Risk Categories in COVID-19 Based on Degrees of Inflammation: Data on More Than 17,000 Patients from the Spanish SEMI-COVID-19 Registry
by
, , , , , , , ,
Manuel Rubio-Rivas
1,*,†
,
Xavier Corbella
1,2,†,
Francesc Formiga
1,
Estela Menéndez Fernández
3,
María Dolores Martín Escalante
4,
Isolina Baños Fernández
5,
Francisco Arnalich Fernández
6,
Esther Del Corral-Beamonte
7,
Antonio Lalueza
8,
Alejandro Parra Virto
9,
Emilia Roy Vallejo
10,
José Loureiro-Amigo
11,
Ana María Álvarez Suárez
12,
Jesica Abadía-Otero
13,
María Navarro De La Chica
14,
Raquel Estévez González
15,
Almudena Hernández Milián
16,
María Areses Manrique
17,
Julio César Blázquez Encinar
18,
Amara González Noya
19,
Ruth González Ferrer
20,
María Pérez Aguilera
21,
Ricardo Gil Sánchez
22,
Jesús Millán Núñez-Cortés
9,
José Manuel Casas-Rojo
23 and add
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1
Department of Internal Medicine, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, University of Barcelona, 08907 Barcelona, Spain
2
Hestia Chair in Integrated Health and Social Care, School of Medicine, Universitat Internacional de Catalunya, 08017 Barcelona, Spain
3
Department of Internal Medicine, San Pedro Hospital, 26006 Logroño, Spain
4
Department of Internal Medicine, Hospital Costa del Sol, 29603 Marbella, Spain
5
Department of Internal Medicine, Hospital Puerta de Hierro Hospital, 28220 Majadahonda, Spain
6
Head of the Department of Internal Medicine, La Paz Hospital, 28046 Madrid, Spain
7
Department of Internal Medicine, Royo Villanova Hospital, 50007 Zaragoza, Spain
8
Department of Internal Medicine, 12 de Octubre University Hospital, 28041 Madrid, Spain
9
Department of Internal Medicine, Gregorio Marañón Hospital, 28009 Madrid, Spain
10
Department of Internal Medicine, La Princesa University Hospital, 28006 Madrid, Spain
11
Department of Internal Medicine, Moisès Broggi Hospital, 08970 Sant Joan Despí, Spain
12
Department of Internal Medicine, Cabueñes Hospital, 33203 Gijón, Spain
13
Department of Internal Medicine, Río Hortega University Hospital, 47014 Valladolid, Spain
14
Department of Internal Medicine, Nuestra Señora del Prado Hospital, 45600 Talavera de la Reina, Spain
15
Department of Internal Medicine, Virgen de la Salud Hospital-Toledo University Hospital, 45004 Toledo, Spain
16
Department of Internal Medicine, Son Llatzer Hospital, 07005 Mallorca, Spain
17
Department of Internal Medicine, Santa Marina Hospital, 48004 Bilbao, Spain
18
Department of Internal Medicine, Torrevieja University Hospital, 03186 Torrevieja, Spain
19
Department of Internal Medicine, Ourense University Hospital, 32005 Ourense, Spain
20
Department of Internal Medicine, Tajo University Hospital, 41007 Toledo, Spain
21
Department of Internal Medicine, Juan Ramón Jiménez University Hospital, 21005 Huelva, Spain
22
Department of Internal Medicine, La Fe Hospital, 46009 Valencia, Spain
23
Department of Internal Medicine, Infanta Cristina University Hospital, 28981 Parla, Spain
*
Author to whom correspondence should be addressed.
†
M. Rubio-Rivas and X. Corbella contributed equally as co-first authors of the study.
‡
A complete list of the SEMI-COVID-19 Network members is provided in the Acknowledgments.
J. Clin. Med. 2021, 10(10), 2214; https://doi.org/10.3390/jcm10102214
Submission received: 12 March 2021
/
Revised: 17 May 2021
/
Accepted: 18 May 2021
/
Published: 20 May 2021
(This article belongs to the Special Issue Clinical Health Care during the COVID-19 Pandemic: Therapeutic and Management Strategies)
Abstract
:(1) Background: The inflammation or cytokine storm that accompanies COVID-19 marks the prognosis. This study aimed to identify three risk categories based on inflammatory parameters on admission. (2) Methods: Retrospective cohort study of patients diagnosed with COVID-19, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish SEMI-COVID-19 Registry. The three categories of low, intermediate, and high risk were determined by taking into consideration the terciles of the total lymphocyte count and the values of C-reactive protein, lactate dehydrogenase, ferritin, and D-dimer taken at the time of admission. (3) Results: A total of 17,122 patients were included in the study. The high-risk group was older (57.9 vs. 64.2 vs. 70.4 years; p < 0.001) and predominantly male (37.5% vs. 46.9% vs. 60.1%; p < 0.001). They had a higher degree of dependence in daily tasks prior to admission (moderate-severe dependency in 10.8% vs. 14.1% vs. 17%; p < 0.001), arterial hypertension (36.9% vs. 45.2% vs. 52.8%; p < 0.001), dyslipidemia (28.4% vs. 37% vs. 40.6%; p < 0.001), diabetes mellitus (11.9% vs. 17.1% vs. 20.5%; p < 0.001), ischemic heart disease (3.7% vs. 6.5% vs. 8.4%; p < 0.001), heart failure (3.4% vs. 5.2% vs. 7.6%; p < 0.001), liver disease (1.1% vs. 3% vs. 3.9%; p = 0.002), chronic renal failure (2.3% vs. 3.6% vs. 6.7%; p < 0.001), cancer (6.5% vs. 7.2% vs. 11.1%; p < 0.001), and chronic obstructive pulmonary disease (5.7% vs. 5.4% vs. 7.1%; p < 0.001). They presented more frequently with fever, dyspnea, and vomiting. These patients more frequently required high flow nasal cannula (3.1% vs. 4.4% vs. 9.7%; p < 0.001), non-invasive mechanical ventilation (0.9% vs. 3% vs. 6.3%; p < 0.001), invasive mechanical ventilation (0.6% vs. 2.7% vs. 8.7%; p < 0.001), and ICU admission (0.9% vs. 3.6% vs. 10.6%; p < 0.001), and had a higher percentage of in-hospital mortality (2.3% vs. 6.2% vs. 23.9%; p < 0.001). The three risk categories proved to be an independent risk factor in multivariate analyses. (4) Conclusion: The present study identifies three risk categories for the requirement of high flow nasal cannula, mechanical ventilation, ICU admission, and in-hospital mortality based on lymphopenia and inflammatory parameters.
1. Introduction
As of 6 February 2021, more than 105 million people have contracted SARS-CoV-2, and more than 2.3 million people have died from COVID-19. After 1 year of advances in the understanding of the disease, several risk factors have been recognized [1,2]. These include older age, male gender, certain comorbidities, and phenotypic clusters based on patient symptomatology [3,4,5,6,7,8,9]. Some analytical parameters have also been identified as poor prognostic factors and are related to the inflammatory state that patients present during the disease, the so-called cytokine storm, the most characteristic features of which are a decrease in the lymphocyte count and an increase in inflammatory parameters such as C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and D-dimer [10]. This accompanying inflammatory process marks the prognosis of COVID-19.
