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).