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Background: Although lung is the primary target organ involvement in coronavirus disease-19 (COVID-19), post-COVID lung pathology and its impact on lung functions are still uncertain. Materials and Methods: Prospective multicentric study conducted during May 2020 to June 2021, to find pulmonary function assessment in post-COVID-19 recovered pneumonia cases irrespective of their symptoms, included 600 cases in symptomatic and asymptomatic group and subjected to inclusion and exclusion criteria. All cases were subjected to Spirometry analysis. Statistical analysis was done by using Chi-test. Results: In Spirometry assessment of post-COVID-19 pneumonia cases at 12 weeks' postdischarge from hospital, abnormal lung function in 77.5% post-COVID-19 pneumonia cases; restrictive pattern was predominant type and documented in 43.33% cases, normal lung functions were documented in 22.5% cases. In age and gender assessment in normal and abnormal lung functions assessment, statistically significant association in males 90/150 versus females 45/315 (P < 0.00001); and in the age of population in study cases as below 50 years 110/300 versus above 50 years 25/165 (P < 0.0001). Computed tomography severity score has shown a negative impact on lung function after recovery at 12 weeks' postdischarge; cases with score <8, 8–15, and >15 documented normal and abnormal lung functions as in 36/54, 60/80, and 39/331 respectively of total 600 study cases (P < 0.00001). The duration of illness has associated negative impact on lung function; <7 days, 8–15 days and >15 days of onset of symptoms documented normal and abnormal lung functions in 108/132, 22/168 and 5/165 cases respectively (P < 0.00001). Low oxygen saturation at entry point has a negative impact on overall outcome on lung function; cases with oxygen saturation < 75%, 75%–90%, and >90% observed as normal and abnormal lung functions in 92/18, 35/135 and 6/314 cases, respectively (P < 0.00001). Timing of biphasic positive airway pressure/noninvasive ventilation (BIPAP/NIV) has a significant association in attaining normal lung functions after post COVID19 pneumonia recovery; cases received BIPAP/NIV at entry point <1 day, 3–7 days and after 7 days of hospitalization were documented normal and abnormal lung functions in 30/150, 40/35 and 5/50 cases, respectively (P < 0.00001). Conclusions: Pulmonary functions abnormality in post-COVID-19 pneumonia cases has been documented and should be assessed cautiously to have successful treatment outcome. Restrictive lung disease is the predominant lung function impairment in post-COVID 19 recovered lung pneumonia cases. Age above 50 years, male gender, diabetes, High CT severity, longer duration of illness, proper timing of initiation of BIPAP/NIV therapy, has documented significant impact on post-COVID lung functions at 12 weeks assessment.
Keywords: Post-COVID-19, pulmonary functions, restrictive pattern, spirometry
How to cite this URL:
Patil S, Patil R, Gondhali G. Pulmonary functions assessment in Post-COVID-19 pneumonia cases by spirometry: Study of 600 cases in tertiary care setting in India. J Appl Sci Clin Pract [Epub ahead of print] [cited 2023 Mar 29]. Available from: http://www.jascp.org/preprintarticle.asp?id=358990 |
| Introduction | |  |
On March 11, 2020, the World Health Organization declared coronavirus disease 2019 (COVID-19) to be a pandemic, with approximately 20% of patients infected requiring hospitalization and 6% in critical care and needing invasive ventilatory assistance.[1] Early epidemiological reports showed that 8.2% of total cases presented with rapid and progressive respiratory failure, similar to acute respiratory distress syndrome (ARDS).[2]
COVID-19 is a heterogeneous disease with most patients experiencing mild illness and spontaneous recoveries, but a relevant subgroup of individuals requires hospitalization for pneumonia and other complications. In the initial reports from Wuhan, China, up to one-third of patients developed severe pneumonia with ARDS.[1]
Previous coronavirus infections include severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). Similar to COVID-19, SARS and MERS typically begin with an acute illness from which most patients recover after 2 weeks. However, up to one-third of SARS patients developed severe pulmonary complications and ARDS.[3] A subgroup of SARS survivors developed persistent lung parenchymal abnormalities, including pulmonary fibrosis.[4],[5] The appearance of pulmonary fibrosis correlated with severity and duration of the acute illness,[6],[7] and radiological features of fibrosis persisted in approximately 30% of patients after three and 6 months.[8],[9] Older age and male sex were identified as risk factors for poor outcomes and development of lung fibrosis.[8],[10] With the anticipation of potential long-term sequelae after COVID-19, follow-up strategies have been proposed by several groups from the US, Great Britain, China, and India.[11],[12],[13],[14]
In the present study, we have evaluated lung function assessment at 12 weeks' postdischarge in treated cases of COVID-19 pneumonia and correlated with computed tomography (CT) severity at entry point, oxygenation status at entry point, total duration of illness at hospitalization, and use of biphasic positive airway pressure/noninvasive ventilation (BIPAP/NIV) during the course of hospitalization.
