COPD and COVID-19: Spain's First vs. Second Wave
COPD and COVID-19: Spain's First vs. Second Wave
Revista Clínica
Española
www.elsevier.es/rce
ORIGINAL ARTICLE
a
Hospital General Universitario Gregorio Marañón, Madrid, Spain
b
Hospital Universitario de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain
c
Hospital Costa del Sol. Marbella, Málaga, Spain
d
Hospital Universitario 12 de Octubre, Madrid, Spain
e
Hospital Clínico Universitario San Juan, San Juan de Alicante, Alicante, Spain
f
Hospital Universitario de Cabueñes, Gijón, Asturias, Spain
g
Hospital Universitario Infanta Cristina, Parla, Madrid, Spain
KEYWORDS Abstract
COPD; Objective: This work aimed to compare the characteristics, progress, and prognosis of patients
COVID-19; with COPD hospitalized due to COVID-19 in Spain in the first wave with those of the second
SARS-CoV-2; wave.
First and second Material and methods: This is an observational study of patients hospitalized in Spain with
wave of infection; a diagnosis of COPD included in the SEMI-COVID-19 registry. The medical history, symptoms,
Prognosis analytical and radiological results, treatment, and progress of patients with COPD hospitalized
in the first wave (from March to June 2020) versus those hospitalized in the second wave (from
July to December 2020) were compared. Factors associated with poor prognosis, defined as all-
cause mortality and a composite endpoint that included mortality, high-flow oxygen therapy,
mechanical ventilation, and ICU admission, were analyzed.
Results: Of the 21,642 patients in the SEMI-COVID-19 Registry, 6.9% were diagnosed with COPD:
1128 (6.8%) in WAVE1 and 374 (7.7%) in WAVE2 (p = 0.04). WAVE2 patients presented less dry
cough, fever and dyspnea, hypoxemia (43% vs 36%, p < 0.05), and radiological condensation (46%
vs 31%, p < 0.05) than WAVE1 patients. Mortality was lower in WAVE2 (35% vs 28.6%, p = 0.01).
In the total sample, mortality and the composite outcome of poor prognosis were lower among
patients who received inhalation therapy.
∗ Corresponding author.
E-mail address: [email protected] (M. Gómez-Antúnez).
1 A full list of the SEMI-COVID-19 Network members can be found in Appendix A.
https://doi.org/10.1016/j.rceng.2023.04.002
2254-8874/© 2023 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.
Revista Clínica Española 223 (2023) 298---309
Conclusions: Patients with COPD admitted to the hospital due to COVID-19 in the second wave
had less respiratory failure and less radiological involvement as well as a better prognosis.
These patients should receive bronchodilator treatment if there is no contraindication for it.
© 2023 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights
reserved.
PALABRAS CLAVE Pacientes con EPOC hospitalizados por COVID-19 en España: comparación entre la
COPD; primera y la segunda ola
COVID-19;
Resumen
SARS-CoV-2;
Objetivo: Comparar las características, evolución y pronóstico de los pacientes con EPOC hos-
Primera y segunda ola
pitalizados por COVID-19 en España en la primera ola con los de la segunda ola.
de infección;
Material y métodos: Estudio observacional de los pacientes hospitalizados en territorio español
Prognosis
con diagnóstico de EPOC incluidos en el registro SEMI-COVID-19.
Se compararon los antecedentes, la clínica, resultados analíticos y radiológicos, tratamiento
y evolución de los pacientes con EPOC hospitalizados en la primera ola (desde marzo hasta
junio 2020) frente a los hospitalizados en la segunda ola (desde julio hasta diciembre 2020). Se
analizaron los factores de mal pronóstico, definidos como mortalidad por todas las causas y un
evento combinado que incluía mortalidad, oxigenoterapia con alto flujo, ventilación mecánica
e ingreso en UCI.
Resultados: De 21,642 pacientes del Registro SEMI COVID-19, están diagnosticados de EPOC el
6,9%, 1128 (6,8%) en la OLA1 y 374 (7,7%) en la OLA2 (p = 0,04). Los pacientes de la OLA2
presentan menos tos seca, fiebre y disnea, hipoxemia (43% vs 36%, p < 0,05) y condensación
radiológica (46% vs 31%, p < 0,05) que los de la OLA1. La mortalidad es menor en la OLA2 (35%
vs 28,6%, p = 0,01). En el global de pacientes la mortalidad y la variable combinada de mal
pronóstico fue menor entre los pacientes que recibieron tratamiento inhalador.
Conclusiones: Los pacientes con EPOC con ingreso hospitalario por COVID-19 en la segunda ola
presentan menos insuficiencia respiratoria y menos afectación radiológica, con mejor pronós-
tico. Estos pacientes deben recibir tratamiento broncodilatador si no hay contraindicación para
el mismo.
© 2023 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). Todos los
derechos reservados.
