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Predicting Clinical Outcome with Phenotypic Clusters in COVID-19 Pneumonia: An Analysis of 12,066 Hospitalized Patients from the Spanish Registry SEMI-COVID-19

Department of Internal Medicine, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, University of Barcelona, 08907 Barcelona, Spain
Hestia Chair in Integrated Health and Social Care, School of Medicine, Universitat Internacional de Catalunya, 08017 Barcelona, Spain
Internal Medicine Department, Moisès Broggi Hospital, Sant Joan Despí, 08970 Barcelona, Spain
Internal Medicine Department, Regional University Hospital of Málaga, 29010 Málaga, Spain
Internal Medicine Department, Virgen de la Salud Hospital, 45071 Toledo, Spain
Internal Medicine Department, San Juan de Alicante University Hospital, San Juan de Alicante, 03550 Alicante, Spain
Internal Medicine Department, Torrecárdenas Hospital, 04009 Almería, Spain
Internal Medicine Department, Tajo Hospital, Aranjuez, 28300 Madrid, Spain
Internal Medicine Department, Severo Ochoa University Hospital, Leganés, 28914 Madrid, Spain
Internal Medicine Department, Valle del Nalón Hospital, Riaño, Langreo, 33920 Asturias, Spain
Internal Medicine Department, Alto Guadalquivir Hospital, Andújar, 23740 Jaén, Spain
Internal Medicine Department, Francesc de Borja Hospital, Gandia, 46702 Valencia, Spain
Internal Medicine Department, Castellón General University Hospital, 12004 Castellón de la Plana, Spain
Internal Medicine Department, Santa Bárbara Hospital, 42005 Soria, Spain
Internal Medicine Department, Salamanca University Hospital Complex, 37007 Salamanca, Spain
Internal Medicine Department, Canarias University Hospital, 38320 Santa Cruz de Tenerife, Spain
Internal Medicine Department, Poniente Hospital, 04700 Almería, Spain
Internal Medicine Department, San Pedro de Alcántara Hospital, 10003 Cáceres, Spain
Internal Medicine Department, Pozoblanco Hospital, Pozoblanco, 14400 Córdoba, Spain
Internal Medicine Department, Palamós Hospital, Palamós, 17230 Girona, Spain
Internal Medicine Department, Virgen de los Lirios Hospital, Alcoy, 03804 Alicante, Spain
Internal Medicine Department, Valladolid Clinical University Hospital, 47003 Valladolid, Spain
Department of Clinical Medicine, Miguel Hernandez University of Elche, 03203 Alicante, Spain
Internal Medicine Department, Regional University Hospital of Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), 29010 Malaga, Spain
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2020, 9(11), 3488;
Received: 14 September 2020 / Revised: 23 October 2020 / Accepted: 27 October 2020 / Published: 29 October 2020
(This article belongs to the Special Issue COVID-19: From Pathophysiology to Clinical Practice)
(1) Background: Different clinical presentations in COVID-19 are described to date, from mild to severe cases. This study aims to identify different clinical phenotypes in COVID-19 pneumonia using cluster analysis and to assess the prognostic impact among identified clusters in such patients. (2) Methods: Cluster analysis including 11 phenotypic variables was performed in a large cohort of 12,066 COVID-19 patients, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish Society of Internal Medicine (SEMI)-COVID-19 Registry. (3) Results: Of the total of 12,066 patients included in the study, most were males (7052, 58.5%) and Caucasian (10,635, 89.5%), with a mean age at diagnosis of 67 years (standard deviation (SD) 16). The main pre-admission comorbidities were arterial hypertension (6030, 50%), hyperlipidemia (4741, 39.4%) and diabetes mellitus (2309, 19.2%). The average number of days from COVID-19 symptom onset to hospital admission was 6.7 (SD 7). The triad of fever, cough, and dyspnea was present almost uniformly in all 4 clinical phenotypes identified by clustering. Cluster C1 (8737 patients, 72.4%) was the largest, and comprised patients with the triad alone. Cluster C2 (1196 patients, 9.9%) also presented with ageusia and anosmia; cluster C3 (880 patients, 7.3%) also had arthromyalgia, headache, and sore throat; and cluster C4 (1253 patients, 10.4%) also manifested with diarrhea, vomiting, and abdominal pain. Compared to each other, cluster C1 presented the highest in-hospital mortality (24.1% vs. 4.3% vs. 14.7% vs. 18.6%; p < 0.001). The multivariate study identified age, gender (male), body mass index (BMI), arterial hypertension, chronic obstructive pulmonary disease (COPD), ischemic cardiopathy, chronic heart failure, chronic hepatopathy, Charlson’s index, heart rate and respiratory rate upon admission >20 bpm, lower PaO2/FiO2 at admission, higher levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH), and the phenotypic cluster as independent factors for in-hospital death. (4) Conclusions: The present study identified 4 phenotypic clusters in patients with COVID-19 pneumonia, which predicted the in-hospital prognosis of clinical outcomes. View Full-Text
Keywords: COVID-19; cluster analysis; prognosis; phenotype COVID-19; cluster analysis; prognosis; phenotype
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MDPI and ACS Style

