Research ArticleOriginal Research

Factors Affecting the Risk of Interstitial Lung Disease Development in Hospitalized Patients With COVID-19 Pneumonia

Gülru Polat, Özer Özdemir, Sinem Ermin, Damla Serçe Unat, Görkem Vayisoğlu Şahin, Merve Ayık Türk, Filiz Güldaval, Seher Susam and Cenk Kıraklı
Respiratory Care October 2022, 67 (10) 1272-1281; DOI: https://doi.org/10.4187/respcare.09816

Abstract

BACKGROUND: Coronavirus disease 2019 (COVID-19) related chronic lung changes secondary to severe disease have become well known. The aim of this study was to determine the risk factors that affect the development of interstitial lung disease in subjects with COVID-19 pneumonia who were hospitalized.

METHODS: Patients hospitalized with COVID-19 pneumonia between June 2020 and March 2021 were retrospectively analyzed. Smoking histories, comorbidities, reverse transcriptase polymerase chain reaction test results, laboratory parameters at the time of the diagnosis, oxygen support, the use of corticosteroids with dosage and duration data, the need for ICU care were recorded. High-resolution computed tomographies (HRCT) were obtained for study population in their 3–6 months follow-up visit. The subjects were classified as having residual parenchymal lung disease if a follow-up HRCT revealed parenchymal abnormalities except pure ground-glass opacities (the residual disease group). The control group consisted of the subjects with normal chest radiograph or HRCT in their follow-up visit or the presence of pure ground-glass opacities. Two groups were compared for their demographic and clinical abnormalities, laboratory parameters, treatment regimens, and the need for ICU care.

RESULTS: The study included 446 subjects. The mean ± SD age was 58.4 ± 13.87 years, with 257 men (57.6%). Although 55 subjects had normal HRCT features on their follow-up HRCT, 157 had abnormal lung parenchymal findings. Univariate logistic regression analysis revealed statistically significant results for age, sex, corticosteroid treatment, and the need for ICU care for predicting interstitial lung disease development (P < .001, P = .003, P < .001, and P < .001, respectively). Also, the residual disease group had significantly higher leukocyte and neutrophil counts and lower lymphocyte counts (P < .001, P < .001, P = .004, respectively). Correlated with these findings, neutrophil-to-lymphocyte ratios and platelet-to-lymphocyte ratios were significantly higher in the residual disease group (P < .001 and P = .008, respectively).

CONCLUSIONS: Residual parenchymal disease was observed 3-6 months after discharge in one third of the subjects hospitalized with COVID-19 pneumonia. It was observed that interstitial lung disease developed more frequently in older men and in those subjects with more-severe disease parameters.

Introduction

COVID-19, caused by SARS-CoV-2, still has enormous impact on health, with increasing mortality. Total death numbers have exceeded 5 million throughout the world, since the beginning of the pandemic to the time of this writing.1 Besides its mortality, the disease may have prolonged and post-sequelae symptoms, such as fatigue, sweating, anxiety, and chest tightness, reaching > 50% in older patients.2 These may accompany decrement in pulmonary function tests (PFT) and pulmonary fibrosis with differing degrees in some patients.3 There are many factors and proposed mechanisms for postacute sequela findings, including prolonged acute disease, protracted elevation of cytokines, immunomodulatory treatments, organizing pneumonia secondary infections, and mechanical ventilation.4 Computed tomography (CT) of the chest plays an important role in the diagnosis and follow-up of patients with COVID-19. Diagnostically, CTs show lung abnormalities, and repeated scans can evaluate disease progression and response to treatment.5,6 Several studies describe the imaging and clinical features of serial thin-section CTs in patients with COVID-19 during hospitalization or discharged after treatment. 7-12

In the acute stage of COVID-19 pneumonia, the most common CT findings are bilateral ground-glass appearance and consolidation in the lower zones.13,14 Although the CT findings improve rapidly in some patients; in other patients, resolution takes longer or the parenchymal changes are permanent.15-17 At present, it is not possible to identify patients in whom pneumonia will result in pulmonary interstitial residual findings. Discrimination of patients at risk for post–COVID-19 interstitial lung disease can provide information about options in the post-treatment period and patient follow-up. Identification of residual lesions could also be an early warning for patients at high risk of developing fibrosis.18 The aim of this study was to determine the risk factors that affect the development of interstitial lung disease in hospitalized patients with a diagnosis of COVID-19 pneumonia.

