Panacea Journal of Medical Sciences

Introduction

Coronavirus Disease 2019 (COVID-19) has emerged as a notable infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).^[1] Recent studies have underscored the profound impact of COVID-19 on the lungs, manifesting in various pathophysiological events such as diffuse alveolar epithelium destruction, hyaline membrane formation, capillary damage and bleeding, alveolar septal fibrous proliferation, and pulmonary consolidation. COVID-19 exhibits a distinctive feature of extensive injury to alveolar epithelial and endothelial cells, with consequential fibroproliferation hinting at the potential for chronic vascular and alveolar remodelling that may lead to lung fibrosis or pulmonary hypertension. ^[2] It raises pertinent concerns regarding the assessment of lung injury in discharged patients.

Various objective assessments of respiratory function are available, with pulmonary function tests (PFTs), including spirometry, diffusion capacity, and lung volumes, being among the most commonly employed. Additional assessments, such as examining respiratory muscles and analyzing airway resistance, offer valuable insights into lung characteristics. These investigations contribute to a holistic comprehension of the implications of acute and chronic respiratory diseases. ^[3]

Spirometry and DLCO measurements offer insights into lung function indices, particularly regarding diffusion impairment. The six-minute walk test (6MWT) is a simple, objective, and reproducible measure of lung functional capacity. In this test, individuals are instructed to walk as far as possible in six minutes, with the primary outcomes being the six-minute walk distance (6MWD) and Oxygen desaturation. These parameters are often utilized as predictive tools for morbidity or mortality. They are frequently employed to assess the functional status of patients with respiratory and cardiovascular diseases before and after interventions or specific treatments. ^[4]

Severe COVID-19 cases demonstrate a higher incidence of impaired diffusion capacity of the lung for carbon monoxide (DLCO) and experience more significant decreases in total lung capacity (TLC) and declines in six-minute walk distance (6MWD) compared to non-severe cases at 30 days post-discharge. However, clinical evidence for the long-term follow-up of pulmonary function and physiological disorders in severe COVID-19 patients is currently lacking. ^[5]

In the Indian population, studies are scarce, and data remains limited, especially concerning post-COVID patients. It underscores the importance of further research to comprehensively understand the implications of COVID-19 on lung function, particularly in the long term, and establish effective post-discharge care strategies. ^[6]

The primary objective of our study is to evaluate post-COVID lung indices, functional capacity, and oxygen desaturation using spirometry, DLCO, and the six-minute walk test (6MWT) through rigorous examination of these parameters. This objective will enhance our understanding of post-COVID lung health and aid in developing targeted interventions and management strategies for individuals in the recovery phase.

Materials and Methods

Results

[Table 1] shows that most of the study population belongs to the age group of more than 60 years (30%), followed by 51 to 60 years (25.7%) and 41 to 50 years (25.7%). There was male predominance (72.9%) amongst the study population compared to females (27.1%). Most of the study population was Overweight (51.4%), followed by normal (31.4%) and obese (17.1%). The study population had a CORADS score of 5 (37.1%) followed by a CORADS score of 6 (17.1%) and CORADS score of 3 & 4 (12.9 each) on HRCT THORAX done during hospitalization for COVID-19. The mean age and BMI were 53.10 ± 13.3 years and 26.34 ± 3.8, respectively.

Hypertension (14.29%) was the most common Comorbidities amongst the study population, followed by Bronchial Asthma (7.14%), DM (5.71 %) and IHD (4.28%) shown in [Figure 1].

70% of the study population were admitted to the ward, while 30% were admitted to ICU during COVID-19 Hospitalization. O2 Requirement during COVID-19 hospitalization was observed in 41.4% of the study population. Restrictive airway disease (57.1%) was the most common PFT abnormality amongst the study population, followed by Obstructive airway disease (12.9%) and Mixed defect (1.4%), shown in [Table 2].

In [Table 3], Baseline SpO2, minimum SpO2, maximum SpO2, End and Mean SpO2 on 6 Minute Walk Test were 97.13 ± 1.2, 94.11 ± 2.8, 97.50 ± 1.2, 95.44 ± 1.9 and 95.03 ± 2 respectively. in 6-minute walk test, actual distance walked, Predicted distance and % predicted was 367.43 ± 83.6, 548.51 ± 77.5 and 67.11 ± 11.6 respectively. Baseline Heart rate, minimum Heart rate, maximum Heart rate, End and Mean Heart rate were 93.00± 12.10, 87.94 ± 9.63, 118.31 ± 19.17, 106.47 ± 16.15and 113.61 ± 12.91, respectively.

