Search

Background: Pressure Injuries (PIs) are major worldwide public health threats within the different health-care settings., Objective: To describe and compare epidemiological and clinical features of PIs in COVID-19 patients and patients admitted for other causes in Internal Medicine Units during the first wave of COVID-19 pandemic., Design: A descriptive longitudinal retrospective study., Setting: This study was conducted in Internal Medicine Units in Salamanca University Hospital Complex, a tertiary hospital in the Salamanca province, Spain., Participants: All inpatients ≥18-year-old admitted from March 1, 2020 to June 1, 2020 for more than 24 hours in the Internal Medicine Units with one or more episodes of PIs., Results: A total of 101 inpatients and 171 episodes were studied. The prevalence of PI episodes was 6% and the cumulative incidence was 2.9% during the first-wave of COVID-19. Risk of acute wounds was four times higher in the COVID-19 patient group (p<0.001). Most common locations were sacrum and heels. Among hospital acquired pressure injuries a significant association was observed between arterial hypertension and diabetes mellitus in patients with COVID-19 diagnosis., Conclusion: During the first wave of COVID-19, COVID-19 patients tend to present a higher number of acute wounds, mainly of hospital origin, compared to the profile of the non-COVID group. Diabetes mellitus and arterial hypertension were identified as main associated comorbidities in patients with COVID-19 diagnosis., Competing Interests: The authors have declared that no competing interests exist.

The study of the interaction between the SARS-CoV-2 spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor is key to understanding binding affinity and stability. In the present report, we sought to investigate the differences between two already sequenced genome variants (Spanish and British) of SARS-CoV-2. Methods: In silico model evaluating the homology, identity and similarity in the genome sequence and the structure and alignment of the predictive spike by computational docking methods. Results: The identity results between the Spanish and British variants of the Spike protein were 28.67%. This close correspondence in the results between the Spanish and British SARS-CoV-2 variants shows that they are very similar (99.99%). The alignment obtained results in four deletions. There were 23 nucleotide substitutions also predicted which could affect the functionality of the proteins produced from this sequence. The interaction between the binding receptor domain from the spike protein and the ACE2 receptor produces some of the mutations found and, therefore, the energy of this ligand varies. However, the estimated antigenicity of the British variant is higher than its Spanish counterpart. Conclusions: Our results indicate that minimal mutations could interfere in the infectivity of the virus due to changes in the fitness between host cell recognition and interaction proteins. In particular, the N501Y substitution, situated in the RBD of the spike of the British variant, might be the reason for its extraordinary infective potential.

Background: Clinical outcomes among COVID-19 patients vary greatly with age and underlying comorbidities. We aimed to determine the demographic and clinical factors, particularly baseline chronic conditions, associated with an increased risk of severity in COVID-19 patients from a population-based perspective and using data from electronic health records (EHR)., Methods: Retrospective, observational study in an open cohort analyzing all 68,913 individuals (mean age 44.4 years, 53.2% women) with SARS-CoV-2 infection between 15 June and 19 December 2020 using exhaustive electronic health registries. Patients were followed for 30 days from inclusion or until the date of death within that period. We performed multivariate logistic regression to analyze the association between each chronic disease and severe infection, based on hospitalization and all-cause mortality., Results: 5885 (8.5%) individuals showed severe infection and old age was the most influencing factor. Congestive heart failure (odds ratio -OR- men: 1.28, OR women: 1.39), diabetes (1.37, 1.24), chronic renal failure (1.31, 1.22) and obesity (1.21, 1.26) increased the likelihood of severe infection in both sexes. Chronic skin ulcers (1.32), acute cerebrovascular disease (1.34), chronic obstructive pulmonary disease (1.21), urinary incontinence (1.17) and neoplasms (1.26) in men, and infertility (1.87), obstructive sleep apnea (1.43), hepatic steatosis (1.43), rheumatoid arthritis (1.39) and menstrual disorders (1.18) in women were also associated with more severe outcomes., Conclusions: Age and specific cardiovascular and metabolic diseases increased the risk of severe SARS-CoV-2 infections in men and women, whereas the effects of certain comorbidities are sex specific. Future studies in different settings are encouraged to analyze which profiles of chronic patients are at higher risk of poor prognosis and should therefore be the targets of prevention and shielding strategies., Competing Interests: The authors have declared that no competing interests exist.

