Discussion
In adults, the most common hematological findings of COVID-19 include lymphocytopenia (11, 12), neutrophilia (2, 13), mild thrombocytopenia (7) and, less frequently, thrombocytosis (9, 17). However, there is paucity of data on hematological findings in affected children (4, 13). In our study, the majority of the SARS-CoV-2 infected children had normal leukocyte count, but 13.3% had leukopenia and 6.7% had leukocytosis, according to age-specific intervals. Despite normal leukocyte count, lymphopenia and neutrophilia were noted in 30.0% and 13.3% of children affected with the disease, respectively. Seven patients with SARS-CoV-2 test positive (23.3%) had neutropenia; this figure was 7.5% in the test negative group. Neutropenia has not been previously reported in adults affected with the disease.
The presence of reactive lymphocytes has been occasionally reported in adults with COVID-19. Fan et al. reported a few lymphoplasmacytoid reactive lymphocytes in peripheral blood of lymphopenic patients with COVID-19 (7). It is well documented in the literature that in response to stress, atypical reactive lymphocytes that are characterized by nuclear and cytoplasmic distortion appear in the blood (18). Reactive lymphocytes were detected in 85.1% of our patients in the whole cohort, 77.8% in the test-positive and 90% in the test-negative groups. The mean ARL count was lower in the COVID-19 positive group, which was statistically different from the COVID-19 negative group. Leukoerythroblastic reaction that reflects the immature erythroid and immature myeloid cells circulating in the peripheral blood has also been reported in adults with COVID-19 (19). However, we did not observe leukoerythroblastosis in the whole cohort, but we noted bands and metamyelocytes in 23% of the COVID-19 patients’ peripheral smear. We detected the lack of concordance between LUC/DNI as measured by the counter and manual counting. This addresses the importance to assess peripheral blood smears.
Thrombocytopenia was detected in only one patient with aplastic anemia and COVID-19; thrombocytosis was not noted in any patient. In a meta-analysis, low platelet count has been associated with the increased severity of the disease and increased mortality in adults with COVID-19, thus serving as an indicator of worsening illness during hospitalization (9). The absence of thrombocytopenia in our series may be related to better clinical prognosis of the disease in children.
Zini et al. from Italy reported marked morphological abnormalities in neutrophil lineage and platelet morphology in adults with COVID-19, mainly very large, usually hyperchromatic platelets, both in patients with thrombocytosis and thrombocytopenia (15). We noted some nonspecific dysplastic changes in peripheral smear of affected children. Giant platelets were noted in 20% of children with COVID-19. Vacuolated monocytes, hypergranulated neutrophils and pseudo Pelger-Huet abnormality were also seen in 13%, 7% and 30% of COVID-19 infected children, respectively. In patients with COVID-19, upregulation of pro-inflammatory cytokines in the blood, including interleukin (IL)-1, IL-6, TNF, and interferon γ has been reported (5). Dysregulation of immunological environment may have an important role in the pathogenesis of myelodysplastic syndromes (20). We do not have the data for pro-inflammatory cytokines in the blood and we speculate that the dysplastic changes of blood cells in our series might be related to those altered cytokines.
In conclusion, leukocyte and neutrophil counts were lower in children with COVID-19 compared with children with similar symptoms. Lymphopenia and reactive lymphocytosis, dysplastic changes of granulocytic lineage and giant platelets on peripheral smear, although not specific, could be noted in children with COVID-19. Further studies on hematological findings linked with the course of the disease in children are warranted.
Conflict of Interest: The authors have indicated they have no potential conflicts of interest to disclose.