Case description
An 11-year-old Chinese boy was presented with fatigue and anosmia for three days in Belarus, whose SARS-CoV-2 of nasopharyngeal and oropharyngeal swabs were positive on December 27, 2020. Therefore, he was diagnosed as mild type of COVID-19 infection, as well as his parents. Without any treatment, the symptoms disappeared three days later. SARS-CoV-2 RNA and COVID-19-specific antibodies IgM were negative after two weeks. About sixty days later from confirmed COVID-19, COVID-19-specific antibodies IgG also turned negative. Since then, SARS-CoV-2 RNA and COVID-19-specific antibodies IgM and IgG were negative by consecutive nasopharyngeal PCR.
About nineteen days later from diagnosed COVID-19, he showed transient pain in his left thigh and waist, however the symptoms disappeared without any treatment. Then he had a fever (38.0-38.6℃) accompanied by chest pain occurred, no cough and short-breath after twenty-nine days confirmed COVID-19. Chest X-ray examination was finished in local hospital of Belarus and showed acute bronchitis. His symptoms relieved with five-day antibiotics treatment. Then he was hospitalized in a local hospital soon, because his complete blood count (CBC) test showed cytopenia (Table S1) and immature cells found in peripheral blood smear, Ultrasound examination of abdomen revealed hepatosplenomegaly, and anti-bacterial treatment was ineffective. About forty days later from diagnosed COVID-19, he was transferred to another hospital of Belarus for further treatment. The bone marrow aspirations at two sites were performed and the procedure indicated immature cells were 18.75% and 10% respectively. The bone marrow biopsy indicated lymphocytes proliferation and blasts cells increased. However, the percentage of immature cells in bone marrow didn’t meet the diagnostic criteria for ALL, the doctor recommended close follow-up. Then the boy didn’t receive any treatment and returned to China for further diagnosis and treatment. The CBC test showed his hemoglobin and platelets value gradually increased to normal during the isolation of COVID-19 (Table S1).
After the end of COVID-19 isolation period, he came to Beijing children’s hospital on March 23 without any symptoms. Physical examination revealed a good general condition and no hepatosplenomegaly. Laboratory findings showed CBC test was at normal level (Table S1). There was 10% blast cells in bone marrow aspirate smears. However, blast cells on peripheral blood smear and flow cytometry (Fig.2A) were not present on March 23. Cytogenetic analyses revealed normal karyotypes. Common fusion genes, such as TEL/AML1, BCR/ABL, E2A/PBX1, MLL/AF4, SIL-TAL1, were negative. One week later, lymphoblasts was identified about 4% in bone marrow by flow cytometry. He was considered to be a reactive blast cells proliferation caused by the SARS-CoV-2 infection and continued to observe without any treatment. Until April 16, the patient was admitted to our hospital with persistent left thigh pain and fever for five days. The CBC test revealed an elevation of white blood cell count and absolute neutrophil count with circulating blasts were present (Fig.1J). Also a significant elevation of C-reactive protein (up to 101.6mg/L ) was found. Lymphoblasts were 50% in bone marrow smear. Lymphoblast B cells expressing CD45dim, TdT, CD19, and CD10bri were found in peripheral blood by flow cytometry (Fig.2B-D). As well, we reviewed HE staining bone marrow biopsy which finished in Belarus, immunohistochemistry was performed to identify the blast cells, which was identified B lymphoblast cell expressing CD34 , TdT , CD10 and CD20 (Fig.1A-F). The patient was diagnosed B-ALL. His family decided to return to the local hospital for chemotherapy. In addition, significant immune dysregulation was observed with higher proportion of regulatory T cells (Treg), double-negative T cells (DNT) and T follicular helper cells (TFH) (Figure.S1).