Effect of in-hospital treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on mortality and complications in patients hospitalized for COVID-19: a large Spanish cohort study.

BackgroundThe use of ACEI (Angiotensin-Converting Enzyme Inhibitor) and ARB (Angiotensin II Receptor Blocker) in COVID-19 remains controversial. Our main aim was to describe the effect of ACEI/ARB treatment during COVID-19 hospitalization on mortality and complications. MethodsRetrospective, observational, multicenter study, part of the SEMI-COVID-19 Registry, comparing patients with COVID-19 treated with ACEI/ARB during hospitalization to those not treated. The primary endpoint was incidence of the composite outcome of prognosis (IMV [Invasive Mechanical Ventilation], NIMV [Non-Invasive Mechanical Ventilation], ICU admission [Intensive Care Unit], and/or all-cause mortality). The secondary endpoint was incidence of MACE (Major Adverse Cardiovascular Events). We evaluated both outcomes in patients whose treatment with ACEI/ARB continued or was withdrawn during hospitalization. ResultsBetween February and June 2020, 11,205 patients were included, with mean age 67 years (SD=16.3) and 43.1% female; 2,162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed a protective effect on all-cause mortality (p<.0001). In hypertensive patients it was also protective in terms of IMV, ICU admission, and the composite outcome of prognosis (p<.0001 for all). No differences were found in incidence of MACE. Patients previously treated with ACEI/ARB who continued treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB had a more beneficial effect on survival than ACEI (HR 0.77, 95%CI 0.62-0.96). ConclusionACEI/ARB treatment during COVID-19 hospitalization had a protective effect on mortality. The benefits were greater in hypertensive patients, those who continued treatment during hospitalization, and those taking ARB. SummaryTreatment with ACEI/ARB during COVID-19 hospitalization showed a beneficial effect on mortality in the general population. The benefit was greater in hypertensive patients, in those who maintained treatment during hospitalization and those taking ARB.

Predicting critical illness on initial diagnosis of COVID-19: Development and validation of the PRIORITY model for outpatient applicability.

ObjectivesCurrently available COVID-19 prognostic models have focused on laboratory and radiological data obtained following admission. However, these tests are not available on initial assessment or in resource-limited settings. We aim to develop and validate a prediction model, based on clinical history and examination findings on initial diagnosis of COVID-19, to identify patients at risk of critical outcomes. MethodsWe used data from the SEMI-COVID-19 Registry, a nationwide multicenter cohort of consecutive patients hospitalized for COVID-19 from 132 centers in Spain. Clinical signs and symptoms, demographic variables, and medical history ascertained at hospital admission were screened using Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to construct a predictive model. We externally validated the final model in a separate cohort of patients admitted at less-complex hospitals (< 300 beds).We undertook decision curve analysis to assess the clinical usefulness of the predictive model. The primary outcome was a composite of in-hospital death, mechanical ventilation or admission to intensive care unit. ResultsThere were 10,433 patients, 7,850 (primary outcome 25.1%) in the development cohort and 2,583 (primary outcome 27.0%) in the validation cohort. Variables in the final model included: age, cardiovascular disease, chronic kidney disease, dyspnea, tachypnea, confusion, systolic blood pressure, and SpO2[≤]93% or oxygen requirement.The C-statistic in the development cohort was 0.823 (95% CI,0.813-0.834). On external validation, the C-statistic was 0.792 (95% CI,0.772-0.812). The model showed a positive net benefit for threshold probabilities between 3% and 79%. ConclusionsAmong patients presenting with COVID-19, the model based on easily-obtained clinical information had good discrimination and generalizability for identifying patients at risk of critical outcomes without the need of additional testing. The online calculator provided would facilitate triage of patients during the pandemic. This study could provide a useful tool for decision-making in health systems under pandemic pressure and resource-limited settings.

Predicting clinical outcome with phenotypic clusters in COVID-19 pneumonia: 2 an analysis of 12,066 hospitalized patients from the Spanish registry SEMI-3 COVID-19.

(1) Background: This study aims to identify different clinical phenotypes in COVID-19 88 pneumonia using cluster analysis and to assess the prognostic impact among identified clusters in 89 such patients. (2) Methods: Cluster analysis including 11 phenotypic variables was performed in a 90 large cohort of 12,066 COVID-19 patients, collected and followed-up from March 1, to July 31, 2020, 91 from the nationwide Spanish SEMI-COVID-19 Registry. (3) Results: Of the total of 12,066 patients 92 included in the study, most were males (7,052, 58.5%) and Caucasian (10,635, 89.5%), with a mean 93 age at diagnosis of 67 years (SD 16). The main pre-admission comorbidities were arterial 94 hypertension (6,030, 50%), hyperlipidemia (4,741, 39.4%) and diabetes mellitus (2,309, 19.2%). The 95 average number of days from COVID-19 symptom onset to hospital admission was 6.7 days (SD 7). 96 The triad of fever, cough, and dyspnea was present almost uniformly in all 4 clinical phenotypes 97 identified by clustering. Cluster C1 (8,737 patients, 72.4%) was the largest, and comprised patients 98 with the triad alone. Cluster C2 (1,196 patients, 9.9%) also presented with ageusia and anosmia; 99 cluster C3 (880 patients, 7.3%) also had arthromyalgia, headache, and sore throat; and cluster C4 100 (1,253 patients, 10.4%) also manifested with diarrhea, vomiting, and abdominal pain. Compared to 101 each other, cluster C1 presented the highest in-hospital mortality (24.1% vs. 4.3% vs. 14.7% vs. 102 18.6%; p<0.001). The multivariate study identified phenotypic clusters as an independent factor for 103 in-hospital death. (4) Conclusion: The present study identified 4 phenotypic clusters in patients with 104 COVID-19 pneumonia, which predicted the in-hospital prognosis of clinical outcomes.

