Case report
The patient was a 17-year-old girl who underwent HSCT in Strasbourg University Hospitals, France on January 7, 2020 for an acute myeloid leukemia subtype M5 according to the French-British-American (FAB) classification diagnosed on October 1, 2019. She was treated initially in the MyeChild protocol (high-risk group) and developed following a severe sepsis in context of aplasia a mild dilated cardiomyopathy with left ventricle ejection fraction around 50% treated by Angiotensin-converting-enzymes (ACE) inhibitors. She had HSCT after consolidation course (first complete remission) with an intrafamilial donor. The conditioning regimen was Fludarabine, Busulfan; Ciclosporine was introduced for the Graft-versus-Host disease (GVHD) prevention. One notable event during HSCT was a cutaneous and digestive GVHD grade III treated by corticosteroids. Bone marrow aspirations realized at D30, D60 and D90 showed cytological remission as well as a complete donor chimerism.
On March 24, 2020 (Day 0), the patient was tested for SARS-CoV-2 due to multiple suspect cases in the family: before lockdown measures one of her brother’s classmates was tested positive, then the brother and both parents showed fever, anosmia and chest pain, and finally the patient’s uncle developed a severe form of the disease. The patient presented only a rhinitis without fever, nor respiratory signs. Real-time PCR SARS-CoV-2 was positive on nasopharyngeal swab specimens (Institut Pasteur, Paris, France; WHO technical guidance). The assay targets two regions of the viral RNA-dependent RNA polymerase (RdRp) gene, and the threshold limit of detection was 10 copies per reaction. No other viral reactivation or infection (CMV, EBV, adenovirus) occurred.
At that time the patient was still treated by prednisolone (0,4mg/kg/d) for her digestive GVHD, ciclosporine (4mg/kg/d), ACE inhibitors (0,12mg/kg/d), preventive anti-infectious treatment by sulfamethoxazole-trimethoprime, posaconazole, phenoxymethylpenicilline and valaciclovir. Cell blood count (CBC) showed an average hematological reconstitution with 3.5 x109/l white blood cell including 2.2 x109/l neutrophils, and a preexisting lymphopenia at 0.43 x109/l, hemoglobin 96 g/l and 53 x109/l platelets (Table 1). All laboratory analyses between March 24 and May 19, 2020, are shown in Table 1. The patient had a perfusion of intravenous immunoglobulin (IVIg, PRIVIGEN®) on March 10 and April 9 (D16), 2020 for the immune deficiency secondary to the HSCT. Immunophenotyping (Table 1) showed that she was cytopenic on every lineage (B, T and NK). Cytokines (IL-6, IL-8, IL-10) were within normal range. Chest computed tomography (CT) on March 31, revealed scattered ground glass opacities in the right lower lobe close to the pleura compatible with COVID-19, and one month later a fibrosis aspect as observed (Figure1) , reported as a usual evolution of COVID-199.
The SARS-CoV-2 real-time PCR on her nasopharyngeal swab was still positive 21 days and 42 days after the initial positive test, while negative on May 19 (D56). Serology tests were performed on serum samples collected at day 7, day 14 and day 56 after the first positive RT-PCR, with 2 different techniques : immunochromatographic lateral flow assay (Biosynex COVID-19 BSS® (Biosynex, Switzerland, Fribourg)), and ELISA to detect IgA and IgG (Euroimmun IgA, IgG, Lübeck, Germany). She developed neither IgA, IgM nor IgG on day 7. IgA remained negative, at day 14 and day 56. IgM were detected at day 14 only and remain weakly positive at day 56 and IgG were positive at day 56 only. The patient was hospitalized on April 7, 2020 for 4 days for an episode of dehydration with renal failure due to an increase of digestive GVHD signs (vomiting and diarrhea). She responded favorably with IV fluids and an increase of prednisolone. Beside this hospitalization unlinked to COVID-19 and the initial rhinitis, she didn’t develop any signs of the disease and is so far doing well.