Clusters of inflammation in COVID-19: descriptive analysis and prognosis on more than 15,000 patients from the Spanish SEMI-COVID-19 Registry.

Uncontrolled inflammation following COVID-19 infection is an important characteristic of the most seriously ill patients. The present study aims to describe the clusters of inflammation in COVID-19 and to analyze their prognostic role. This is a retrospective observational study including 15,691 patients with a high degree of inflammation. They were included in the Spanish SEMI-COVID-19 registry from March 1, 2020 to May 1, 2021. The primary outcome was in-hospital mortality. Hierarchical cluster analysis identified 7 clusters. C1 is characterized by lymphopenia, C2 by elevated ferritin, and C3 by elevated LDH. C4 is characterized by lymphopenia plus elevated CRP and LDH and frequently also ferritin. C5 is defined by elevated CRP, and C6 by elevated ferritin and D-dimer, and frequently also elevated CRP and LDH. Finally, C7 is characterized by an elevated D-dimer. The clusters with the highest in-hospital mortality were C4, C6, and C7 (17.4% vs. 18% vs. 15.6% vs. 36.8% vs. 17.5% vs. 39.3% vs. 26.4%). Inflammation clusters were found as independent factors for in-hospital mortality. In detail and, having cluster C1 as reference, the model revealed a worse prognosis for all other clusters: C2 (OR = 1.30, p = 0.001), C3 (OR = 1.14, p = 0.178), C4 (OR = 2.28, p < 0.001), C5 (OR = 1.07, p = 0.479), C6 (OR = 2.29, p < 0.001), and C7 (OR = 1.28, p = 0.001). We identified 7 groups based on the presence of lymphopenia, elevated CRP, LDH, ferritin, and D-dimer at the time of hospital admission for COVID-19. Clusters C4 (lymphopenia + LDH + CRP), C6 (ferritin + D-dimer), and C7 (D-dimer) had the worst prognosis in terms of in-hospital mortality.

WHO Ordinal Scale and Inflammation Risk Categories in COVID-19. Comparative Study of the Severity Scales.

BACKGROUND: The WHO ordinal severity scale has been used to predict mortality and guide trials in COVID-19. However, it has its limitations. OBJECTIVE: The present study aims to compare three classificatory and predictive models: the WHO ordinal severity scale, the model based on inflammation grades, and the hybrid model. DESIGN: Retrospective cohort study with patient data collected and followed up from March 1, 2020, to May 1, 2021, from the nationwide SEMI-COVID-19 Registry. The primary study outcome was in-hospital mortality. As this was a hospital-based study, the patients included corresponded to categories 3 to 7 of the WHO ordinal scale. Categories 6 and 7 were grouped in the same category. KEY RESULTS: A total of 17,225 patients were included in the study. Patients classified as high risk in each of the WHO categories according to the degree of inflammation were as follows: 63.8% vs. 79.9% vs. 90.2% vs. 95.1% (p<0.001). In-hospital mortality for WHO ordinal scale categories 3 to 6/7 was as follows: 0.8% vs. 24.3% vs. 45.3% vs. 34% (p<0.001). In-hospital mortality for the combined categories of ordinal scale 3a to 5b was as follows: 0.4% vs. 1.1% vs. 11.2% vs. 27.5% vs. 35.5% vs. 41.1% (p<0.001). The predictive regression model for in-hospital mortality with our proposed combined ordinal scale reached an AUC=0.871, superior to the two models separately. CONCLUSIONS: The present study proposes a new severity grading scale for COVID-19 hospitalized patients. In our opinion, it is the most informative, representative, and predictive scale in COVID-19 patients to date.

The Use of Corticosteroids or Tocilizumab in COVID-19 Based on Inflammatory Markers.

BACKGROUND: The inflammatory cascade is the main cause of death in COVID-19 patients. Corticosteroids (CS) and tocilizumab (TCZ) are available to treat this escalation but which patients to administer it remains undefined. OBJECTIVE: We aimed to evaluate the efficacy of immunosuppressive/anti-inflammatory therapy in COVID-19, based on the degree of inflammation. DESIGN: A retrospective cohort study with data on patients collected and followed up from March 1st, 2020, to May 1st, 2021, from the nationwide Spanish SEMI-COVID-19 Registry. Patients under treatment with CS vs. those under CS plus TCZ were compared. Effectiveness was explored in 3 risk categories (low, intermediate, high) based on lymphocyte count, C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and D-dimer values. PATIENTS: A total of 21,962 patients were included in the Registry by May 2021. Of these, 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ). MAIN MEASURES: The primary outcome of the study was in-hospital mortality. Secondary outcomes were the composite variable of in-hospital mortality, requirement for high-flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), invasive mechanical ventilation (IMV), or intensive care unit (ICU) admission. KEY RESULTS: A total of 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ). No significant differences were observed in either the low/intermediate-risk category (1.5% vs. 7.4%, p=0.175) or the high-risk category (23.1% vs. 20%, p=0.223) after propensity score matching. A statistically significant lower mortality was observed in the very high-risk category (31.9% vs. 23.9%, p=0.049). CONCLUSIONS: The prescription of CS alone or in combination with TCZ should be based on the degrees of inflammation and reserve the CS plus TCZ combination for patients at high and especially very high risk.

Real-Life Impact of Glucocorticoid Treatment in COVID-19 Mortality: A Multicenter Retrospective Study.

