Complement mediated hemolysis in a child with COVID-19 infection
The novel coronavirus disease 2019 (COVID-19) is a member of Beta coronaviruses that became pandemic by March of 2020. The illness is classified as asymptomatic, mild (predominantly upper respiratory tract infection symptoms with no frank respiratory distress), moderate (presence of pneumonia, frequent fever, and cough but with no obvious hypoxemia), severe (presence of dyspnea with central cyanosis, oxygen saturation <92% with other hypoxia manifestations) and critical (acute respiratory distress syndrome, respiratory failure, shock, encephalopathy, myocardial injury, heart failure, coagulation dysfunction, and organ dysfunction) (1). Several complications include autoimmune disorders such as autoimmune thrombocytopenia, Guillain–Barré, and the antiphospholipid syndrome, were reported (2, 3)
The hematological manifestations related to COVID-19 are mostly lymphopenia, thrombocytopenia, elevated D-dimer, and ferritin levels (4-6). Autoimmune hemolytic anemia (AIHA) associated with COVID-19 has been described rarely (7); however, to our knowledge, complement-mediated autoimmune hemolytic anemia (CM-AIHA) has not been reported in children. Here, we report a child with COVID-19 associated with CM-AIHA.
CASE REPORT
A 12-year-old boy who has been examined and followed-up for the suspected primary immune deficiency in our hospital presented with fever, dyspnea, and cough to the Emergency Department. He had several severe pneumonia episode histories, particularly after viral infections beginning from his first year of life. Screening tests for the common defects of antibody production, cellular immunity, complement, and phagocyte deficiencies were normal. At admission, he had tachycardia and fever (38,8oC) with hemodynamic stability. His oropharynx was hyperemic, and bilateral serous conjunctivitis and decreased breath sound on the left hemithorax were detected on physical examination. Computed tomography scan of the chest showed predominantly peripherally located, multiple patchy ground-glass density areas with consolidation in both lower lobes of the lungs. The nasopharyngeal swab polymerase chain reaction (PCR) test for SARS-CoV 2 was positive, and with the diagnosis of COVID-19, favipiravir, dexamethasone, and prophylactic low molecular weight heparin were started. Furthermore, considering the patient’s underlying primary immune deficiency predisposed to severe viral pneumonia, prophylactic interferon (IFN) was administered.
On the fifth day of admission, while high fever continued, the patient’s urine became red, and urine analysis revealed 3+ hemoglobin and 30 red blood cells. His sclera was icteric. Hemoglobin level decreased 12,8 g/dL to 8.3g/dL. Haptoglobin level was 27.8 mg/dl (40-180 mg/dl), and reticulocyte count increased to 9.10%. High lactate dehydrogenase (669 U/L; (0-265 U/L) and hyperbilirubinemia (3.23 mg/dL) with indirect dominance (2.25mg/dL) were detected. Platelet and leukocytes count, serum ions, and transaminases were in the normal range. The peripheral blood smear displayed anisocytosis and polychromasia with red cell agglutinations and spherocytes (Figure 1). C-reactive protein was 0.146 g/L (0-0.005 g/L) and serum ferritin was 4194 ng/mL (10-291 ng/ml). Glucose-6-phosphate dehydrogenase level was normal. Vitamin B12 and folate levels were normal. Coagulation parameters and D-dimer levels did not alter. The direct antiglobulin test (DAT) was positive with anti-C3d (4+) but negative with anti-IgG, anti-IgA, and anti-IgM. The indirect antiglobulin test (IAT) was negative. Cold agglutinin disease was suspected; unfortunately, a cold agglutinin test could not be performed. Antinuclear antibodies, extractable nuclear antigen (ENA) screening, antiphospholipid antibody, and rheumatoid factor were negative. Other etiological factors such as Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, Influenza A, and Adenovirus and Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV) IgMs were all negative.
On the follow-up, the patient was kept warm, and treatment for COVID-19 continued. However, on the day forth, as a result of hemoglobin decline, tachycardia developed, and he received warmed erythrocyte suspension transfusion, and hemoglobin level increased to 10,6 g/dl. Plasmapheresis did not require. On the 7th day of admission, his hemoglobin level was 10,2 g/dl, and he was discharged.