, indicating which vaccine was administered. Statistical analysis was performed using SPSS software. Groups were compared using the Chi-square test and Fisher’s exact test when necessary.Results1249 respondents completed the survey (25% of all hospital staff);52% (650) received BNT162b2 vaccine and 48% (599) mRNA-1273. 14 402 adverse reactions were recorded. 6896 were local: 3939 were with mRNA-1273 and 2957 with BNT162b2 (6.6 vs 4.4 reactions per patient);and 7506 were systemic: 4460 with mRNA-1273 and 3046 with BNT162b2 (7.4 vs 4.7 per patient). The occurrence of local reactions was 95.8% after the first dose/89.1% after the second dose with mRNA-1273 versus 89.7%/82.5% with BNT162b2. For systemic reactions, this proportion was 64.3%/93.3% versu 46.8%/73.2% (p value<0.05).In terms of severity, 379 patients (63.3%) with mRNA-1273 confirmed a severe reaction versus 222 (34.2%) with BNT162b2 and 60 patients (10%) with mRNA-1273 confirmed an urgent reaction versus 33 (5.1%) with BNT162b2 (p value<0.001). For both vaccines, there was no difference in the occurrence of local or systemic reactions between patients seropositive and seronegative for SARS-CoV-2.Conclusion and relevanceThe results are consistent with the limited data available to date, confirming that although these are not particularly serious adverse effects, they do occur in a large majority of vaccinated persons and in greater numbers after administration of the mRNA-1273 vaccine. The Hospital Pharmacy Service is a key agent in pharmacovigilance within the healthcare system and must be aware of the safety profile of new drugs. This study is an essential tool to detect and prevent adverse events.References and/or acknowledgementsConflict of interestNo conflict of interest

Remote Electronic Engineering Teaching during Lockdown: Lessons Learned

The devastating effects of COVID-19 pandemic led the Spanish government to adopt exceptional emergency regulations that forced the confinement of the entire population and, therefore, the cessation of on-site teaching. This forced the migration of teaching methodologies to virtual formats in a few weeks. The lack of specific resources and experience in online teaching, and the need of a rapid response meant that the measures adopted fostered a hybrid model between online and face-to-face teaching. This paper presents the context and the approach taken in the methodological adaptation of three subjects of Electronic Engineering with different characteristics. In addition, the results of the evaluation of these measures by students, obtained through a survey, are presented. The results show that virtualisation has produced a fictitious improvement in students' grades, as the assessment evidences. The students considered very positive the use of synchronous learning as opposed to asynchronous format, as well as all the activities that promoted direct communication between the student and the lecturer. Another generalised opinion extracted from the results of the survey is that the new measures have implied an excess of work for students. The experience gained and the students' opinions can be very useful for the design of blended learning formats, which seem to be a very promising alternative in the future of University, although this change seems to be non-trivial in such experimental studies as engineering.

Recommendations for precise health information to avoid confusion and inaccuracies regarding the knowledge of mortality due to COVID-19 infection in Spain

Introduction: Accurate communication of the fatality rate associated to COVID-19 pandemic should be a priority in the fight against it;having a reliable knowledge of this information concerns social rights, and it is a key aspect of public awareness Aims: Mortality data from Spain and the European neighborhood have been assessed, with regards to the importance of providing precise information about the mortality of COVID-19. Methodology: Excess mortality and COVID-19 official data deaths have been compared from different institutions, paying special attention to the Spanish case. Likewise, the national situation has been analyzed with respect to the European neighboring countries. Results: Relevant disagreement and absence of uniform criteria, in the communication of the information regarding COVID-19 deaths are found;this hinders the proper communication to population and threatens decision-taking. Conclusions: Communication of pandemic-related deaths from the official institutions should follow the criteria from WHO, and official data should include clinical suspicious deaths in order to reduce uncertainties and misleads in subsequent diffusion of these data by the media.