QUICK LOOK

Current Knowledge

At present, chest computed tomography plays an important role in the diagnosis and treatment of patients with COVID-19. Computed tomography aids diagnosis by indicating lung abnormalities and assisting in eval-uating disease progress and response to treatment. Identifying patients at high risk can provide information about the treatment options in the post-treatment period. Identification of residual lesions may also be an early warning for which patients will develop fibrosis.

What This Paper Contributes to Our Knowledge

Residual parenchymal lung disease was observed 3–6 months after discharge in one third of the subjects hospitalized with COVID-19 pneumonia. It was observed that interstitial lung disease developed more frequently in older men and in those subjects with more-severe disease.

Methods

This study was conducted in a tertiary level reference hospital and received review and approval from local ethical board (18 – 24/9.4.2021). Patients hospitalized with the diagnosis of COVID-19 pneumonia between June 2020 and March 2021 were retrospectively analyzed for the study. Clinical diagnosis of COVID-19 was made by either positive reverse transcriptase polymerase chain reaction results of oronasopharyngeal swabs, or compatible clinical, laboratory, and radiologic findings in the absence of reverse transcriptase polymerase chain reaction positivity. Patients who had follow-up visits 3–6 months after discharge from the hospital were included in the study. Patients who died during the management and follow-up period or who had a history of pulmonary disease were excluded. On their follow-up visits, the subjects were evaluated by chest radiograph. The subjects without normal radiographic findings of the chest were evaluated by high-resolution CT (HRCT) for residual lung parenchymal changes.

The clinical characteristics and laboratory parameters of the study population were obtained from the hospital records. Smoking histories, comorbidities, reverse transcriptase polymerase-chain-reaction test results for SARS-CoV-2, complete blood cell counts, C-reactive protein, ferritin, D-dimer, albumin, lactate dehydrogenase, and fasting blood glucose levels at the time of the diagnosis were recorded. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios were calculated for all the subjects indivi-dually. All laboratory data were obtained before any treatment was started. Oxygen requirements on admission and the use of corticosteroids in the treatment regimen with dosage (normal dose or pulse dose) and duration data were recorded. The subjects who required transfer to the ICU during the treatment period were identified.

HRCTs were obtained for all the subjects during the diagnostic workup and, for predefined subjects, in their follow-up visit. The Supria True64 CT device (Fujifilm Healthcare Americas, Lexington, Massachusetts) was used. Scanning parameters were the following: tube voltage, 120 kVp; automatic tube current modulation; tube current, 100–250 mAs; pitch, 1.0–1.2 mm; matrix, 512 × 512; slice thickness, 1.250 mm. All images were then reconstructed with 0.625 mm with the same increment. The CT severity scores were calculated for each subject.19 Each lobe was visually scored according to the extent of lobar involvement: score 0, 0% involvement; score 1, <5% involvement; score 2, 5%–25% involvement; score 3, 26%–49% involvement; score 4, 50%–75% involvement; and score 5, >75% involvement. The total score was obtained by the addition of individual lobar scores.

For the follow-up scan, residual lung parenchymal changes were classified as parenchymal bands, reticulations, traction bronchiectasis, ground-glass opacities, interlobular septal thickenings, and “honeycombing.” Distribution and location of parenchymal abnormalities were recorded as diffuse, lower zone or upper zone, and central or peripheral involvement. The extent of lung involvement was determined by calculating the total number of lung segments involved. According to the presence and characteristics of the parenchymal abnormalities, further classification was made to better define lung sequela: usual interstitial pneumonia like, probable usual interstitial pneumonia like, indeterminate usual interstitial pneumonia like, and others.

