Researchers explore long-term pulmonary sequelae of SARS-CoV-2 infection in the pediatric population

By Tarun Sai LomteJul 5 2022Reviewed by Aimee Molineux

In a recent study published in Pediatric Pulmonology, researchers described the long-term pulmonary sequelae of coronavirus disease 2019 (COVID-19) in the pediatric population.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants resulted in an unprecedented surge in COVID-19 cases among the pediatric population in the United States (US). Post-acute sequelae of COVID-19 (PASC) have been described in adults. The subjective respiratory symptoms include chest tightness, cough, fatigue, and dyspnea.

Similar subjective symptoms have been observed in pediatric cases even after asymptomatic or mild COVID-19. One study reported that exercise tolerance, exertional dyspnea, and cough were the common respiratory symptoms in children with PASC. However, there is a paucity of data on how objective abnormalities and symptoms evolve.

About the study

The present study described pediatric patients' objective and subjective pulmonary abnormalities. The authors started a pediatric pulmonary post-COVID clinic in February 2021 and all patients referred to this clinic until December 2021 were enrolled in this study. All participants were evaluated at the first visit, which included chest radiography, a six-minute walk test (6MWT) with Borg rating of perceived exertion, plethysmography, diffusion capacity of the lung for carbon monoxide, and pre-and post-bronchodilator spirometry.

All subjects were recommended to follow up after two/three months. All objective assessments were performed following American Thoracic Society standards. The obstructive deficit was defined as the ratio between forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) of less than 80%. They defined restrictive deficits as the total lung capacity (TLC) less than 80% on plethysmography.

Bronchodilator response was defined as an increase in forced expiratory flow 25 – 75 (FEF_25-75) by ≥ 25% or FEV₁ by ≥ 12% from baseline. The following outcomes were evaluated– Borg dyspnea and fatigue scores, 6MWT distance, and heart rate variation during 6MWT.

Findings

The study population was predominantly White (80.5%) and competitive athletes (in schools). Twenty-four patients (29%) had a previous history of asthma. Nearly half the cohort returned for at least one follow-up visit. Five reinfection cases were recorded during the study while still being evaluated/treated for sequelae of the first infection. About 23% of subjects had been partially vaccinated at initial presentation.

Respiratory symptoms at the time of clinic presentation included cough, resting, exertional dyspnea, and chest pain. A majority of patients (80%) had two or more symptoms. Exertional dyspnea improved at follow-up visits though it was still a common symptom, while other symptoms improved significantly. 6MWT data was available for 27 subjects, and 67% showed an increased distance from the initial visit.

At the first visit, Borg dyspnea/fatigue scores were higher after 6MWT in most patients. Although perceived dyspnea after the test improved significantly, fatigue was unchanged. Significant tachycardia was noted at the initial visit, with a median heart rate change of 47 beats before and after the walk. In the follow-up visits, heart rate decreased for most individuals; however, change in heart rate pre- and post-walk was unaffected.

Spirometry measurements for 77% of subjects were within normal limits; 14 and five patients had obstructive and restrictive deficits, respectively. A positive bronchodilator response was evident for 31% of individuals, and of these, 38% had prior asthma. Because of normal spirometry at baseline, only 29 patients underwent spirometry measurements at follow-up, and 90% were normal. Pulse oximetry readings were 96% to 100% in all individuals.

Inhaled corticosteroid or its combination with long-acting beta-agonist was prescribed for 43% of patients. Two subjects with asthma had normal bronchodilator and spirometry measurements and thus did not need steroid therapy. Around 85% of the treated patients reported clinical response to the medications and had improved pulmonary function tests. Based on their clinical history and normal functional tests, about 13% of subjects were diagnosed with paradoxical vocal fold motion disorder (PVFMD).

Univariable regression models revealed an association of anxiety, resting dyspnea, obesity, and cough with reduced 6MWT. Multivariable regression models showed similar relationships. Nevertheless, exertional dyspnea was associated with lower 6MWT when adjusted for sex, race, age, and insurance status.

In univariable models, exertional dyspnea and female sex were associated with increased Borg dyspnea scores; in contrast, female sex and exertional and resting dyspnea were significantly associated in multivariable models. In both models, exertional and resting dyspnea and the female sex were associated with higher Borg fatigue scores.

Conclusions

In summary, the study identified three clinical phenotypes that require further investigation. These included patients with PVFMD, airway hyper-reactivity, subjective dyspnea/fatigue, and few objective abnormalities. Almost all patients complained of dyspnea and fatigue often at rest, which worsened with exertion. Notably, only those patients referred to the clinic (single-center) were evaluated; thus, it may not represent the entire pediatric population.