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test of a nasopharyngeal or sputum sample or a positive possible to obtain it in writing due to biosafety issues or
result on serological tests and a clinically compatible pre- because the patient was already discharged from the hos-
sentation. The description, characteristics, and baseline pital, verbal informed consent was requested and recorded
results of the SEMI-COVID-19 registry can be consulted in on the medical record.
the work published by Casas-Rojo et al.2
Patients diagnosed with COPD were selected from the
SEMI-COVID-19 registry without needing to have a confirma- Results
tory spirometry. Patients hospitalized from March to June
2020 were considered to belong to the first wave (WAVE1) Of a total of 21,642 patients in the SEMI-COVID-19 Registry,
and those hospitalized from July to December 2020 were 1502 patients (6.9%) had been diagnosed with COPD. Of
considered to belong to the second wave (WAVE2). them, 1128 (6.8%) corresponded to WAVE1 and 374 (7.7%)
The variables selected for the analysis were demographic to WAVE2. The proportion of patients with COPD hospital-
variables; medical history; comorbidities; chronic treat- ized due to COVID-19 was significantly greater in WAVE2
ment; signs and symptoms of patients upon admission; (p < 0.05).
analytical data; radiological findings; treatment received Eighty-two percent of patients in the first wave and 88%
upon admission; radiological progress; ventilatory support: of patients in the second wave were men. Thirty-six percent
high-flow nasal cannula (HFNC) oxygen therapy, noninvasive of patients in WAVE1 and 46% of patients in WAVE2 were older
mechanical ventilation (NIMV), or invasive mechanical ven- than 80 years (Table 1).
tilation (IMV); admission to the ICU; and death. The clinical presentation of patients with COPD contin-
The medical history, symptoms, analytical and radiologi- ued to mainly be dyspnea, fever, and dry cough, but in the
cal results, treatment, and clinical progress of patients with second wave, patients presented with significantly less dry
COPD hospitalized in the first wave were compared to those cough, fever, and dyspnea (p < 0.05). Differences were found
hospitalized in the second wave. Factors associated with in hypoxemia, with 43% of patients in WAVE1 and 36% of
poor prognosis, defined as all-cause mortality and a compo- patients in WAVE2 presenting with SatO2 <92% (p < 0.05).
site variable that included mortality; need for HFNC oxygen Patients in WAVE2 presented with more kidney failure (42%
therapy, NIMV, or IMV; or ICU admission were analyzed. vs 50%, p < 0.05) and less radiological condensation (46% vs
The calculations for the descriptive analysis were per- 31%, p < 0.05) than those in WAVE1 (Table 1). Symptoms
formed using the EXCEL computer program using the differed somewhat in women, who presented with more
dynamic tables tool and the advanced data analysis fea- nonspecific symptoms such as arthromyalgia (27% vs 21%,
ture. Qualitative variables were expressed as absolute p < 0.05), headache (13% vs 5%, p < 0.05), and absence of
frequency (n) and percentage (%). Quantitative variables fever or low-grade fever (59% vs 47%, p < 0.05).
were expressed as medians, interquartile range, and range There were differences in the treatments used in both
with a 95% confidence interval. The Student’s t-test was waves. In WAVE2, lopinavir/ritonavir, hydroxychloroquine,
used. Statistical significance was defined as p < 0.05. A logis- and chloroquine were not used; 15% of patients received
tic regression analysis was performed using the R statistical remdesivir (1% in WAVE1); and 88% of patients received
program to control for confounding bias. To do so, WAVE1 treatment with systemic glucocorticoids, compared to 51%
was treated as the cause or independent variable, mortality in the first wave. Fewer antibiotics were used (82% vs 91%)
and the composite variable as the dependent variable, and and a lower rate of polypharmacy was observed in patients
respiratory failure and radiological involvement as possible in WAVE2.
confounding factors because they were found to be associ- The overall mortality rate in patients with COPD was
ated with mortality. The regression coefficients obtained on 33.4%: 35% in WAVE1 and 28.6% in WAVE2. Mortality declined
two different models were compared and when the magni- in the second wave, with the decline being greater than what
tude of the change in OR was close to or greater than 10%, occurred in the total population of patients with COVID-19
it was considered that there was confounding bias. (Fig. 1). Mortality was greater in men with COPD than in
women (35.2% vs 24.5%, p < 0.001) and declined in WAVE2,
with the decline being greater in women: 26.1% vs 17.4%.
Ethical considerations The probability of death in those older than 80 years is
significantly greater than in the rest of patients (p < 0.05).