Rubio-Rivas, M.; Corbella, X.; Mora-Luján, J.M.; Loureiro-Amigo, J.; López Sampalo, A.; Yera Bergua, C.; Esteve Atiénzar, P.J.; Díez García, L.F.; Gonzalez Ferrer, R.; Plaza Canteli, S.; Pérez Piñeiro, A.; Cortés Rodríguez, B.; Jorquer Vidal, L.; Pérez Catalán, I.; León Téllez, M.; Martín Oterino, J.Á.; Martín González, M.C.; Serrano Carrillo de Albornoz, J.L.; García Sardon, E.; Alcalá Pedrajas, J.N.; Martin-Urda Diez-Canseco, A.; Esteban Giner, M.J.; Tellería Gómez, P.; Ramos-Rincón, J.M.; Gómez-Huelgas, R. Predicting Clinical Outcome with Phenotypic Clusters in COVID-19 Pneumonia: An Analysis of 12,066 Hospitalized Patients from the Spanish Registry SEMI-COVID-19. J. Clin. Med. 2020, 9, 3488.

AMA Style

Rubio-Rivas M, Corbella X, Mora-Luján JM, Loureiro-Amigo J, López Sampalo A, Yera Bergua C, Esteve Atiénzar PJ, Díez García LF, Gonzalez Ferrer R, Plaza Canteli S, Pérez Piñeiro A, Cortés Rodríguez B, Jorquer Vidal L, Pérez Catalán I, León Téllez M, Martín Oterino JÁ, Martín González MC, Serrano Carrillo de Albornoz JL, García Sardon E, Alcalá Pedrajas JN, Martin-Urda Diez-Canseco A, Esteban Giner MJ, Tellería Gómez P, Ramos-Rincón JM, Gómez-Huelgas R. Predicting Clinical Outcome with Phenotypic Clusters in COVID-19 Pneumonia: An Analysis of 12,066 Hospitalized Patients from the Spanish Registry SEMI-COVID-19. Journal of Clinical Medicine. 2020; 9(11):3488.

Chicago/Turabian Style

Rubio-Rivas, Manuel, Xavier Corbella, José M. Mora-Luján, Jose Loureiro-Amigo, Almudena López Sampalo, Carmen Yera Bergua, Pedro J. Esteve Atiénzar, Luis F. Díez García, Ruth Gonzalez Ferrer, Susana Plaza Canteli, Antía Pérez Piñeiro, Begoña Cortés Rodríguez, Leyre Jorquer Vidal, Ignacio Pérez Catalán, Marta León Téllez, José Á. Martín Oterino, María C. Martín González, José L. Serrano Carrillo de Albornoz, Eva García Sardon, José N. Alcalá Pedrajas, Anabel Martin-Urda Diez-Canseco, María J. Esteban Giner, Pablo Tellería Gómez, José M. Ramos-Rincón, and Ricardo Gómez-Huelgas. 2020. "Predicting Clinical Outcome with Phenotypic Clusters in COVID-19 Pneumonia: An Analysis of 12,066 Hospitalized Patients from the Spanish Registry SEMI-COVID-19" Journal of Clinical Medicine 9, no. 11: 3488.

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