Infectious complications following CAR-t cell therapy for B cell non-Hodgkin lymphoma: a single-center experience and review of the literature.

Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed (R/R) B-cell non-Hodgkin lymphoma (NHL). Several risk factors including CAR-T cell-related toxicities and their treatments often lead to infectious complications (ICs); however, the pattern and timeline is not well established. We evaluated ICs in 48 patients with R/R B-cell NHL following CAR-T cell therapy at our institution. Overall, 15 patients experienced 22 infection events. Eight infections (4 bacterial, 3 viral and 1 fungal) occurred within the first 30 days and 14 infections (7 bacterial, 6 viral, 1 fungal) between days 31 to 180 following CAR-T infusion. Most infections were mild-to-moderate and fifteen infections involved the respiratory tract. Two patients developed mild-to-moderate COVID-19 infection and one patient a cytomegalovirus reactivation after CAR-T infusion. Two patients developed IFIs: one case each of fatal disseminated candidiasis and invasive pulmonary aspergillosis at day 16 and 77, respectively. Patients with more than 4 prior antitumor regimens and patient's ≥ 65 years had a higher infection rate. Infections in patients with relapsed/refractory B-cell NHL are common after CAR-T despite the use of infection prophylaxis. Age ≥ 65 years and having > 4 prior antitumor treatments were identified as risk factors for infection. Fungal infections carried significant impact in morbidity and mortality, suggesting a role for increase fungal surveillance and/or anti-mold prophylaxis following high-dose steroids and tocilizumab. Four of ten patients developed an antibody response following two doses of SARS-CoV-2 mRNA vaccine.

Validation of the Attitude Scale on Prospective Teachers' Perceptions of the Consequences on Their Psychological State: Well-Being and Cognition.

The aim of this study was to analyse the validated psychometric characteristics of the "Scale of Attitudes towards New Post-Pandemic Scenarios" (SANPS) tool using a short version on Perceptions of Future Teachers towards the New Post-Pandemic Educational Scenarios; describe the attitudes of future teachers towards motivation, collaboration, and emerging active pedagogies; and determine the internal consistency and reliability of the tool. The design structure of the instrument consists of the following three latent factors, which were obtained through an exploratory factor analysis (EFA): empowerment/motivation, autonomy/situated learning and emerging digital pedagogies. The questionnaire was administered to a sample of 966 participants. In the confirmatory factor analysis (CFA), a previous hypothesis was established regarding the relationship of the factors and their number and nature, specifying the number of factors and the way in which the variables are related to each other. The 66.53% of total variance was explained. The reliability, calculated with Cronbach's alpha, reached a global value of over 0.90 (α = 0.94). This valid and reliable questionnaire, which incorporates a dimension that measures the transfer of learning in hybrid and multimodal models of digital ecosystems in Higher Education, can be applied in the evaluation of online education processes.

Models of Future Teachers' Adaptation to New Post-Pandemic Digital Educational Scenarios

The aim of this study was to determine the post-pandemic learning adaptation scenarios from the perspective of university students from the Faculty of Education Science of the University of Seville (Spain) as a function of the competencies identified in the context of digital transformation. This was a non-experimental, descriptive study that used a short version of the Scale of Attitudes on the Perceptions of Future Teachers toward the New Post-pandemic Educational Scenarios (SANPES). The sample consisted of 972 students of the University of Seville (Spain) (72% women, 28% men), registered in the academic year 2021–2022. A cluster analysis was performed, using a hierarchical procedure (dendrogram), followed by a non-hierarchical procedure (k-means algorithm). The results show significant differences in the responses of the university students. Conclusions: progressive models or scenarios of adaptation to post-pandemic learning based on some student competencies, such as motivation, collaboration, self-learning and digital methodology: (a) initial adaptation model, (b) moderate adaptation model, and (c) advanced adaptation model.

Polyserositis as a Post-Covid-19 Complication.

