Study design and setting
We conducted a nationwide retrospective cohort study in Mexico from November 2021 to January 2022. Children that were hospitalized due to laboratory-confirmed (reverse-transcription polymerase chain reaction, RT-PCR) COVID-19 were potentially eligible. They were identified from the nominal records found in a national and normative system for epidemiological surveillance of respiratory viruses, which belongs to the Mexican Institute of Social Security (IMSS, the Spanish acronym). IMSS is part of the public healthcare system. It provides medical assistance, social protection, and integral services to its users through more than 6.5 thousand medical units (350 and 36 of them being secondary and tertiary care hospitals, respectively) located across Mexico.
According to normative standards, RT-PCR testing is performed in all suspected cases of COVID-19 requiring hospital admission . Hospitalized children aged 9 years or younger, with the onset of symptoms of COVID-19 from March 2020 to December 2021 and with conclusive test results, were eligible. Individuals with missing clinical or epidemiologic data of interest were excluded.
Data of interest were retrieved from the audited surveillance system, which primary data sources were the medical records of enrolled patients and death certificates, if applicable. Analyzed information included demographic characteristics (sex, age), personal history of noncommunicable diseases (no/yes: obesity, type 1 diabetes mellitus, asthma, chronic kidney disease, immunosuppression or cardiovascular disease), administration of antibiotics (any; no/yes) at hospital admission, clinical manifestations (no/yes: fever or chills, cough, shortness of breath, and tachypnea) and pneumonia-related radiographic findings (no/yes: ground glass patterns in X-ray or computed tomography scanning). Hospitalized children with pneumonia at admission were those with both clinical manifestations and radiographic findings of this abnormality .
Date of healthcare-seeking and dates of hospital admission and discharge (and the causes of hospital discharge [recovery/death], were also extracted from the audited database. The interval (days) elapsed between the symptoms onset and the date of healthcare-seeking were computed.
We used the date of symptom onset as an approximation for the SARS-COV-2 variant causing the infection and were categorized as March 2020–April 2021 or May 2021–December 2021, when the dominant variants were the ancestral and Delta (B.1.617.2), respectively .
The primary outcome was the cause [recovery or death (due to any immediate cause)] of hospital discharge of children hospitalized due to COVID-19.
Clinical specimens (deep nasal swabs) were analyzed (SuperScript™ III Platinum™ One-Step qRT-PCR Kits) at four specialized regional laboratories integrated into the IMSS network for epidemiologic surveillance. A broader description of the laboratory methods has already been published elsewhere .
We computed summary statistics and the significance level (α) at 5%. The Kaplan–Meier method calculated survival functions and 95% confidence intervals (CI). The log-rank test was used to compare the survival distributions of the study groups. The effect of the prescription of antibiotics (any) was evaluated through hazard ratios (HR), and 95% CI was computed using a multivariate Cox proportional hazard regression model. All analyses were conducted using Stata version 16.0 (StataCorp; College Station, TX, USA).