Personal data were processed in strict compliance with Nearly all comorbidities increased mortality, but only HT
Law 14/2007, of July 3, on Biomedical Research; Regula- (WAVE1: 38.4% vs WAVE2: 29.3%, p = 0.005) and obesity
tion (EU) 2016/679 of the European Parliament and of the (40.4% vs 27.9%, p = 0.018) significantly increased mortality
Council, of 27 April 2016, on the protection of natural per- between waves.
sons with regard to the processing of personal data and on In all patients with COPD, the presence of dyspnea is an
the free movement of such data, and repealing Directive indicator of poor prognosis (49% vs 30%, p < 0.05) and mor-
95/46/EC (General Data Protection Regulation); and Organic tality (37.3% vs 23.2%, p < 0.05). On the contrary, patients
Law 3/2018, of December 5, on the Protection of Personal who had anosmia (mortality 11.5% vs 34.2%, p < 0.05), ageu-
Data and Guarantee of Digital Rights. The SEMI-COVID-19 sia (mortality 14.8% vs 34%, p < 0.05), or arthromyalgias
Registry was approved for the first time by the Provincial (mortality 27% vs 35.2%, p < 0.05) had a better prognosis.
Research Ethics Committee of Málaga (Spain), following the Patients with SatO2 < 92%, creatinine >1.2 mg/dL, or
recommendation of the Spanish Agency of Medicines and bilateral lung lesions on radiologic tests had greater mor-
Health Products (AEMPS, for its initials in Spanish). Informed tality and a worse prognosis (Table 2). No differences were
consent was requested from all patients. When it was not found between waves in levels of procalcitonin or D-dimer.
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Revista Clínica Española 223 (2023) 298---309
Table 1 Characteristics of patients with COPD hospitalized due to COVID-19. Comparison between WAVE1 and WAVE2.
Total (1502) WAVE1 (1128) WAVE2 (374) p WAVE1 vs WAVE2
Men 84% 82% 88% p < 0.01
>80 years 39% 36% 46%
HT 70% 69% 72% NS
Dyslipidemia 54% 54% 54% NS
AF 23% 24% 22% NS
Obesity 28% 28% 30% NS
Dry cough 45% 48% 36% p< 0.05
Fever 50% 52% 44% p< 0.05
Dyspnea 72% 74% 66% p< 0.05
SatO2 < 92% 41% 43% 36% p< 0.05
Kidney failure 44% 42% 50% p< 0.05
Radiological condensation 43% 46% 31% p< 0.05
Prone positioning 11% 12% 6% NS
HFNC oxygen therapy 13% 12% 14% NS
NIMV 11% 11% 10% NS
IMV 6% 6% 7% NS
ICU 8% 8% 10% NS
Mortality 33.4% 35% 28.6% p< 0.05
HT: hypertension. AF: atrial fibrillation. SatO2 : pulse oxymetry oxygen saturation. Renal failure: creatinine >1.2 mg/dL. HFNC: high-flow
nasal cannula oxygen therapy. NIMV: non-invasive mechanical ventilation. IMV: invasive mechanical ventilation. ICU: intensive care unit.
Figure 1 Mortality in total admissions due to COID-19, mortality in patients with and without COPD and decline in mortality in
WAVE1 and WAVE2.
No differences in mortality were found among patients patients who did not use them. Patients treated with sys-
with chronic habitual use of inhaled corticosteroids, inhaled temic glucocorticoids had greater overall mortality (47.1%
beta-adrenergics, and inhaled anticholinergics compared to vs 32.2%, p < 0.001) and a worse prognosis on the combined
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Table 2 Indicators of a poor prognosis in patients with COPD hospitalized due to COVID-19.
Total Mortality Mortality p WAVE1 vs Poor Poor Poor p WAVE1 vs
mortality WAVE1 WAVE2 WAVE2 overall prognosis prognosis WAVE2
prognosis WAVE1 WAVE2
33% 35% 28.6% 44% 46% 38%
Confusion 52% 54% 47% p<0.05 62% 64% 57% p < 0.05
Tachypnea 46% 47% 40% p<0.05 59% 60% 53% p < 0.05
Sat02* <92% 45% 46% 43% p<0.05 59% 60% 55% p < 0.05
Creatinine 44% 46% 39% p<0.05 53% 56% 47% p < 0.05
>1.2 mg/dL
Bilateral 44% 46% 36% p<0.05 54% 57% 42% p < 0.05
condensation on
X-ray**
Bilateral interstitial 39% 40% 34% p < 0.05 52% 54% 48% p < 0.05
pattern on X-ray**
* SatO2 : pulse oxymetry oxygen saturation.