INTRODUCTION: Polyserositis is described as inflammation with effusion of more than one serous membrane. There is very little published literature linking it to COVID-19 as a late complication. OBJECTIVE: Present and describe a case of post-COVID-19 polyserositis. METHODS: Data were collected from the medical record of a female patient admitted for fainting spells and marked weakness. The patient underwent a clinical evaluation, additional hematology, imaging and histopathology tests, and a surgical procedure. The new index, called the abdominal adipose deposit index, was obtained by multiplying the subcutaneous fat thickness by visceral fat thickness, both measured by ultrasound. A cutoff point was established that facilitated discernment of an unhealthy phenotype: normal weight but metabolically obese, a cardiometabolic risk factor. RESULTS: We present the case of a 57-year-old female patient admitted to hospital for fainting spells and marked weakness, four months after COVID-19 infection. She also had a history of obesity, asthma, type 2 diabetes mellitus and a cholecystectomy in December 1992 for gallstones. Clinical assessment revealed pericardial effusion and bilateral pleural effusion, in addition to a tumor-like lesion outside the pericardium, proximal to the right ventricular wall. A surgical procedure and findings from additional tests led to diagnoses of thymic remnants and polyserositis. CONCLUSIONS: This is a case of polyserositis in a post-COVID-19 patient. After other causes of polyserositis were ruled out, and since there is a likely physiological and pathogenic mechanism operating between the two diseases, the polyserositis was determined to be a late complication of COVID-19. To date, it is the second case reported in the world and the first reported in Cuba.

Genitourinary tract symptoms in patients admitted with COVID-19: Exploring changes in frequency by determinants and pandemic waves.

Background: Urothelial cells exhibit increased expression of angiotensin-converting enzyme-2 receptor, which is the binding site of severe acute respiratory syndrome coronavirus 2 to cells. The frequency and distribution of genitourinary tract symptoms in patients diagnosed with coronavirus disease 2019 (COVID-19) is unknown. Objective: We explored trends in genitourinary tract symptoms by gender and each of six pandemic waves in patients admitted for COVID-19, and related them with severity, death and length of hospitalization. Design Setting and Participants: A retrospective study took place in our institution of COVID-19 admitted patients. Only patients with RT-PCR or antigen test confirmed SARS-CoV-2 infection were included. Demographic, clinical, and genitourinary symptoms were explored. Outcome Measurements and Statistical Analysis: COVID-19 patients with genitourinary tract symptoms were compared with those without. Statistical comparisons were conducted by parametric and nonparametric tests for quantitative variables, and χ 2 test for qualitative variables. Results and limitations: Out of a total of 4,661 COVID-19 patients, genitourinary symptoms were found in 21,1%. These symptoms were more frequent in patients admitted for longer than 30 days, except for urinary incontinence (UI) and erectile dysfunction (ED). Acute kidney injury (AKI) and urinary tract infections (UTI) had a higher presence in the 5th (16.7%; 12.8% respectively) and 3rd wave (13.3%; 12.6% respectively). Genitourinary symptoms were higher for those patients admitted in critical care units. Frequency of AKI, UI, UTI and acute urinary retention (AUR) were higher for patients who were finally deceased (26.2%; 3.5%; 13.6% and 3.6% respectively). Conclusions: A high frequency of genitourinary symptoms in patients admitted for COVID-19 was observed, whose frequency and distribution varied according to pandemic waves. Specific genitourinary conditions were associated with worse outcomes and poorer prognosis.

Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial.

