Because SARS-CoV-2 is a relatively new virus with emerging clinical characteristics in children and adolescents, we used broad inclusion criteria to identify SARS-CoV-2 associated hospital admissions, before classifying the admissions by type (box 1; also see supplementary table A). Basing our approach on formative NHS based research in children and adolescents with SARS-CoV-2,1011 we included first SARS-CoV-2 associated hospital admissions where at least one of the following criteria was met: from HES Admitted Patient Care, a primary cause for hospital admission was one of ICD-10 (international classification of diseases, 10th revision) codes U07.1, U07.2, U07.3, or U07.4, or a non-primary cause for hospital admission was U07.1 or U07.211; from HES Admitted Patient Care, a primary or non-primary cause for admission an ICD-10 code used to identify paediatric inflammatory multisystem syndrome (introduced from May 2020): R65, M30.3, or, from November 2020, U07.5,11 and no exclusion codes were present that indicated an alternative diagnosis; or there was a positive SARS-CoV-2 test result from up to 14 days before hospital admission until the date of hospital discharge.18
List of hospital admission types in order of assignment for categorising SARS-CoV-2 associated hospital admissions, using hierarchical criteria
Nosocomial SARS-CoV-2 infection
Consistent with definitions used by NHS England,18 admissions were classified as nosocomial if the first associated positive SARS-CoV-2 test result occurred between day 8 of hospital admission and hospital discharge and there were no covid-19 codes (U07.1, U07.2) provided as a cause for hospital admission before day 8 of the admission.
Type C: Incidental SARS-CoV-2 infection
Admissions judged to be incidental to SARS-CoV-2 infection were identified before those due to SARS-CoV-2 or SARS-CoV-2 was a contributory factor, to avoid misclassification. These are admissions where SARS-CoV-2 is not the cause but is coincidental as a result of community transmission. Incidental admissions all had codes U07.1 or U07.2 as a non-primary reason for admission or a positive test result before day 8 of the admission, or both. Candidate reasons were identified in the ISARIC prospective study of covid-19 in children, such as trauma, poisoning, or elective surgery.19 A wider range of relevant primary reasons for admission than used by ISARIC was identified and included by iterative clinical review of codes present in the hospital admission dataset: mental health disorders, eye conditions, dental conditions, injuries, trauma, assault, self-harm, poisoning, surgical problems such as those affecting bowel or testis, and certain pregnancy related conditions.
Paediatric inflammatory multi system syndrome (PIMS-TS)
Admissions were identified as due to PIMS-TS if a reason for hospital admission was PIMS-TS code U07.5, or a paediatric inflammatory multisystem syndrome code R65 or M30.311 AND no reason for admission was a prespecified exclusion code indicating an alternative diagnosis of sepsis, specified bacterial or viral infections, or known causes of systemic inflammatory response. Patients admitted to hospital with PIMS-TS could also have a covid-19 code as a reason for admission and may or may not have a positive SARS-CoV-2 test result, as it has previously been shown that most are polymerase chain reaction negative at onset of PIMS-TS.202122 After clinical review of the ICD-10 codes listed as the reasons for admission among children who had a PIMS-TS code as a non-primary reason for admission, these were included because (after applying the listed exclusion codes) these codes were consistent with a diagnosis of PIMS-TS.
Type A: Caused by or suspected caused by SARS-CoV-2 infection
Admissions caused by or suspected caused by SARS-CoV-2 infection.