Beneficial and Harmful Outcomes of Tocilizumab in Severe COVID-19: A Systematic Review and Meta-Analysis

BackgroundPending for randomized control trials, the use of tocilizumab (TCZ) in COVID-19 is based on observational studies and remains controversial. PurposeTo summarize evidence about the effect of TCZ to treat severe COVID-19. Data sourcesPubMed (via MEDLINE), Scopus, and medRxiv repository databases from 1 January to 21 August 2020. Study SelectionObservational studies in any language reporting efficacy and safety outcomes of TCZ use in hospitalized adults with COVID-19. Data ExtractionIndependent, dually performed data extraction and quality assessments. Data synthesisOf 57 eligible studies, 27 were controlled and 30 were not. The overall included patients were 8,128: 4,021 treated with TCZ, in addition to standard of care (SOC), and 4,107 only receiving SOC. The pooled mortality was lower in the TCZ-group vs. the control group, with a relative risk (RR) of 0.73 (95%CI 0.57-0.93; p = 0.010). The overall NNT to avoid one death was 20. In hospital wards, patients in the TCZ-group were transferred to intensive care unit (ICU) in a higher proportion than those in the control group; however, ICU mortality of the TCZ-group was lower than in the control group. Secondary infections occurred in a higher proportion in TCZ-treated patients. Among survivors, the length of stay was similar in both groups. LimitationsConclusions should be considered as weak evidence since they are based on observational studies, most of them retrospective. A variety of factors influencing the indication and effect of TCZ could not be evaluated in-depth. ConclusionsTCZ seems beneficial in preventing in-hospital mortality in severe, non-critically ill COVID-19 patients. Conversely, patients receiving TCZ appear to be at higher risk for secondary infections, especially those admitted to ICU. Funding sourceNo funding or sponsorship was received for this study or publication of this article. The protocol was published in the National Institute for Health Research international register of systematic reviews (PROSPERO); registration number CRD42020204934.

Beneficial Effect of Corticosteroids in Preventing Mortality in Patients Receiving Tocilizumab to Treat Severe COVID-19 Illness

IntroductionOn the basis of the preliminary report from the RECOVERY trial, the use of dexamethasone or alternative corticosteroids (CS) is currently recommended in severe COVID-19 patients requiring supplemental oxygen. However, last updated recommendations have not taken a position either for or against the use of other immunomodulators such as tocilizumab (TCZ), with or without CS, since results are still limited. MethodsFrom March 17 to April 7, 2020, a real-world observational retrospective analysis was conducted at our 750-bed university hospital to study the characteristics and risk factors for mortality in patients with severe COVID-19 treated with TCZ +/-CS, in addition to standard of care (SOC). Data were obtained from routine clinical practice, stored in electronic medical records. The main outcome was all-cause in-hospital mortality. ResultsA total of 1,092 COVID-19 patients were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186, 155 (83.3 %) patients were receiving non-invasive ventilation when TCZ +/-CS was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 ({+/-} 4.3) and 4.3 days ({+/-} 3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR=1.09, p<0.001), chronic heart failure (HR=4.4, p=0.003), and chronic liver disease (HR=4.69, p=0.004). The use of CS, in combination with TCZ, was the main protective factor against mortality (HR=0.26, p<0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. ConclusionsIn severe COVID-19 patients receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed beneficial effect in preventing in-hospital mortality.

Clinical characteristics of patients hospitalized with COVID-19 in Spain: results from the SEMI-COVID-19 Network.

BackgroundSpain has been one of the countries most affected by the COVID-19 pandemic. ObjectiveTo create a registry of patients with COVID-19 hospitalized in Spain in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease. MethodsA multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records. ResultsUp to April 30th 2020, 6,424 patients from 109 hospitals were included. Their median age was 69.1 years (range: 18-102 years) and 56.9% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.2%, 39.7%, and 18.7%, respectively. The most frequent symptoms were fever (86.2%) and cough (76.5%). High values of ferritin (72.4%), lactate dehydrogenase (70.2%), and D-dimer (61.5%), as well as lymphopenia (52.6%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.7%) and lopinavir/ritonavir (62.4%). 31.5% developed respiratory distress. Overall mortality rate was 21.1%, with a marked increase with age (50-59 years: 4.2%, 60-69 years: 9.1%, 70-79 years: 21.4%, 80-89 years: 42.5%, [≥] 90 years: 51.1%). ConclusionsThe SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.