Anecdotal evidence suggests that community infection control measures during the COVID-19 outbreak have modified the number and natural history of acute surgical inflammatory processes (ASIP-appendicitis, cholecystitis, diverticulitis and perianal abscesses) admissions. This study aims to evaluate the impact of the COVID-19 pandemic on the presentation and treatment ASIP and quantify the effect of COVID-19 infection on the outcomes of ASIP patients. This was a multicentre, comparative study, whereby ASIP cases from 2019, 2020 and 2021 (March 14th to May 2nd) were analyzed. Data regarding patient and disease characteristics as well as outcomes, were collected from sixteen centres in Madrid, and one in Seville (Spain). The number of patients treated for ASIP in 2019 was 822 compared to 521 in 2020 and 835 in 2021. This 1/3rd reduction occurs mainly in patients with mild cases, while the number of severe cases was similar. Surgical standards suffered a step back during the first wave: Lower laparoscopic approach and longer length of stay. We also found a more conservative approach to the patients this year, non-justified by clinical circumstances. Luckily these standards improved again in 2021. The positive COVID-19 status itself did not have a direct impact on mortality. Strikingly, none of the 33 surgically treated COVID positive patients during both years died postoperatively. This is an interesting finding which, if confirmed through future research with a larger sample size of COVID-19 positive patients, can expedite the recovery phase of acute surgical services., (© 2021. The Author(s).)

Background: Whether immunosuppressed (IS) patients have a worse prognosis of COVID-19 compared to non-IS patients is not known. The aim of this study was to evaluate the clinical characteristics and outcome of IS patients hospitalized with COVID-19 compared to non-IS patients., Methods: We designed a retrospective cohort study. We included all patients hospitalized with laboratory-confirmed COVID-19 from the SEMI-COVID-19 Registry, a large multicentre national cohort in Spain, from March 27th until June 19th, 2020. We used multivariable logistic regression to assess the adjusted odds ratios (aOR) of in-hospital death among IS compared to non-IS patients., Results: Among 13 206 included patients, 2 111 (16.0%) were IS. A total of 166 (1.3%) patients had solid organ (SO) transplant, 1081 (8.2%) had SO neoplasia, 332 (2.5%) had hematologic neoplasia, and 570 (4.3%), 183 (1.4%) and 394 (3.0%) were receiving systemic steroids, biological treatments, and immunosuppressors, respectively. Compared to non-IS patients, the aOR (95% CI) for in-hospital death was 1.60 (1.43-1.79) for all IS patients, 1.39 (1.18-1.63) for patients with SO cancer, 2.31 (1.76-3.03) for patients with haematological cancer and 3.12 (2.23-4.36) for patients with SO transplant. The aOR (95% CI) for death for patients who were receiving systemic steroids, biological treatments and immunosuppressors compared to non-IS patients were 2.16 (1.80-2.61), 1.97 (1.33-2.91) and 2.06 (1.64-2.60), respectively. IS patients had a higher odds than non-IS patients of in-hospital acute respiratory distress syndrome, heart failure, myocarditis, thromboembolic disease and multiorgan failure., Conclusions: IS patients hospitalized with COVID-19 have a higher odds of in-hospital complications and death compared to non-IS patients., Competing Interests: The authors have declared that no competing interests exist.

The natural history of COVID-19 and predictors of mortality in older adults need to be investigated to inform clinical operations and healthcare policy planning. A retrospective study took place in 80 long-term nursing homes in Catalonia, Spain collecting data from March 1st to May 31st, 2020. Demographic and clinical data from 2,092 RT-PCR confirmed cases of SARS-CoV-2 infection were registered, including structural characteristics of the facilities. Descriptive statistics to describe the demographic, clinical, and molecular characteristics of our sample were prepared, both overall and by their symptomatology was performed and an analysis of statistically significant bivariate differences and constructions of a logistic regression model were carried out to assess the relationship between variables. The incidence of the infection was 28%. 71% of the residents showed symptoms. Five major symptoms included: fever, dyspnea, dry cough, asthenia and diarrhea. Fever and dyspnea were by far the most frequent (50% and 28%, respectively). The presentation was predominantly acute and symptomatology persisted from days to weeks (mean 9.1 days, SD = 10,9). 16% of residents had confirmed pneumonia and 22% required hospitalization. The accumulated mortality rate was 21.75% (86% concentrated during the first 28 days at onset). A multivariate logistic regression analysis showed a positive predictive value for mortality for some variables such as age, pneumonia, fever, dyspnea, stupor refusal to oral intake and dementia (p<0.01 for all variables). Results suggest that density in the nursing homes did not account for differences in the incidence of the infection within the facilities. This study provides insights into the natural history of the disease in older adults with high dependency living in long-term nursing homes during the first pandemic wave of March-May 2020 in the region of Catalonia, and suggests that some comorbidities and symptoms have a strong predictive value for mortality., Competing Interests: The authors have declared that no competing interests exist.