Telmisartan for treatment of Covid-19 patients: An open randomized clinical trial

Background: The imbalance of the Renin Angiotensin System in favor of the angiotensin II has been described in Covid-19-patients. Angiotensin II regulates life processes, such as cell growth and division and can promote apoptosis initiating an inflammatory process with release of proinflammatory cytokines. Angiotensin receptor blockers (ARBs) block the AT1 receptor and could have a beneficial effect reducing Covid-19 inflammation. Purpose: To assess whether Telmisartan is effective in reducing C-reactive protein (CRP) plasma levels in hospitalized patients with Covid-19, and improves clinical outcomes and length of stay and morbimortality. Trial design: This is a parallel-group, randomized, two-arm, open-label, multicenter superiority trial with 1:1 allocation ratio. Methods: Inclusion criteria: patients aged more than 18 years with less than 5 days of symptoms onset and after informed consent was obtained. Exclusion criteria: Patients admitted to intensive care unit (ICU) or using mechanical ventilatory support or ongoing ARBs / angiotensin-converting enzyme inhibitors treatment at the time of randomization. Control arm received standard care alone and treatment arm Telmisartan 80 mg bid 14 days added to standard care. Primary outcome were CRP plasma levels at day 5 and 8 after randomization. Secondary outcomes included time to discharge at 15 days, admission to ICU and death at 15 and 30 days. Results: 158 patients were included in the analysis, 80 in the control and 78 in the telmisartan group. Day 5 control-group CRP levels were 6.06±6.95 mg/dL (n=66) while telmisartan group were 3.83±5.08 mg/dL (mean±SD;n=66, p<0.05). Day 8 CRP levels were 6.30±8.19 mg/dL (n=44) and 2.37±3.47 mg/dl (mean±SD;n=43, p<0.05) in the control and telmisartan groups, respectively. Kaplan-Meier analysis showed that Telmisartan-treated patients had lower median time to discharge (control= 15 days;telmisartan=9 days). Death by day 30 was reduced by 81% in the telmisartan-treated group (control 22.54%, 16/71;telmisartan 4.29%, 3/70 participants;p=0.0023). Composite ICU, mechanical ventilation or death was reduced by telmisartan treatment at days 15 and 30. No telmisartan-related adverse events were reported. Conclusions: Telmisartan, an inexpensive safe drug, in high doses, demonstrated anti-inflammatory effects and reduced morbimortality in Covid-19-hospitalized patients.

Novel Sensing Algorithm for Linear Read-out of Bimodal Waveguide Interferometric Biosensors

Biosensors employing photonics integrated circuits, and specifically those that rely on interferometric evanescent wave working principles, have outstanding performances due to the extreme sensitivity exhibited in one-step and direct assay, without the need of amplification. Within the interferometric configurations, the Bimodal Waveguide (BiMW) interferometric sensor stands out due to its demonstrated sensitivity for real-life applications and the simplicity of its design. To overcome the ambiguities that arise from the periodic nature of interferometric read-outs, a new all-optical modulation and the subsequent trigonometry-based algorithm have been proposed and applied to the BiMW biosensor. This new algorithm has been successfully employed for the selective identification and quantification of the external Spike (S) protein of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Our biosensing results from this simple, quick, and user-friendly method demonstrate high sensitivity and specificity and pave the way towards a point-of-care device for general use. Author

[Usefulness and acceptance of telephone monitoring by a virtual assistant for patients with COVID-19 following discharge]. / Utilidad y aceptación del seguimiento telefónico de un asistente virtual a pacientes COVID-19 tras el alta.

COVID-19 has placed a significant burden on the healthcare system, making it necessary to implement new tools that allow patients to be monitored remotely and guarantee quality and continuity of care. The usefulness and acceptance by patients of a virtual caregiver designed for follow-up in the month following hospital discharge for COVID-19 are evaluated. The virtual assistant, based on voice and artificial intelligence technology, made telephone calls at 48 hours, seven days, 15 days, and 30 days after discharge and asked five questions about the patient's health. If the answer to any of the questions was affirmative, it generated an alert that was transferred to a healthcare professional One hundred patients were included in the project and 85 alerts were generated in 45 of the patients, most at one month after hospital discharge. The nursing staff resolved 94% of them by telephone. Patient satisfaction with the virtual caregiver was high.