** X-ray: chest X-ray.
variable (57% vs 43%, p < 0.001) than those who did not use study. However, in this series, the proportion of patients with
them. COPD increased significantly in the second wave compared
Among all patients, those who received inhaled therapy to the first.2---4
had lower mortality (35.8% vs 27.3%, p < 0.05) and a lower Previous works have described that patients with COPD
percentage on the composite poor prognosis variable (46% vs who are hospitalized due to SARS-CoV-2 infection are pre-
39%, p < 0.05). Patients who received beta-adrenergics had dominantly men; are older adults; have high comorbidity;
lower mortality (23% vs 33%, p < 0.05). Those who received have symptoms which consist of an increase in dyspnea and
ipratropium (30% vs 44%, p < 0.05; 35% vs 44%, p < 0.05, expectoration with fever or low-grade fever; and present
respectively) had a better prognosis on the combined vari- with hypoxemia, tachypnea, and confusional syndrome upon
able (Fig. 2). admission.4
Patients who did not receive any antibiotics had a This work found that patients in the second wave con-
lower mortality rate (25% vs 33%, p < 0.05) and a bet- tinued to mainly be older men. These patients in the
ter prognosis (35% vs 44%, p < 0.05) than the mean. second wave presented with fewer symptoms, less respira-
Comparing other treatments received during hospital- tory failure, and less condensation on radiological tests. This
ization (angiotensin-converting enzyme (ACE) inhibitors, suggests that patients in WAVE2 arrived to the hospital ear-
angiotensin II receptor blockers (ARB), statins, acetylsal- lier, with less advanced disease, and in better condition than
icylic acid (ASA), low-molecular-weight heparin (LMWH)), in WAVE1. This could have been influenced by the general
there were no differences in mortality or the composite poor population’s better knowledge on the disease and its symp-
prognosis variable except for LMWH at full anticoagulation toms and consequently, patients may have consulted sooner;
doses, which was associated with a poor prognosis (55% vs an improvement in diagnostics, with an earlier diagnosis and
44%, p < 0.05). a diagnosis in milder phases; less collapse of the healthcare
On the regression analysis, WAVE1 was treated as the system; and a change in virologic pattern given that in the
main independent variable and mortality and the composite second wave, the mean viral load value was lower and the
poor prognosis variable as the dependent variable. Respi- highest levels were detected among younger patients, which
ratory failure and radiological involvement were treated as could be explained by a lower level of viral inoculation as
possible confounding factors. If respiratory failure and radi- a consequence of the use of masks, social distancing, and
ological involvement are analyzed separately, there is no restrictions on gatherings.1---9
sufficiently strong statistical evidence that these factors are As previous publications have described, age continues to
responsible for the differences in mortality and poor prog- be one of the main prognostic factors in SARS-CoV-2 infec-
nosis between waves. On the contrary, when the two factors tion in patients with COPD.
are analyzed jointly, there are differences (Table 3). Although mortality decreased in the second wave, the
mortality rate in patients with COPD is nearly double that of
Discussion the population without COPD. In addition to this, the older
age of patients with COPD than the rest of the hospitalized
population and the high comorbidity of patients with COPD,
According to other published works, the percentage of
especially cardiovascular disease, diabetes, and obesity, are
patients with COPD hospitalized due to COVID-19 is lower
clear factors of a poor prognosis in COVID-19. In this work,
than the overall prevalence of the disease in the popula-
the comorbidity of patients with COPD continues to be very
tion. In the previously reported SEMI-COVID-19 registry, the
high, with no differences between the two waves, as has
prevalence of COPD in the first wave was 7.6% and the preva-
been reported in other publications.4,10,11
lence in this study is 6.9%, a variation that may be due to the
inclusion of more cases following publication of the initial
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Figure 2 Patients with COPD admitted to the hospital due to COVID-19 in the first and second wave. Mortality and poor prognosis
according to the received inhaled treatment during hospital admission.
Table 3 Characteristics of patients with COPD hospitalized due to COVID-19. Logistic regression study.
