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.