Dear Editor,
The pandemic outbreak of SARS-CoV-2 is the greatest challenge ever faced by intensive care units throughout the globe. Most studies report a low incidence and little need for hospitalization in children. Nevertheless, up to 10% of hospitalized children under 1 year of age require PICU admission [1]. The first cases of SARS-CoV-2 infection in Spain were identified in February. The number of cases increased significantly during the following weeks [2]. Although children appear to be relatively spared of severe disease, the Spanish Ministry of Health reported over 200 children requiring admission to a pediatric ward, 10% of which were admitted to a PICU [3].
We present the preliminary results of a national multi-center registry of SARS-CoV-2 infection in children requiring intensive care. This initiative was launched by the Spanish Pediatric Intensive Care Society and included 47 PICUs. More than 90% of the PICUs included in the Spanish Public Healthcare System were represented in the study. Fifty patients were included in the registry between the 1st of March and 1st of May 2020. Underlying health conditions were reported in 24% of the patients. Table 1 shows the differences between patients requiring and those not mechanical ventilation.
Table 1.
Characteristics of patients with SARS-CoV-2 infection admitted to Spanish PICUs
| All patients (N = 50) | Patients requiring MV 14/50 (28%) | Patients not requiring MV 36/50 (72%) | p value | |
|---|---|---|---|---|
| Medical history | ||||
| Sex (male) | 31/50 (62%) | 11/14 (78.6%) | 20/36 (55.6%) | 0.197 |
| Age (years) median (IQR) | 6.7 (1.5–11.8) | 2.8 (0.4–9.5) | 8.6 (4.1–12.6) | 0.049 |
| Weight (kg) median (IQR) | 27 (12.3–41.5) | 19 (6.8–35.5) | 29.5 (15–44.5) | 0.163 |
| Previously healthy | 38/50 (76%) | 6/14 (42.9%) | 32/36 (88.9%) | 0.002 |
| Cause of admission | ||||
| Hemodynamic instability | 23/50 (46%) | 6/14 (42.9%) | 17/36 (47.2%) | 0.781 |
| Respiratory difficulty | 20/50 (40%) | 10/14 (71.4%) | 10/36 (27.8%) | 0.009 |
| Neurological symptoms | 1/50 (2%) | 0/14 (0%) | 1/36 (2.8%) | 1 |
| Clinic upon the first 24 h of admission to PICU | ||||
| ARDSa | 9/49 (18.4%) | 7/13 (53.8%) | 2/36 (5.6%) | 0.001 |
| Shock | 25/50 (50%) | 6/14 (42.9%) | 19/36 (52.8%) | 0.529 |
| PMIS | 27/50 (54%) | 4/14 (28.6%) | 23/36 (63.9%) | 0.031 |
| Renal failure | 8/50 (16%) | 3/14 (21.4%) | 5/36 (13.9%) | 0.670 |
| Heart dysfunction | 17/50 (34%) | 7/14 (50%) | 10/36 (27.8%) | 0.136 |
| PRISM III | 7 (4–13) | 9 (4–10.5) | 7 (4–10) | 0.302 |
| p-SOFA Median (IQR) | 4 (2–6) | 6.5 (4–10.5) | 3 (1–5) | 0.008 |
| Critical care needs | ||||
| HFNCa | 20/49 (50%) | 6/14 (42.9%) | 14/35 (40%) | 0.854 |
| NIVa | 9/48 (18.8%) | 3/14 (21.4%) | 6/34 (17.6%) | 0.760 |
| Blood product transfussiona | 11/48 (22.9%) | 5/14 (35.7%) | 6/34 (17.6%) | 0.258 |
| Vasoactive drugsa | 28/49 (57.1%) | 9/14 (64.3%) | 19/35 (54.3%) | 0.750 |
| Laboratory markersb | ||||
| Total leukocytes (/mcl) Median (IQR) | 9260 (5645–14,460) | 7860 (3757–11,375) | 9380 (6907–14,870) | 0.196 |
| Lymphocytes (/mcl) Median (IQR) | 1026 (420–2593) | 738 (313–4201) | 1168 (450–2601) | 0.712 |
| PCT (mcg/L) Median (IQR) | 6 (0.6–16.1) | 1.5 (0.2–20) | 7 (1.5–18.9) | 0.170 |
| CRP (mg/dl) median (IQR) | 13.9 (4.9–27) | 7.1 (0.3–22.6) | 19.1 (7.1–27.2) | 0.077 |
| Pharmacological management | ||||
| Antibiotica | 43/46 (93.5%) | 12/12 (100%) | 31/34 (91.2%) | 0.557 |
| Lopinavir-ritonavira | 22/44 (50%) | 6/12 (50%) | 16/32 (50%) | 1 |