Usual interstitial pneumonia like involvement was defined as the presence of honeycombing with lower zone predominance disease. Probable usual interstitial pneumonia like involvement was defined as the presence of traction bronchiectasis with reticular pattern and lower zone predominant disease. Indeterminate usual interstitial pneumonia like disease was defined as lower zone predominant reticulations or interlobular septal thickening without honeycombing or traction bronchiectasis. Other detected abnormalities were classified as only parenchymal bands, upper zone honeycombing, ground-glass opacities with or without parenc-hymal bands, diffuse reticulations, upper lobe traction bronchiectasis and reticulations, traction bronchiectasis without reticulations, and only interlobular septal thickenings. The subjects were classified as having residual parenchymal lung disease if a follow-up HRCT revealed prementioned parenchymal abnormalities like parenchymal bands, reticulations, traction bronchiectasis, interlobular septal thickenings, and honeycombing, but not pure ground-glass opacities (residual disease group). The control group consisted of the subjects with a normal chest radiograph or HRCT in their follow-up visit, or the presence of pure ground-glass opacities on their follow-up HRCTs. Two groups were compared for their demographic and clinical abnormalities, laboratory parameters, treatment regimens, and need for care in the ICU.

Statistical Analysis

IBM SPSS Statistics software program version 22 (IBM, Armonk, New York) was used for statistical analysis. Data were presented as means ± SDs or medians (interquartile range [IQR]) according to the distribution of the data. The chi-square test was used for comparison of categorical variables, and the t test or Mann-Whitney U test was used for comparison of continuous variables. P = .05 was taken as the level of significance. Univariate logistic regression analysis was carried out for determining predictive variables of outcome. Leukocyte and lymphocyte counts were dichotomized by cutoff levels with the best sensitivity and specificity values, which were calculated by receiver operating characteristic curve analysis. Odds ratios (OR) with lower and upper limit CIs were obtained. Variables with P < .25 was included in the model of multivariate logistic regression analysis unless they were correlated. Backwards Wald statistics were used for multivariate analysis.

Results

A total of 646 patients hospitalized with a clinical diagnosis of COVID-19 between June 2020 and March 2021 were screened for the study. Forty-eight patients were excluded due to the absence of radiologic involvement in their HRCT assessment. Sixty-eight patients who did not survive during their management period and 84 with incomplete follow-up data were also excluded from the study. A total of 446 subjects were included. Regression of baseline radiologic involvement on chest radiograph was observed in 234 subjects; 212 subjects were evaluated with follow-up HRCT of the lungs for interstitial lung disease. A flow chart of the study population is shown in Figure 1.

Figure 1.
Figure 1.

Flow chart. HRCT = high-resolution computed tomography.

The mean ± SD age of the study population was 58.4 ± 13.87 years, with 257 men (57.6%). A history of smoking, either active or former, was present in 21.5% of the study population (n = 96). Of the subjects, 61.2% had at least one comorbidity (n = 267). Hypertension and diabetes mellitus were the most seen comorbidities (n = 152 [34.1%] and n = 112 [25.1%], respectively). Of the subjects, 7.4% had positive reverse transcriptase polymerase chain reaction results for SARS-CoV-2 on their oronasopharyngeal swabs, and 95.9% (n = 422) had typical HRCT characteristics for COVID-19. The median (IQR) CT severity score of the total study population was 11 (0–25). More than half of the subjects were treated with corticosteroids (52.5% [n = 234]), whereas 11% (n = 49) needed pulse dose corticosteroids (250–1000 mg/d). Fifty subjects (11.2%) needed to be transferred to the ICU during their management, and 288 patients needed oxygen supply on admission.