| Materials and Methods | | |
Prospective multicentric observational study conducted in Venkatesh Chest Hospital, and Pulmonary Medicine, MIMSR Medical College Latur from May 2020 to June 2021, to find out lung function assessment of post-COVID-19 recovered pneumonia cases after 12 weeks of discharge from hospital. Total 600 cases were enrolled in study after IRB approval and written informed consent of patient.
Inclusion criteria
- All treated and recovered cases of COVID-19 pneumonia cases above 18-year age, admitted in indoor unit has been enrolled in study
- Recovered cases of COVID-19 pneumonia irrespective of CT severity were enrolled in study
- Recovered cases of COVID-19 pneumonia irrespective oxygen saturation were enrolled in study
- Recovered cases of COVID-19 pneumonia with comorbidity such as diabetes mellitus (DM), ischemic heart disease, cardiovascular diseases, chronic kidney disease, chronic obstructive pulmonary disease (COPD) were enrolled in study
- Recovered cases of COVID-19 pneumonia cases willing to undergo spirometry test were enrolled in study.
Exclusion criteria
- Recovered cases of COVID-19 pneumonia cases not willing to undergo spirometry test
- Recovered cases of COVID-19 pneumonia cases not able to perform spirometry test
- Recovered cases of COVID-19 pneumonia cases with neurological issues like hemiparesis or hearing difficulty and having co-ordination problem during spirometry
- Recovered cases of COVID-19 pneumonia cases with tachypnea or tachycardia and cases with oxygen supplementation at rest were excluded from study
- Recovered cases of COVID-19 pneumonia below 18 years of age
- Recovered cases of COVID-19 pneumonia in pregnant females (any trimester was excluded).
All study cases were undergone the following assessment before enrolling in study
- Clinical assessment as-vital parameters such as heart rate, respiratory rate, blood pressure, and documentation of respiratory adventitious sounds
- Laboratory parameters-hemoglobin, renal functions, blood sugar level, kidney functions, electrocardiogram
- Spirometry.