| Remdesivira | 4/43 (9.3%) | 3/12 (25%) | 1/31 (3.2%) | 0.059 |
| Hydroxychloroquinea | 29/46 (63%) | 10/12 (83.3%) | 19/34 (55.9%) | 0.163 |
| Steroidsa | 32/44 (72.7%) | 9/12 (75%) | 23/32 (71.9%) | 1 |
| Intravenous Immunoglobulinsa | 15/44 (34.1%) | 2/12 (16.7%) | 13/32 (40.6%) | 0.171 |
| Tocilizumaba | 14/43 (32.6%) | 6/12 (50%) | 8/31 (25.8%) | 0.160 |
Patients requiring mechanical ventilation and patients not requiring mechanical ventilation are compared. ARDS was defined according to the Pediatric Acute Respiratory Distress Syndrome Consensus Recommendations from the Pediatric Acute Lung Injury Consensus Conference. PMIS was defined according to the Royal College of Paediatrics and Child Health. Shock was defined as blood pressure below 5th percentile reference values for age or the need of vasoactive drugs to maintain blood pressure in normal range or by the existence of signs of tissue hypoperfusion despite adequate fluid resuscitation. Renal failure was defined according to the KDIGO guidelines as the presence of urine output below 0.5 ml/kg/h for more than 6 h or as an increase on serum creatinine by 0.3 mg/dl within 48 h or 1.5 baseline values. Heart dysfunction was defined using echocardiography as the existence of global or segmental motion abnormalities, dilated ventricles, reduced ejection fraction or by the presence of pericardial effusion. p-SOFA scores were calculated using the information of the first 24 h of admission
IQR interquartile range, ADRS acute respiratory distress syndrome, PMIS pediatric multisystem inflammatory syndrome, HFNC high flow nasal cannula, NIV non invasive ventilation, MV mechanical ventilation, PCT procalcitonin, CRP C-reactive protein
aSome data were not available for all patients
bLaboratory markers were available in 48 out of 50 patients
Our results show that, even though SARS-CoV-2 infection has a mild clinical course in most cases, some children can present with a severe disease requiring respiratory and haemodynamic support. Suspected paediatric multisystem inflammatory syndrome (PMIS) as described by Riphagen et al. [3] was present in more than a half of these patients.
The need for mechanical ventilation (MV) was higher in younger patients, in those with higher organ failure scores, in those with pre-existing medical conditions and in those presenting with respiratory difficulty and ARDS, as described in adult patients [4]. Patients requiring MV were less likely to present with PMIS upon admission. Many adult studies have pointed out an association between the severity of the disease or the need for mechanical ventilation and some laboratory markers [4]. Nevertheless, we did not find any statistically significant differences regarding total leukocyte and lymphocyte count, C reactive protein or procalcitonin in our patients. None of the participating units reported any COVID-19 deaths as of the date of data collection.
Our study has several limitations. A complete analysis of the course of SARS-CoV-2 infection in Spanish critically ill children is not possible yet, as some patients are still hospitalized. Though our registry includes more than 90% of Spanish PICUs, the absence of non-participating units may have created a selection bias. Another limitation is that it was not possible to discern whether SARS-CoV-2 infection was fully responsible or only a contributing factor for the whole clinical picture in some cases. Finally, statistical significance may be difficult to achieve due to small sample size, especially in some laboratory markers.