Results for mortality
The better prognosis in women is notable, with a greater bination of lesser respiratory failure and lesser radiologic
decline in mortality in the second wave than in men with involvement----would be behind the lower mortality rate
COPD. One of the hypotheses that could explain this differ- and better prognosis observed in WAVE2. Other works have
ence due to sex is based on the role of sex in the genetic suggested that the pattern of inflammation in the second
and hormonal regulation of immune responses and in the wave----measured through biomarkers such as LDH, ferritin,
different ACE2 activity between men and women; men with CRP, IL-6, and D-dimer----was lower. This was not able to
hypertension and heart failure tend to have a higher level be confirmed in this series, in which no differences were
of ACE2 serum activity compared to women.12,13 found in the lymphocytes or d-dimer figures between the
There was a lower mortality and better prognosis in waves.15
WAVE2. In a work comparing mortality in the two waves Contou et al. described less of a need for invasive
in Japan, mortality was also lower in the second wave, mechanical ventilation in the second wave of patients hos-
even when stratified by age and severity upon admis- pitalized in the ICU, but did not find any differences in
sion. The authors linked this to a shorter period of time mortality. Other authors have also reported greater use of
between disease onset and admission and that the patients non-invasive mechanical ventilation in the second wave. In
had milder disease upon admission.14 After the regres- this study, no differences were found between waves in the
sion analysis in this series, it was also observed that the need for high-flow oxygen therapy, non-invasive or invasive
patients’ better clinical situation----reflected in the com- mechanical ventilation, or ICU admission.16
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Alonso Beato, Leyre Alonso Gonzalo, Jaime Alonso Muñoz, Oñoro López, Esmeralda Palmier Peláez, Marina Palomar
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Nicolás Alcalá Rivera, Anxela Crestelo Vieitez, Esther Mar Carmona Martín, María José Fabiá Valls, Maria de Mar
del Corral Beamonte, Jesús Díez Manglano, Isabel Fiteni Fernández Garcés, Ana Belén Gómez Belda, Ian López Cruz,
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Sergio Jansen-Chaparro, Maria Dolores López-Carmona, Fuente Moral, Alberto Díaz de Santiago, Itziar Diego Yagüe,
Pablo López Quirantes, Almudena López Sampalo, Eliza- Ignacio Donate Velasco, Ana María Duca, Pedro Durán del
beth Lorenzo-Hernández, Juan José Mancebo Sevilla, Jesica Campo, Gabriela Escudero López, Esther Expósito Palomo,
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dez, Francisco Blanco Quintana, Carmen Busca Arenzana, Fátima Ibáñez Estéllez, Pedro Laguna del Estal, Ma Carmen
Sergio Carrasco Molina, Aranzazu Castellano Candalija, Ger- Máinez Sáiz, Carmen de Mendoza Fernández, María Martínez
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M. Gómez-Antúnez, A. Muiño-Míguez, M. Bacete-Cebrián et al.
Palomo, Ilduara Pintos Pascual, Arturo José Ramos Martín- Valle López, Isabel Rábago Lorite, Rebeca Fuerte Martínez,
Vegue, Antonio Ramos Martínez, Celia Rodríguez Olleros, Inés Suárez García, Llanos Soler Rangel
Alberto Roldán Montaud, Yolanda Romero Pizarro, Silvia H. U. de A Coruña
Rosado García, Diana Ruiz de Domingo, David Sánchez Ortiz, Alicia Alonso Álvarez, Olaya Alonso Juarros, Ariadna Aré-
Enrique Sánchez Chica, Irene Solano Almena, Elena Suanzes valo López, Carmen Casariego Castiñeira, Ana Cerezales
Martin, Yale Tung Chen, Pablo Tutor de Ureta, Ángela Valen- Calviño, Marta Contreras Sánchez, Ramón Fernández Varela,
cia Alijo, Jose Manuel Vázquez Comendador, Juan Antonio Santiago J. Freire Castro, Ana Padín Trigo, Rafael Prieto
Vargas Núñez. Jarel, Fátima Raad Varea, Ignacio Ramil Freán, Laura Ramos
H. Clínico San Carlos. Madrid Alonso, Francisco Javier Sanmartín Pensado, David Vieito
Inés Armenteros Yeguas, Javier Azaña Gómez, Julia Bar- Porto
