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.