To the editor:
We describe the clinical course, laboratory and radiological findings
and follow-up of a 4-month-old boy who experienced severe COVID-19
pneumonia with necrotizing pneumonia following a catheter-related
bloodstream infection (CR-BSI) by methicillin-susceptible Staphylococcus
aureus (MSSA).
He presented to the Emergency Department with a 3-days history of high
fever and cough. Since his birth, he had been followed by Hematologists
for the occurrence of severe thrombocytopenia, responding to intravenous
immunoglobulin (IVIG) administration, associated with neutropenia and
hypo-regenerative anemia successfully treated with weekly erythropoietin
administration. Diagnostic work-up revealed a post-natal cytomegalovirus
infection. Whole Exome Sequencing analysis resulted negative.
A central venous catheter (CVC) had been placed since the age of 2
months for periodic blood tests and erythropoietin treatment.
His last full blood count 10 days before admission was normal (WBC
6270/mm3, Hb 10,5 g/dl, platelets
213000/mm3).
At clinical examination he was dehydrated and irritable, with moderate
respiratory distress and oxygen saturation of 90% in room air. Chest
X-ray demonstrated bilateral peribronchovasal thickening and C reactive
protein was increased (Table 1) .
Reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2
on nasopharyngeal swab sample tested positive in both child and his
mother.
High flow nasal cannula (HFNC) and empiric antibiotic therapy with
vancomycin and piperacilline-tazobactam were started and mild clinical
improvement was noticed in the 2 following days.
On day 3 blood cultures turned positive for MSSA and the CVC was
removed. Echocardiography did not detect any endocavitary thrombus or
bacterial vegetation. Antibiotic therapy was shifted to daptomycin.
On day 4 fever relapsed and increased irritability with nuchal rigidity
was noted. Lumbar puncture was performed showing pleocytosis (200
cells/μL, prevalence of lymphomononuclear cells), normal glucose (64
mg/dl) and elevated protein levels (364 mg/dl). RT-PCR for viruses and
bacteria resulted negative, as well as cerebrospinal fluid culture.
Brain MRI did not detect any pathological findings.
Antibiotic therapy was implemented with ceftriaxone and co-trimoxazole
– trimethoprim.
The following day the child developed acute respiratory failure.
Emergency intubation and mechanical ventilation were required. High
frequency oscillatory ventilation was started with high parameters (MAP
20 cm H2O, amplitude 60, frequency 10 Htz, FiO2 0.6) and a
PaO2/FiO2 ratio of 100. Chest X-ray
showed low lung volumes, interstitial thickening associated to bilateral
granular opacities and air bronchograms, supporting a diagnosis of acute
respiratory distress syndrome (ARDS). Milrinone was started for severe
peripheral vasoconstriction and lactic acidosis with stable hemodynamic
parameters. Inotropic support was not necessary during the acute phase
and metabolic and respiratory acidosis resolved with intensive care
support. A marked increase of ferritin, triglyceridemia and lactic
dehydrogenase with decrease of platelets count were observed(Table 1) . Echocardiography confirmed normal bilateral
ventricular function. Treatment with high dose steroids (intravenous
methylprednisolone 30 mg/kg for 5 days with subsequent tapering) plus
IVIG (2 g/kg) was administered in suspicion of macrophage activation
syndrome (MAS). In the following days the fever disappeared,
inflammatory markers decreased (Table 1) , and it was possible
to reduce the respiratory support to PC-AC with intermediate parameters
and lower FiO2 (0.45).
On day 15, a new chest X-ray showed increased lung volumes with
persistent bilateral lung opacities of the lower lobes and a cavitary
lesion within right lower field. Computed Tomography (CT) confirmed
bilateral ground glass of lower lobes with a large cavitary lesion
within right lower lobe (Figure 1a ).
On day 18 the child was extubated and placed in HFNC.
On day 42 the antibiotic therapy was stopped, and on day 59 the child
was discharged without the need for respiratory support.
At follow-up, he appeared in good general condition. Chest CT was
repeated at 3-6-12 months showing a progressive reduction of ground
glass and complete resolution of cavitary lesion (Figure 1
b-d ). Last blood tests showed a normal full blood count (Table
1) .
Discussion :
Since the beginning of the COVID-19 pandemic, it was evident that
pediatric clinical manifestations were milder, compared to adult
patients.
Nevertheless, severe acute COVID-19 complicated by life-threatening
conditions, like ARDS and multiple organ failure, has been reported in
children, particularly in those affected by underlying respiratory,
neurological, or immune disorders1.
However, definitive data about the risk factors related to clinical
outcomes in children are not available.
The presence of secondary infections or co-infections is a recognized
factor affecting mortality in adults2, although it has
received inadequate attention among children with COVID-19. In
particular, data on CR-BSI during COVID-19 are lacking.
Bloodstream infections are the second most common secondary infection in
critically ill COVID-19 patients, following ventilator-assisted
pneumonia, with incidences ranging from 3.4 to 50%3.
Buetti et al. found that COVID-19 pneumonia patients had a higher risk
of developing ICU bloodstream infections compared to patients who were
critically ill without COVID-19 infection and that Staphylococcus aureus
was identified in 7.7% of cases4.
Some of these cases led to necrotizing pneumonia, likely induced by
Panton–Valentine leukocidin (PVL) secreting MSSA.
When Staphylococcus aureus is detected as the cause of pneumonia,
especially with an underlying influenza-like infection, such as
SARS-CoV-2, it is usually associated with severe disease, potentially
leading to pulmonary necrosis, and shock.
Choudhury and colleagues speculated that SARS-CoV-2 infection would have
been the possible cause of functional exhaustion of CD4 and CD8 T-cells
and persistent cause of MSSA bacteremia5.
Although in our patient sepsis by MSSA was likely facilitated by
SARS-CoV-2, this association remains an extremely rare condition as very
few cases have been reported in children, despite over 20 million
infected children and adolescents worldwide.
Usually SARS-CoV-2 infection in children has a benign course and we may
have initially underestimated the clinical impact of COVID-19 in
determining our patient’s clinical worsening.
Nevertheless, COVID-19 pneumonia causes a clinical syndrome that is
often difficult to distinguish from bacterial pneumonia and hospitalized
patients with COVID-19 may develop a persistent inflammatory syndrome
that has overlapping clinical features with bacterial sepsis.