Although 55 subjects had normal HRCT features on their follow-up HRCT, 157 had abnormal lung parenchymal findings. Major observed lung parenchymal abnormalities were parenchymal bands (n = 94 [59.9%]), reticulations (n = 94 [59.9%]), ground-glass opacities (n = 75 [47.8%]), and traction bronchiectasis (n = 56 [35.7%]). Extension of lesions, calculated by the total number of segments involved, was 8.7 ± 5.31, and the most involved parts were the lower lobes, especially the right lower lobe. Distribution of parenchymal abnormalities in follow-up HRCT is presented in Table 1. Among the subjects with residual parenchymal findings, 4 (2.5%) had a usual interstitial pneumonia like pattern, 32 subjects (20.4%) had a probable usual interstitial pneumonia like pattern, and 57 subjects (36.3%) had indeterminate usual interstitial pneumonia like pattern. Only parenchymal bands, ground-glass opacities with parenchymal bands, and traction bronchiectasis without reticular abnormalities were other major patterns frequently detected (n = 18 [11.5%]; n = 17 [10.8%], and n = 16 [10.2%], respectively). Radiologic patterns of residual findings in follow-up HRCT of subjects are presented in Table 2.

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Table 1.

Distribution of Lung Parenchymal Abnormalities in Subjects Evaluated by HRCT of Lungs on Their Follow-Up Visit

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Table 2.

Distribution Patterns of Lung Parenchymal Abnormalities in Subjects Who Have Abnormal HRCT Findings on Their 3–6 Months Follow-Up Visit

Except for the 7 subjects (3.3%) who had only ground-glass opacities on their follow-up HRCT, the other 150 subjects (33.6%) were considered to have residual parenchymal changes on HRCT. The remaining 296 subjects (66.4%) who had a normal chest radiograph or CT, or only residual ground-glass opacities formed the of the study. The subjects in the residual disease group were older versus the control group (mean ± SD ages 62.3 ± 12.1 years vs 56.4 ± 14.31 years; P < .001), and proportion of male subjects was significantly higher (n = 101 [67.3%]; P = .003). The residual disease group had significantly higher median (IQR) leukocyte and neutrophil counts, and lower median (IQR) lymphocyte counts compared to the control group (7,950/mm3 [2,600–37,000/mm3] vs 6,400/mm3 [1,200–24,000/mm3], P < .001; 5,800/mm3 [1,500–33,500/mm3] vs 4,500/mm3 [600–22,900/mm3], P < .001; and 1,000/mm3 [100–10,000/mm3] and 1,200/mm3 [200–18,300/mm3], P = .004, respectively). Correlated with these findings, median (IQR) neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios were significantly higher in the residual disease group compared to the control group (n = 5.6 [0.58–65] vs n = 3.6 [0.21–48], P < .001; and n = 243.7 [43.5–3520] vs n = 206.7 [16.61–2733.3], P = .008, respectively).

Among other laboratory parameters median (IQR) C-reactive protein, ferritin, D-dimer, and albumin levels were significantly higher in the residual disease group compared to the control group (66 [0.8–407] mg/dL vs 48.8 [0.9–377] mg/dL, P = .007; 381 [12.8–2219] ng/mL vs 266.1 [11.3–2277] ng/mL, P = .006; 1130.5 [124–10,000] ng/mL vs 893 [149–10,000] ng/mL, P = .02; and 3.5 [1.81–4.38] g/L vs 3.8 [1.87–4.79] g/L, P = .001, respectively). The median (IQR) CT severity scores were also higher in residual disease group compared to the control group (10 [0–25] vs 12.5 [0–25]; P < .001). The CT severity score was ≥ 18 in 25.3% (n = 38) of the subjects in residual disease group, compared with 11.8% (n = 35) of the control group (P < .001).