Methodology of spirometry
Subsequently, spirometry evaluation was done by a portable spirometer, SPIROLAB II (manufactured by Medical International Research, Italy); and meets American Thoracic Society and European Respiratory Society standards (ATS and ERS), before and 15 min after administration of 400 microgram salbutamol using pressurized metered-dose inhaler with a small-volume spacer device. All patients were instructed not to use any bronchodilator on the preceding night and on day of procedure. Spirometry procedure was carried out as per ATS/ERS task force recommendation for standardization of lung function testing.[15] Subjects who were found to have postbronchodilator forced expiratory volume in first second (FEV1)/forced vital capacity (FVC) <0.7 were taken up for final analysis as this value indicates the cut-off for diagnosis of obstructive airway disease according to GOLD guideline. Bronchodilator Reversibility was defined as an improvement in FEV1 by at least 12% and 200 ml over prebronchodilator value. FEV1/FVC ≥0.7 were excluded as those patients had either a normal spirometry or a purely restrictive ventilatory abnormality. Furthermore, the individuals who failed to fulfill acceptability and reproducibility criteria of spirometry were excluded. FVC, FEV1, and FEV1/FVC ratio values for case-patients were compared with gender-specific and race-specific adult predicted normative population values and the control group.[16],[17]
The British thoracic society (BTS) guidelines recommend the evaluation of pulmonary function testing (PFTs) at 3 months' postdischarge, especially at follow-up with patients suspected of having an interstitial disease.[17]
Interpretive algorithms were used in determining restrictive or obstructive patterns and spirometry results were analyzed and categorized in four groups as follows:[15],[16],[18],[19]
- Normal-FEV1/FVC ratio of >70% and an FVC of >80% predicted
- Obstructive-Airway obstruction was defined as an FEV1/FVC ratio of <70% and an FVC of >
- 80% predicted
- Mixed-combined defects were FVC of <80% predicted and an FEV1/FVC ratio of <70%
- Restrictive-restrictive defects as an FEV1/FVC ratio of >70% with an FVC of <80% predicted.
The statistical analysis was done using Chi-squared test. Significant values of Chi-squared were seen from the probability table for different degrees of freedom required. P value was considered significant if it was below 0.05 and highly significant in case if it was <0.001.
Observation and analysis
In this study, a total of 600 post-COVID-19 recovered pneumonia cases were enrolled, between the age group of 18–95 years of age; age above 50 years were 60% (360/600) and age below 50 were 40% (240/600). In gender distribution in study group, male population was 68.33% (410/600) and females were 31.66% (190/600). The main symptoms in the study group were shortness of breath in 79% cases, cough especially dry in 48% cases, and fatigability in 79% cases, tachycardia in 72% cases, tachypnea in 24% cases and oxygen desaturation on 6 min walk in 21% cases.
In Spirometry assessment of post-COVID 19 pneumonia cases at 12 weeks' postdischarge form hospital, restrictive pattern was predominant type documented in 43.33% cases, normal lung functions were documented in 22.5% cases [Table 1]. | Table 1: Spirometry assessment of post-coronavirus disease 2019 pneumonia cases at 12 weeks of discharge from hospital (n=600)
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We observed abnormal lung function in 77.5% post-COVID-19 pneumonia cases, and statistically significant association in males (90/150) versus females (45/315) normal and abnormal lung functions respectively (P < 0.00001); similar observation also documented in age of population in study cases as below 50 years (110/300) versus above 50 years (25/165) (P < 0.0001) [Table 2]. | Table 2: Age and gender distribution in post-coronavirus disease-2019 pneumonia cases (n=600) with lung function patterns
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CT severity score has shown a negative impact on lung function after recovery at 12 weeks' postdischarge; cases with score <8, 8–15, and >15 documented normal and abnormal lung functions as in 36/54, 60/80, and 39/331 respectively of total 600 study cases (P < 0.00001) [Table 3]. | Table 3: Correlation of computed tomography severity (at entry point) and lung function assessment by spirometry in post-coronavirus disease-2019 pneumonia cases after 12 weeks postdischarge from hospital