Primary aim was to assess prevalence and severity of potential and real drug-drug interactions (DDIs) among therapies for COVID-19 and concomitant medications in hospitalized patients with confirmed SARS-CoV-2 infection. The secondary aim was to analyze factors associated with rDDIs. An observational single center cohort study conducted at a tertiary hospital in Spain from March 1st to April 30th. rDDIs refer to interaction with concomitant drugs prescribed during hospital stay whereas potential DDIs (pDDIs) refer to those with domiciliary medication. DDIs checked with The University of Liverpool resource. Concomitant medications were categorized according to the Anatomical Therapeutic Chemical classification system. Binomial logistic regression was carried out to identify factors associated with rDDIs. A total of 174 patients were analyzed. DDIs were detected in 152 patients (87.4%) with a total of 417 rDDIs between COVID19-related drugs and involved hospital concomitant medication (60 different drugs) while pDDIs were detected in 105 patients (72.9%) with a total of 553 pDDIs. From all 417 rDDIs, 43.2% (n = 180) were associated with lopinavir/ritonavir and 52.9% (n = 221) with hydroxychloroquine, both of them the most prescribed (106 and 165 patients, respectively). The main mechanism of interaction observed was QTc prolongation. Clinically relevant rDDIs were identified among 81.1% (n = 338) ('potential interactions') and 14.6% (n = 61) (contraindicated) of the patients. Charlson index (OR 1.34, 95% IC 1.02-1.76) and number of drugs prescribed during admission (OR 1.42, 95% IC 1.12-1.81) were independently associated with rDDIs. Prevalence of patients with real and pDDIs was high, especially those clinically relevant. Both comorbidities and polypharmacy were found as risk factors independently associated with DDIs development.

Background: COVID-19 may predispose to both venous and arterial thromboembolism event (TEE). Reports on the prevalence and prognosis of thrombotic complications are still emerging., Objective: To describe the rate of TEE complications and its influence in the prognosis of hospitalized patients with COVID-19 after a cross-sectional study., Methods: We evaluated the prevalence of TEE and its relationship with in-hospital death among hospitalized patients with COVID-19 who were admitted between 1st March to 20th April 2020 in a multicentric network of sixteen Hospitals in Spain. TEE was defined by the occurrence of venous thromboembolism (VTE), acute ischemic stroke (AIS), systemic arterial embolism or myocardial infarction (MI)., Results: We studied 1737 patients with proven COVID-19 infection of whom 276 died (15.9%). TEE were presented in 64 (3.7%) patients: 49 (76.6%) patients had a VTE, 8 (12.5%) patients had MI, 6 (9.4%%) patients had AIS, and one (1.5%) patient a thrombosis of portal vein. TEE patients exhibited a diffuse profile: older, high levels of D-dimer protein and a tendency of lower levels of prothrombin. The multivariate regression models, confirmed the association between in-hospital death and age (odds ratio [OR] 1.12 [95% CI 1.10-1.14], p<0.001), diabetes (OR 1.49 [95% CI 1.04-2.13], p = 0.029), chronic obstructive pulmonary disease (OR 1.61 [95% CI 1.03-2.53], p = 0.039), ICU care (OR 9.39 [95% CI 5.69-15.51], p<0.001), and TTE (OR 2.24 [95% CI 1.17-4.29], p = 0.015)., Conclusions: Special attention is needed among hospitalized COVID-19 patients with TTE and other comorbidities as they have an increased risk of in-hospital death., Competing Interests: The authors have declared that no competing interests exist.