The oxygen requirement on admission and ICU need during management were higher in the residual disease group compared to the control group (n = 106 [70.7%] vs n = 182 [61.5%], P = .060; and n = 31 [20.7%] vs n = 19 [6.4%], P < .001, respectively). Oxygen support was given as low-flow oxygen support. Also, corticosteroids were applied significantly more with longer durations in the residual disease group versus the control group (n = 105 [70%] vs n = 129 [43.6%], P < .001; and median [IQR] 6 [0–30] d vs 5 [0–22] d, P = .007, respectively). Any immunomodulatory treatment other than corticosteroids, such as tocilizumab, baricitinib, or tofacitinib was not used in the study population. A comparison of the residual disease group and the control group as well as characteristics of the total population is presented in Table 3. A subgroup analysis of only the subjects with an oxygen support requirement was made. A total of 106 subjects were present in the residual disease group, whereas 182 subjects were in the control group. A comparison of both groups were generally similar, but there was not any significant difference of C-reactive protein, D-dimer, platelet-to-lymphocyte ratio, and pulse steroid treatment among the groups (P = .09, P = .11, P = .08, and P = .10, respectively). Results of the subgroup analysis of the subjects with an oxygen requirement are presented in Table 4.

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Table 3.

Demographic and Clinical Characteristics of the Study Population and Comparison of the Subjects With Residual Disease and Control Group

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Table 4.

Subgroup Analysis of Only Subjects Who Were Oxygenated: Comparison of Subjects in the Residual Disease Group and the Control Group

Univariate logistic regression analysis revealed statistically significant results for age, sex, corticosteroid treatment, and the need for ICU care for predicting interstitial lung disease development (OR 1.03 [95% CI 1.02–1.05], P < .001; OR 1.85 [95% CI 1.23–2.79], P = .003; OR 3.12 [95% CI 2.05 – 4.75], P < .001; and OR 3.8 [95% CI 2.06 – 6.99], P < .001, respectively). Leukocyte and lymphocyte levels were dichotomized by using cutoff levels of 7,250/mm3 and 1,150/mm3, which were derived from receiver operating characteristic curves as having best sensitivity and specificity levels (area under curve of 0.61, sensitivity 58.7%, and specificity 58.4%; and area under the curve of 0.58, sensitivity 58.7%, and specificity 51.2%, respectively). Among laboratory parameters, lymphocyte counts < 1,150/mm3, leukocyte counts ≥ 7,250/mm3 and higher C-reactive protein, ferritin, D-dimer levels were predictive for interstitial lung disease development (OR 1.49 [95% CI 1.00–2.21], P = .050; OR 1.99 [95% CI 1.34–2.98], P = .001; OR 1.04 [95% CI 1.01–1.07], P = .005; OR 1.00 [95% CI 1.00–1.01], P = .003; and OR 1.15 [95% CI 1.02–1.30], P = .03, respectively). On multivariate analysis, the use of corticosteroids in the treatment regimen, a need for ICU care during management, and a CT severity score ≥ 18 remained significant for prediction of interstitial lung disease development (OR 2.89 [95% CI 1.36–6.11], P = .006; OR 4.69 [95% CI 1.51–14.60], P = .008; and OR 2.27 [95% CI 0.91–5.66], P = .08, respectively). Results of uni- and multivariate analyses are presented in Table 5.

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Table 5.

Uni- and Multivariate Logistic Regression Analysis for Factors that Predicted Post–COVID-19 Interstitial Lung Disease Development

Discussion

In this study, we examined interstitial lung disease detected by 3-6 months follow-up HRCTs of the subjects hospitalized with the diagnosis of COVID-19 pneumonia. Residual parenchymal lung disease was detected in 33.6% of the subjects with the most prominent pattern, the indeterminate usual interstitial pneumonia like pattern. Residual parenchymal lung disease was associated with more-severe disease. More-severe baseline lung involvement on HRCT, ICU care, and corticosteroid requirement are predictive parameters for residual interstitial disease.

