Discussion
After widespread distribution of COVID 19 in pediatric patients, one of
the most important issues was long-lasting complications in our next
generation. Current evidences have mentioned increased risk of diabetes
mellitus type I and severe diabetes ketoacidosis in children infected by
SARS-CoV-2 (20). Autoimmune disorders might be more expected in coming
years due to impact of COVID 19 on immune system (21). One of the most
prevalent symptoms in children infected by SARS-CoV-2 is respiratory
manifestation (22). There are increasing evidences of pulmonary sequel
especially in adult population after infection (23). To the best of our
knowledge present study is the first systematic review and meta-analysis
evaluating the impact of COVID 19 on respiratory system of younger
generation in long-term. In six eligible studies, 272 pediatric patients
(143 females and 129 males) were evaluated with the mean age of 12.68
years. The mean of recovery time after SARS-CoV-2 infection was 3.94
months.
Infection generally was mild and most of patients had no or only mild
symptoms. All spirometry parameters were in normal range. Two studies
were evaluated post bronchodilator parameters. Their results showed no
reversible obstructive changes in airways of children with history of
COVID 19. Fortunately, all studies reported FEF 25-75%. It is one of
the most sensitive measures of obstructive diseases in peripheral
airways (24-27). The meta-mean of FEF25-75% was 105.05%, which was in
normal range. According to our meta-results, no obstructive disease in
studied population was detected.
One of the most expected involved areas in respiratory system during
COVID 19 is alveolar epithelial cells (28, 29). It seems that peripheral
airways with an internal diameter less than 2 millimeters are more prone
to impair after SARS-CoV-2 infection. While these parts of respiratory
system represent 90% of total lung capacity but only have role in less
than 20% of airflow (30, 31). So, simple spirometry which measuring
FEV1 and FVC hardly might detect early stages of pulmonary involvement
after COVID 19. Measuring diffusion capacity is more sensitive in
detection of pulmonary diseases especially in early stages (32).
Unfortunately, only 177 out of 238 participants had DLCO values.
However, according to meta-results the mean of DLCO was within normal
range (108.97 %, 95%CI: (86.15, 131.79)). A meta-analysis in adults
was evaluated pulmonary function post-COVID 19 infection. Results showed
decreased DLCO in nearly 40% of survivors (33, 34). Decreased DLCO
might be an early indicator of interstitial lung diseases even before
change in lung volumes (35, 36). Chronic interstitial pneumonia and
diffuse alveolar hemorrhage are demonstrated in few studies, which have
reported histological finding in autopsy (37-39). Patients with
SARS-CoV-2 may had pulmonary fibrosis, which is considered as defined
sequel of barotrauma. All of these pathologies can impair carbon
monoxide diffusion capacity (40). In present study, one explanation for
normal DLCO may be none-severe infection in most of studied children. We
have tried to evaluate impact of disease severity in spirometry
parameters. However, there were not significant difference between the
result in symptomatic and asymptomatic patients. Future studies with
longer period of follow-up and evaluating patients with more severe
respiratory presentation are needed. We had also heterogeneity in atopy
and asthma background of our included studies. However, according to
meta-regression chronic pulmonary disease (such as asthma) had not a
significant effect on pooled mean of major outcomes.
Less severity of respiratory system involvement in children infected by
SARS-CoV-2 comparing with adult, might be possible explanation for
different outcome between them (3). In addition, preexisting diseases in
adults like chronic respiratory diseases, cardiac diseases and diabetes
mellitus may induce impairment in pulmonary function. On the other hand,
children during infancy and preschool age usually have more severe
course during infection (41, 42). Because majority of our included
participants were teenage, more studies which can evaluate pulmonary
sequel in infants and young toddlers, should be designed. In addition,
different variants of SARS-CoV-2 like Delta or Omicron had resulted to
different presentation and probably different outcomes. Therefore,
studies, which determine type of variants, may be useful. It is possible
that pulmonary sequel of survived children is so tiny and routine
pulmonary function test cannot detect abnormalities. It is useful to
design exercise-challenging studies in survived children after COVID 19
to detect subtle or mild changes in pulmonary function.