Our study aimed to identify three risk categories based on inflammatory parameters on admission.
2. Materials and Methods
2.1. Study Design, Patient Selection, and Data Collection
This is a retrospective cohort study with data on patients collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish SEMI-COVID-19 Registry. The characteristics of the patients included in this registry have been extensively described [11]. This is a multicenter, nationwide registry with over 150 hospitals registered so far. From 1 March to 31 July 2020, a total of 17,122 hospitalized patients diagnosed with COVID-19 on admission were included in the Registry. All included patients were diagnosed by polymerase chain reaction (PCR) test taken from a nasopharyngeal sample, sputum, or bronchoalveolar lavage. All patients’ symptoms were collected on admission. Likewise, blood values were collected on the first day of hospital admission and prior to receiving any type of therapy. The collection of data from each patient in terms of laboratory data, treatments, and outcomes was verified by the principal investigator of each center through the review of clinical records. The patients included in the present study had not received corticosteroid or anti-inflammatory therapy prior to hospital admission. To assess functional status prior to admission, the Barthel index was used: independent or mild dependence, 100–91; moderate dependence, 90–61; and severe dependence, ≤60.
All participating centers in the register received confirmation from the relevant Ethics Committees, including Bellvitge University Hospital (PR 128/20).
2.2. Categories of Risk
The three categories of low, intermediate, and high risk were determined by taking into consideration the terciles of the total lymphocyte count, and the CRP, LDH, ferritin, and D-dimer values taken at the time of admission. The low-risk category was defined when all parameters were in the first tercile. The high-risk category was defined when any of the parameters were in the third tercile. The intermediate risk category was defined when the defining conditions of low or high risk were not met.
2.3. Outcomes Definition
The primary outcome of the study was in-hospital mortality. The secondary outcomes were the requirement of high flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), invasive mechanical ventilation (IMV), or intensive care unit (ICU) admission.
2.4. Statistical Analysis
Categorical variables were expressed as absolute numbers and percentages. Continuous variables are expressed as mean plus standard deviation (SD) in the case of parametric distribution, or median (IQR) in the case of non-parametric distribution. Differences among groups were assessed using the chi-square test for categorical variables and ANOVA or the Kruskal–Wallis test, as appropriate, for continuous variables; p-values <0.05 indicated statistical significance.
For the assessment of risk factors for each of the outcomes, binary logistic regression was performed, including the three risk categories in the model. In multivariate analyses, variables with a significance of <0.10 in the univariate analyses plus age and sex were included. Subsequently, the differences in mortality were shown graphically using Kaplan–Meier curves, with their log-rank test (event: death; censored data: hospital discharge). Missing data were treated with multiple imputation.
Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY, USA, IBM Corp.
3. Results
3.1. General Data and Symptoms
A total of 17,122 patients were included in the study. Table 1 shows the three categories of low, intermediate, and high risk and their cut-off points. Table 2 shows the overall data for the three risk categories. Of note, members of the high-risk group were older (57.9 years vs. 64.2 vs. 70.4; p < 0.001) and more predominantly male (37.5% vs. 46.9% vs. 60.1%; p < 0.001). They had a higher degree of dependency prior to admission and certain comorbidities were more prevalent (arterial hypertension, dyslipidemia, diabetes mellitus, ischemic heart disease, chronic heart failure, chronic liver disease, severe chronic renal failure, cancer, and chronic obstructive pulmonary disease). In contrast, asthma was less prevalent in this group of patients.
Symptoms at the time of hospital admission are shown in Table 3. The high-risk group presented more frequently with fever (71.3% vs. 83% vs. 84.3%; p < 0.001), dyspnea (52.3% vs. 51.1% vs. 59.1%; p < 0.001), and vomiting (3.4% vs. 7.8% vs. 8%; p = 0.007).
3.2. Lab Tests among Categories
The lab test results (on admission) for the three categories are shown in Table 4.
3.3. Outcomes
The outcomes by risk category are shown in Table 5. All outcomes were more prevalent in the high-risk group. Thus, these patients more frequently required HFNC (3.1% vs. 4.4% vs. 9.7%; p < 0.001), NIMV (0.9% vs. 3% vs. 6.3%; p < 0.001), IMV (0.6% vs. 2.7% vs. 8.7%; p < 0.001), or ICU admission (0.9% vs. 3.6% vs. 10.6%; p < 0.001), and had a higher percentage of in-hospital mortality (2.3% vs. 6.2% vs. 23.9%; p < 0.001).
Figure 1 shows the survival curves for the three risk categories. Figure 2 shows the survival curves in high-risk patients depending on the number of high-risk criteria (lymphocytes, CRP, LDH, ferritin, or D-dimer) above the predetermined threshold. Table S1 shows the outcomes in high-risk patients depending on how many high-risk parameters each patient had.
3.4. Risk Factors for HFNC, NIMV, IMV, ICU Admission and in-Hospital Mortality
The multivariate binary logistic regression shown in Table 6, and in supplemental files, Tables S2–S5, identify the three risk categories as an independent risk factor for HFNC, NIMV, MIV, ICU admission, and in-hospital death. Taking the low-risk category as a reference, the attributed risk of in-hospital death was OR = 1.91 (0.9–4.05; p = 0.093) for the intermediate risk category and 7.31 (3.49–15.28; p < 0.001) for the high-risk category.
4. Discussion
The present study identifies three risk categories based on degrees of lymphopenia and inflammatory parameters present on hospital admission as part of the host-immune response and cytokine storm that accompanies severe COVID-19 [10]. Since the beginning of the pandemic, inflammation has been synonymous with clinical complications during admission and has ultimately increased the likelihood of death. This study not only confirms this observation, but also defines three clearly differentiated prognostic groups, both in terms of resource use (HFNC, NIMV, IMV) and in terms of ICU admission or in-hospital death. Furthermore, our study clearly and concisely describes the cut-off points that define each of these categories so that the research can inform clinical practice.
The high-risk category presents socio-demographic and comorbidity characteristics already recognized as poor prognostic factors [3,4,5,6,7,8,9]. There is no definitive answer to date as to why older patients, especially men and those with certain comorbidities, become more inflamed, but what is clear is that such patients’ inflammatory response is certainly greater. Nor is it surprising that these older men present more frequently with fever, dyspnea, and vomiting. Such symptoms may indicate phenotypic clusters C1 and C4, previously described by our group as poor prognostic factors [9].
Based on the figures for outcomes by category, the need to maintain hospital admission for patients in the low-risk category should be carefully considered. We believe that close outpatient follow-up would be more appropriate for such patients. Although results in all outcomes are worse for the intermediate-risk category with respect to the low-risk category, the most substantial changes occur in the high-risk category. We believe it is crucial to detect patients belonging to this category at the outset and take more intensive therapeutic management measures.
