Parvovirus B19 is a single-stranded DNA virus with a 5.6 kilobase DNA genome and a diameter of 22–24 nm.1 This virus does not possess an envelope and it is the most pathogenic virus belonging to the family of Parvoviridae that infects human beings.2 The main diseases caused by parvovirus B19 are as follows: (1) infectious erythema (also known as fifth disease, erythema infection), a cause of a common rash in pediatric patients; (2) joint disease; (3) aplastic anemia crisis in patients with chronic hemolytic disease; (4) chronic anemia in immunodeficient patients; (5) fetal hydrops in addition to stillbirth and abortion (fetal death).3–7 The B19 virus primarily causes severe infections in individuals with hematopoietic dysfunctions and immune deficiencies. Anemia in young patient who are not using immunosuppressive agents and do not have immunodeficiency syndromes can often be overlooked. Here, we report a case of 36-year-old female patient with reduced T cell immune function, who was infected with parvovirus B19 and presented with persistent low-grade fever, systemic lymph node enlargement, and severe anemia. Next generation sequencing was used to screen and identify the pathogen in this patient.
In June 2019, a 36-year-old female presented with a persistent fever for 10 days, accompanied by chills, soreness, and multiple lymph node enlargements. A blood test revealed: white blood cells 1.5 × 109/L; hemoglobin 78 g/L; and platelets 129 × 109/L. The patient was sent to the local hospital due to a potential virus or bacterial infection. Treatment of cefminol (1 g, q12 h) combined with acyclovir (250 mg, q8 h) was administered; however, the patient continued to exhibit a low-grade fever, with obvious fatigue and enlarged lymph nodes throughout the body. On June 24, 2019, the patient was sent to the First Affiliated Hospital of Zhejiang University. When the patient was admitted to the Department of Infection, the patient had a fever and displayed obvious systemic pain. Enlarged lymph nodes could be felt in several parts of the body (neck, armpit, and groin). Routine blood examination showed: white blood cells 4.0 × 109/L; hemoglobin 53 g/L; and platelets 122 × 109/L. A B-ultrasound showed axillary and bilateral supraclavillae lymphadenectasis. The alanine aminotransferase was 148 U/L, aspartate aminotransferase was 105 U/L, creatinine was 49 μmol/L, albumin was 36.8 g/L, uric acid was 234 μmol/L, and the erythrocyte sedimentation rate was 30 mm/h. When detecting lymphocytes, T cells, especially CD3CD4+ T cells, were found to be decreased. Of the 2425 total lymphocytes, only 581 were T cells, of which 303 were CD3CD4+ T cells. Patient's triiodothyronine, thyroid-stimulating hormone, and thyroxine were normal. The routine tumor index (Alpha-fetoprotein, sugar chain antigen 199, carcinoembryonic antigen, ferritin, sugar chain antigen 125, and sugar chain antigen 153) was normal. No monoclonal immunoglobulins were observed by immunoglobulin fixation electrophoresis. The inguinal and posterior occipital lymph nodes were enlarged, and the larger lymph nodes were 1.4 cm × 0.6 cm. A positron emission computed tomography revealed an enlarged spleen. Based on the relevant examinations, blood disorder, viral infection, and other conditions were considered. The patient was administered fluid rehydration and symptomatic treatment (including blood transfusion, stomach-protecting treatment, and liver protection therapy). On June 27, 2019, we decisively improved the bone marrow biopsy examination, performed lymph node biopsies, and observed the changes in body temperature and clinical manifestations at the later stage. The pathological results of the bone marrow and lymph node biopsies are presented in Figure 1. No evidence of a blood disorder was identified.
During hospitalization, the patient was treated with blood transfusion due to severe anemia. However, after many tests (like bone marrow biopsy and lymph node biopsy) a blood disorder was ruled out. The patient was suspected to be infected with a virus (Human immunodeficiency virus, Epstein-Barr virus, Cytomegalovirus, BK virus, JC virus, Dengue virus, severe fever with thrombocytopenia syndrome bunyavirus, or Herpes simplex virus). However, the above viruses were negative by polymerase chain reaction. Finally, we performed next generation sequencing on serum, which revealed that the patient was infected with parvovirus B19 (Figure 2), thus confirming the diagnosis. The treatment plan was adjusted by adding polysaccharide iron complex supplementation. After treatment, the patient's hemoglobin increased to 84 g/L, her liver function was normal, and the fever disappeared. The patient recovered and was discharged from the hospital on July 6, 2019. Two months after discharge, the patient's hemoglobin increased to 106 g/L. The virus content (1.4 × 103 copies/mL) of parvovirus B19 was at a low level. At the same time, the T cell function of the patient became normal. Follow-up was performed for more than 3 months, during which time the patient did not experience fever and her hemoglobin increased to normal levels.
Discussion and conclusion
Human parvovirus B19 virus infection is widespread, in some specific countries with an infection rate of more than 60%.8,9 The virus can be transmitted by therapeutic use of blood products not screened for B19 and is most common in patients treated with concentrated coagulation factors.10 At present, the respiratory tract has been identified as a portal of entry for the virus, and direct close contact is the likely means of transmission.11 In addition, B19 virus can be transmitted from mother to child as well as from donor to recipient during organ transplantation.12,13 The symptoms associated with B19 virus infection are generally mild and easily overlooked in individuals with a competent immune system. However, in individuals with hematopoietic dysfunctions and immune deficiencies, B19 virus infection often results into serious disease or chronic conditions. Therefore, in patients with reduced T cell immune function, lymph node enlargement and decreased red blood cells there is need to investigate the potential effects of B19 virus as this is crucial for effective patient management. In addition, treatment with intravenous immunoglobulin can be used to effectively treat B19 virus infections in adults.14
In patients with mild T cell hypofunction, viral load in the respiratory tract and blood may be low and in this context this infection may be overlooked. However, for a good diagnosis to be made while screening for other pathogens, polymerase chain reaction can be combined with next generation sequencing to provide good guidance for clinical treatment.15 Thus, next generation sequencing can be used to detect B19 virus fragments, after excluding blood disorder, tumors, and other common infections. B19 infections can cause serious disease in adults with mild T cell hypofunction, which can easily be ignored. Patients that present with typical influenza-like symptoms, enlarged lymph nodes, and marked reduction in red blood cells should be considered for B19 virus diagnosis.
The English in this document has been checked by at least two professional, native-English speaking editors from Elixigen. Thank you HuaDa gene co., Ltd. for helping us complete the next generation sequence of the pathogen.
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