RESULTS
After removing duplicates, the first search yielded eight systematic reviews(5, 8-14). Three of them were eliminated because they did include information on clinical characteristics in children(8-10). Therefore, we evaluated five systematic reviews done at different periods during the pandemic and thus including somewhat different primary studies(11-14). Castagnoli et al.(11) included 18 articles, 17 from China and 1 from Singapore (444 patients <10 years old and 553 aged 10-19 years), published up to March 3, 2020. Choi et al.(12)included 7 articles from China (225 pediatric patients) up to March 12, 2020. Chang et al.(13) included 9 studies from China (93 pediatric patients) up to March 15, 2020. The review by Ludvigsson(14) included 45 studies from China (the total number of patients was not described) up to March 19, 2020. And Streng et al.(15) included 8 studies from China (ranging from 6 to 2,143 patients) and one survey from Germany (33 patients) in hospitalized children, up to March 31, 2020. After excluding duplicates, we identified and reviewed 67 primary studies included in those five reviews (see Supplementary Table 1 ).
None of the primary studies reviewed reported asthma or recurrent wheezing as a comorbidity or risk factor for COVID-19. Instead, some of those studies reported young age (especially children <1 year of age) as a group with more severe COVID-19. One large Chinese study(16) reported non-respiratory chronic conditions (hydronephrosis, leukemia receiving chemotherapy, and intussusception) among the 3 children required ICU support and mechanical ventilation all had coexisting conditions; one death occurred in the 10-month child with intussusception. Another study reported a patient develop shock with metabolic acidosis requiring ICU(17); while a report from China(18) described one patient aged 10-19 years who died, without other clinical information, that probably is the same death in a 14-year-old boy described by Dong and colleagues(19). Unfortunately, the two larger studies in Chinese pediatric patients, Dong et al.(19) (2,413 children) and Wu and MacGoogan(20) (965 children) did not report enough clinical data to identify comorbidities or risk factors for COVID-19 severity. In the German survey of 33 hospitalized children, 4 out of 22 (18%) children with clinical information had “respiratory comorbidities” without further details(15).
Our second search yielded 34 results in PubMed. Of those, five were primary studies that reported on asthma in adults(21-25); one other was a guidance statement(26) that referenced a primary report that also included information on asthma in adults(27). No studies from that search included information on asthma in children, although one case series reported two young children (ages 2 and 3 years) with history of atopic dermatitis and allergic rhinitis, who were hospitalized with COVID-19; both patients recovered(28).
Our third search yielded 26 pre-prints in BioRxiv and 137 in MedRxiv. None of the BioRxiv posts were relevant to our topic. Of the 137 pre-prints in MedRxiv, 23 non-duplicate studies included information on asthma(29-51), but none of them included specific information in children.
More recently, the CDC published a Morbidity Mortality Weekly Report (MMWR)(52) that included information from 2,572 U.S. children aged < 18 years. Of those cases, 345 had data on clinical and underlying conditions, and 80 of those children (23%) had at least one underlying condition. The most common underlying conditions were “chronic lung diseases (including asthma)” in 40 children, cardiovascular disease in 25, and immunosuppression in 10; separate information on asthma was not provided. Among the 295 cases for which data on both hospitalization status and underlying medical conditions was available, 28/37 (77%) hospitalized patients had one or more underlying medical condition (including all six patients admitted to an ICU); compared to 30/258 (12%) patients who were not hospitalized(52). Finally, a recently published Italian study, including100 children seen in 17 emergency departments, reported that 27% had comorbidities without more specifications, and no deaths occurred(53).