DISCUSSION
In this case control study, we present iPFT data in infants with
persistent respiratory complaints and a history of SARS-CoV-2 infection.
Our results show that when compared to a large control group of infants
who were evaluated at our center prior to the COVID-19 era, infants who
suffered an acute SARS-CoV-2 infection have very similar iPFT results.
This suggests that a SARS-CoV-2 infection does not have lasting impact
on pulmonary function in infants. Results from this study add data in
infants to the already present data in children regarding the minimal
long-term effect of SARS-CoV-2 infection on pulmonary function.
No prior study has evaluated pulmonary function tests in infants
recovering from a SARS-CoV-2 infection. Most studies that have evaluated
pulmonary function tests in children and adolescents with respiratory
symptoms following a SARS-CoV-2 infection, found no significant
differences in spirometry, body plethysmography, impulse oscillometry,
lung clearance index and diffusion lung capacity for carbon monoxide
(DLCO) results between the study groups and healthy children and
adolescents 6–9. One study found evidence of a mild
obstructive pattern, in 45% of school age children with ongoing
cardiorespiratory symptoms following a SARS-CoV-2 infection20. We evaluated children with persistent respiratory
complaints several months after a SARS-CoV-2 infection and found
evidence of mild expiratory airflow limitation present in 63% of cases.
However, in some of the included cases the respiratory complaints were
present also prior to the SARS-CoV-2 infection, thus not necessarily a
result of the SARS-CoV-2 infection itself.
When comparing iPFT results of cases included in the study, to a large
group of infants evaluated at our center by iPFT prior to the COVID-19
pandemic, our study did not find any significant differences between the
two groups. Cases and controls had similar demographic features and
underwent a respiratory evaluation for similar persistent respiratory
complaints. Cases showed a similar distribution in the pattern of
pulmonary function tests results as the controls, with similar rates of
obstructive, restrictive, and normal iPFT results. A mild but
statistically significant difference in expiratory flow limitation was
observed, with greater prominence in the control group. However, this
difference lost significance when comparing only infants with an
obstructive pattern. Thus, our results do not show evidence of a
long-lasting effect of SARS-CoV-2 infection on iPFT. These findings are
clinically relevant in view of the limited available evidence regarding
the long-term sequela of SARS-CoV-2 infection in children and due to the
ongoing reports of chronic residual symptoms following a SARS-CoV-2
infection, collectively termed Long-COVID.
Long-COVID is an ill-defined sequela of SARS-CoV-2 infection. It
includes a wide range of ongoing, new or recurring symptom and there is
currently little agreement worldwide in its definition and
categorization 21. Only a few studies have
investigated persistent symptoms in young children and infants following
a SARS-CoV-2 infection, making the categorization and diagnosis of
long-COVID in young children difficult. Data that is available show that
preschool aged children take longer to recover from a SARS-CoV-2
infection when compared to older children and that the ongoing
respiratory conditions may persist up to six months among children aged
1-5 years 22. Epidemiological studies further report
an increase in the prevalence of respiratory symptoms, mainly cough and
difficulty breathing, in young children recovering from
SARS-CoV-2 infection6–9,23–26.
We evaluated infants with persistent respiratory complaints and a
history of SARS-CoV-2 infection. Some of the included cases presented
with respiratory symptoms prior to the SARS-CoV-2 infection, while
others only following the infection. However, the occurrence of a
SARS-CoV-2 infection in infants suffering from persistent respiratory
complaints, present for months, calls for consideration that these
ongoing symptoms are a manifestation of long-COVID. Furthermore, the
anxiety surrounding a SARS-CoV-2 infection and its unknown long-term
outcomes in children and infants 27, further augments
the attention for an association between the persistent respiratory
complaints and the SARS-CoV-2 infection. We did not find any distinct
clinical or physiological features in cases included in our study which
may characterize them as a group and differentiate them from infants
with persistent respiratory complaints never infected by SARS-CoV-2.
This suggests that the SARS-CoV-2 infection did not uniquely influence
the disease course in included cases. This is further supported by the
finding that no association was present between the severity of the
acute SARS-CoV-2 infection and the iPFT results. Indeed, many
controversies exist regarding the diagnosis of long-COVID and it is not
currently established whether the long-term effects of COVID-19 are
specific to a SARS-CoV-2 infection or are similar to other post-viral
syndromes frequent in infancy 27.
A main strength of our study is the comprehensive data of PFT in infants
following documented SARS-CoV-2
infection, which, to the best of our knowledge, has not been previously
reported in the literature. However, our study has several limitations.
The primary concern is that the iPFT were conducted in infants with
pre-existing respiratory complaints, which in some were present before
their SARS-CoV-2 infection. This means that the assessment was not
focused on testing previously healthy infants with symptoms following a
SARS-CoV-2 infection. To address this bias, we did not compare our cases
to controls with normal iPFT results but to a large control group of
infants who underwent iPFT due to respiratory complains prior to the
COVID-19 era, speculating that the SARS-CoV-2 infection may cause
characteristic clinical and physiological abnormalities if associated
with the ongoing symptoms. Other limitations include the retrospective
design with missing clinical information regarding the control group and
the inclusion of a small number of cases.
In conclusion, we present iPFT results in infants following a SARS-CoV-2
infection. Our study demonstrates that pulmonary function tests (PFT) in
infants evaluated for various respiratory complaints, a few months after
a SARS-CoV-2 infection, are comparable to infants who underwent iPFT
prior to the COVID-19 era. These findings suggest that SARS-CoV-2
infection may not have a lasting impact on lung function in infants.
However, further studies are required, particularly in infants who
suffered a severe respiratory COVID-19 illness, to validate and
strengthen these findings.