BACKGROUND: The COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear. OBJECTIVE: To evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial). DESIGN: ACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov: NCT04280705 [ACTT-1], NCT04401579 [ACTT-2], NCT04492475 [ACTT-3], and NCT04640168 [ACTT-4]). SETTING: 94 hospitals in 10 countries (86% U.S. participants). PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: SOC. MEASUREMENTS: 28-day mortality and recovery. RESULTS: Although outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages. LIMITATION: Unmeasured confounding. CONCLUSION: Changes in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Implementation of machine learning in a care pathway for advanced epithelial ovarian cancer: a National Cancer Institute experience

Introduction/BackgroundNowadays, the knowledge of quality indicators may enable physicians to adapt the patients’ care to current standards and recommendations. Thus, the implementation of machine learning in a care pathway can be observed as an asset. The objective of this work was to describe the development of a care pathway for advanced epithelial ovarian cancer (AEOC) using artificial intelligence, in a National Comprehensive Cancer Institute.MethodologyA multidisciplinary team defined the key steps of the AEOC pathway. Valuable indicators were defined based upon national and international guidelines. The software was educated to extract items of interest from the patient’s electronic medical record. Automatic alerts are controlled by the medical referents. Data are automatically updated daily.ResultsGradually, 17 AEOC keys steps and 21 indicators were selected. From January 2018 to April 2022, 403 patients were identified in the Turquoise pathway. The median delays were: from first call to first medical appointment, 6 days;from first appointment to laparoscopic diagnostic procedure, 12 days;from first appointment to start of primary chemotherapy if indicated: 33 days. Our center is a European Society of Gynaecological Oncology (ESGO) accredited center for ovarian cancer: the ESGO indicators for AEOC were easily available, and confirmed the intermediate center status with 72 to 117 cytoreductive surgeries per year. Adverse events were prospectively recorded, with a 8% rate of surgical complications after cytoreductive surgery. Twelve to 18% of patients were included in clinical trials. The SARS-CoV-2 pandemic impact was clearly identified with an increased number of neoadjuvant chemotherapy.ConclusionThe use of artificial intelligence has enabled the construction of a critical care pathway with real time feedback that’s helps to target the best quality of medical and surgical care. In the future, appointments will be streamlined to enhance the patients’ treatment course.

Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.

BACKGROUND: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS: Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION: In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING: National Institute of Allergy and Infectious Diseases.

The Flipped Classroom and the Development of Competences: A Teaching Innovation Experience in Higher Education

Because of the changes in society, the educational scope must implement teaching–learning methodologies that help students to develop the competences that will be necessary in their academic–professional journey. This study presents a teaching innovation experience that is based on the flipped classroom methodology, which was carried out with 136 students (academic year: 2019–2020) in the subject of “Theory and History of Physical Education, Physical Activity and Sport” of the degree of Physical Activity and Sport Sciences of the University of Seville. The methodology of the study combines qualitative and quantitative approaches (mixed methods) through a pre-experimental design. The results show that there were significant differences in the acquisition of knowledge after the application of the methodology, which had a significant impact on the students’ competence levels. Moreover, the students presented high levels of satisfaction in different areas. This allows for the conclusion that it is important for this methodology to continue in later courses, given its contribution to the competences that are related to the formal aspects and that are linked to research and organisation. Recommendations for practice are presented at the end of this article.

The cognitive and psychiatric subacute impairment in severe Covid-19.

Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases.

Analysis of the factors predicting clinical response to tocilizumab therapy in patients with severe COVID-19.

BACKGROUND: Controversy remains about the efficacy of tocilizumab (TCZ) for the treatment of severe COVID-19. We aimed to analyze the profile of TCZ-respondent patients. METHODS: We retrospectively analyzed a cohort of patients with severe COVID-19 who received off-label TCZ after recommendation by a local committee and were admitted to the University Hospital "12 de Octubre" until May 2020. The primary end point was a significant clinical improvement (SCI) on day 14 after administration of TCZ. Factors independently related to SCI were analyzed by multivariate logistic regression models. RESULTS: Of 428 (63.3%) patients treated with TCZ, 271 (63.3%) experienced SCI. After adjustment for factors related to unfavorable outcomes, TCZ administration within the first 48 hours from admission (odds ratio [OR]: 1.98, 95% confidence Interval [95% CI]: 1.1-3.55; P = 0.02) and ALT levels >100 UI/L at day 0 (OR: 3.28; 95% CI: 1.3-8.1; P = 0.01) were independently related to SCI. The rate of SCI significantly decreased according to the time of TCZ administration: 70.2% in the first 48 hours from admission, 58.5% on days 3-7, and 45.1% after day 7 (P = 0.03 and P = 0.001, respectively). CONCLUSION: TCZ improves the prognosis of patients with COVID-19 the most if treatment starts within the first 48 hours after admission.