It is not yet clear how often long-term complications can be seen in COVID-19 pneumonia. However, the phylogenetic similarities of SARS-CoV-1 and SARS-CoV-2 viruses and the clinical, radiologic, and pathologic features of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome pneumonia caused by these viruses are similar to COVID-19 pneumonia. This shows that the risk of progression may be similar.20 Therefore, the results of the study that investigated the long-term complications of SARS and Middle East respiratory syndrome help us to understand the long-term sequelae of COVID-19 pneumonia. It was observed that 36% of the subjects with SARS had reticular images on the chest radiograph 3 months after discharge, and reticulation and alveolar shadowing still continued in 30% of the subjects at 6 months.21 In a study of 97 subjects who survived SARS, at the end of 1 year, 28% of the subjects had sequelae lesions on chest radiograph, FVC was below the normal values in 4%, diffusion capacity was below normal values in 24%, and radiologic findings were correlated with respiratory dysfunction.22 However, 36% of the subjects who survived after Middle East respiratory syndrome had sequelae images on CT at 6 weeks.23 These findings showed that the vast majority of the subjects with SARS and Middle East respiratory syndrome continued to have radiologic findings when they were discharged from the hospital, but 3 months after discharge, radiologic findings returned to normal in two thirds of the subjects, similar to the subjects with SARS-COV-2 in our study, it showed that ∼30% of the subjects continued to have radiologic sequelae.

In a study in which 90 subjects with COVID-19 pneumonia were examined to investigate the early changes, it was reported that 94% of the subjects who were discharged after an average of 24 d still had radiologic changes, predominantly a ground-glass appearance.24 In another study,25 PFT performed during discharge in 110 subjects who were discharged after an average of 27 d of hospitalization were examined, and the PFT findings of 24 subjects without pneumonia, 67 subjects with pneumonia, and 19 subjects with severe pneumonia were compared. Although the diffusion capacity was low in 30% of those without pneumonia, 42% of those with pneumonia, and 82% of those with severe pneumonia, the total lung capacity was below normal in 47% of subjects with severe pneumonia. It was observed that there was no difference in terms of PFT parameters.25 Contrary to this, in another study, it was observed that there was no decrease in PFT performed at the sixth week after discharge in the subjects who were treated for severe COVID-19 pneumonia that did not require mechanical ventilation.26 However, we could not evaluate the PFT parameters in our subjects due to the risk of transmission of COVID-19.

If we look at the subjects with longer follow-up, it was reported in a study that in half of the subjects in CTs taken after 120 d, fibrotic lesions were observed and this rate was at a level that competes with the fibrotic lesion rates seen after SARS and Middle East respiratory syndrome infections.27 In a study in which the subjects were followed up at 1 year, 60% of the residual lesions were observed in CTs taken at the third month, but complete resolution was observed in 98% of these subjects with moderate pneumonia. Residual lesion was observed in %25 of total number of subjects.28 Han et al29 performed a study of 114 participants with severe COVID-19 diagnosis and residual CT abnormalities (including ground-glass opacities, bronchial dilatation, parenchymal bands, and honeycombing) were observed in 62% of recovered participants (71/114) after 6 months. These CT abnormalities were the typical manifestations of interstitial fibrosis.30

In our study, residual parenchymal lung disease was observed at a rate of 33.6% in CTs taken at the third month and later, and it was found at a lower rate compared with the control CTs of these studies in those months. When we look at the literature, there are studies about the development of interstitial lung disease in subjects who mostly move to mechanical ventilation, and mechanical ventilation has been shown as a risk factor.31,32 Because our study consisted of subjects with bilateral pneumonia, most of whom were hospitalized in the ward, many other factors that affect the developing interstitial lung disease were identified.

Clinically, the subjects with residual parenchymal lung disease after 3–6 months from the onset were significantly older and with a male predominance, and associated with more-severe disease because this group had a significantly higher need for ICU care, higher corticosteroid use, and higher laboratory parameters. This is similar to those subjects with SARS.33 Reverse transcriptase polymerase chain reaction positivity of oronasopharyngeal swabs was higher, and this may represent higher viral load in these subject which may result in more damage in patient's lungs. A need for corticosteroid and the need for ICU care was associated with 2.41- and 2.21-times higher risks for interstitial lung disease development, which suggests the importance of seeking medical advice for patients with COVID-19.