A large variation in the severity of disease symptoms is one of the key open questions in coronavirus disease 2019 (COVID-19) pandemics. The fact that only a small subset of people infected with severe acute respiratory syndrome coronavirus 2 develops severe disease suggests that there have to be some predisposing factors, but biomarkers that reliably predict disease severity have not been found so far. Since overactivation of the immune system is implicated in a severe form of COVID-19 and the immunoglobulin G (IgG) glycosylation is known to be involved in the regulation of different immune processes, we evaluated the association of interindividual variation in IgG N-glycome composition with the severity of COVID-19. The analysis of 166 severe and 167 mild cases from hospitals in Spain, Italy and Portugal revealed statistically significant differences in the composition of the IgG N-glycome. The most notable difference was the decrease in bisecting N-acetylglucosamine in severe patients from all three cohorts. IgG galactosylation was also lower in severe cases in all cohorts, but the difference in galactosylation was not statistically significant after correction for multiple testing., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Deterioration is sometimes unexpected in SARS-CoV2 infection. The aim of our study is to establish laboratory predictors of mortality in COVID-19 disease which can help to identify high risk patients. All patients admitted to hospital due to Covid-19 disease were included. Laboratory biomarkers that contributed with significant predictive value for predicting mortality to the clinical model were included. Cut-off points were established, and finally a risk score was built. 893 patients were included. Median age was 68.2 ± 15.2 years. 87(9.7%) were admitted to Intensive Care Unit (ICU) and 72(8.1%) needed mechanical ventilation support. 171(19.1%) patients died. A Covid-19 Lab score ranging from 0 to 30 points was calculated on the basis of a multivariate logistic regression model in order to predict mortality with a weighted score that included haemoglobin, erythrocytes, leukocytes, neutrophils, lymphocytes, creatinine, C-reactive protein, interleukin-6, procalcitonin, lactate dehydrogenase (LDH), and D-dimer. Three groups were established. Low mortality risk group under 12 points, 12 to 18 were included as moderate risk, and high risk group were those with 19 or more points. Low risk group as reference, moderate and high patients showed mortality OR 4.75(CI95% 2.60-8.68) and 23.86(CI 95% 13.61-41.84), respectively. C-statistic was 0-85(0.82-0.88) and Hosmer-Lemeshow p-value 0.63. Covid-19 Lab score can very easily predict mortality in patients at any moment during admission secondary to SARS-CoV2 infection. It is a simple and dynamic score, and it can be very easily replicated. It could help physicians to identify high risk patients to foresee clinical deterioration.

Objectives: To investigate which were the most relevant sociodemographic and clinical variables associated with COVID-19 severity, and uncover how their inter-relations may have affected such severity., Design: A retrospective observational study based on electronic health record data., Participants: Individuals ≥14 years old with a positive PCR or serology test, between 28 February and 31 May 2020, belonging to the Basque Country (Spain) public health system. Institutionalised and individuals admitted to a hospital at home unit were excluded from the study., Main Outcome Measure: Three severity categories were established: primary care, hospital/intensive care unit admission and death., Results: A total of n=14 197 cases fulfilled the inclusion criteria. Most variables presented statistically significant associations with the outcome (p<0.0001). The Classification and Regression Trees recursive partitioning methodology (based on n=13 792) suggested that among all associations, those with, age, sex, stratification of patient healthcare complexity, chronic consumption of blood and blood-forming organ, and nervous system drugs, as well as the total number of chronic Anatomical Therapeutic Chemical types were the most relevant. Psychosis also emerged as a potential factor., Conclusions: Older cases are more likely to experience more severe outcomes. However, the sex, underlying health status and chronic drug consumption may interfere and alter the ageing effect. Understanding the factors related to the outcome severity is of key importance when designing and promoting public health intervention plans for the COVID-19 pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The novel coronavirus (COVID-19) that was first reported at the end of 2019 has impacted almost every aspect of life as we know it. This paper focuses on the incidence of the disease in Italy and Spain-two of the first and most affected European countries. Using two simple mathematical epidemiological models-the Susceptible-Infectious-Recovered model and the log-linear regression model, we model the daily and cumulative incidence of COVID-19 in the two countries during the early stage of the outbreak, and compute estimates for basic measures of the infectiousness of the disease including the basic reproduction number, growth rate, and doubling time. Estimates of the basic reproduction number were found to be larger than 1 in both countries, with values being between 2 and 3 for Italy, and 2.5 and 4 for Spain. Estimates were also computed for the more dynamic effective reproduction number, which showed that since the first cases were confirmed in the respective countries the severity has generally been decreasing. The predictive ability of the log-linear regression model was found to give a better fit and simple estimates of the daily incidence for both countries were computed., Competing Interests: The authors have declared that no competing interests exist.