Incidence of thrombohaemorrhagic complications in the periprocedural of oral anticoagulant treatment with vitamin k antagonists

Background: During the follow-up of oral anticoagulation therapy (OAT) with vitamin K antagonists (VKA), the patient undergo invasive procedures. The decision wether to withdraw or maintain the OAT, as well as the needing or not to implement low molecular weight heparin (LMWH) as bridge therapy, will be determined by the patient's thrombotic risk (TR) and the haemorrhagic risk (HR) of the surgery. Aims: To determine the incidence of thrombohemorrhagic complications in the periprocedural of the patient with OAT, limiting the use of LMWH to patients at high TR looking for decreasing bleeding events related to surgery. Methods: Prospective, unicentric and observational study including 200 patients with OAT who had had surgery between December 2019 and February 2021, with a subsequent follow-up of 4 weeks. The periprocedural management of the OAT was carried out in the anticoagulation consultation according to the hospital protocol approved in the Thrombosis Committee, which classifies patients according to TR (High TR: Prosthetic heart valves, atrial fibrillation (AF) with CHA2DS2- VASc score 7-9, Severe rheumatic mitral valvulopathy, Venous Thromboembolism less tan 3 months ago and Severe thrombophilia, define as Leyden's factor V in homozygosis, 20210 prothrombin mutation, protein C, S or antithrombin III deficiency, múltiples deficiencys or Antiphospholipid Syndrome), and surgeries in three groups according to HR. Thus, the VKA is suspended 3 days before the intervention and resumed 24 hours after. The use of LMWH as bridge therapy (BT) is reserved for patients with high TR or suspected active cancer. It starts the moment OAT is suspended and it is reintroduced along with it 24 hours after surgery for 3 days (if there are no bleeding complications). The dose of LMWH is therapeutic (as patients requiring BT are high TR). Given the coagulopathy inherent to COVID infection, no positive COVID patients were included. Results: The median age of the population is 73 (range 33-93). The main reason for anticoagulation is AF (64.5%). Most patients are low TR and HR on the CHADs-VASc and HAS-BLED scales (76% and 64% respectively). 26.5% of the patients had personal history (PH) of thrombosis and 5.5% had PH of Hemorrhagic Diathesis. Table shows the interventions performed and clinical events during the follow-up period.0 post-surgical haemorrhagic events (5%) are described. Three of them (hemoperitoneum after cholecystectomy, hemoperitoneum after laparoscopic tubular gastrectomy, and haematoma of the anterior rectus abdominis muscle with secondary anemization after ventral hernia repair) required hospitalisation for management, all of which were solved with conservative treatment. The other 7 were mild events that were handled outpatiently. In addition, intra-procedure bleeding during bronchoscopy is described in patient with BT, that was controlled on the spot with amchafibrin and adrenaline. No thrombotic events were recorded. Generally, OAT was re-induced the day after surgery in patients undergoing minimal and low HR interventions, being the percentage somewhat lower in patients undergoing high HR interventions, both in high or low TR patients. Summary/Conclusion: Standardization by means of a periprocedural management protocol of the OAT that adjusts BT with LMWH according to the risk factors of each patient, results in a reduction of the incidence of haemorrhagic complications without secondary increase of thromboembolic events. This study demonstrates the importance of centralizing unified periprocedural management using an established protocol.

Mesenchymal Stromal Cell (MSC) Compassionate Use in France in Treatment of Steroid-Refractory Graft-Versus-Host-Disease (GVHD) after Approval By the Expert Committee of Société Française De Greffe De Moelle Et Thérapie Cellulaire (SFGM-TC)