It is evident from the results obtained that it is not only important whether patients belong to the high-risk category or not, but also how many high-risk parameters are fulfilled. In this regard, it is still unclear whether one of the analyzed parameters is of greater importance than the others.
To date, guidelines, protocols, and trials are overly focused on oxygenation/ventilation status. Respiratory status is at the end of the slope of different causes, not only COVID-19 (obesity, previous pulmonary pathologies, hospital resources, etc). The cornerstone of any COVID-19 protocol should be inflammation. It precedes respiratory deterioration and has a remarkably high predictive power, given the results of the present study. Another factor to be considered in trials is assessing the effectiveness of anti-inflammatory/immunosuppressive drugs.
We believe that the usefulness of this risk stratification strategy is that it is not only prognostic in allowing us to identify those patients at greatest risk; this study can also serve as a generator of hypothesis to be confirmed in prospective studies on drug regimens [12,13]. Defining the target of patients likely to improve with such treatments has been the fundamental question for some time now, and we believe that these risk categories can help to define it. In fact, the next step in our research is to precisely explore this question. We believe that identification of these patients is a necessary step that will shed light on many uncertainties to date and will explain the discrepancies in the tocilizumab trials in COVID-19 in recent months [14,15,16,17].
In order to understand the risk factors for HFNC, NIMV, or IVM use, or ICU admission, it should be taken into account that some paradoxical “protective” factors in the logistic regression (degree of dependency in daily tasks, presence of severe comorbidities, etc.) are not such. This is because there is a limitation on the critical care therapeutic efforts in very old and highly dependent patients with severe comorbidities, in whom the more likely predicted outcome will result in mortality.
The present study has several strengths. Most notably, the large sample size from a consolidated national registry. In addition, the inclusion of first, second, and third level hospitals provides us with a broader picture of the pandemic in our territory.
As regards limitations, there is a notable predominance of Caucasian population in our registry and less representation of other ethnic groups, as reported previously [11]. In addition, we would have liked to include data referring to interleukin 6 as part of the panel of inflammatory parameters assessed, but, unfortunately, the high percentage of missing values in the registry did not allow us to do so. Finally, the registry allows us to identify patients with active cancer, but not if they were undergoing chemotherapy or active immunotherapy. Likewise, for the present study, we do not have data on body mass index or immunosuppressive treatments administered prior to admission.
5. Conclusions
The present study identifies three risk categories for HFNC, NIMV, or IMV use, ICU admission, and in-hospital mortality based on degrees of lymphopenia and inflammatory parameters that show severe COVID-19 patients on hospital admission. We believe their early identification and appropriate clinical management based on this risk stratification strategy may be crucial in improving the prognosis of COVID-19 patients requiring hospitalization.
Supplementary Materials
The following are available online at https://www.mdpi.com/article/10.3390/jcm10102214/s1, Table S1. Outcomes in high-risk patients according to the number of high-risk criteria; Table S2. Risk factors of the requirement of HFNC; Table S3. Risk factors of the requirement of NIMV; Table S4. Risk factors of the requirement of IMV; Table S5. Risk factors of ICU admission; Table S6. Matrix of correlations between prognostic factors.
Author Contributions
Conceptualization, M.R.-R.; methodology, M.R.-R.; software, M.R.-R.; validation, M.R.-R. and X.C.; formal analysis, M.R.-R.; investigation, M.R.-R. and X.C.; resources, J.M.N.-C. and J.M.C.-R.; data curation, M.R.-R., X.C., F.F., E.M.F., M.D.M.E., I.B.F., F.A.F., E.D.C.-B., A.L., A.P.V., E.R.V., J.L.-A., A.M.Á.S., J.A.-O., M.N.D.L.C., R.E.G., A.H.M., M.A.M., J.C.B.E., A.G.N., R.G.F., M.P.A., and R.G.S.; writing—original draft preparation, M.R.-R.; writing—review and editing, M.R.-R. and X.C.; visualization M.R.-R. and X.C.; supervision, M.R.-R. and X.C.; project administration, J.M.N.-C. and J.M.C.-R. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Bellvitge University Hospital (PR 128/20).
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement
Restrictions apply to the availability of these data. Data was obtained from SEMI-COVID-19 registry and are available from the authors with the permission of SEMI-COVID-19 registry.
Acknowledgments
We gratefully acknowledge all the investigators who participated in the SEMI-COVID-19 Registry. We also thank the SEMI-COVID-19 Registry Coordinating Centre, S&H Medical Science Service, for their quality control data and logistic and administrative support. We also thank CERCA Programme/Generalitat de Catalunya for institutional support.
List of the SEMI-COVID-19 Network members
Coordinator of the SEMI-COVID-19 Registry: José Manuel Casas Rojo
SEMI-COVID-19 Scientific Committee Members:
José Manuel Casas Rojo, José Manuel Ramos Rincón, Carlos Lumbreras Bermejo, Jesús Millán Núñez-Cortés, Juan Miguel Antón Santos, Ricardo Gómez Huelgas.
Members of the SEMI-COVID-19 Group:
H. Univ. de Bellvitge. L’Hospitalet de Llobregat (Barcelona)
Xavier Corbella, Narcís Homs, Abelardo Montero, Jose María Mora-Luján, Manuel Rubio-Rivas.
H. U. 12 de Octubre. Madrid
Paloma Agudo de Blas, Coral Arévalo Cañas, Blanca Ayuso, José Bascuñana Morejón, Samara Campos Escudero, María Carnevali Frías, Santiago Cossio Tejido, Borja de Miguel Campo, Carmen Díaz Pedroche, Raquel Diaz Simon, Ana García Reyne, Lucia Jorge Huerta, Antonio Lalueza Blanco, Jaime Laureiro Gonzalo, Jaime Lora-Tamayo, Carlos Lumbreras Bermejo, Guillermo Maestro de la Calle, Barbara Otero Perpiña, Diana Paredes Ruiz, Marcos Sánchez Fernández, Javier Tejada Montes.
H. U. Gregorio Marañon. Madrid
Laura Abarca Casas, Álvaro Alejandre de Oña, Rubén Alonso Beato, Leyre Alonso Gonzalo, Jaime Alonso Muñoz, Crhistian Mario Amodeo Oblitas, Cristina Ausín García, Marta Bacete Cebrián, Jesús Baltasar Corral, Maria Barrientos Guerrero, Alejandro D. Bendala Estrada, María Calderón Moreno, Paula Carrascosa Fernández, Raquel Carrillo, Sabela Castañeda Pérez, Eva Cervilla Muñoz, Agustín Diego Chacón Moreno, Maria Carmen Cuenca Carvajal, Sergio de Santos, Andrés Enríquez Gómez, Eduardo Fernández Carracedo, María Mercedes Ferreiro-Mazón Jenaro, Francisco Galeano Valle, Alejandra Garcia, Irene Garcia Fernandez-Bravo, María Eugenia García Leoni, María Gómez Antúnez, Candela González San Narciso, Anthony Alexander Gurjian, Lorena Jiménez Ibáñez, Cristina Lavilla Olleros, Cristina Llamazares Mendo, Sara Luis García, Víctor Mato Jimeno, Clara Millán Nohales, Jesús Millán Núñez-Cortés, Sergio Moragón Ledesma, Antonio Muiño Míguez, Cecilia Muñoz Delgado, Lucía Ordieres Ortega, Susana Pardo Sánchez, Alejandro Parra Virto, María Teresa Pérez Sanz, Blanca Pinilla Llorente, Sandra Piqueras Ruiz, Guillermo Soria Fernández-Llamazares, María Toledano Macías, Neera Toledo Samaniego, Ana Torres do Rego, Maria Victoria Villalba Garcia, Gracia Villarreal, María Zurita Etayo.