We believe there is an urgent need for multicentre international studies in order to provide a better understanding of the specific features, needs and challenges of critically ill children with SARS-COV-2 infection, especially in those with pre-existing medical conditions.
Acknowledgements
The members of SECIP Study Group on SARS-CoV-2 in Critically Ill Pediatric Patients are: María Slöcker Barrio (Pediatric Intensive Care Unit, Gregorio Marañón General University Hospital, Madrid, Spain), Amaya Bustinza Arriortua (Pediatric Intensive Care Unit, Gregorio Marañón General University Hospital, Madrid, Spain), Jesús López-Herce Cid (Pediatric Intensive Care Unit, Gregorio Marañón General University Hospital, Madrid, Spain), Juan Carlos de Carlos Vicente (Pediatric Intensive Care Unit, Son Espases University Hospital, Palma de Mallorca, Spain), Maite Cuervas-Mons Tejedor (Complejo Asistencial Universitario de Burgos, Burgos, Spain), Pedro Pablo Oyágüez Ugidos (Complejo Asistencial Universitario de Burgos, Burgos, Spain), Iolanda Jordan (Hospital Sant Joan de Déu, Barcelona, Spain), Carmina Guitart (Hospital Sant Joan de Déu, Barcelona, Spain), Sonia Sánchiz Cárdenas (Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain), Javier Gil-Antón (Hospital Universitario de Cruces, Barakaldo, Spain), Belén Joyanes (Hospital Clínico Universitario San Carlos, Madrid, Spain), Ainhoa Jiménez Olmos (Hospital Universitario Miguel Servet, Zaragoza, Spain), Antonio Rodríguez Núñez (Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain), Javier Trastoy Trastoy Quintela (Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain), Alexandra Hernández Yuste (Hospital Materno Infantil Universitario de Málaga, Malaga, Spain), Laura Díaz Munilla (Complejo Hospitalario de Navarra, Pamplona, Spain), Carlos Solís Reyes (Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain), Laura Medina Ramos (Hospital General Universitario de Alicante, Alicante, Spain), David Roca Pascual (Pediatric Intensive Care Unit, Vall d’Hebron Hospitalary Campus of Barcelona, Barcelona, Spain), Joan Ballcels (Pediatric Intensive Care Unit, Vall d’Hebron Hospitalary Campus of Barcelona, Barcelona, Spain), Mario Sánchez Fernández (Hospital Universitari Dr. Josep Trueta, Girona, Spain), Inés Leoz Gordillo (Hospital Infantil Universitario Niño Jesús, Madrid, Spain), Corsino Rey Galán (Hospital Universitario Central de Asturias, Oviedo, Spain), Alfredo Molina Cambra (Hospital Universitario y Policlínico La Fé, Valencia, Spain), Manuel González-Ripoll Garzón (Hospital Universitario Torrecardenas, Almería, Spain), Pepe Fernández-Cantalejo Padial (Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain), Ignacio Oulego-Erroz (Hospital Universitario de León, León, Spain), Laia Vega Puyal (Hospital Universitari Dexeus, Barcelona, Spain), Daniel Moreno (Hospital Universitario de A Coruña, A Coruña, Spain), Emilia Fernández Romero (Hospital Universitario Virgen de la Macarena, Sevilla, Spain), María García Besteiro (Corporación Sanitaria Parc Taulí, Sabadell, Spain), José Carlos Flores González (Hospital Universitario Puerta del Mar, Cádiz, Spain), Carmen Medina Monzón (Hospital General Universitario de Albacete, Albacete, Spain), Beatriz Huidobro Labarga (Complejo Hospitalario Universitario Virgen de la Salud, Toledo, Spain), Rosa María Hernández Palomo (Hospital Universitario Quirónsalud, Madrid, Spain), Cristina Calvo Monge (Hospital Universitario Donostia, San Sebastián, Spain), Francisco Fernández (Hospital Universitario de Salamanca, Salamanca, Spain), Nieves González (Hospital