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The duration of illness has associated negative impact on lung function; <7 days, 8–15 days, and >15 days of onset of symptoms documented normal and abnormal lung functions in 108/132, 22/168, and 5/165 cases, respectively (P < 0.00001) [Table 4]. | Table 4: Duration of illness at entry point during hospitalization and its effect on lung functions at 12 weeks of discharge in post-coronavirus disease-2019 pneumonia cases
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Low oxygen saturation at entry point has a negative impact on overall outcome on lung function; cases with oxygen saturation <75%, 75%–90%, and >90% observed as normal and abnormal lung functions in 92/18, 35/135, and 6/314 cases, respectively (P < 0.00001) [Table 5]. | Table 5: Oxygen saturation at entry point and its effect on lung function at 12 weeks of discharge in post-coronavirus disease-2019 pneumonia cases
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Timing of BIPAP/NIV has a significant association in attaining normal lung functions after post-COVID19 pneumonia recovery; cases received BIPAP/NIV at entry point <1 day, 3–7 days and after 7 days of hospitalization were documented normal and abnormal lung functions in 30/150, 40/35, and 5/50 cases, respectively (P < 0.00001) [Table 6]. | Table 6: BIPAP/noninvasive ventilation initiation time at entry point and its effect on lung function at 12 weeks of discharge in post-coronavirus disease-2019 pneumonia cases (n=310)
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| Discussion | | |
Pattern of spirometry analysis in study cases
In the present study, spirometry assessment of post-COVID-19 pneumonia cases at 12 weeks' post discharge from hospital, restrictive pattern was predominant type documented in 43.33% cases, normal lung functions were documented in 22.5% cases. Guler et al.[20] demonstrated lower lung volumes (total lung capacity, FVC, and FEV1) in patients after severe/critical COVID-19, the higher FEV1/FVC ratio in the severe/critical subgroup suggests a tendency toward a restrictive physiology, and the lack of difference in respiratory muscle strength suggest a lung parenchymal rather than a respiratory muscle issue. Mo et al.[21] reported an impairment of diffusion capacity followed by restrictive ventilatory defects, which are both associated with the severity of the disease. You et al.[22] published first reports on lung function related to COVID-19 indicated that patients have a restrictive defect and a small airways dysfunction that can be persistent and not related to the disease severity.
Seven studies Frija-Masson et al.,[23] Huang et al.,[24] Li et al.,[25] Liu et al.,[26] Mo et al.[21] You et al.,[22] Zhao et al.[27] reported the spirometry test in post-COVID cases and documented reported variable prevalence of restrictive pattern in severe COVID-19 infection that ranges from (10.53%) to (50%). All studies showed FVC, FEV1, and FEV1/FVC ratio. Liu et al.[26] did not report patterns of PFT abnormality; six studies[21],[22],[23],[24],[25],[27] found a prevalent restrictive pattern in 59% and obstructive pattern in 16% post-COVID pneumonia cases. Similarly, in our study, we have documented restrictive pattern in 43.33% and obstructive pattern in 14.16% of cases.
Torres-Castro et al.[28] done systematic review and meta-analysis of respiratory function in post-COVID-19 cases and observed altered diffusion capacity, restrictive pattern, and obstructive pattern were found in 39%, 15%, and 7% of patients, respectively. Salem et al.[29] in their study documented finding of restrictive lung impairment in about 50% of post-COVID-19 pneumonia survivors is in line with several previous studies. A recent study done by Fumagalli et al.[30] found a significant incidence of a restrictive pattern in 10 (76%) out of 13 patients after 6 weeks from recovery in COVID pneumonia cases. These variations in the prevalence of restrictive lung defect among COVID-19 pneumonia survivors could be explained by the differences in the time of assessment which range from close to discharge to 3 months after discharge. These studies suggest that patients affected by COVID-19 pneumonia are at increased risk of developing restrictive pulmonary diseases after recovery from the acute illness.
Timing of spirometry analysis was important in follow-up post-COVID cases, as ongoing inflammation till 1 month of duration of illness has a negative impact on real-time lung function assessment by spirometry. We have followed BTS recommendations[17] as for 3 months' postdischarge in all post-COVID cases. All above-mentioned studies[21],[22],[23],[24],[25],[26],[27] have performed spirometry analysis in 1-month postdischarge.