H. de Cabueñes. Gijón (Asturias)
Ana María Álvarez Suárez, Carlos Delgado Vergés, Rosa Fernandez-Madera Martínez, Eva Mª Fonseca Aizpuru, Alejandro Gómez Carrasco, Cristina Helguera Amezua, Juan Francisco López Caleya, María del Mar Martínez López, Aleida Martínez Zapico, Carmen Olabuenaga Iscar, María Luisa Taboada Martínez, Lara María Tamargo Chamorro.
H. U. La Paz. Madrid
Jorge Álvarez Troncoso, Francisco Arnalich Fernández, Francisco Blanco Quintana, Carmen Busca Arenzana, Sergio Carrasco Molina, Aranzazu Castellano Candalija, Germán Daroca Bengoa, Alejandro de Gea Grela, Alicia de Lorenzo Hernández, Alejandro Díez Vidal, Carmen Fernández Capitán, Maria Francisca García Iglesias, Borja González Muñoz, Carmen Rosario Herrero Gil, Juan María Herrero Martínez, Víctor Hontañón, Maria Jesús Jaras Hernández, Carlos Lahoz, Cristina Marcelo Calvo, Juan Carlos Martín Gutiérrez, Monica Martinez Prieto, Elena Martínez Robles, Araceli Menéndez Saldaña, Alberto Moreno Fernández, Jose Maria Mostaza Prieto, Ana Noblejas Mozo, Carlos Manuel Oñoro López, Esmeralda Palmier Peláez, Marina Palomar Pampyn, Maria Angustias Quesada Simón, Juan Carlos Ramos Ramos, Luis Ramos Ruperto, Aquilino Sánchez Purificación, Teresa Sancho Bueso, Raquel Sorriguieta Torre, Clara Itziar Soto Abanedes, Yeray Untoria Tabares, Marta Varas Mayoral, Julia Vásquez Manau.
H. Costa del Sol. Marbella (Málaga)
Victoria Augustín Bandera, Javier García Alegría, Nicolás Jiménez-García, Jairo Luque del Pino, María Dolores Martín Escalante, Francisco Navarro Romero, Victoria Nuñez Rodriguez, Julián Olalla Sierra.
H. Royo Villanova. Zaragoza
Nicolás Alcalá Rivera, Anxela Crestelo Vieitez, Esther del Corral Beamonte, Jesús Díez Manglano, Isabel Fiteni Mera, Maria del Mar Garcia Andreu, Martin Gericó Aseguinolaza, Claudia Josa Laorden, Raul Martínez Murgui, Marta Teresa Matía Sanz.
H. Clínico de Santiago de Compostela (A Coruña)
Maria del Carmen Beceiro Abad, Maria Aurora Freire Romero, Sonia Molinos Castro, Emilio Manuel Paez Guillan, María Pazo Nuñez, Paula Maria Pesqueira Fontan.
H. Clínico San Carlos. Madrid
Inés Armenteros Yeguas, Javier Azaña Gómez, Julia Barrado Cuchillo, Irene Burruezo López, Noemí Cabello Clotet, Alberto E. Calvo Elías, Elpidio Calvo Manuel, Carmen María Cano de Luque, Cynthia Chocron Benbunan, Laura Dans Vilan, Claudia Dorta Hernández, Ester Emilia Dubon Peralta, Vicente Estrada Pérez, Santiago Fernandez-Castelao, Marcos Oliver Fragiel Saavedra, José Luis García Klepzig, Maria del Rosario Iguarán Bermúdez, Esther Jaén Ferrer, Alejandro Maceín Rodríguez, Alejandro Marcelles de Pedro, Rubén Ángel Martín Sánchez, Manuel Méndez Bailón, Sara Miguel Álvarez, Maria José Nuñez Orantos, Carolina Olmos Mata, Eva Orviz García, David Oteo Mata, Cristina Outon González, Juncal Perez-Somarriba, Pablo Pérez Mateos, Maria Esther Ramos Muñoz, Xabier Rivas Regaira, Laura Mª Rodríguez Gallardo, Iñigo Sagastagoitia Fornie, Alejandro Salinas Botrán, Miguel Suárez Robles, Maddalena Elena Urbano, Andrea María Vellisca González, Miguel Villar Martínez.
H. Universitario Dr. Peset. Valencia
Juan Alberto Aguilera Ayllón, Arturo Artero, María del Mar Carmona Martín, María José Fabiá Valls, Maria de Mar Fernández Garcés, Ana Belén Gómez Belda, Ian López Cruz, Manuel Madrazo López, Elisabeth Mateo Sanchis, Jaume Micó Gandia, Laura Piles Roger, Adela Maria Pina Belmonte, Alba Viana García.
H. U. La Princesa. Madrid
María Aguilera García, Ester Alonso Monge, Jesús Álvarez Rodríguez, Claudia Alvarez Varela, Miquel Berniz Gòdia, Marta Briega Molina, Marta Bustamante Vega, Jose Curbelo, Alicia de las Heras Moreno, Ignacio Descalzo Godoy, Alexia Constanza Espiño Alvarez, Ignacio Fernández Martín-Caro, Alejandra Franquet López-Mosteiro, Gonzalo Galvez Marquez, María José García Blanco, Yaiza García del Álamo Hernández, Clara García-Rayo Encina, Noemí Gilabert González, Carolina Guillamo Rodríguez, Nicolás Labrador San Martín, Manuel Molina Báez, Carmen Muñoz Delgado, Pedro Parra Caballero, Javier Pérez Serrano, Laura Rabes Rodríguez, Pablo Rodríguez Cortés, Carlos Rodriguez Franco, Emilia Roy-Vallejo, Monica Rueda Vega, Aresio Sancha Lloret, Beatriz Sánchez Moreno, Marta Sanz Alba, Jorge Serrano Ballesteros, Alba Somovilla, Carmen Suarez Fernández, Macarena Vargas Tirado, Almudena Villa Marti.
