Long-term Respiratory Complications in Infants With Perinatal COVID-19 (COLF)

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

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).

Study Overview

• Status: Completed
• Conditions: COVID-19; Infant, Newborn, Diseases; Respiratory Function Tests
• Intervention / Treatment: Diagnostic test: Pulmonary function testing device

Detailed Description

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).

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00168
    • Fondazione Policlinico Gemelli IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 2 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

In this prospective, observational longitudinal study, infants with and without history of COVID-19 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. Pulmonary function tests will be performed during spontaneous, quiet sleep.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases; Infants with confirmed neonatal COVID-19 infection	Diagnostic test: Pulmonary function testing device; 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.
Controls; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Stefano Nobile, MD, PhD, MSc, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2022
• Primary Completion (Actual): May 7, 2025
• Study Completion (Actual): May 30, 2025

Study Registration Dates

• First Submitted: February 8, 2023
• First Submitted That Met QC Criteria: March 30, 2023
• First Posted (Actual): March 31, 2023

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; COVID-19; Infant, Newborn, Diseases
• Other Study ID Numbers: 4949

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No