During COVID-19 emergency the majority of health structures in Europe saturated or nearly saturated their availabilities already in the first weeks of the epidemic period especially in some regions of Italy and Spain. The aim of this study is to analyse the efficiency in the management of hospital beds before the COVID-19 outbreak at regional level in France, Germany, Italy and Spain. This analysis can indicate a reference point for future analysis on resource management in emergency periods and help hospital managers, emergency planners as well as policy makers to put in place a rapid and effective response to an emergency situation. The results of this study clearly underline that France and Germany could rely on the robust structural components of the hospital system, compared to Italy and Spain. Presumably, this might have had an impact on the efficacy in the management of the COVID-19 diffusion. In particular, the high availability of beds in the majority of the France regions paired with the low occupancy rate and high turnover interval led these regions to have a high number of available beds. Consider also that this country generally manages complex cases. A similar structural component is present in the German regions where the number of available beds is significantly higher than in the other countries. The impact of the COVID-19 was completely different in Italy and Spain that had to deal with a relevant large number of patients relying on a reduced number of both hospital beds and professionals. A further critical factor compared to France and Germany concerns the dissimilar distribution of cases across regions. Even if in these countries the hospital beds were efficiently managed, the concentration of hospitalized patients and the scarcity of beds have put pressure on the hospital systems., Competing Interests: The authors have declared that no competing interests exist.

In this work, a SEIR-type mathematical model of the COVID-19 outbreak was developed that describes individuals in compartments by infection stage and age group. The model assumes a close well-mixed community with no migrations. Infection rates and clinical and epidemiological information govern the transitions between stages of the disease. The impact of specific interventions (including the availability of critical care) on the outbreak time course, the number of cases and the outcome of fatalities were evaluated. Data available from the COVID-19 outbreak from Spain as of mid-May 2020 was used. Key findings in our model simulation results indicate that (i) universal social isolation measures appear effective in reducing total fatalities only if they are strict and the number of daily interpersonal contacts is reduced to very low numbers; (ii) selective isolation of only the elderly (at higher fatality risk) appears almost as effective as universal isolation in reducing total fatalities but at a possible lower economic and social impact; (iii) an increase in the number of critical care capacity directly avoids fatalities; (iv) the use of personal protective equipment (PPE) appears to be effective to dramatically reduce total fatalities when adopted extensively and to a high degree; (v) extensive random testing of the population for more complete infection recognition (accompanied by subsequent self-isolation of infected aware individuals) can dramatically reduce the total fatalities only above a high percentage threshold that may not be practically feasible., Competing Interests: The authors have declared that no competing interests exist.