H. U. Puerta de Hierro. Madrid
María Álvarez Bello, Ane Andrés Eisenhofer, Ana Arias Milla, Isolina Baños Pérez, Laura Benítez Gutiérrez, Javier Bilbao Garay, Silvia Blanco Alonso, Jorge Calderón Parra, Alejandro Callejas Díaz, José María Camino Salvador, Mª Cruz Carreño Hernández, Valentín Cuervas-Mons Martínez, Sara de la Fuente Moral, Miguel del Pino Jimenez, Alberto Díaz de Santiago, Itziar Diego Yagüe, Ignacio Donate Velasco, Ana María Duca, Pedro Durán del Campo, Gabriela Escudero López, Esther Expósito Palomo, Ana Fernández Cruz, Esther Fiz Benito, Andrea Fraile López, Amy Galán Gómez, Sonia García Prieto, Claudia García Rodríguez-Maimón, Miguel Ángel García Viejo, Javier Gómez Irusta, Edith Vanessa Gutiérrez Abreu, Isabel Gutiérrez Martín, Ángela Gutiérrez Rojas, Andrea Gutiérrez Villanueva, Jesús Herráiz Jiménez, Pedro Laguna del Estal, Mª Carmen Máinez Sáiz, Cristina Martín Martín, María Martínez Urbistondo, Fernando Martínez Vera, Susana Mellor Pita, Patricia Mills Sánchez, Esther Montero Hernández, Alberto Mora Vargas, Cristina Moreno López, Alfonso Ángel-Moreno Maroto, Victor Moreno-Torres, Concha, Ignacio Morrás De La Torre, Elena Múñez Rubio, Rosa Muñoz de Benito, Ana Muñoz Gómez, Alejandro Muñoz Serrano, Jose María Palau Fayós, Lina Marcela Parra Ramírez, Ilduara Pintos Pascual, Arturo José Ramos Martín-Vegue, Antonio Ramos Martínez, Isabel Redondo Cánovas del Castillo, Alberto Roldán Montaud, Lucía Romero Imaz, Yolanda Romero Pizarro, Enrique Sánchez Chica, David Sánchez Órtiz, Mónica Sánchez Santiuste, Patricia Serrano de la Fuente, Pablo Tutor de Ureta, Ángela Valencia Alijo, Mercedes Valentín-Pastrana Aguilar, Juan Antonio Vargas Núñez, Jose Manuel Vázquez Comendador, Gema Vázquez Contreras, Carmen Vizoso Gálvez.
H. Reg. Univ. de Málaga
Mª Mar Ayala-Gutiérrez, Rosa Bernal López, José Bueno Fonseca, Verónica Andrea Buonaiuto, Luis Francisco Caballero Martínez, Lidia Cobos Palacios, Clara Costo Muriel, Francis de Windt, Ana Teresa Fernandez-Truchaud Christophel, Paula García Ocaña, Ricardo Gómez Huelgas, Javier Gorospe García, Sergio Jansen-Chaparro, Maria Dolores López-Carmona, Pablo López Quirantes, Almudena López Sampalo, Elizabeth Lorenzo-Hernández, Juan José Mancebo Sevilla, Jesica Martín Carmona, Luis Miguel Pérez-Belmonte, Iván Pérez de Pedro, Araceli Pineda-Cantero, Carlos Romero Gómez, Michele Ricci, Jaime Sanz Cánovas.
H. Moisès Broggi. Sant Joan Despí (Barcelona)
Judit Aranda Lobo, Lucía Feria Casanovas, Jose Loureiro Amigo, Miguel Martín Fernández, Isabel Oriol Bermúdez, Melani Pestaña Fernández, Nicolas Rhyman, Nuria Vázquez Piqueras.
H. U. Río Hortega. Valladolid
Irene Arroyo Jiménez, Marina Cazorla González, Marta Cobos-Siles, Luis Corral-Gudino, Pablo Cubero-Morais, María González Fernández, José Pablo Miramontes González, Marina Prieto Dehesa, Pablo Sanz Espinosa.
H. Nuestra Señora del Prado. Talavera de la Reina (Toledo)
Sonia Casallo Blanco, Jeffrey Oskar Magallanes Gamboa, Cristina Salazar Mosteiro, Andrea Silva Asiain.
H. U. S. Juan de Alicante (Alicante)
Marisa Asensio Tomás, David Balaz, David Bonet Tur, Ruth Cañizares Navarro, Paloma Chazarra Pérez, Jesús Corbacho Redondo, Eliana Damonte White, Leticia Espinosa Del Barrio, Pedro Jesús Esteve Atiénzar, Carles García Cervera, David Francisco García Núñez, Vicente Giner Galvañ, Angie Gómez Uranga, Javier Guzmán Martínez, Isidro Hernández Isasi, Lourdes Lajara Villar, Verónica Martínez Sempere, Juan Manuel Núñez Cruz, Sergio Palacios Fernández, Juan Jorge Peris García, Andrea Riaño Pérez, José Miguel Seguí Ripoll, Azucena Sempere Mira, Philip Wikman-Jorgensen.
H. Virgen de la Salud. Toledo
Ana Maria Alguacil Muñoz, Marta Blanco Fernández, Veronica Cano, Ricardo Crespo Moreno, Fernando Cuadra Garcia-Tenorio, Blanca Díaz-Tendero Nájera, Raquel Estévez González, María Paz García Butenegro, Alberto Gato Díez, Verónica Gómez Caverzaschi, Piedad María Gómez Pedraza, Julio González Moraleja, Raúl Hidalgo Carvajal, Patricia Jiménez Aranda, Raquel Labra González, Áxel Legua Caparachini, Pilar Lopez Castañeyra, Agustín Lozano Ancin, Jose Domingo Martin Garcia, Cristina Morata Romero, María Jesús Moya Saiz, Helena Moza Moríñigo, Gemma Muñiz Nicolás, Enriqueta Muñoz Platon, Filomena Oliveri, Elena Ortiz Ortiz, Raúl Perea Rafael, Pilar Redondo Galán, María Antonia Sepulveda Berrocal, Vicente Serrano Romero de Ávila, Pilar Toledano Sierra, Yamilex Urbano Aranda, Jesús Vázquez Clemente, Carmen Yera Bergua.
H. U. Reina Sofía. Córdoba
Antonio Pablo Arenas de Larriva, Pilar Calero Espinal, Javier Delgado Lista, Francisco Fuentes-Jiménez, María Jesús Gómez Vázquez, Jose Jiménez Torres, Laura Limia Pérez, José López-Miranda, Laura Martín Piedra, Marta Millán Orge, Javier Pascual Vinagre, Pablo Pérez-Martinez, María Elena Revelles Vílchez, Angela Rodrigo Martínez, Juan Luis Romero Cabrera, José David Torres-Peña.
C. H. U. de Badajoz
Rafael Aragon Lara, Inmaculada Cimadevilla Fernandez, Juan Carlos Cira García, Gema Maria García García, Julia Gonzalez Granados, Beatriz Guerrero Sánchez, Francisco Javier Monreal Periáñez, Maria Josefa Pascual Perez.
H. Santa Marina. Bilbao
María Areses Manrique, Ainara Coduras Erdozain, Ane Labirua-Iturburu Ruiz.
H. Juan Ramón Jiménez. Huelva
Francisco Javier Bejarano Luque, Francisco-Javier Carrasco-Sánchez, Mercedes de-Sousa-Baena, Jaime Díaz Leal, Aurora Espinar Rubio, Maria Franco Huertas, Juan Antonio García Bravo, Andrés Gonzalez Macías, Encarnación Gutiérrez Jiménez, Alicia Hidalgo Jiménez, Constantino Lozano Quintero, Carmen Mancilla Reguera, Francisco Javier Martínez Marcos, Francisco Muñoz Beamud, Maria Pérez-Aguilar, Alícia Pérez Jiménez, Virginia Rodríguez Castaño, Alvaro Sánchez de Alcazar del Río, Leire Toscano Ruiz.