Hematopoietic stem cell transplantation is a well-established efficient therapy for hematological diseases, but Graft-Versus-Host Disease (GVHD) is a major and frequent complication encumbering its outcome despite the administration of calcineurin inhibitor based GvHD-prophylaxis. Corticosteroids represent the worldwide first line treatment, however in case of steroid refractory acute GVHD there is no consensus about a subsequent treatment although Ruxolitinib is subject to a phase III trial. Multiple molecules have been tried, most of them immunosuppressive, increasing the risk of deadly infections and transplantation-related mortality (TRM). Recent studies reported that mesenchymal stromal cells (MSC) infusion which have immune modulatory abilities might be effective and harmless in steroid or treatment-refractory GVHD (R-GVHD). In France, MSCs are considered as an Advanced Therapy Medicinal Product. For 4 years, its administration as a compassionate use is subject to approval by an expert committee from SFGM-TC before its validation by the French regulatory agency (ANSM). We retrospectively analyzed the demands for MSC use in France since 2011 for patients suffering from R-GVHD. We evaluated the response at day 28 (range 23-28) and at the last follow-up and its safety. Eleven demands were validated by both expert committee and ANSM, 8 patients (pts) received ex-vivo expanded MSCs, 1 pt refused the therapy, 1 infusion was postponed due to COVID-19 related sanitary crisis and the last 1 didn't receive MSCs due to relapse. Among pts who received MSCs, median age was 6 years (2-69), sex ratio was 0,6. All pts underwent their first HSCT for either malignant disease (62,5%) or non-malignant disease (37,5%). Four pts were transplanted from sibling donor, 2 pts from mismatched unrelated donors and 2 pts from haplo-identical donors. Stem cells source was bone marrow for 4 pts, peripheral blood stem cells for 3 and cord blood for 1. Donors median age was 28,8 years (0-49,5), 1 male had a female donor. Six pts got a myeloablative conditioning regimen (TBI-based for 2). All pts received a ciclosporin-based (CSA) GVHD prophylaxis (CSA alone, n=1;CSA + Mycophenolate Mofetil (MMF) or Methotrexate, n=7). Five pts had ATG. Six pts were suffering from acute GVHD, while 2 from extensive chronic GVHD (cGVHD). All 6 pts with acute GVHD presented a grade III or IV, refractory to corticosteroids and at least 2 other lines of GVHD therapy. All but one had a multipolar GVHD with at least 2 affected organs. Five pts were still taking corticosteroids, and six were taking additional immunosuppressive molecules (Tacrolimus, Ruxolitinib, Etanercetp, Inolimomab, MMF) at time of MSC infusion. Five pts received German commercialized MSCs (Obnitixâ, MEDAC, Germany;see Bader et al, 2018), 2 get mother's derived MSCs (not the initial donor), and 1 from a third-party donor. A median of 4 infusions were administered (1-4), once a week for 4 weeks. Mean single dose of MSCs was 1.23.10e6/kg (range: 0,86 - 3). No toxicity was reported except for 1 pt who experienced anaphylactic reaction within minutes, leading to the interruption of infusion (mother's derived MSCs prepared with fetal bovine serum where all other preparations were performed with platelet lysate). The median time from GVHD onset to first MSC infusion was 135 days (63-457). Overall response rate was 86% (6/7) at the first and at the last evaluation with 1 complete response (CR) and 5 partial responses (reduction of at least one grade of at least one affected organ). One pt did not respond and the last 1 was not evaluable due to anaphylactic reaction. Both were suffering from cGVHD. Among the seven pts who received complete MSC infusions, median follow-up was 1,5 months (1,1-18,5) due to premature TRM, overall survival (OS) at six months was 33,3%. Five pts died, all of them from a transplantation-related cause: GVHD n=2, severe infections n=3. Literature reported better outcomes lately, Bader and al, 2019 reported a 64% OS at 6 months and 51% of CR at last follow up. Those disparities might be explained by a delayed treatment after GVHD onset (135 days versus 28 days) and a median of 3 (2-10) therapies after receiving corticosteroids before MSC infusion due to difficulty to obtain MSCs in France. Besides, we included patient suffering from R-cGVHD. Regarding those results, MSC efficacy and safety should be confirmed in a proper clinical trial. [Formula presented] Disclosures: Rubio: Neovii: Research Funding;Novartis: Honoraria;MSD: Honoraria;Gilead: Honoraria;Medac: Consultancy. Dalle: Jazz Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;bluebird bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees;Gilead: Honoraria;AbbVie Pharmacyclics: Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sanofi-Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Bellicum: Consultancy, Honoraria;Medac: Consultancy, Honoraria;Orchard: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.