However, lesions of COVID-19 are more likely to impact bilateral pulmonary and multiple lobs than those of SARS. Previous studies have been reported that SARS has long-term effects on lung function, chest CT scans, and related physiological characteristics in part of survivors, even at 1 year after discharge.[8],[31],[32],[33]
Age and gender distribution with lung function patterns in post-COVID-19 pneumonia cases
We observed abnormal lung function in 77.5% post-COVID-19 pneumonia cases, and statistically significant association in males (90/150) versus females (45/315) normal and abnormal lung functions respectively (P < 0.00001); similar observation also documented in age of population in the study cases as below 50 years (110/300) versus above 50 years (25/165) (P < 0.0001) Salem et al.[29] observed that the female sex was an independent predictor for impaired lung diffusion using multivariable logistic regression (P = 0.024), and no significant predictor for the restrictive pattern was detected. Seven studies[21],[22],[23],[24],[25],[26],[27] documented most affected age groups as Frija-Masson et al. as 54 years (46–62 years), Huang et al., as 46.7 ± 13.7 years, Li et al., did not document age group affection in their study, Liu et al. as 69.1 ± 7.8 years, Mo et al. as 49.1 ± 14.0, You et al. as 50.7 ± 12.1 years, Zhao et al. as 47.7 ± 15.5 years reported in their study.
Is there any correlation between computed tomography severity (at entry point) and lung function assessment by spirometry in post-COVID-19 pneumonia cases after 12 weeks postdischarge from hospital?
In the present study, CT severity score has shown a negative impact on lung function after recovery at 12 weeks postdischarge; cases with score <8, 8–15 and >15 documented normal and abnormal lung functions as in 36/54, 60/80, and 39/331 respectively of total 600 study cases (P < 0.00001).
This is the first study included large number of post-COVID cases and documenting the effect of CT Severity illness score when the patient was hospitalized to indoor unit and its impact on overall pulmonary functions outcome at 12 weeks of discharge from the hospital.
Lewis et al.[34] in their study included mild and moderate disease with 20% of patients being severe or critical disease. Based on the small numbers of critically ill patients, a trend towards worsening lung function, there is likely a component of lung fibrosis and destruction of alveoli causing reduced PFT values.
Does duration of illness at entry point during hospitalization and its effect on Lung functions at 12 weeks of discharge in post-COVID-19 pneumonia cases?
In the present study, duration of illness has a negative impact on lung function at 12 weeks of discharge; as duration <7 days, 8–15 days, and >15 days of onset of symptoms documented normal and abnormal lung functions in 108/132, 22/168 and 5/165 cases respectively (P < 0.00001).
This is the first study included large number of post-COVID cases and documenting the effect of duration of illness when the patient was hospitalized to indoor unit and its impact on overall pulmonary functions outcome at 12 weeks of discharge from the hospital.
Oxygen saturation at entry point and its effect on lung function at 12 weeks of discharge in post-COVID-19 pneumonia cases
In the present study, low oxygen saturation at entry point has a negative impact on the overall outcome on lung function; and cases with oxygen saturation <75%, 75%–90%, and >90% observed as normal and abnormal lung functions in 92/18, 35/135 and 6/314 cases respectively (P < 0.00001).
This is the first study included large number of post-COVID cases and documenting the effect of hypoxia (oxygen saturation at entry point) during hospitalization in indoor unit and its impact on overall pulmonary functions outcome at 12 weeks of discharge from the hospital.
Does biphasic positive airway pressure/noninvasive ventilation initiation time at entry point has any effect on lung function at 12 weeks of discharge in post-COVID-19 pneumonia cases (n = 310)?
In the present study, timing of BIPAP/NIV has a significant association in attaining normal lung functions after post-COVID19 pneumonia recovery. COVID-19 pneumonia cases received BIPAP/NIV at entry point <1 day, 3–7 days and after 7 days of hospitalization were documented normal and abnormal lung functions in 30/150, 40/35, and 5/50 cases, respectively (P < 0.00001) Guler et al.[20] documented a negative correlation between the duration of mechanical ventilation during the acute disease and pulmonary function at 4-month follow-up. This might be due to a prolonged impairment after very severe COVID-19 or related to more severe disease course in susceptible patients. Alternatively, Herridge et al.[35] proposed ventilator-induced lung-injury is a well-described challenge post-ARDS, which can impact on pulmonary function after recovery from the acute illness. Faverio et al.[36] documented radiological abnormalities and abnormal lung functions in up to 58% of patients with COVID-19, which was present as pulmonary sequelae, although of a mild entity in the majority of cases, at 6-month follow-up, the need for invasive ventilatory support during hospitalization is a risk factor for the detection of radiological abnormalities, but not for DLCO impairment, at follow-up.