H. U. Son Llàtzer. Palma de Mallorca
Andrés de la Peña Fernández, Almudena Hernández Milián.
H. del Henares. Coslada (Madrid)
Jesús Ballano Rodríguez-Solís, Luis Cabeza Osorio, María del Pilar Fidalgo Montero, Mª Isabel Fuentes Soriano, Erika Esperanza Lozano Rincón, Ana Martín Hermida, Jesús Martínez Carrilero, José Ángel Pestaña Santiago, Manuel Sánchez Robledo, Patricia Sanz Rojas, Nahum Jacobo Torres Yebes, Vanessa Vento.
H. U. Ramón y Cajal. Madrid
Luis Fernando Abrego Vaca, Ana Andréu Arnanz, Octavio Arce García, Marta Bajo González, Pablo Borque Sanz, Alberto Cozar Llisto, Sonia de Pedro Baena, Beatriz Del Hoyo Cuenda, Martin Fabregate-Fuente, María Alejandra Gamboa Osorio, Isabel García Sánchez, Andrés González García, Oscar Alberto López Cisneros, Luis Manzano, Miguel Martínez-Lacalzada, Borja Merino Ortiz, Jimena Rey-García, Elisa Riera González, Cristina Sánchez Díaz, Grisell Starita Fajardo, Cecilia Suárez Carantoña, Adrian Viteri-Noël, Svetlana Zhilina Zhilina.
H. U. Infanta Cristina. Parla (Madrid)
Gonzalo García Casasola Sánchez, Juan Miguel Antón Santos, Elena Sierra Gonzalo, Elena Garcia Guijarro, José Manuel Casas Rojo, Lorea Roteta García, Davide Luordo, Ana Belén Barbero Barrera, María Mateos González, Irene Casado Lopez, Andrés Cortés Troncoso, Francesco Deodati, Javier Villanueva Martínez, Ruth Calderón Hernaiz, Mayte De Guzmán García-Monge, Coralia Bueno Muiño, Jose A Melero Bermejo.
H. U. Torrevieja (Alicante)
Julio César Blázquez Encinar.
C. H. U. Ourense
Raquel Fernández González, Amara Gonzalez Noya, Carlos Hernández Ceron, Isabel Izuzquiza Avanzini, Ana Latorre Diez, Pablo López Mato, Ana María Lorenzo Vizcaya, Daniel Peña Benítez, Milagros María Peña Zemsch, Lucía Pérez Expósito, Marta Pose Bar, Lara Rey González, Laura Rodrigo Lara.
H. San Pedro. Logroño (La Rioja)
Diana Alegre González, Irene Ariño Pérez de Zabalza, Sergio Arnedo Hernández, Jorge Collado Sáenz, Beatriz Dendariena, Marta Gómez del Mazo, Iratxe Martínez de Narvajas Urra, Sara Martínez Hernández, Estela Menendez Fernández, Jose Luís Peña Somovilla, Elisa Rabadán Pejenaute.
H. U. La Fe. Valencia
Dafne Cabañero, María Calabuig Ballester, Pascual Císcar Fernández, Ricardo Gil Sánchez, Marta Jiménez Escrig, Cristina Marín Amela, Laura Parra Gómez, Carlos Puig Navarro, José Antonio Todolí Parra.
H. de Mataró. Barcelona
Raquel Aranega González, Ramon Boixeda, Javier Fernández Fernández, Carlos Lopera Mármol, Marta Parra Navarro, Ainhoa Rex Guzmán, Aleix Serrallonga Fustier.
H. Alto Guadalquivir. Andújar (Jaén)
Begoña Cortés Rodríguez.
H. de Sagunto (Valencia)
Enrique Rodilla Sala, Jose María Pascual Izuel, Zineb Karroud Zamrani.
H. G. U. de Elda (Alicante)
Carmen Cortés Saavedra, Jennifer Fernández Gómez, Borja González López, María Soledad Hernández Garrido, Ana Isabel López Amorós, Santiago López Gil, Maria de los Reyes Pascual Pérez, Nuria Ramírez Perea, Andrea Torregrosa García.
H. de Pozoblanco (Córdoba)
José Nicolás Alcalá Pedrajas, Antonia Márquez García, Inés Vargas.
H. Infanta Margarita. Cabra (Córdoba)
María Esther Guisado Espartero, Lorena Montero Rivas, Maria de la Sierra Navas Alcántara, Raimundo Tirado-Miranda.
C. H. U. de Ferrol (A Coruña)
Hortensia Alvarez Diaz, Tamara Dalama Lopez, Estefania Martul Pego, Carmen Mella Pérez, Ana Pazos Ferro, Sabela Sánchez Trigo, Dolores Suarez Sambade, Maria Trigas Ferrin, Maria del Carmen Vázquez Friol, Laura Vilariño Maneiro.
H. Marina Baixa. Villajoyosa (Alicante)
Javier Ena, José Enrique Gómez Segado.
H. del Tajo. Aranjuez (Madrid)
Ruth Gonzalez Ferrer, Virginia Gracia Lorenzo, Raquel Monsalvo Arroyo.
H. Dr. José Molina Orosa. Arrecife (Lanzarote)
Virginia Herrero García, Berta Román Bernal.
H. U. Virgen del Rocío. Sevilla
Máximo Bernabeu-Wittel, Santiago Rodríguez Suárez, María Nieto, Luis Giménez Miranda, Rosa María Gámez Mancera, Fátima Espinosa Torre, Carlos Hernandez Quiles, Concepción Conde Guzmán, Juan Delgado de la Cuesta, Jara Eloisa Ternero Vega, María del Carmen López Ríos, Pablo Díaz Jiménez, Bosco Baron Franco, Carlos Jiménez de Juan, Sonia Gutiérrez Rivero, Julia Lanseros Tenllado, Verónica Alfaro Lara, Aurora González Estrada.
H. U. Marqués de Valdecilla. Santander
Marta Fernández-Ayala Novo, José Javier Napal Lecumberri, Nuria Puente Ruiz, Jose Riancho, Isabel Sampedro García.
H. U. Virgen de las Nieves. Granada
Pablo Conde Baena, Joaquín Escobar Sevilla, Laura Gallo Padilla, Patricia Gómez Ronquillo, Pablo González Bustos, María Navío Botías, Jessica Ramírez Taboada, Mar Rivero Rodríguez.
H. General Defensa. Zaragoza
Anyuli Gracia Gutiérrez, Leticia Esther Royo Trallero.
H. G. U. de Castellón
Jorge Andrés Soler, Marián Bennasar Remolar, Alejandro Cardenal Álvarez, Daniela Díaz Carlotti, María José Esteve Gimeno, Sergio Fabra Juana, Paula García López, María Teresa Guinot Soler, Daniela Palomo de la Sota, Guillem Pascual Castellanos, Ignacio Pérez Catalán, Celia Roig Martí, Paula Rubert Monzó, Javier Ruiz Padilla, Nuria Tornador Gaya, Jorge Usó Blasco.