Autonomy, Motivation, and Digital Pedagogy Are Key Factors in the Perceptions of Spanish Higher-Education Students toward Online Learning during the COVID-19 Pandemic.

This paper proposes a development model of the adaptation capacity of students to digital transformation in university teaching through three constructs: motivations, digital pedagogy, and student autonomy. For this study, an ad hoc scale was created to record the adaptation capacity of students to digital transformation. The sample was 483 students from the University of Seville (Spain), to whom an online survey was administered during the development of online teaching in the period of November 2020 using the Google Forms platform. The findings of this study showed that university student motivation acquired a greater threshold than autonomy, whose threshold in turn, was greater than that of digital pedagogy in the ability to adapt to online teaching and that the capacity of adaptation to the online modality is explained by the perception that university students have of the usefulness, products, and learning outcomes, among others. In conclusion, the lack of adequate and enabled study spaces is key to developing the online model. We consider all these aspects as prospective research objectives.

Perceptions of University Students towards Digital Transformation during the Pandemic

The aim of this study is to determine the perceptions of university students toward teaching–learning processes during the COVID-19 pandemic. This research gathers inquiries made worldwide on the perceptions of students in higher education during a state of alarm. The proposed objectives were (a) to analyse the perception of students toward teaching–learning processes in university;(b) to determine the assessment given by students about the changes that took place in university teaching as a result of COVID-19;and (c) to explore resources (hardware and software), professional collaboration, digital pedagogy and student empowerment (motivation) regarding digital education and recent changes in university teaching due to the pandemic. This study used a non-experimental, descriptive design based on opinion polls or surveys. The results show a positive correlation between digital pedagogy, student motivation and digital environments. As a conclusion, we encourage the scientific community to continue delving into the motivation, collaboration and reflective exchange of experiences, self-learning and promotion of initiatives that foster the development of competencies in future teachers. It is also important to continue the research on integrated designs in training processes in university, tutoring and continuous evaluation, as they are key for digital transformation in universities.

Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. METHODS: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 µg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475. FINDINGS: Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. INTERPRETATION: Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. FUNDING: The National Institute of Allergy and Infectious Diseases (USA).

Mortality and risk factors associated with pulmonary embolism in coronavirus disease 2019 patients: a systematic review and meta-analysis.

To determine, in patients with coronavirus disease 2019 (COVID-19) infection, the associations of pulmonary embolism (PE) with mortality and risk factors for PE as well as the therapeutic benefit of anticoagulant prophylaxis. Embase, PubMed, Cochrane controlled trials register, and Web of Science databases were searched from inception to October 10, 2020. We included all published trials on PE in patients diagnosed with COVID-19 with eligibility of the trials assessed following the PRISMA guidelines. Sixteen clinical trials with 5826 patients were eligible. There were significant associations of PE with the male gender [odd ratio (OR) = 1.59, 95% CI 1.28-1.97], mechanical ventilation (OR = 3.71, 95% CI 2.57-5.36), intensive care unit admission (OR = 2.99, 95% CI 2.11-4.23), circulating D-dimer [mean difference (MD) = 5.04 µg/mL, 95% CI 3.67-6.42) and CRP (MD = 1.97 mg/dL, 95% CI 0.58- 3.35) concentrations without significant correlation between PE and mortality (OR = 1.31, 95% CI 0.82-2.08) as well as other parameters or comorbidities. After omitting one trial with strict patient selection criteria for anticoagulant prophylaxis, significant prophylactic benefit was noted (OR = 0.31, 95% CI 0.1-0.91). Our findings identified the risk factors associated with PE in COVID-19 patients and supported the therapeutic benefit of anticoagulant prophylaxis against PE in this patient population.