We aimed to determine the impact of steroid use in COVID-19 in-hospital mortality, in a retrospective cohort study of the SEMICOVID19 database of admitted patients with SARS-CoV-2 laboratory-confirmed pneumonia from 131 Spanish hospitals. Patients treated with corticosteroids were compared to patients not treated with corticosteroids; and adjusted using a propensity-score for steroid treatment. From March-July 2020, 5.262 (35.26%) were treated with corticosteroids and 9.659 (64.73%) were not. In-hospital mortality overall was 20.50%; it was higher in patients treated with corticosteroids than in controls (28.5% versus 16.2%, OR 2.068 [95% confidence interval; 1.908 to 2.242]; p = 0.0001); however, when adjusting by occurrence of ARDS, mortality was significantly lower in the steroid group (43.4% versus 57.6%; OR 0.564 [95% confidence interval; 0.503 to 0.633]; p = 0.0001). Moreover, the greater the respiratory failure, the greater the impact on mortality of the steroid treatment. When adjusting these results including the propensity score as a covariate, in-hospital mortality remained significantly lower in the steroid group (OR 0.774 [0.660 to 0.907], p = 0.002). Steroid treatment reduced mortality by 24% relative to no steroid treatment (RRR 0.24). These results support the use of glucocorticoids in COVID-19 in this subgroup of patients.

Clinical Features and Risk Factors for Mortality Among Long-term Care Facility Residents Hospitalized Due to COVID-19 in Spain.

BACKGROUND: COVID-19 severely impacted older adults and long-term care facility (LTCF) residents. Our primary aim was to describe differences in clinical and epidemiological variables, in-hospital management, and outcomes between LTCF residents and community-dwelling older adults hospitalized with COVID-19. The secondary aim was to identify risk factors for mortality due to COVID-19 in hospitalized LTCF residents. METHODS: This is a cross-sectional analysis within a retrospective cohort of hospitalized patients ≥75 years with confirmed COVID-19 admitted to 160 Spanish hospitals. Differences between groups and factors associated with mortality among LTCF residents were assessed through comparisons and logistic regression analysis. RESULTS: Of 6 189 patients ≥75 years, 1 185 (19.1%) were LTCF residents and 4 548 (73.5%) were community-dwelling. LTCF residents were older (median: 87.4 vs 82.1 years), mostly female (61.6% vs 43.2%), had more severe functional dependence (47.0% vs 7.8%), more comorbidities (Charlson Comorbidity Index: 6 vs 5), had dementia more often (59.1% vs 14.4%), and had shorter duration of symptoms (median: 3 vs 6 days) than community-dwelling patients (all, p < .001). Mortality risk factors in LTCF residents were severe functional dependence (adjusted odds ratios [aOR]: 1.79; 95% confidence interval [CI]: 1.13-2.83; p = .012), dyspnea (1.66; 1.16-2.39; p = .004), SatO2 < 94% (1.73; 1.27-2.37; p = .001), temperature ≥ 37.8°C (1.62; 1.11-2.38; p = .013); qSOFA index ≥ 2 (1.62; 1.11-2.38; p = .013), bilateral infiltrates (1.98; 1.24-2.98; p < .001), and high C-reactive protein (1.005; 1.003-1.007; p < .001). In-hospital mortality was initially higher among LTCF residents (43.3% vs 39.7%), but lower after adjusting for sex, age, functional dependence, and comorbidities (aOR: 0.74, 95%CI: 0.62-0.87; p < .001). CONCLUSION: Basal functional status and COVID-19 severity are risk factors of mortality in LTCF residents. The lower adjusted mortality rate in LTCF residents may be explained by earlier identification, treatment, and hospitalization for COVID-19.

Clinical Characteristics and Prognosis of COPD Patients Hospitalized with SARS-CoV-2.

Objective: To describe the characteristics and prognosis of patients with COPD admitted to the hospital due to SARS-CoV-2 infection. Methods: The SEMI-COVID registry is an ongoing retrospective cohort comprising consecutive COVID-19 patients hospitalized in Spain since the beginning of the pandemic in March 2020. Data on demographics, clinical characteristics, comorbidities, laboratory tests, radiology, treatment, and progress are collected. Patients with COPD were selected and compared to patients without COPD. Factors associated with a poor prognosis were analyzed. Results: Of the 10,420 patients included in the SEMI-COVID registry as of May 21, 2020, 746 (7.16%) had a diagnosis of COPD. Patients with COPD are older than those without COPD (77 years vs 68 years) and more frequently male. They have more comorbidities (hypertension, hyperlipidemia, diabetes mellitus, atrial fibrillation, heart failure, ischemic heart disease, peripheral vascular disease, kidney failure) and a higher Charlson Comorbidity Index (2 vs 1, p<0.001). The mortality rate in COPD patients was 38.3% compared to 19.2% in patients without COPD (p<0.001). Male sex, a history of hypertension, heart failure, moderate-severe chronic kidney disease, presence of cerebrovascular disease with sequelae, degenerative neurological disease, dementia, functional dependence, and a higher Charlson Comorbidity Index have been associated with increased mortality due to COVID-19 in COPD patients. Survival was higher among patients with COPD who were treated with hydroxychloroquine (87.1% vs 74.9%, p<0.001) and with macrolides (57.9% vs 50%, p<0.037). Neither prone positioning nor non-invasive mechanical ventilation, high-flow nasal cannula, or invasive mechanical ventilation were associated with a better prognosis. Conclusion: COPD patients admitted to the hospital with SARS-CoV-2 infection have more severe disease and a worse prognosis than non-COPD patients.