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.