A previous study indicated that early treatment with corticosteroids was well tolerated and associated with rapid and significant improvement for the subjects with persistent inflammatory interstitial lung disease after SARSCoV-2 infection.34 Also in our study, nearly half of the subjects hospitalized with COVID-19 who recovered without sequela had received corticosteroid treatment in the early stage of treatment, which might play a role in the resolution of some of the CT findings, aid in the initial treatment of this patient population, and prevent long-term irreversible lung damage. Another difference of our study from previous studies was that we classified pulmonary lesions as usual interstitial pneumonia like, probable usual interstitial pneumonia like, and indeterminate usual interstitial pneumonia like.30 The most common pattern we saw was indeterminate usual interstitial pneumonia like (36.3%), which was defined as lower zone reticulations or interlobular septal thickenings. The first reports of honeycomb-shaped fibrosis in COVID-19 pneumonia were reported in case studies in May 2020.35 We found a low rate (4.5%) of this pattern, which is consistent with the literature. In various studies, transforming growth factor β, interleukin 6, tumor necrosis factor alpha, which play an important role in pulmonary fibrosis, are also increased in the subjects with COVID-19, which indirectly contributes to the development of fibrosis in COVID-19.36-38 However, in another study, Pan et al avoided using the term of pulmonary fibrosis, such as traction bronchiectasis, honeycomb, and reticular pattern, because of the limited follow-up period and of the concern that it might lead to fibrosis overdiagnosis.28

In a meta-analysis of 380 subjects, a decrease in diffusion capacity, a restrictive pattern, and a obstructive pattern were found in 39%, 15%, and 7%, respectively.3 We found a high prevalence of decreased diffusion capacity. A possible explanation for this finding may be the time of assessment. Zhao et al,39 reported 16% prevelance of decreased diffusion capacity in PFTs performed 3 months after discharge of COVID-19 patients. Three other studies reported a prevalence of decreased diffusion capacity between 44% and 56% in performed PFTs after the first month of infection.25,40,41 An important aspect to consider is the ideal time to perform respiratory assessment tests. The British Thoracic Society guide recommends the evaluation of PFTs at 3 months after discharge, especially at follow-up with patients suspected of having an interstitial disease process.42 As a result, patients after infection with COVID-19 showed impaired lung function; the most important of the PFTs affected was the diffusion capacity.3 Also, our subjects were at the third month and later, and could be evaluated in terms of pulmonary function. We are planning to conduct a follow-up study, including PFT values, at the end of the first year in these patients who could not undergo PFT due to the pandemic. In a study that evaluated health-related quality of life in subjects after COVID-19, a reduction in physical health was found; however, normal mental health was reported, despite the long period of isolation and extreme uncertainty during COVID-19, which could have created psychological and mood disturbances.43 We could not evaluate the health-related quality of life.

This study had some limitations. First, the follow-up time for these subjects is not long enough, and it is unknown whether the pulmonary lesions will permanently remain. Second, this study lacked symptom assessment and PFTs at follow-up to evaluate whether persistent imaging abnormalities correlate with symptoms and PFTs. Follow-up HRCT scans were not available for all discharged patients, HRCT was performed on the subjects when a lesion was observed on the chest radiograph at the third month and later in accordance with the British Thoracic Society guidelines.42,44

Conclusions

We observed that interstitial lung disease developed more frequently in older men and in those subjects with more-severe disease parameters. Future follow-up studies with a longer follow-up period would be necessary to see whether these residual lesions resolve and to determine the long-term outcomes of the subjects who recovered from COVID-19. We are also planning to study the 1-year results of our subjects in future research. In the first year, we will have the chance to monitor how much of the lesions will regress or whether residual parenchymal lung disease will progress. Thus, we will have a chance to comment on whether antifibrotic treatment can be started early in some subjects.

Footnotes

  • Correspondence: Gülru Polat, Assistant Prof, Department of Respiratory Medicine, Dr. Suat Seren Chest Disease and Thoracic Surgery Training and Research Hospital, University of Health Sciences, Gaziler Street, No 331, 35170, Konak/Izmir, Turkey. E-mail: gulruerbay{at}yahoo.com

  • The study was performed at the University of Health Sciences, Dr Suat Seren Chest Diseases and Surgery Training and Research Hospital, Izmir, Turkey.

  • The authors have disclosed no conflicts of interest.

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