Acute events in children with sickle cell disease in Italy during the COVID‐19 pandemic: useful lessons learned

On March 12th 2021 the Italian Government decided to implement a national lockdown in almost all the regions of the country. It was the second most severe measure taken after the March 2020 national lockdown, due to the rising of coronavirus disease 2019 (COVID-19) cases and the overcrowding of the hospitals. Italy was the first European country hit by the COVID-19 pandemic in February 2020. The first ‘red’ zones under severe lockdown in the Regions of Northern Italy were established on February 26th 2020, when all the schools were closed. Phase I of a nationwide lockdown began on March 8th and lasted until April 30th 2020. The Regions of Northern Italy were the most impacted by the COVID-19 pandemic in the first months of 2020, with the highest incidence of COVID-19 cases, leading to a dramatic surge in the need for emergency rooms (ERs) and wards, and a high mortality rate. The first peak of 29 000 hospitalised individuals, including children, except those in intensive care units (ICUs) was recorded in April 2020. Most hospitals had to rapidly implement strategies to ensure care for non-COVID-19 patients. The majority of children with sickle cell disease (SCD) live in the Northern regions of Italy. Therefore, the dramatic scenario represented an opportunity to explore the challenges presented for children with SCD who lived in Italy during the first outbreak, so that the lessons learned could be used to guide clinical management in the upcoming months. SCD is characterised by the presence of unpredictable and frequent acute events such as painful vaso-occlusive crises (VOCs), acute chest syndrome (ACS) and febrile episodes with risk of severe infections. VOCs, ACS and fever are the most frequent reasons for access to the ER and for hospitalisation. In previous years, data from the Network of Centres belonging to the Italian Association of Paediatric Haematology and Oncology [Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP)] showed a high frequency of access to the ER and admission to hospital for VOCs, ACS and fever for children with SCD living in Italy during the coldest months, due to the trigger of seasonal infections (January–March). The viral pandemic and the presence of febrile respiratory tract symptoms characteristic of the COVID-19 infection suggested a greater risk of acute events in children with SCD. Several reports have focussed on service provision to children with SCD or the clinical manifestations of COVID-19 infection in children with SCD, but to date, less information is available on the burden of acute events in children with SCD during the COVID-19 pandemic. The primary aim of the present multicentre retrospective study was to evaluate acute disease burden for children with SCD in Italy, measured as acute events (VOCs, ACS, fever), accesses to the ER and hospitalisations during the national lockdown of the first wave (21 February–30 April 2020), in which the same restrictive measures were applied homogeneously nationwide, compared to the same period in 2019. The secondary aim was to assess if the care provided to manage acute events had to be modified from the best practices recommended by the AIEOP National Guidelines due to the pandemic. A standardised survey in Excel (Data S1) was sent to the AIEOP Centres. Summary data were collected from individual chart review, or through specific queries in health databases, according to the usual practices in place in each centre. Fisher’s exact test was used to compare dichotomous data or low frequencies and Pearson chi-square test for analysing associations. A total of 839 patients (male 419 and female 420) with SCD (63% SS, 10% Sb°, 17% SC, 8% Sb+, 2% other) were followed in 22 AIEOP Centres at the time of the survey in 2020; 782 were followed in 2019 (62% SS, 10% Sb°, 17% SC, 8% Sb+, 3% other). Overall, 721/839 (86%) and 671/782 (86%) were living in the Northern regions of Italy in 2020 and 2019 respectively. In 2020, overall, there was a significant reduction in ER access compared to the previous year (43% vs. 73%, 40%; P = 0 001) with no differences in the three areas (Northern, Central, Southern) of the country. Hospitalisations also decreased (55% vs. 77%, 30%; P = 0 025), but the majority of the reduction occurred in the Northern Regions that were most impacted by the pandemic (P = 0 016) (Fig 1). Considering the causes of hospitalisation, admissions due to VOCs, ACS and fever were reduced overall, but those due to other causes (haemolytic crises/seizures/other) remained unchanged (Fig 2). No deaths occurred. In Italy, surprisingly, compared to all other European countries, there were no positive cases of COVID-19 in children with SCD during the first national lockdown, despite the very high number of COVID-19-positive cases in the general population, including children. Moreover, unlike other European countries, children with SCD had fewer accesses for acute events than are typical of SCD and they correspondence