To the editor,
Following the online podcast recorded the 31 March 2020 by the
International Committee of the American Thoracic Society Pediatrics
Assembly and recently published in Pediatric
Pulmonology1, we have interesting discussion with my
international colleagues about the likelihood of acute bronchiolitis
caused by SARS-CoV-2 infection in absence of RSV co-infection. Here, we
report 2 cases of COVID-19 in infants < 3 months old admitted
to our paediatric unit. The infants presented fever and neurological
symptoms and after a short period, acute bronchiolitis.
Case 1 : A term-born boy with unremarkable history was
admitted to the emergency department with
poorly tolerated high fever
(38.8°C) and rhinitis. The parents, who had no history of asthma or
allergy, showed clinical signs suggesting SARS-CoV-2 infection. RT-PCR
for SARS-CoV-2 on a nasopharyngeal swab was positive for the father and
the grandfather, who was hospitalized in the intensive care unit.
Neurologic examination of the infant revealed lethargy and hypotonia
with a bulging anterior fontanelle. The respiratory condition and
clinical examination findings including hemodynamics were normal.The
first blood test showed isolated lymphopenia (lymphocyte count 1.56
x109/L; normally 4-6x109/L) without
modification of biological inflammatory parameters, as assessed by
normal levels of C-reactive protein (CRP) and procalcitonin (PCT).
Spinal fluid analysis, cytobacteriological urine analysis and blood
culture were negative. RT-PCR of a nasopharyngeal swab was positive for
SARS-CoV-2 but negative for respiratory syncytial virus (RSV) and
influenza virus (IV). The patient received fluid volume expansion(20
ml/Kg of 0.9% sodium chloride solution) together with antibiotic
treatment (cefotaxime, amoxicillin and gentamicin at meningeal doses)
for 24 hr, that was stopped with a positive RT-PCR test for SARS-CoV-2
and negative blood culture. Favourable clinical outcome was obtained
shortly thereafter, allowing the infant to return home 2 days later.
Ten days later, the child returned with acute bronchiolitis. Respiratory
symptoms included polypnea, shortness of breath, wheezing and hypoxia
(SpO2< 92 %). Lung ultrasonography revealed signs of
interstitial syndrome with thickened and irregular pleural line
associated with confluent B lines and small multifocal subpleural
consolidations. RT-PCR for RSV and IV remained negative. Treatment
associated supplemental oxygen and enteral nutrition for 6 days. A
second episode of acute bronchiolitis occurred 1 month later, but a
RT-PCR test for SARS-CoV-2 was negative. The chest X-ray was normal. The
child remained hospitalized for 5 days with enteral nutrition support
but did not require oxygen supplementation. Long-term treatment with
inhaled daily corticosteroids (fluticasone) was introduced.
Case 2 : A term-born eutrophic male with otherwise
unremarkable neonatal history was referred for poorly tolerated high
fever at age 2 months. Both parents had clinical signs of COVID-19 but
were not tested (a member of the family had a positive test). The
neurologic examination revealed lethargia and hypotonia in the child;
the respiratory condition and clinical examination findings including
hemodynamics were normal. The first blood test showed lymphopenia
(lymphocyte count: 1.86 x109/L; normally
4-6x109/L)without modification of biological
inflammatory parameters. Cytobacteriological examination of urine and
blood culture were negative and spinal fluid analysis was not performed.
RT-PCR testing of a nasopharyngeal swab was positive for SARS-CoV-2 but
negative for RSV and IV. The patient did not receive any antibiotics. On
day 3 after admission, the respiratory condition progressively worsened,
with retraction, wheezing, increased respiratory rate at 80/min and
hypoxia (SpO2 < 92%) requiring supplemental oxygen together
with enteral nutrition for 3 days. The chest X-ray was normal, and no
lung ultrasonography was performed. The infant was returned to the
emergency department 2 weeks later with a non-severe wheezing episode
and was discharged at home.
These 2 cases of COVID-19 in infants hospitalized for poorly tolerated
high fever and neurological symptoms in whom acute bronchiolitis
developed at a delay of 2 to 8 days suggest that SARS-CoV-2 infection
may cause acute bronchiolitis in absence of viral co-infection such as
RSV. Pneumonia is the most common diagnosis among symptomatic children
with COVID-191. High-resolution CT scan usually shows
ground-glass opacities or bilateral lung consolidations, especially in
the periphery, and lung ultrasonography, as in our case 1, reveals signs
of lung involvement. In contrast, to the best of our knowledge, acute
bronchiolitis due to SARS-CoV-2 infection has never been reported. The
wheezing episodes described in our patients were likely due to
SARS-CoV-2 infection for the following reasons: first, RT-PCR tests for
RSV and IV were always negative in both children, and second, the
epidemic season for both viruses was over and the lockdown in France was
still active at the time of the cases. Finally, previous study of virus
repartition in positive respiratory samples from infants with acute
bronchiolitis detected close to a 5% frequency of coronaviruses OC43
and 229E2. Moreover, a recent experimental model of
COVID-19 in ferrets showed lung lesions compatible with
bronchiolitis3. Our patients showed bronchiolitis
symptoms several days after those of COVID-19, which may explain the
lack of wheezing episodes reported in the literature. Case 2 was
diagnosed with recurrent wheezing presumably due to SARS-CoV-2
infection. RSV as well as rhinovirus bronchiolitis is a risk factor for
recurrent wheezing and asthma4,5,but little is known
about the long-term impact of SARS-CoV-2 infection in lung function
trajectory, which emphasizes the need to follow these children. Whether
the infection in symptomatic or asymptomatic infants may predispose to
recurrent wheezing or asthma remains to be determined.