Long-term Respiratory Complications in Infants With Perinatal COVID-19

Study Overview
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Brief Summary
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Study outcomes and endpoints: Primary outcome: to assess clinical characteristics of infants with confirmed COVID-19 infection at birth and to evaluate long-term respiratory consequences of neonatal COVID-19 infection. Secondary outcome: to evaluate the prevalence and natural history of lung function impairment among infants with confirmed COVID-19 compared to infants with no history of COVID-19. To this end, infants will undergo pulmonary function testing (PFT) with the Exhalyzer D device (Eco Medics, Switzerland).

Detailed Description
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In this prospective, observational longitudinal study, infants will undergo clinical and growth assessment at 6 and 12 months' follow-up. Respiratory complications, such as wheezing, infections, chronic cough will be recorded along with hospital admissions and drug prescription or use. Infants will undergo PFT with the infants in the supine position, during quiet, natural sleep, according to American Thoracic Society/European Respiratory Society recommendations with measurement of lung volumes, flow, functional residual capacity, time to peak tidal expiratory flow/expiratory time ratio (tPTEF/tE)10. Lung ultrasound will be performed to rule out lung abnormalities. After allowing adaptation to the mask, the investigators will record tidal breathing, flow volume loops for >2 minutes or >20 artifact-free breaths. Using commercially available software (Spiroware, Ecomedics), the investigators will extract tidal breathing parameters: ratio of time to reach peak tidal expiratory flow to expiratory time (tPTEF/tE), tidal volume (VT), and respiratory rate (RR). tPTEF/tE is a reproducible and reliable marker of airway obstruction, can detect severe expiratory airway obstruction in infants with respiratory complaints and is associated with subsequent wheezing in infancy. Appropriate statistical methods will be used to describe clinical characteristics of patients and compare groups (T-test, Mann-Whitney test, chi-squared test, multivariate analysis, mixed models depending on data distribution - evaluated with Shapiro-Wilk test - and data characteristics).

Official Title
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Evaluation of Long-term Respiratory Complications in Infants With Perinatal COVID-19: a Pilot Study.

Conditions
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COVID-19, Infant, Newborn, Diseases, Respiratory Function Tests

Intervention / Treatment
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* Diagnostic Test: Pulmonary function testing device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: term infants; informed consent; history of perinatal COVID-19 (confirmed by nasopharyngeal swab tests, study group) Exclusion Criteria: congenital malformations (particularly airway malformations); lack of informed consent

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases<br>Infants with confirmed neonatal COVID-19 infection | Diagnostic Test: Pulmonary function testing device<br>* Patients will undergo pulmonary function tests with the Exhalyzer D (Ecomedics, Switzerland) device. This device consists of 1) an ultrasonic flow measuring system for measuring flow, volume and molecular mass, 2) a nitrogen washout system to measure functional residual capacity (FRC) and other indices, 3) a carbon dioxide infrared measurement device for monitoring the level of carbon dioxide in exhaled breath.<br>|
| Controls<br>Infants born to mothers with no history of COVID-19 infection during pregnancy and no neonatal COVID-19 infection | Diagnostic Test: Pulmonary function testing device<br>* Patients will undergo pulmonary function tests with the Exhalyzer D (Ecomedics, Switzerland) device. This device consists of 1) an ultrasonic flow measuring system for measuring flow, volume and molecular mass, 2) a nitrogen washout system to measure functional residual capacity (FRC) and other indices, 3) a carbon dioxide infrared measurement device for monitoring the level of carbon dioxide in exhaled breath.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical respiratory consequences of neonatal COVID-19 infection | Number or patients with wheezing, use of bronchodilators, steroids, hospitalizations for respiratory causes | 6 months of life | 
| Clinical respiratory consequences of neonatal COVID-19 infection (i.e. wheezing) | Number or patients with wheezing, use of bronchodilators, steroids, hospitalizations for respiratory causes | 12 months of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung function parameters | Tidal volume (ml) | 6 months of life | 
| Lung function parameters 2 | Respiratory rate (breaths per minute) | 6 months of life | 
| Lung function parameters 3 | Time to peak expiratory flow/expiratory time (ratio) | 6 months of life | 
| Lung function parameters 4 | Functional residual capacity (ml) | 12 months of life | 
| Lung function parameters 5 | Lung clearance index 2.5 and 5. | 12 months of life |