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Alberto E. Calvo Elías, Elpidio Calvo Manuel, Carmen María Judit Aranda Lobo, Lucía Feria Casanovas, Jose Loureiro
Cano de Luque, Cynthia Chocron Benbunan, Laura Dans Amigo, Miguel Martín Fernández, Isabel Oriol Bermúdez,
Vilan, Claudia Dorta Hernández, Ester Emilia Dubon Peralta, Melani Pestaña Fernández, Nicolas Rhyman, Nuria Vázquez
Vicente Estrada Pérez, Santiago Fernandez-Castelao, Mar- Piqueras
cos Oliver Fragiel Saavedra, José Luis García Klepzig, Maria H. de Pozoblanco (Córdoba)
del Rosario Iguarán Bermúdez, Esther Jaén Ferrer, Alejan- José Nicolás Alcalá Pedrajas, Antonia Márquez García,
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Álvarez, Maria José Nuñez Orantos, Carolina Olmos Mata, Irene Arroyo Jiménez, Marina Cazorla González, Marta
Eva Orviz García, David Oteo Mata, Cristina Outon González, Cobos-Siles, Luis Corral-Gudino, Pablo Cubero-Morais, María
Juncal Perez-Somarriba, Pablo Pérez Mateos, Maria Esther González Fernández, José Pablo Miramontes González,
Ramos Muñoz, Xabier Rivas Regaira, Laura Ma Rodríguez Gal- Marina Prieto Dehesa, Pablo Sanz Espinosa
lardo, Iñigo Sagastagoitia Fornie, Alejandro Salinas Botrán, H. Nuestra Señora del Prado. Talavera de la Reina
Miguel Suárez Robles, Maddalena Elena Urbano, Andrea (Toledo)
María Vellisca González, Miguel Villar Martínez Sonia Casallo Blanco, Jeffrey Oskar Magallanes Gamboa,
H. G. U. de Elda (Alicante) Cristina Salazar Mosteiro, Andrea Silva Asiain
Carmen Cortés Saavedra, Jennifer Fernández Gómez, H. U. Infanta Cristina. Parla (Madrid)
Borja González López, María Soledad Hernández Garrido, Juan Miguel Antón Santos, Ana Belén Barbero Barrera,
Ana Isabel López Amorós, Santiago López Gil, Maria de los Blanca Beamonte Vela, Coralia Bueno Muiño, Charo Burón
Reyes Pascual Pérez, Nuria Ramírez Perea, Andrea Torre- Fernández, Ruth Calderón Hernáiz, Irene Casado López,
grosa García José Manuel Casas Rojo, Andrés Cortés Troncoso, Pilar Cubo
Complejo Asistencial de Segovia Romano, Francesco Deodati, Alejandro Estrada Santiago,
Daniel Monge Monge, Eva María Ferreira Pasos, Alba Gonzalo García Casasola Sánchez, Elena García Guijarro,
Varela García Francisco Javier García Sánchez, Pilar García de la Torre,
H. Miguel Servet. Zaragoza Mayte de Guzmán García-Monge, Davide Luordo, María
Luis Sáez Comet, Laura Letona Giménez, Uxua Asín Sam- Mateos González, José A. Melero Bermejo, Cruz Pastor
per, Gonzalo Acebes Repiso, José Miguel García Bruñén, Valverde, José Luis Pérez Quero, Fernando Roque Rojas,
Mónica Llorente Barrio, María Aranzazu Caudevilla Martínez, Lorea Roteta García, Elena Sierra Gonzalo, Francisco Javier
Jesús Javier González Igual, Rosa García Fenoll Teigell Muñoz, Juan Vicente de la Sota, Javier Villanueva
H. U. La Princesa. Madrid Martínez
María Aguilera García, Ester Alonso Monge, Jesús H. de Urduliz Alfredo Espinosa (Vizcaya)
Álvarez Rodríguez, Claudia Alvarez Varela, Miquel Berniz Miriam García Gómez, Pablo Ramírez Sánchez, Gorka
Gòdia, Marta Briega Molina, Marta Bustamante Vega, Jose Arroita Gonzalez, Alazne Lartategi Iraurgi, Asier Aranguren
Curbelo, Alicia de las Heras Moreno, Ignacio Descalzo Arostegui, Paula Arriola Martínez, Isabel María Portales
Godoy, Alexia Constanza Espiño Alvarez, Ignacio Fernández Fernández, Esther Martinez Becerro, Amalur Iza Jiménez,
Martín-Caro, Alejandra Franquet López-Mosteiro, Gonzalo Cristian Vidal Núñez, María Aparicio López, Eduardo García
Galvez Marquez, María José García Blanco, Yaiza García López, Ma Soledad Azcona Losada, Beatriz Ruiz Estévez
del Álamo Hernández, Clara García-Rayo Encina, Noemí H. Virgen de la Salud. Toledo
Gilabert González, Carolina Guillamo Rodríguez, Nicolás Ana Maria Alguacil Muñoz, Marta Blanco Fernández,
Labrador San Martín, Manuel Molina Báez, Carmen Muñoz Veronica Cano, Ricardo Crespo Moreno, Fernando Cuadra
Delgado, Pedro Parra Caballero, Javier Pérez Serrano, Garcia-Tenorio, Blanca Díaz-Tendero Nájera, Raquel Estévez
Laura Rabes Rodríguez, Pablo Rodríguez Cortés, Carlos González, María Paz García Butenegro, Alberto Gato Díez,
Rodriguez Franco, Emilia Roy-Vallejo, Monica Rueda Vega, Verónica Gómez Caverzaschi, Piedad María Gómez Pedraza,