Background: The role of vitamin D status in COVID-19 patients is a matter of debate., Objectives: To assess serum 25-hydroxyvitamin D (25OHD) levels in hospitalized patients with COVID-19 and to analyze the possible influence of vitamin D status on disease severity., Methods: Retrospective case-control study of 216 COVID-19 patients and 197 population-based controls. Serum 25OHD levels were measured in both groups. The association of serum 25OHD levels with COVID-19 severity (admission to the intensive care unit, requirements for mechanical ventilation, or mortality) was also evaluated., Results: Of the 216 patients, 19 were on vitamin D supplements and were analyzed separately. In COVID-19 patients, mean ± standard deviation 25OHD levels were 13.8 ± 7.2 ng/mL, compared with 20.9 ± 7.4 ng/mL in controls (P < .0001). 25OHD values were lower in men than in women. Vitamin D deficiency was found in 82.2% of COVID-19 cases and 47.2% of population-based controls (P < .0001). 25OHD inversely correlates with serum ferritin (P = .013) and D-dimer levels (P = .027). Vitamin D-deficient COVID-19 patients had a greater prevalence of hypertension and cardiovascular diseases, raised serum ferritin and troponin levels, as well as a longer length of hospital stay than those with serum 25OHD levels ≥20 ng/mL. No causal relationship was found between vitamin D deficiency and COVID-19 severity as a combined endpoint or as its separate components., Conclusions: 25OHD levels are lower in hospitalized COVID-19 patients than in population-based controls and these patients had a higher prevalence of deficiency. We did not find any relationship between vitamin D concentrations or vitamin deficiency and the severity of the disease., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: While SARS-CoV-2 similarly infects men and women, COVID-19 outcome is less favorable in men. Variability in COVID-19 severity may be explained by differences in the host genome., Methods: We compared poly-amino acids variability from WES data in severely affected COVID-19 patients versus SARS-CoV-2 PCR-positive oligo-asymptomatic subjects., Findings: Shorter polyQ alleles (≤22) in the androgen receptor (AR) conferred protection against severe outcome in COVID-19 in the first tested cohort (both males and females) of 638 Italian subjects. The association between long polyQ alleles (≥23) and severe clinical outcome (p = 0.024) was also validated in an independent cohort of Spanish men <60 years of age (p = 0.014). Testosterone was higher in subjects with AR long-polyQ, possibly indicating receptor resistance (p = 0.042 Mann-Whitney U test). Inappropriately low serum testosterone level among carriers of the long-polyQ alleles (p = 0.0004 Mann-Whitney U test) predicted the need for intensive care in COVID-19 infected men. In agreement with the known anti-inflammatory action of testosterone, patients with long-polyQ and age ≥60 years had increased levels of CRP (p = 0.018, not accounting for multiple testing)., Interpretation: We identify the first genetic polymorphism that appears to predispose some men to develop more severe disease. Failure of the endocrine feedback to overcome AR signaling defects by increasing testosterone levels during the infection leads to the polyQ tract becoming dominant to serum testosterone levels for the clinical outcome. These results may contribute to designing reliable clinical and public health measures and provide a rationale to test testosterone as adjuvant therapy in men with COVID-19 expressing long AR polyQ repeats., Funding: MIUR project "Dipartimenti di Eccellenza 2018-2020" to Department of Medical Biotechnologies University of Siena, Italy (Italian D.L. n.18 March 17, 2020) and "Bando Ricerca COVID-19 Toscana" project to Azienda Ospedaliero-Universitaria Senese. Private donors for COVID-19 research and charity funds from Intesa San Paolo., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: During the coronavirus disease 2019 (COVID-19) pandemic, organisations have produced management guidance for cancer patients and the delivery of cytotoxic chemotherapy, but none has offered estimates of risk or the potential impact across populations., Materials and Methods: We combined data from four countries to produce pooled age-banded case fatality rates, calculated the sex difference in survival and used data from four recent studies to convert case fatality rates into age/sex-stratified infection fatality rates (IFRs). We estimated the additional risk of death in cancer patients and in those receiving chemotherapy. We illustrate the impact of these by considering the impact on a national incident cancer cohort and analyse the risk-benefit in some clinical scenarios., Results: We obtained data based on 412 985 cases and 41 854 deaths. The pooled estimate for IFR was 0.92%. IFRs for patients with cancer ranged from 0 to 29% and were higher in patients receiving chemotherapy (0.01-46%). The risk was significantly higher with age and in men compared with women. 37.5% of patients with a new diagnosis of cancer in 2018 had an IFR ≥5%. Survival benefits from adjuvant chemotherapy ranged from 5 to 10% in some common cancers, compared with the increased risk of death from COVID-19 of 0-3%., Conclusions: Older male patients are at a higher risk of death with COVID-19. Patients with cancer are also at a higher risk, as are those who have recently received chemotherapy. We provide well-founded estimates to allow patients and clinicians to better balance these risks and illustrate the wider impact in a national incident cohort., (Copyright © 2020. Published by Elsevier Ltd.)

