key: cord-0851060-83etsaw8 authors: Kato, Shota; Nakano, Yoshiko; Nakano, Yuki; Okamoto, Koh; Takasugi, Nao; Hidaka, Moe; Sekiguchi, Masahiro; Hiwatari, Mitsuteru; Kurano, Makoto; Kato, Motohiro title: COVID‐19 in an adolescent with aplastic anemia undergoing immunosuppressive therapy: A case report and details of antibody testing for SARS‐CoV‐2 date: 2021-09-05 journal: Pediatr Blood Cancer DOI: 10.1002/pbc.29332 sha: 6c227b1187c21e56203dcb1e6408990c6ff69426 doc_id: 851060 cord_uid: 83etsaw8 nan To the Editor: The increase in the cumulative incidence of COVID-19 cases was accompanied by a gradual increase in reported pediatric cases. 1 However, the clinical course of COVID-19 in pediatric patients with aplastic anemia (AA) has not been thoroughly investigated. As of June 2021, only one pediatric and eight adult cases of COVID-19 in patients with AA have been reported. Some patients exhibited mild and transient symptoms, while others experienced severe manifestations with fatal outcomes. [2] [3] [4] [5] [6] Data on the ability of these patients to produce antibodies against the virus under insufficient immune function are also limited. We report our experience with COVID-19 in a patient with AA receiving immunosuppressive therapy (IST) and the dynamic results of the serological assay. A 15-year-old male receiving cyclosporine for AA was admitted to the University of Tokyo Hospital due to fever. He was diagnosed with very severe AA 4 months prior. Since a human leukocyte antigenmatched sibling donor was unavailable, he received IST with corticosteroids, rabbit antithymocyte globulin, and cyclosporine combined with eltrombopag. He was discharged and barely achieved a partial response 2 months after IST initiation ( Figure S1 ). At the time of this hospitalization, he presented with a fever and mild sore throat that was noted one day previously. His white blood cell count was 1.0 × 10 9 /L, with absolute neutrophil and lymphocyte counts of 0.67 × 10 9 /L and 0.18 × 10 9 /L, respectively. The hemoglobin level was 9.8 g/dl, and the platelet count was 45 × 10 9 /L without transfusion for more than 2 months. The serum immunoglobulin G (IgG) level was low at 503 mg/dl (reference value, 861-1747 mg/dl). Other blood examinations were unremarkable. The chest radiograph did not show any evidence of pneumonia. On day 2 (the onset of COVID-19 was considered day 0), the patient tested positive on nasopharyngeal swab polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As a part of IST, cyclosporine was continued with trough concentrations of 150-250 ng/ml. After receiving intravenous immunoglobulin and a single dose of hydrocortisone, he became afebrile on day 2. Although the complete blood count fluctuated slightly, he did not require transfusion or granulocyte-colony stimulating factor supplementation ( Figure S2 ). He was discharged on day 10 and had no sequelae attributed to COVID-19 for 5 months. We analyzed IgG, immunoglobulin M (IgM), and immunoglobulin A (IgA) titers against three different proteins of SARS-CoV-2: the S1 sub-unit of spike protein (S1); receptor-binding domain (RBD) within the S1 subunit, which is a major target of anti-SARS-CoV-2 neutralizing antibodies 7-9 ; and nucleocapsid protein (N) (Figure 1 ). The anti-S1 and anti-RBD IgA levels exceeded the cutoff levels on day 9 and rapidly decreased thereafter. The anti-N IgM level was elevated on day 32. The anti-S1 IgG and IgM and the anti-N IgG levels also increased; however, their titers did not exceed the cutoff values. Meanwhile, the anti-RBD IgG and IgM levels hardly changed. Our patient exhibited no severe symptoms and fully recovered from COVID-19 despite his immunosuppressed status. The clinical course of COVID-19 was reportedly less severe in the pediatric population than in adults. 1 His young age possibly contributed to the mild clinical course. Other known risk factors for severe COVID-19 include underlying diseases such as hypertension, diabetes, obesity, and lung diseases. However, the relationship between immunocompromised states due to the underlying disease or immunosuppressive treatment and COVID-19 severity remains controversial. Some studies reported that immunocompromised patients had more favorable outcomes than the general population. 10, 11 Hyperactivation of immune response and excessive inflammatory reaction were associated with the pathogenesis of severe COVID-19. 12 Among the previously reported nine cases of COVID-19 in patients with AA, there was one patient who developed COVID-19 during cyclosporine treatment and the patient fully recovered. 3 Therefore, immunosuppression from AA and IST, including continued cyclosporine use, possibly contributed to the uncomplicated course in our patient, despite an increased risk of viral invasion and delayed viral elimination. The anti-S1 and anti-RBD IgA levels increased before the changes in the IgG and IgM levels in our patient. This observation was consistent with the findings of a previous study, which conducted a serological assay in a non-AA cohort. 13 Since spike proteins are integral to viral entry into cells, 14 patients without AA were not evaluated in that study. 3 The effect of IST on decreased IgG production and a favorable outcome warrants additional investigation. In summary, we report a case of COVID-19 in a patient with AA undergoing IST. Together with previous reports, our findings suggest Epidemiology of COVID-19 among children in China COVID-19 in a child with severe aplastic anemia COVID-19 infection in patients with severe aplastic anaemia Case Report: tocilizumab for the treatment of SARS-CoV-2 infection in a patient with aplastic anemia COVID-19-related acute necrotizing encephalopathy with brain stem involvement in a patient with aplastic anemia Lessons from a patient with severe aplastic anemia complicated with COVID-19 Comparative analyses of SARS-CoV-2 binding (IgG, IgM, IgA) and neutralizing antibodies from human serum samples Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients How is immunosuppressive status affecting children and adults in SARS-CoV-2 infection? 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