DISCUSSION
In this study, we compared CAP in patients with SARS-CoV-2 with patients
positive for other viral infections. We found that the former was
associated with less wheezing and work of breathing, a significantly
lower lymphocyte fraction and lower CRP levels. During evolution, the
SARS-CoV-2-associated CAP group had significantly higher MV use (almost
ten-fold) but less requirement for oxygen. No significant differences
were found in terms of days of hospitalization, PICU admission or
CPAP/HFV use.
Several studies have reviewed the characteristics of adults with
SARS-CoV-2 and pneumonia17–21, but these remain
scarce in the pediatric population22,23. However,
among hospitalized children and adolescents, pneumonia is a major cause
of disease (approximately –gativizes after a median of 17-e
PCR15%)5–8.
Similar to other studies22,23, the most frequent
symptoms in our patients were fever, cough, wheezing or shortness of
breath. We found that SARS-CoV-2-associated CAP occurred in older
children (8 years on average, as reported
previously24), with a longer duration of fever, more
cases with chest and abdominal pain and fewer cases with cough, wheezing
or dyspnea than in non-SARS-CoV-2-associated CAP. Symptoms often
overlapped, making it challenging to discern between the two. Given that
the median time to RT-PCR negativity for SARS-CoV-2 is 17–19 days, and
can remain positive for several weeks up to 3
months25,26, a means of differentiating SARS-CoV-2
from other etiologies is important.
Many studies evaluating the utility of biomarkers in defining the
etiology of pediatric CAP have been performed using FBC, neutrophil
percentage, serum CRP or procalcitonin, although the cut-off points are
not well defined. As reported in other studies, we found significant
differences in terms of FBC and inflammatory
markers6,22,23,27, with increased CRP in almost 50%
of the patients, but less intense in the SARS-CoV-2 group than in the
non-SARS-CoV-2 group. Some studies have reported very high rates of
lymphocytopenia6,23, but it appears to be less common
in children than in adults12,13. Variable
ymphocytopenia values have been found in children, between
3–33%8,21,22,28,29. In our cohort, 42% of the
children presented with lymphocytopenia. Both leukocytes and lymphocytes
were significantly lower in patients with SARS-CoV-2-associated CAP than
in other viral-associated CAP.
The evolution in children was usually good. Mortality in children with
SARS-CoV-2-associated CAP is rare, less than 5% in different
series7,23,30 (3% in our study). It seems that
patients with comorbidities are at higher risk23,30:
In this context, about 50% of the EPICO group had underlying
conditions.
The radiological presentation of SARS-CoV-2 can be non-specific and
indistinguishable from other pathologies. The first published studies of
children reported few findings in radiographs15;
however, subsequent reports have revealed a higher proportion of
radiographic abnormalities11, which depend on the
severity of pulmonary involvement31,32. In adults,
most computed tomography studies in SARS-CoV-2-associated CAP show
ground-glass opacities (25–60% according to different
studies)33–38 that can progress to white lung. The
proportion of white lung in children is low, and the mechanism is worth
further study. Here, the proportion of other infiltrates was 58%, which
might correspond to ground-glass opacities, but they did not often
progress to white lung, perhaps because of the limited inflammatory
response in children. The proportion of consolidations in
SARS-CoV-2-associated CAP (42%) was lower than that found in the other
viral CAP group (64%), and again the interpretation is unclear. It
might reflect different possible patterns of the infection or different
susceptibility to bacterial superinfection. Although bacterial
coinfections are frequent in viral CAP4,38,39, they
were very rare in our cohort (2%). However, a full work-up was not
performed for most patients (due to laboratory overload during the
pandemic). In some severe cases, pleural effusion may be found but it is
rare10-11,34 (in our series we found it only in 6
patients, 4%).
Severe COVID-19 is rare in children, with variable PICU admission
rates22,23,30. In our cohort, 15% of children with
SARS-CoV-2-associated CAP required PICU admission and while this was
almost double the proportion of the other viral CAP group, the
differences were not significant, which may be due to a limited sample
size.
Usually, viral-associated CAP in young infants resolves with oxygen
therapy or CPAP. The evidence for an effective treatment for SARS-CoV-2
is evolving rapidly. Most reports mention supportive
treatment12, including oxygen therapy and MV, but MV
requirements are highly variable according to different studies in
adults (18–42%40). Approximately, half of all our
COVID-19 patients required oxygen therapy, up to 10% needed additional
noninvasive respiratory support (CPAP, HFV), and 15% required MV. In
our cohort, patients with other viral-associated CAP required oxygen
more frequently, but SARS-CoV-2-associated CAP had more complications
with a greater use of MV. Lung damage associated with SARS-CoV-2 appears
different to other viruses, as patients need oxygen less often and MV
more often. We hypothesize that part of the respiratory damage is
vascular, neuro-muscular, or heart-mediated, rather than solely
hypoxemia.
Although a high percentage of patients (74%) in our series received
antibiotic treatment, it is often not needed in SARS-CoV-2-associated
pneumonia owing to the viral etiology. The reason for this high
proportion might lie in the fact that most of our cases were during the
first wave of the pandemic when treatment was not yet well established,
and by the high percentage of severe cases, as only hospitalized
patients were included. Even so, most cases of viral-associated CAP
receive antimicrobials at admission11.
Our study has some limitations. First, only hospitalized patients were
included, and so the results are not representative for ambulatory CAP.
Second, some cases had incomplete documentation of the exposure history
or clinical features, and not all patients underwent a complete blood
test or microbiological workup. The third limitation is the variation in
the interpretation of radiographs depending on the observer, which can
lead to different interpretations. Likewise, both cohorts were not
paired in time, which can complicate the comparability of the results.