H. de Palamós (Girona)
Ana Alberich Conesa, Mari Cruz Almendros Rivas, Miquel Hortos Alsina, José Marchena Romero, Anabel Martin-Urda Diez-Canseco.
C. A. U. de Salamanca
Gloria María Alonso Claudio, Víctor Barreales Rodríguez, Cristina Carbonell Muñoz, Adela Carpio Pérez, María Victoria Coral Orbes, Daniel Encinas Sánchez, Sandra Inés Revuelta, Miguel Marcos Martín, José Ignacio Martín González, José Ángel Martín Oterino, Leticia Moralejo Alonso, Sonia Peña Balbuena, María Luisa Pérez García, Ana Ramon Prados, Beatriz Rodríguez-Alonso, Ángela Romero Alegría, Maria Sanchez Ledesma, Rosa Juana Tejera Pérez.
H. Platón. Barcelona
Ana Suárez Lombraña.
H. Público de Monforte de Lemos (Lugo)
José López Castro, Manuel Lorenzo López Reboiro, Cristina Sardiña González.
H. Santa Bárbara. Soria
Marta León Téllez.
H. Parc Tauli. Sabadell (Barcelona)
Francisco Epelde, Isabel Torrente.
H. U. Lucus Augusti. Lugo
Raquel Gómez Méndez, Ana Rodríguez Álvarez.
H. Comarcal de Blanes (Girona)
Oriol Alonso Gisbert, Mercé Blázquez Llistosella, Pere Comas Casanova, Angels Garcia Flores, Anna Garcia Hinojo, Ana Inés Méndez Martínez, Maria del Carmen Nogales Nieves, Agnés Rivera Austrui, Alberto Zamora Cervantes.
H. de la Axarquía. Vélez-Málaga (Málaga)
Antonio López Ruiz.
H. do Salnes. Vilagarcía de Arousa (Pontevedra)
Vanesa Alende Castro, Ana María Baz Lomba, Ruth Brea Aparicio, Marta Fernández Morales, Jesús Manuel Fernández Villar, María Teresa López Monteagudo, Cristina Pérez García, Lorena Rodríguez Ferreira, Diana Sande Llovo, Maria Begoña Valle Feijoo.
H. U. HM Montepríncipe
José F. Varona.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1.
Time to death for the three categories (Log rank 325.6 p < 0.001).
Figure 2.
Time to death for high-risk patients according to the number of high-risk criteria.
Table 1.
Categories of risk.
| Low Risk | Intermediate Risk | High Risk | |
|---|---|---|---|
| Lymphocyte count ×106/L | >1150 | 760–1150 | <760 |
| CRP (mg/L) | <31.8 | 31.8–101.5 | >101.5 |
| LDH (U/L) | <271 | 271–394 | >394 |
| Ferritin (mcg/L) | <572.9 | 572.9–1359.9 | >1359.9 |
| D-dimer (ng/mL) | <539 | 539–1580 | >1580 |
CRP: C-reactive protein. LDH: lactate dehydrogenase. The colors in the table indicate the risk traffic light in 3 categories: low risk (green), intermediate risk (yellow), and high risk (red).
Table 2.
General data for the three categories.
| Low Risk | Intermediate Risk | High Risk | p-Value | |
|---|---|---|---|---|
| N | 352 | 3018 | 13,752 | |
| Age, median (IQR) | 57.9 (43.7–71.3) | 64.2 (51.7–76.5) | 70.4 (57.8–80.3) | <0.001 |
| Gender (males) | 132 (37.5) | 1416 (46.9) | 8264 (60.1) | <0.001 |
| Days from onset to admission, median (IQR) | 6 (3–10) | 7 (4–9) | 6 (3–9) | 0.005 |
| Smoking behaviour | <0.001 | |||
| Never smoker | 254 (72.2) | 2201 (72.9) | 9485 (69) | |
| Former smoker | 71 (20.2) | 664 (22) | 3582 (26) | |
| Current smoker | 27 (7.7) | 153 (5.1) | 685 (5) | |
| Degree of dependency | <0.001 | |||
| None or mild | 314 (89.2) | 2595 (86) | 11,423 (83.1) | |
| Moderate | 24 (6.8) | 231 (7.7) | 1329 (9.7) | |
| Severe | 14 (4) | 192 (6.4) | 1000 (7.3) | |
| Arterial hypertension | 130 (36.9) | 1365 (45.2) | 7260 (52.8) | <0.001 |
| Dyslipidemia | 100 (28.4) | 1118 (37) | 5584 (40.6) | <0.001 |
| Diabetes mellitus | 42 (11.9) | 516 (17.1) | 2822 (20.5) | <0.001 |
| Ischaemic cardiopathy | 13 (3.7) | 196 (6.5) | 1151 (8.4) | <0.001 |
| Chronic heart failure | 12 (3.4) | 158 (5.2) | 1045 (7.6) | <0.001 |
| Chronic liver disease | 4 (1.1) | 91 (3) | 537 (3.9) | 0.002 |
| Severe chronic renal failure | 8 (2.3) | 108 (3.6) | 920 (6.7) | <0.001 |
| Cancer | 23 (6.5) | 216 (7.2) | 1521 (11.1) | <0.001 |
| COPD | 20 (5.7) | 163 (5.4) | 972 (7.1) | 0.003 |
| Asthma | 40 (11.4) | 279 (9.2) | 895 (7.1) | <0.001 |
| OSAS | 16 (4.5) | 188 (6.2) | 839 (6.1) | 0.455 |
IQR: interquartile range. COPD: chronic obstructive pulmonary disease. OSAS: obstructive sleep apnea syndrome. Severe chronic renal failure: Creatinin >300 mg/dL or dyalisis.
Table 3.
Symptoms and physical examination upon admission for the three categories.
| Low Risk | Intermediate Risk | High Risk | p-Value | |
|---|---|---|---|---|
| Cough, n (%) | 258 (73.3) | 2269 (75.2) | 9950 (72.4) | 0.007 |
| Arthromyalgias, n (%) | 108 (30.7) | 1027 (34) | 4011 (29.2) | <0.001 |
| Ageusia, n (%) | 39 (11.1) | 343 (11.4) | 1070 (7.8) | <0.001 |
| Anosmia, n (%) | 43 (12.2) | 303 (10) | 926 (6.7) | <0.001 |
| Sore throat, n (%) | 50 (14.2) | 344 (11.4) | 1237 (9) | <0.001 |
| Headache, n (%) | 58 (16.5) | 448 (14.8) | 1499 (10.9) | <0.001 |
| Fever, n (%) | 251 (71.3) | 2506 (83) | 11,592 (84.3) | <0.001 |
| Dyspnea, n (%) | 184 (52.3) | 1542 (51.1) | 8121 (59.1) | <0.001 |
| Diarrhea, n (%) | 83 (23.6) | 790 (26.2) | 3224 (23.4) | 0.006 |
| Vomiting, n (%) | 12 (3.4) | 235 (7.8) | 1097 (8) | 0.007 |
| Abdominal pain, n (%) | 26 (7.4) | 195 (6.5) | 894 (6.5) | 0.795 |
| Heart rate, bpm median (IQR) | 85.5 (75–98) | 85 (75–97) | 88 (77–100) | <0.001 |
| Respiratory rate >20 rpm, n (%) | 45 (12.8) | 579 (19.2) | 4809 (35) | <0.001 |
IQR: interquartile range.