Objectives: Tocilizumab has been proposed as a candidate therapy for patients with severe coronavirus disease 2019 (COVID-19), especially among those with higher systemic inflammation. We investigated the association between receipt of tocilizumab and mortality in a large cohort of hospitalized patients., Methods: In this cohort study of patients hospitalized with COVID-19 in Spain, the primary outcome was time to death and the secondary outcome time to intensive care unit (ICU) admission or death. We used inverse probability weighting to fit marginal structural models adjusted for time-varying covariates to determine the causal relationship between receipt of tocilizumab and outcome., Results: Data from 1229 patients were analysed, with 261 patients (61 deaths) in the tocilizumab group and 969 patients (120 deaths) in the control group. In the adjusted marginal structural models, a significant interaction between receipt of tocilizumab and high C-reactive protein (CRP) levels was detected. Tocilizumab was associated with decreased risk of death (adjusted hazard ratio 0.34, 95% confidence interval 0.16-0.72, p 0.005) and ICU admission or death (adjusted hazard ratio 0.39, 95% confidence interval 0.19-0.80, p 0.011) among patients with baseline CRP >150 mg/L but not among those with CRP ≤150 mg/L. Exploratory subgroup analyses yielded point estimates that were consistent with these findings., Conclusions: In this large observational study, tocilizumab was associated with a lower risk of death or ICU admission or death in patients with higher CRP levels. While the results of ongoing clinical trials of tocilizumab in patients with COVID-19 will be important to establish its safety and efficacy, our findings have implications for the design of future clinical trials., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters., Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs)., Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001)., Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: In December 2019, a new respiratory disease, named COVID-19, caused by a novel coronavirus, emerged in Wuhan and since then spread rapidly throughout China and worldwide. Hemodialysis patients are an especially vulnerable subgroup of the general population. However, there are only a few reports on the course of COVID-19 in maintenance hemodialysis patients., Case Report: We describe in depth the clinical, analytical, and radiological details of 9 hemodialysis patients from a single center in Madrid (Spain) diagnosed with COVID-19. Furthermore, we describe and discuss the therapeutic aspects and the patients' outcomes., Discussion: We present one of the first case series of chronic hemodialysis patients with COVID-19. Between March 14 and April 8, 2020, out of 76 prevalent patients in our hemodialysis unit, 9 (11.8%) patients were diagnosed with COVID-19. The most common symptoms were fever (77.8%), asthenia (77.8%), cough (55.6%), and dyspnea (33.3%). A total of 3 patients developed severe pneumonia, whereas 4 patients developed mild pneumonia. In 2 patients, no pathologic changes were found on chest radiography. All patients presented lymphopenia. While 6 (66.7%) patients required hospitalization, none of them was admitted to intensive care unit. The most common treatments used were azithromycin (100%), hydroxychloroquine (66.7%), lopinavir/ritonavir (55.6%) and β-interferon (22.2%). In general, we observed a mild to moderate severity of disease in our case series. One patient died, however due to a cause not related to COVID-19.

Background: 15% of COVID-19 patients develop severe pneumonia. Non-invasive mechanical ventilation and high-flow nasal cannula can reduce the rate of endotracheal intubation in adult respiratory distress syndrome, although failure rate is high., Objective: To describe the rate of endotracheal intubation, the effectiveness of treatment, complications and mortality in patients with severe respiratory failure due to COVID-19., Methods: Prospective cohort study in a first-level hospital in Madrid. Patients with a positive polymerase chain reaction for SARS-CoV-2 and admitted to the Intermediate Respiratory Care Unit with tachypnea, use of accessory musculature or SpO2 <92% despite FiO2> 0.5 were included. Intubation rate, medical complications, and 28-day mortality were recorded. Statistical analysis through association studies, logistic and Cox regression models and survival analysis was performed., Results: Seventy patients were included. 37.1% required endotracheal intubation, 58.6% suffered medical complications and 24.3% died. Prone positioning was independently associated with lower need for endotracheal intubation (OR 0.05; 95% CI 0.005 to 0.54, p = 0.001). The adjusted HR for death at 28 days in the group of patients requiring endotracheal intubation was 5.4 (95% CI 1.51 to 19.5; p = 0.009)., Conclusions: The rate of endotracheal intubation in patients with severe respiratory failure from COVID-19 was 37.1%. Complications and mortality were lower in patients in whom endotracheal intubation could be avoided. Prone positioning could reduce the need for endotracheal intubation., Competing Interests: The authors have declared that no competing interests exist.