Aresio Sancha Lloret, Beatriz Sánchez Moreno, Marta Sanz Julio González Moraleja, Raúl Hidalgo Carvajal, Patricia
Alba, Jorge Serrano Ballesteros, Alba Somovilla, Carmen Jiménez Aranda, Raquel Labra González, Áxel Legua Capara-
Suarez Fernández, Macarena Vargas Tirado, Almudena Villa chini, Pilar Lopez Castañeyra, Agustín Lozano Ancin, Jose
Marti Domingo Martin Garcia, Cristina Morata Romero, María Jesús
H. Infanta Sofía. SS de los Reyes (Madrid) Moya Saiz, Helena Moza Moríñigo, Gemma Muñiz Nicolás,
José Francisco Pascual Pareja, Isabel Perales Fraile, Enriqueta Muñoz Platon, Filomena Oliveri, Elena Ortiz Ortiz,
Arturo Muñoz Blanco, Rafael del Castillo Cantero, José Luis Raúl Perea Rafael, Pilar Redondo Galán, María Antonia
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Sepulveda Berrocal, Vicente Serrano Romero de Ávila, Pilar Carlota Tuñón de Almeida, María Esther Fraile Villarejo,
Toledano Sierra, Yamilex Urbano Aranda, Jesús Vázquez Victoria Palomar Calvo, Sara Pintos Otero, Beatriz García
Clemente, Carmen Yera Bergua López, Carlos Aldasoro Frías, Víctor Madrid Romero, Luis
H. U. Son Llàtzer. Palma de Mallorca Arribas Pérez, Emilia Martínez Velado
Andrés de la Peña Fernández, Almudena Hernández Milián H. de Mataró. Barcelona
H. Santa Marina. Bilbao Raquel Aranega González, Ramon Boixeda, Javier Fer-
María Areses Manrique, Ainara Coduras Erdozain, Ane nández Fernández, Carlos Lopera Mármol, Marta Parra
Labirua-Iturburu Ruiz Navarro, Ainhoa Rex Guzmán, Aleix Serrallonga Fustier
H. Juan Ramón Jiménez. Huelva H. Público de Monforte de Lemos (Lugo)
Francisco Javier Bejarano Luque, Francisco-Javier José López Castro, Manuel Lorenzo López Reboiro,
Carrasco-Sánchez, Mercedes de-Sousa-Baena, Jaime Díaz Cristina Sardiña González
Leal, Aurora Espinar Rubio, Maria Franco Huertas, Juan H. de Sagunto (Valencia)
Antonio García Bravo, Andrés Gonzalez Macías, Encarnación Enrique Rodilla Sala, Jose María Pascual Izuel, Zineb Kar-
Gutiérrez Jiménez, Alicia Hidalgo Jiménez, Constantino roud Zamrani
Lozano Quintero, Carmen Mancilla Reguera, Francisco C. H. U. de Ferrol (A Coruña)
Javier Martínez Marcos, Francisco Muñoz Beamud, Maria Hortensia Alvarez Diaz, Tamara Dalama Lopez, Estefania
Pérez-Aguilar, Alícia Pérez Jiménez, Virginia Rodríguez Martul Pego, Carmen Mella Pérez, Ana Pazos Ferro, Sabela
Castaño, Alvaro Sánchez de Alcazar del Río, Leire Toscano Sánchez Trigo, Dolores Suarez Sambade, Maria Trigas Ferrin,
Ruiz Maria del Carmen Vázquez Friol, Laura Vilariño Maneiro
H. San Pedro. Logroño (La Rioja) H. Alto Guadalquivir. Andújar (Jaén)
Diana Alegre González, Irene Ariño Pérez de Zabalza, Begoña Cortés Rodríguez
Sergio Arnedo Hernández, Jorge Collado Sáenz, Beatriz Den- H. Infanta Margarita. Cabra (Córdoba)
dariena, Marta Gómez del Mazo, Iratxe Martínez de Narvajas María Esther Guisado Espartero, Lorena Montero Rivas,
Urra, Sara Martínez Hernández, Estela Menendez Fernández, Maria de la Sierra Navas Alcántara, Raimundo Tirado-
Jose Luís Peña Somovilla, Elisa Rabadán Pejenaute Miranda
H. del Henares. Coslada (Madrid) H. U. San Agustin. Avilés (Asturias)
Jesús Ballano Rodríguez-Solís, Luis Cabeza Osorio, María Marta Nataya Solís Marquínez, Víctor Arenas García,
del Pilar Fidalgo Montero, Ma Isabel Fuentes Soriano, Demelsa Blanco Suárez, Natalia García Arenas, Paula
Erika Esperanza Lozano Rincón, Ana Martín Hermida, Jesús Martínez García, David Castrodá Copa, Andrea Álvarez Gar-
Martínez Carrilero, José Ángel Pestaña Santiago, Manuel cía, Jaime Casal Álvarez, María Jose Menéndez Calderón,
Sánchez Robledo, Patricia Sanz Rojas, Nahum Jacobo Torres Raquel García Noriega, María Caño Rubia, Joaquin Llorente
Yebes, Vanessa Vento García, Luis Trapiella Martínez, José Ferreiro Celeiro, Diego
H. U. Ramón y Cajal. Madrid Eduardo Olivo Aguilar, Irene Maderuelo Riesco, Juan Valdés
Luis Fernando Abrego Vaca, Ana Andréu Arnanz, Octavio Bécares, Alba Barragán Mateos, Andrés Astur Treceño García
Arce García, Marta Bajo González, Pablo Borque Sanz, H. Univ. Ntra. Sra. Candelaria. Sta. Cruz de Tenerife
