Pulmonary and functional hallmarks after SARS-CoV-2 infection across three WHO severity level-groups: an observational study

Abstract

Background: The manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection range from flu-like symptoms to severe lung disease. The consequences of this inflammatory process impact overall function, which can be detected through both short- to long-term assessments. This study aimed to assess the pulmonary functional and structural characteristics of post-SARS-CoV-2 infection in patients with mild/moderate, severe, and critical clinical presentations.

Methods: An observational, analytical, and cross-sectional study was conducted between 2020 and 2022, including participants with a confirmed diagnosis of coronavirus disease (COVID)-19, with mild/moderate (G1), severe (G2), and critical (G3) clinical presentations, all evaluated at least 3 months after acute infection. Spirometry, impulse oscillometry, fractional exhaled nitric oxide (FeNO), chest computed tomography, the 6-min walk test (6MWT), hand grip strength, maximum inspiratory pressure, and maximum expiratory pressure were assessed.

Results: We enrolled 210 participants aged 18-70 years, 32.6% of whom were male, with older age observed in G3. The participants were grouped as follows: G1 (42.3%), G2 (25.7%), and G3 (31.9%). Percentage of predicted X5 differed between G1 and G2, being higher in G1. The percentage of predicted forced vital capacity (FVC) according to the Global Lung Function Initiative and its z-score were higher in G1. The FVC by Pereira was lower in G3 compared to G1. The percentage of predicted forced expiratory volume in 1 s (FEV₁) by Pereira was also lower in G3. The Tiffeneau (FEV₁/FVC) index was different among groups, increasing with disease severity. The percentage of predicted forced expiratory flow rate at 25-75% (FEF_25-75%) of the FVC and FeNO were both higher in G2 than G1. Chest computed tomography revealed the presence of interstitial abnormalities, associated with disease severity. The respiratory muscle strength evaluation showed an association between higher maximum expiratory pressure values in G3 compared to G1, but no association with maximum inspiratory pressure was observed. The 6MWT distance covered decreased with increasing severity, with a lower percentage of predicted values in G3 compared to G1. The right-hand grip strength was also lower in G3 compared to G1.

Conclusion: Alterations in pulmonary and functional markers were observed in post-COVID-19 evaluations, increasing with disease severity, as seen in G2 and G3. These findings highlight the complexity of post-COVID-19 functional assessments, given the long-term pulmonary sequelae and the consequent impairment of functional capacity.

Keywords: 6-min walk test; chest computed tomography; fractional exhaled nitric oxide; hand grip strength; impulse oscillometry; lung function; maximum expiratory pressure; maximum inspiratory pressure.

Figure 1

Complete representation of the study protocol. Disease severity was determined by a physician, according to the World Health Organization (WHO) criteria. The G1 phenotype was characterized by mild-to-moderate clinical symptoms, with possible radiological findings or the presence of pneumonia on chest computed tomography. The G2 phenotype was characterized by respiratory distress and/or hypoxia/hypoxemia, whereas the G3 phenotype involved respiratory failure requiring mechanical ventilation, shock, and/or multiorgan dysfunction (5, 16). Coronavirus disease (COVID)-19 (COVID-19).

Figure 2

Distribution of lung function variables differing among coronavirus disease (COVID)-19 severity groups. Percentage of predicted reactance at 5 Hz (X5%); percentage of predicted forced vital capacity (FVC) by GLI (FVC% GLI—Global Lung Function Initiative); FVC z-score by GLI (zFVC GLI); percentage of predicted FVC by Pereira (FVC% Pereira); forced expiratory volume in 1 s (FEV₁) z-score by GLI (zFEV₁ GLI); percentage of predicted FEV₁/FVC by GLI (FEV₁/FVC% GLI); FEV₁/FVC z-score by GLI (zFEV₁/FVC GLI); percentage of predicted FEV₁/FVC by Pereira (FEV₁/FVC% Pereira); percentage of predicted FEF_25–75 by Pereira (FEF_25–75%); not significant (NS). Disease severity was determined by a physician, according to the World Health Organization criteria. The G1 phenotype was characterized by mild-to-moderate clinical symptoms, with possible radiological findings or the presence of pneumonia on chest computed tomography. The G2 phenotype was characterized by respiratory distress and/or hypoxia/hypoxemia, whereas the G3 phenotype involved respiratory failure requiring mechanical ventilation, shock, and/or multiorgan dysfunction (5, 16).

Figure 3

Distribution of functional test variables differing among coronavirus disease (COVID)-19 severity groups. Fractional exhaled nitric oxide (FeNO); maximum expiratory pressure (MEP); distance covered in the 6-min walk test (DC-6MWT); percentage of predicted DC (DC-6MWT%); right-hand grip strength (HGS-R); not significant (NS). Disease severity was determined by a physician, according to the World Health Organization criteria. The G1 phenotype was characterized by mild-to-moderate clinical symptoms, with possible radiological findings or the presence of pneumonia on chest computed tomography. The G2 phenotype was characterized by respiratory distress and/or hypoxia/hypoxemia, whereas the G3 phenotype involved respiratory failure requiring mechanical ventilation, shock, and/or multiorgan dysfunction (5, 16).