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Differences between children with severe acute lower respiratory infection with or without SARS-Cov-2 infection

Aim to compare clinical features and outcome of children with severe acute lower respiratory infection (ALRI) with or without SARS-CoV-2 infection admitted to Paediatric Intensive Care Unit (PICU). Methods for this retrospective cohort study, all children aged<17 years admitted with severe ALRI at a PICU, in Salvador, Brazil were evaluated. Investigation of SARS-CoV-2 infection was performed by real-time reverse-transcription PCR. Clinical data, physical findings upon admission and outcome were registered. Patients were categorized by with or without SARS-Cov-2 infection. Outcomes were death and invasive mechanical ventilation (IMV). Results we enrolled 210 patients, whose median age was 2.8 years (IQR: 7.1 months–6.2 years). IMV was used in 33 (15.7%; 95%CI 11.3%-21.1%) patients. Eight (3.8%; 95%CI 1.8%-7.1%) cases died. 62 patients (29.5%) tested positive for SARS-CoV-2. Male gender (67.7% vs. 52.7%, P = 0.045) and sickle cell disease (6.5% vs. 0%, P = 0.007) were associated with SARS-CoV-2 infection. Wheezing upon admission was more common in patients without SARS-CoV-2 infection (38.5% vs. 21.0%, P = 0.01). IMV was more frequent among patients with SARS-CoV-2 infection (25.8% vs. 11.5%, P = 0.009) as well as death (8.1% vs. 2.0%, P = 0.05). Conclusion children with severe ALRI infection with SARS-CoV-2 need IMV more frequently than those without it.

It has been known that severe acute lower respiratory infection (ALRI) is a major cause of hospital admission in young children. 1 The COVID-19 pandemic due to SARS-CoV-2 has changed the epidemiology of ALRIs, resulting in a high demand for inpatient hospital services that has stretched healthcare systems to their capacity. We read with interest the article by Dr. Melé M and colleagues 2 where 110 children admitted with acute lower respiratory disease with (29%) or without (9%) SARS-CoV-2 infection were transferred to Paediatric Intensive Care Unit (PICU) ( P = 0.145). It is not clear if children admitted with severe ALRI with or without SARS-CoV-2 infection differ between them. We evaluated patients with severe ALRI admitted to PICU and compared the clinical features and outcome of cases with or without SARS-CoV-2 infection. Patients were enrolled from April 2020 to April 2021 in a public tertiary care unit for infectious diseases assistance in Salvador, Brazil.
All patients were managed at the discretion of the assistant physician. Clinical data, findings on physical examination performed upon PICU admission, treatment, and outcome data were collected through a review of medical charts and were recorded in standardized forms. Patients were categorized by with or without SARS-Cov-2 infection. Outcomes were death and invasive mechanical ventilation (IMV). This study was approved by the institutional ethical research committee.
Our results showed that pediatric patients admitted to the PICU with severe ALRI infected with SARS-CoV-2 more frequently required IMV (25.8% vs. 11.5%, P = 0.009) and died (8.1% vs. 2.0%, P = 0.05). To the best of our knowledge, these are original findings. Additionally, male gender and SCD were baseline characteristics associated with SARS-CoV-2 infection among those patients.
About one quarter of our SARS-CoV-2 positive cases required IMV. This is in line with the results from an American study which enrolled 394 children admitted to PICU with SARS-CoV-2 infection and 23.1% needed IMV. 6 Conversely, a British study reported that 57.5% of 73 SARS-CoV-2 infected children admitted to PICU needed IMV. 7 Those authors acknowledged different thresholds for intubation as possible cause for such high rate (57.5%); they compared their results with data from PICU admitted children with influenza in 2019 and reported no difference in IMV use (57.5% vs. 66.3%). This finding contradicts our finding. However, we concomitantly included patients with and without SARS-CoV-2 infection whereas the British study used an historical group for comparison, which may have biased their results.
Noteworthily, SCD was associated with SARS-CoV-2 infection among our cases. Considering that all cases had severe ALRI, it is possible to observe that patients with SCD infected with SARS-Cov-2 are prone to evolve severely. A recently published review pointed out that pediatric SCD patients with SARS-CoV-2 infection need more intensive care that the global pediatric population. 8 It means that as soon as COVID-19 vaccination is approved for the pediatric population, children with SCD should be in high priority groups.
terial and viral infections were thoroughly investigated, wheezing was associated with viral infection. 9 Our finding suggests that SARS-Cov-2 is not among the wheezing trigger viruses.
It is worth mentioning that even during COVID-19 pandemic, about two-thirds of our patients were admitted with severe ALRI without SARS-CoV-2 infection. In 2016, 3 years before the beginning of the current COVID-19 pandemic, ALRI was estimated to cause 652 572 deaths among children younger than 5 years all over the world. 10 Therefore, besides SARS-CoV-2, other causative agents remain causing severe ALRI.
In conclusion, children with severe ALRI infection with SARS-CoV-2 need IMV more frequently than those without it. Children with SCD should be prioritized for COVID-19 vaccination, as soon as possible.

Finance
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Cristiana Nascimento-Carvalho is a senior investigator at the Brazilian Council for Scientific and Technological Development (CNPq), Brazil. CNPq did not have any role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.