Type A1—Primary reason for hospital admission was identified by one of four covid-19 codes: U07.1, U07.2, U07.3, or U07.4.11
Type A2—Primary reason for hospital admission was a sign, symptom, or condition or presentation consistent with an acute illness with SARS-CoV-2 infection (and did not definitively indicate an alternative diagnosis); AND a non-primary reason for hospital admission was a covid-19 code (U07.1 or U07.2) AND there was no excluded code indicating a reason for hospital admission was an alternative or co-infection. The candidate list of signs, symptoms, and conditions of SARS-CoV-2 infection was identified from prospective studies, including ISARIC and international studies1923242526 and includes: unspecified viral infections, viral conjunctivitis, volume depletion, shock, acidosis, otitis media, croup, non-specific bronchiolitis, cough, fever, vomiting, diarrhoea, myalgia, headache, certain types of arrhythmias, tonsilitis, pharyngitis, and laryngitis. The candidate code list was checked iteratively against primary reasons for hospital admission in the cohort admitted to hospital, to generate the final code list. These admissions may or may not have been linked to a positive SARS-CoV-2 test result.
Type B: SARS-CoV-2 infection as likely contributory factor
Admissions where SARS-CoV-2 infection was likely to be on the causal pathway, albeit not the primary cause of the admission. These hospital admissions may or may not have been linked to a positive SARS-CoV-2 test result, and all these patients had a covid-19 code (U07.1 or U07.2) as a non-primary reason for hospital admission, combined with one of the following primary reasons for admission that were all deemed relevant based on published reports1923272829 or, given the emerging nature of the topic, based on expert clinical experience:
Type B1—A condition known to co-occur with SARS-CoV-2 infection (co-infections or secondary infections due to, for example, respiratory syncytial virus, parainfluenza, adenovirus, staphylococcal pneumonia, streptococcal pneumonia)272829; a condition that has been clinically linked to SARS-CoV-2 infection in children and adolescents2829 (type 1 diabetes mellitus, status epilepticus, or febrile seizures); or a small number of treatments that could be linked to SARS-CoV-2 infection (isolation in cubicle for droplet precautions)
Type B2—A pre-existing or newly diagnosed condition associated with higher risk of severe illness with SARS-CoV-2 infection1923 (conditions treated with immunosuppressants, any cancer, neurodevelopmental conditions that may affect breathing, neonatal conditions such as poor feeding, respiratory diseases such as asthma)
ISARIC=International Severe Acute Respiratory and emerging Infection Consortium; PIMS-TS=paediatric inflammatory multisystem syndrome with a temporal association with SARS-CoV-2.
For each patient in whom at least one Hospital Episode Statistics Admitted Patient Care consultant episode met one of the current study’s cohort inclusion criteria, all the episodes were grouped within the relevant hospital admission and all ICD-10 codes recorded as a reason for admission were collated, whether primary or non-primary. The ICD-10 codes as reason for admission were then used to identify hospital admission types.
Definition of codes: U07.1=covid-19 with virus identified; U07.2=covid-19 with virus not identified; U07.3=personal history of covid-19; U07.4=post-covid-19 condition.
Definition of paediatric inflammatory multisystem syndrome codes: R65=systemic inflammatory response; M30.3=Kawasaki disease; U07.5=paediatric inflammatory multisystem syndrome.
Supplementary table A provides detailed code descriptions and lists for each hospital admission type.
From among first SARS-CoV-2 associated hospital admissions, we used a hierarchical approach to identify mutually exclusive admission types, using a combination of the ICD-10 codes listed as a reason for admission in HES Admitted Patient Care records, and positive SARS-CoV-2 test results in the Second Generation Surveillance System testing data. For clinical reasons developed by consensus, SARS-CoV-2 associated hospital admission types were identified in the order: admissions with nosocomial infection; admissions with incidental infection; admissions with paediatric inflammatory multisystem syndrome hospital; admissions due to or suspected to be due to SARS-CoV-2 infection (not paediatric inflammatory multisystem syndrome); and admissions where SARS-CoV-2 infection was a contributory factor (not paediatric inflammatory multisystem syndrome). The consultant paediatrician panel, all of whom have direct experience of caring for children and adolescents admitted to hospital with SARS-CoV-2 (KB, HKK, NP, MJ, PDP, PR) contributed to the methods, and at least two members had to agree on each clinical code.