[Table 4] shows the Mean and Standard deviation of CTSS and Follow-up was 10.16 ± 5.4 and 61.70 ± 21.9, respectively. Mean FVC %, FEV1 %, FEV1/FVC %, DLCO %, KCO, RV/TLC % and RV/TLC % pred was 72.17 ± 14.86, 73.77 ± 15.81, 82.94 ± 9.57, 63.04 ± 18.00, 2.935 ± 1.090, 91.31 ± 21.69 and 121.87 ± 18.35 respectively. mean D Dimer and CRP was 570.63 ± 493.12 and 19.17 ± 22.59, respectively.

Discussion

The current study aimed to comprehensively evaluate pulmonary function, gas exchange abnormalities, and exercise limitations in COVID-19 survivors nearly 2 months after hospital discharge. In agreement with previous studies on SARS and MERS epidemics, ^[7] we found evidence of persistent lung impairment and disability in many COVID-19 patients (71.4 % patients).

Pulmonary function tests revealed restrictive ventilatory defects in 57.1 % of the patients, with mean FVC and FEV1 approximately 70% of predicted. While airway obstruction was not observed based on preserved FEV1/FVC ratios, the substantially reduced DLCO (63% predicted) confirms parenchymal dysfunction and impaired gas exchange.^[8] Our findings parallel those of Mo et al. and Huang et al., who also reported persistent restriction following COVID-19 pneumonia.^[2], ^[5] However, the severity of impairment was greater in our cohort, likely reflecting differences in illness severity given 30% of ICU admissions.

In keeping with the restrictive physiology, we provide initial evidence of gas trapping on lung volume assessment. The increased RV/TLC ratio in 17% of the patients indicates the involvement of the larger airways from residual cellular inflammation rather than small airway disease. This metric has not been previously investigated in the post-COVID-19 setting by George et al.^[9]

Alongside the abnormalities in static lung volumes and diffusion capacity, we also observed significant exertional oxygen desaturation in 45.7% of patients on the six-minute walk test (Figure 2). The distance walked was also substantially reduced compared to healthy predictions. Our findings align with previous reports confirming impaired exercise capacity and dynamic gas exchange abnormalities after COVID-19. ^[10]

These quantitative lung function and exercise test findings likely arise from parenchymal scarring and fibrosis triggered by COVID-19 pneumonia. The initial severe inflammatory response causes diffuse alveolar damage, activation of myofibroblasts, and extracellular matrix deposition.^[11] Persistence of these histopathological changes despite radiographic and clinical recovery can lead to restrictive ventilatory changes, reduced gas transfer efficiency, expiratory flow limitation, and dynamic hyperinflation - all observed in the present study.^[12]

We found more pronounced physiological impairments compared to prior post-COVID-19 literature, which likely relates to differences in cohort illness severity. Our study comprised older patients with high rates of ICU admissions, oxygen requirements, and radiological injury based on CT severity scores. Previous autopsy and radiological descriptions suggest extensive pulmonary fibrosis in severe COVID-19 cases.^[13], ^[14] Hence, the magnitude of the initial inflammatory insult likely underlies the extent of permanent parenchymal scarring and physiological dysfunction.^[15] Close monitoring of lung function and exercise capacity is warranted in severe post-COVID-19 patients to guide supportive therapies.

Strengths of the present study include the comprehensive panel of physiological tests performed and analysis of key predictors of persistent disability like illness severity, oxygen needs, and radiologic scores. However, longer-term follow-up is required to definitively characterize the natural history of post-COVID-19 lung disease over time. Serial physiological and radiographic surveillance will clarify recovery trajectories and enable testing of novel anti-inflammatory and antifibrotic agents.^[9] Our findings add to the emerging literature on post-COVID-19 syndrome, highlighting the pulmonary morbidities seen in severe illness survivors.

Conclusion

The current study demonstrates that COVID-19 survivors experience persistent lung function impairment and reduced exercise tolerance in the 2 months following hospital discharge. Specifically, over half of the patients exhibited restrictive defects and diminished diffusion capacity and gas exchange efficiency. Additionally, a significant proportion was desaturated during the six-minute walk test, confirming exertional oxygen impairment.

These findings underline the importance of close monitoring and pulmonary rehabilitation for post-COVID-19 patients. Tailored rehabilitative strategies can help mitigate persistent respiratory disability through assessment, active exercise training, patient education, nutritional support, and psychosocial care. Early integration of pulmonary rehabilitation is advocated in the post-acute recovery phase to optimize long-term outcomes for COVID-19 survivors. However, longer-term studies are warranted to characterize this population's physiological recovery trajectories.

Ethical Consideration

Ethical approval was diligently obtained from the institutional ethics committee before initiating the study, ensuring compliance with established ethical standards.

Informed Consent

A detailed written informed consent process was followed for each participant, emphasizing transparency and comprehension. An informative sheet was distributed to all participating patients, ensuring clarity regarding the study's nature and objectives.

Source of Funding

None.

Conflict of Interest

None.