Tocilizumab for the treatment of adult patients with severe COVID-19 pneumonia: A single-center cohort study.

Coronavirus disease 2019 (COVID-19) can lead to a massive cytokine release. The use of the anti-interleukin-6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID-19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6-point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6-point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon-ß (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06-0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06-0.99; P = .048) were negatively associated with clinical improvement by day 7. All-cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C-reactive protein levels dropped by day 2. There were no TCZ-attributable adverse events. In this observational single-center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID-19 pneumonia.

The Pediatric Intensive Care Unit as a Critical Care Setting for Adults during the COVID-19 Pandemic: A Service Evaluation.

One strategy to expand critical care capacity during the coronavirus disease 2019 (COVID-19) pandemic within the United Kingdom has been to repurpose other clinical departments, including the pediatric intensive care unit (PICU) and pediatric multidisciplinary team, to accommodate critically unwell adult patients. While multiple PICUs have treated adult patients with COVID-19, there is an absence of data on the characteristics of patients transferred to pediatric care and their resulting outcomes in comparison to standard adult intensive care unit (AICU) provision. Data were collected for all adult COVID-19 intensive care admissions between March and May 2020, in three ICUs within a single center: PICU, AICU, and theater recovery ICU (RICU). Patient characteristics, severity of illness, and outcomes were described according to the ICU where most of their bed-days occurred. Outcomes included duration of organ support and ICU admission, and mortality at 30 days. Mortality was compared between patients in PICU and the other adult ICUs, using a logistic regression model, adjusting for known confounding variables. Eighty-eight patients were included: 15 (17.0%) in PICU, 57 (64.7%) in AICU, and 16 (18.1%) in RICU. Patients' characteristics and illness severity on admission were comparable across locations, with similar organ support provided. Ten (66.7%) patients survived to hospital discharge from PICU, compared with 27 (47.4%) and nine (56.3%) patients from AICU and RICU, respectively, with no significant difference in 30-day mortality (OR 0.46, 95% CI 0.12-1.85; p = 0.276). Our analysis illustrates the feasibility of evaluating outcomes of patients who have been cared for in additional, emergency ICU beds, whilst demonstrating comparable outcomes for adults cared for in pediatric and adult units.

Autoimmune Diseases and COVID-19 as Risk Factors for Poor Outcomes: Data on 13,940 Hospitalized Patients from the Spanish Nationwide SEMI-COVID-19 Registry.

(1) Objectives: To describe the clinical characteristics and clinical course of hospitalized patients with COVID-19 and autoimmune diseases (ADs) compared to the general population. (2) Methods: We used information available in the nationwide Spanish SEMI-COVID-19 Registry, which retrospectively compiles data from the first admission of adult patients with COVID-19. We selected all patients with ADs included in the registry and compared them to the remaining patients. The primary outcome was all-cause mortality during admission, readmission, and subsequent admissions, and secondary outcomes were a composite outcome including the need for intensive care unit (ICU) admission, invasive and non-invasive mechanical ventilation (MV), or death, as well as in-hospital complications. (3) Results: A total of 13,940 patients diagnosed with COVID-19 were included, of which 362 (2.6%) had an AD. Patients with ADs were older, more likely to be female, and had greater comorbidity. On the multivariate logistic regression analysis, which involved the inverse propensity score weighting method, AD as a whole was not associated with an increased risk of any of the outcome variables. Habitual treatment with corticosteroids (CSs), age, Barthel Index score, and comorbidity were associated with poor outcomes. Biological disease-modifying anti-rheumatic drugs (bDMARDs) were associated with a decrease in mortality in patients with AD. (4) Conclusions: The analysis of the SEMI-COVID-19 Registry shows that ADs do not lead to a different prognosis, measured by mortality, complications, or the composite outcome. Considered individually, it seems that some diseases entail a different prognosis than that of the general population. Immunosuppressive/immunoregulatory treatments (IST) prior to admission had variable effects.