Universitario de Canarias, La Laguna, Spain), Cesar Villa Francisco (Hospital Clínico Universitario de Valladolid, Valladolid, Spain), Lorena Bermúdez Barrezueta (Hospital Clínico Universitario de Valladolid, Valladolid, Spain), Ana Abril Molina (Hospital Materno Infantil Virgen de las Nieves, Granada, Spain), Mónica Valerón (Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas de Gran Canaria, Spain), Ramón Hernández Rastrollo (Hospital Universitario de Badajoz, Badajoz, Spain), Sylvia Belda Hofheinz (Hospital Universitario Doce de Octubre, Madrid, Spain), Manuel Gijón Mediavilla (Hospital Universitario Doce de Octubre, Madrid, Spain), José Luis Vázquez Martínez (Hospital Universitario Ramón y Cajal, Madrid, Spain), Manuel Frías (Hospital Universitario Reina Sofía, Córdoba, Spain), Raúl Montero Yéboles (Hospital Universitario Reina Sofía, Córdoba, Spain), Juan Ignacio Muñóz Bonet (Hospital Clínico Universitario de Valencia, Valencia, Spain), María Velázquez (Hospital Universitario La Moraleja, Madrid, Spain), Inma Sánchez Ganfornina (Hospital Universitario Virgen del Rocío, Sevilla, Spain), Antonio Pérez Iranzo (Hospital General Universitario de Castellón, Castellón, Spain)47, David Lozano (Hospital General La Mancha Centro, Alcazar de San Juan, Spain), Clara Sorribes (Hospital Universitario Joan XXIII, Tarragona, Spain), María Soledad Holanda Peña (Hospital Universitario Marqués de Valdecilla, Santander, Spain), Miriam Gutiérrez Jimeno (Clínica Universidad de Navarra, Pamplona, Spain)
Funding
Funding was provided by Ministerio de Ciencia, Innovación y Universidades (Instituto de Salud Carlos III. Grant no. COV20/00944).
Compliance with ethical standards
Conflicts of interest
All authors confirm that they have no potential conflict of interest regarding the submitted manuscript.
Footnotes
The members of SECIP Study Group on SARS-COV2 in Critically Ill Pediatric Patients are listed in Acknowledgements. All members of the study group have collaborated to the study design and have approved final submitted manuscript version.
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Contributor Information
Rafael González Cortés, Email: Rafa_gonzalez_cortes@hotmail.com.
SECIP Study Group on SARS-CoV-2 in Critically Ill Pediatric Patients:
María Slöcker Barrio, Amaya Bustinza Arriortua, Jesús López-Herce Cid, Juan Carlos de Carlos Vicente, Maite Cuervas-Mons Tejedor, Pedro Pablo Oyágüez Ugidos, Iolanda Jordan, Carmina Guitart, Sonia Sánchiz Cárdenas, Javier Gil-Antón, Belén Joyanes, Ainhoa Jiménez Olmos, Antonio Rodríguez Núñez, Javier Trastoy Quintela, Alexandra Hernández Yuste, Laura Díaz Munilla, Carlos Solís Reyes, Laura Medina Ramos, David Roca Pascual, Joan Ballcels Ramírez, Mario Sánchez Fernández, Inés Leoz Gordillo, Corsino Rey Galán, Alfredo Molina Cambra, Manuel González-Ripoll Garzón, Pepe Fernández-Cantalejo Padial, Ignacio Oulego-Erroz, Laia Vega Puyal, Daniel Moreno, Emilia Fernández Romero, María García Besteiro, José Carlos Flores González, Carmen Medina Monzón, Beatriz Huidobro Labarga, Rosa María Hernández Palomo, Cristina Calvo Monge, Francisco Fernández, Nieves González, Cesar Villa Francisco, Lorena Bermúdez Barrezueta, Ana Abril Molina, Mónica Valerón, Ramón Hernández Rastrollo, Sylvia Belda Hofheinz, Manuel Gijón Mediavilla, José Luis Vázquez Martínez, Manuel Frías, Raúl Montero Yéboles, Juan Ignacio Muñóz Bonet, María Velázquez, Inma Sánchez Ganfornina, Antonio Pérez Iranzo, David Lozano, Clara Sorribes, María Soledad Holanda Peña, and Miriam Gutiérrez Jimeno
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