Other important observations in the present study
- Inhaled corticosteroids (ICS) given to post-COVID patients at the time of discharge were having symptomatic improvement in terms of dyspnea index, although head-to-head comparison of lung functions assessment before and after ICS was not available as we have performed spirometry after 12 weeks of discharge and initial spirometry assessment was not available
- Inhaled ciclesonide does not show any symptomatic benefit as compared to inhaled budesonide or fluticasone at any point during the course of COVID pneumonia from evolution to resolution
- Although higher CT severity scores were associated with a higher proportion of lung parenchymal abnormalities, lung function assessment (spirometry) shows a mixed pattern (mixed obstructive-restrictive) in 20% study cases, and we assume rational for these observations may be “mosaic type” with “parenchymal fibrosis,” i.e., heterogeneous lung involvement; and majority of these cases shown slowly resolving over 12 weeks. In these categories of mixed spirometry function abnormality (20% cases), significant symptomatic improvement was documented with inhaled budesonide and formoterol and we repeated after 3 months of therapy and documented near-complete resolution of lung functions after prompt evaluation and targeted these patients with conventional lung anti-fibrotic, pirfenidone and Nintedanib over 12 weeks with inhaled bronchodilators with ICS. The exact mechanism of the injury of the lungs by COVID-19 is still a new subject that is under debate. Studies[37],[38],[39] that included autopsies of COVID-19 patients described an acute lung injury with diffuse alveolar damage associated with fibrotic changes and microthrombi in the pulmonary vasculature
- Does post-COVID fibrosis behaves like any other chronic postinfective lung disease like tuberculosis (TB) in concern with spirometry abnormality?
We have performed spirometry analysis in post-TB cases and published data as-spirometry assessment of symptomatic post-TB cases, obstructive pattern was predominant type documented in 42% cases. In spirometry assessment of asymptomatic post-TB cases, obstructive pattern is documented in 32%, mixed pattern in 14%, and normal spirometry is documented in 46% cases.[40] similar findings we have documented in postcovid pneumonia cases at 12 weeks' postdischarge from hospital
- Limitations of study-DLCO assessment were not available at our center and it was not done in study cases. DLCO assessment in post-COVID cases will help in documenting micro-thrombosis and macro-thrombosis in pulmonary vasculature in post COVID setting, also it will help in predicting response to anticoagulants and antiplatelets and need for same in follow up settings. We have used D-dimer assessment, and resting plus exertional heart rate (heart rate after 6 min walk) as an alternative option to DLCO in predicting need of anticoagulation, while antiplatelets we continued for 12 weeks in all cases and recommended to use for 1 year in comorbid cases, especially in presence of DM, hypertension, recent stroke, obesity, malignancy, and COPD.
| Conclusions and Important Clinical Lessons Learned | | |
- COVID-19 pneumonia is heterogeneous disease with a variable effect on lung parenchyma, airways, and vasculature leading to long-term effects on lung functions
- Spirometry is cost-effective, noninvasive, easily available, sensitive tool for assessment lung function in post COVID care setting and it will help management of these cases by assessing response to treatment
- Pulmonary functions abnormality in post-COVID-19 pneumonia cases has been documented and should be assessed cautiously to have successful treatment outcome
- Restrictive lung disease is the predominant lung function impairment in post-COVID-19 recovered lung pneumonia cases
- Age above 50 years, male gender, DM, High CT severity, longer duration of illness, proper timing of initiation of BIPAP/NIV therapy, has documented significant impact on post-COVID lung functions at 12 weeks assessment
- All post-COVID cases need lung functions assessment by spirometry to predict the course of underlying lung pathology and targeting interventions accordingly.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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Correspondence Address:
Shital Patil,
Department of Pulmonary Medicine, MIMSR Medical College, Latur, Maharashtra
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/jascp.jascp_3_22
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6] |
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