Alberto Cozar Llisto, Sonia de Pedro Baena, Beatriz Del Joaquín Delgado Casamayor, Diego García Silvera, Andrea
Hoyo Cuenda, Martin Fabregate-Fuente, María Alejandra Afonso Díaz, Carolina Hernández Carballo, Alicia Tejera,
Gamboa Osorio, Isabel García Sánchez, Andrés González María José Monedero Prieto, María Blanca Monereo Muñoz,
García, Oscar Alberto López Cisneros, Luis Manzano, Miguel José Manuel Del Arco Delgado, Daniel Rodríguez Díaz, Marta
Martínez-Lacalzada, Borja Merino Ortiz, Jimena Rey-García, Bethencourt Feria, Francisco Javier Herrera Herrera, María
Elisa Riera González, Cristina Sánchez Díaz, Grisell Starita de la Luz Padilla Salazar, Rubén Hernández Luis, Eduardo
Fajardo, Cecilia Suárez Carantoña, Adrian Viteri-Noël, Svet- Mauricio Calderón Ledezma, María del Mar López Gámez,
lana Zhilina Zhilina Laura Torres Hernández, Sara Castaño Pérez, Selena Gala
H. U. Torrevieja (Alicante) Aguilera García, Guillermo Castro Gainett, Alba Gómez
Julio César Blázquez Encinar Hidalgo, Julia Marfil Daza, Marcelino Hayek Peraza
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Carmen Martínez Cilleros, Isabel Jiménez Martínez, Reyes Aparicio Santos, Máximo Bernabeu-Wittel, Santiago
Teresa García Delange Rodríguez Suárez, María Nieto, Luis Giménez Miranda, Rosa
C. H. U. Ourense María Gámez Mancera, Fátima Espinosa Torre, Carlos Her-
Raquel Fernández González, Amara Gonzalez Noya, Car- nandez Quiles, Concepción Conde Guzmán, Juan Delgado
los Hernández Ceron, Isabel Izuzquiza Avanzini, Ana Latorre de la Cuesta, Jara Eloisa Ternero Vega, María del Carmen
Diez, Pablo López Mato, Ana María Lorenzo Vizcaya, Daniel López Ríos, Pablo Díaz Jiménez, Bosco Baron Franco, Car-
Peña Benítez, Milagros María Peña Zemsch, Lucía Pérez los Jiménez de Juan, Sonia Gutiérrez Rivero, Julia Lanseros
Expósito, Marta Pose Bar, Lara Rey González, Laura Rodrigo Tenllado, Verónica Alfaro Lara, Aurora González Estrada
Lara H. Marina Baixa. Villajoyosa (Alicante)
H. U. La Fe. Valencia Javier Ena, José Enrique Gómez Segado
Dafne Cabañero, María Calabuig Ballester, Pascual Cís- H. San Juan de la Cruz. Úbeda (Jaén)
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Cristina Marín Amela, Laura Parra Gómez, Carlos Puig dez
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Rosario María García Die, Alberto Muela Molinero, Manuel H. U. del Sureste. Arganda del Rey (Madrid)
Martín Regidor, Raquel Rodríguez Díez Jon Cabrejas Ugartondo, Ana Belén Mancebo Plaza,
H. Torrecárdenas. Almería Arturo Noguerado Asensio, Bethania Pérez Alves, Natalia
Bárbara Hernández Sierra, Luis Felipe Díez García, Iris El Vicente López
Attar Acedo, Carmen Mar Sánchez Cano H. Parc Tauli. Sabadell (Barcelona)
H. Dr. José Molina Orosa. Arrecife (Lanzarote) Francisco Epelde, Isabel Torrente
Virginia Herrero García, Berta Román Bernal H. U. Quironsalud Madrid
H. Clinic Barcelona Pablo Guisado Vasco, Ana Roda Santacruz, Ana Valverde
Júlia Calvo Jiménez, Emmanuel Coloma Bazán, Aina Muñoz
Capdevila Reniu, Joan Ribot Grabalosa, Joaquim Fernández H. Santa Bárbara. Soria
Solà, Irene Carbonell De Boulle, Cristina Gabara Xancó, Olga Marta León Téllez
Rodríguez Núñez H. Virgen de los Lirios. Alcoy (Alicante)
H. Insular de Gran Canaria. Las Palmas G. C. Ma José Esteban Giner
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García Antonio González Nieto
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H. U. Virgen de las Nieves. Granada H. U. Lucus Augusti. Lugo
Pablo Conde Baena, Joaquín Escobar Sevilla, Laura Gallo Raquel Gómez Méndez, Ana Rodríguez Álvarez
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Rodríguez Suárez, Silvia Suárez Díaz, Lucia Suárez Pérez, Toledo, Esther Martin Ponce
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García, Antía Pérez Piñeiro Comas Casanova, Angels Garcia Flores, Anna Garcia Hinojo,
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H. Francesc de Borja. Gandía (Valencia) Viviana Romero Echevarry
M Angeles Martinez Pascual, Leyre Jorquer Vidal H. de Poniente. El Ejido (Almería)
H. de Palamós (Girona) Juan Antonio Montes Romero, Jose Luis Serrano Carrillo
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