Table 4.
Lab tests upon admission for the three categories.
| Low Risk | Intermediate Risk | High Risk | p-Value | |
|---|---|---|---|---|
| Lymphocytes ×106/L, median (IQR) | 1605 (1340–2100) | 1180 (960–1500) | 860 (600–1200) | <0.001 |
| CRP mg/L, median (IQR) | 6.3 (2.2–14.9) | 30 (10.7–57) | 81.5 (28.2–151) | <0.001 |
| LDH U/L, median (IQR) | 203 (175–230) | 261 (213–312) | 360 (267–486.4) | <0.001 |
| Ferritin mcg/L, median (IQR) | 220.3 (103.5–371) | 534 (259.2–891) | 1144.7 (532–1834.5) | <0.001 |
| D-dimer ng/mL, median (IQR) | 286.5 (210.8–400) | 490 (280–776.3) | 1131 (510–4347.8) | <0.001 |
CRP: C-reactive protein. LDH: lactate dehydrogenase. IQR: interquartile range.
Table 5.
Outcomes for the three categories.
| Low Risk | Intermediate Risk | High Risk | p-Value | |
|---|---|---|---|---|
| HFNC, n (%) | 11 (3.1) | 132 (4.4) | 1319 (9.7) | <0.001 |
| NIMV, n (%) | 3 (0.9) | 90 (3) | 857 (6.3) | <0.001 |
| IMV, n (%) | 2 (0.6) | 80 (2.7) | 1195 (8.7) | <0.001 |
| ICU admission, n (%) | 3 (0.9) | 109 (3.6) | 1453 (10.6) | <0.001 |
| In-hospital mortality, n (%) | 8 (2.3) | 186 (6.2) | 3291 (23.9) | <0.001 |
HFNC: high Flow nasal cannula. NIMV: non-invasive mechanical ventilation. IMV: invasive mechanical ventilation. ICU: intensive care unit.
Table 6.
Risk factors of in-hospital mortality.
| Univariate Analysis | Multivariate Analysis | |||
|---|---|---|---|---|
| OR (95% CI) | p-Value | OR (95% CI) | p-Value | |
| Age | 1.08 (1.08–1.09) | <0.001 | 1.07 (1.07–1.08) | <0.001 |
| Gender (female) | 0.76 (0.70–0.82) | <0.001 | 0.67 (0.61–0.74) | <0.001 |
| Smoking behaviour | ||||
| Never smoker | 1 ref. | 1 ref. | ||
| Former smoker | 1.57 (1.45–1.70) | <0.001 | 1.12 (1.00–1.24) | 0.052 |
| Current smoker | 1.06 (0.89–1.26) | 0.540 | 1.27 (1.03–1.58) | 0.025 |
| Degree of dependency | ||||
| None or mild | 1 ref. | 1 ref. | ||
| Moderate | 4.20 (3.77–4.69) | <0.001 | 1.60 (1.41–1.83) | <0.001 |
| Severe | 4.99 (4.42–5.63) | <0.001 | 2.01 (1.73–2.33) | <0.001 |
| Arterial hypertension | 2.77 (2.56–3.00) | <0.001 | - | NS |
| Dyslipidemia | 1.77 (1.64–1.91) | <0.001 | - | NS |
| Diabetes mellitus | 1.97 (1.81–2.15) | <0.001 | 1.21 (1.09–1.34) | <0.001 |
| Ischaemic cardiopathy | 2.41 (2.14–2.71) | <0.001 | 1.25 (1.08–1.44) | 0.002 |
| Chronic heart failure | 3.32 (2.94–3.74) | <0.001 | - | NS |
| Chronic liver disease | 1.49 (1.24–1.78) | <0.001 | 1.32 (1.07–1.63) | 0.011 |
| Severe chronic renal failure | 3.19 (2.80–3.62) | <0.001 | 1.50 (1.29–1.76) | <0.001 |
| Cancer | 2.04 (1.83–2.27) | <0.001 | 1.54 (1.35–1.75) | <0.001 |
| COPD | 2.53 (2.24–2.87) | <0.001 | - | NS |
| Asthma | 0.62 (0.52–0.73) | <0.001 | - | NS |
| OSAS | 1.36 (1.18–1.57) | <0.001 | - | NS |
| Respiratory rate > 20 rpm | 3.91 (3.62–4.22) | <0.001 | 3.21 (2.94–3.51) | <0.001 |
| Three risk categories | ||||
| Low risk | 1 ref. | 1 ref. | ||
| Intermediate risk | 2.82 (1.38–5.78) | 0.005 | 1.91 (0.90–4.05) | 0.093 |
| High risk | 13.53 (6.7–27.30) | <0.001 | 7.31 (3.49–15.28) | <0.001 |
NS: Not significant. COPD: chronic obstructive pulmonary disease. OSAS: obstructive sleep apnea syndrome.
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Rubio-Rivas, M.; Corbella, X.; Formiga, F.; Menéndez Fernández, E.; Martín Escalante, M.D.; Baños Fernández, I.; Arnalich Fernández, F.; Del Corral-Beamonte, E.; Lalueza, A.; Parra Virto, A.; et al. Risk Categories in COVID-19 Based on Degrees of Inflammation: Data on More Than 17,000 Patients from the Spanish SEMI-COVID-19 Registry. J. Clin. Med. 2021, 10, 2214. https://doi.org/10.3390/jcm10102214
AMA Style
Rubio-Rivas M, Corbella X, Formiga F, Menéndez Fernández E, Martín Escalante MD, Baños Fernández I, Arnalich Fernández F, Del Corral-Beamonte E, Lalueza A, Parra Virto A, et al. Risk Categories in COVID-19 Based on Degrees of Inflammation: Data on More Than 17,000 Patients from the Spanish SEMI-COVID-19 Registry. Journal of Clinical Medicine. 2021; 10(10):2214. https://doi.org/10.3390/jcm10102214
Chicago/Turabian StyleRubio-Rivas, Manuel, Xavier Corbella, Francesc Formiga, Estela Menéndez Fernández, María Dolores Martín Escalante, Isolina Baños Fernández, Francisco Arnalich Fernández, Esther Del Corral-Beamonte, Antonio Lalueza, Alejandro Parra Virto, and et al. 2021. "Risk Categories in COVID-19 Based on Degrees of Inflammation: Data on More Than 17,000 Patients from the Spanish SEMI-COVID-19 Registry" Journal of Clinical Medicine 10, no. 10: 2214. https://doi.org/10.3390/jcm10102214
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