CT of COVID-19 - Noor PDF

3 Materials and Methods 3.1 Patients This is an observational, prospective and cohort study conducted on 150 patients, 93 males and 57 females, aged between 26 and 50 years, who attended the Respiratory Diseases Consultation Clinic in Al-Hussien Teaching Hospital during the period from June 202...

3 Materials and Methods 3.1 Patients This is an observational, prospective and cohort study conducted on 150 patients, 93 males and 57 females, aged between 26 and 50 years, who attended the Respiratory Diseases Consultation Clinic in Al-Hussien Teaching Hospital during the period from June 2023 to January 2024 in Al Nasiriyah City, Thi-Qar Province, Iraq. All patients suffered from ongoing symptoms after an acute mild or moderate SARS- CoV-2 infection and had a chest CT scan performed at least 1 month after acute infection. For all patients who completed the study, chest CT scans via Revolution EVO, GE Healthcare, Japan, were mainly done for them to exclude relevant structural lung damage without previous clinical findings (e.g., impaired lung function or low oxygen saturation). 3.1.1 Inclusion Criteria All patients, over the age of 15, regardless of gender, who were confirmed to have Covid-19 infection with positive PCR result and had mild to moderate symptoms according to WHO classification. All patient who were able to participate and complete the CT examination. All patients who were willing to give a written informed consent form to participate in the clinical study. 3.1.2 Exclusion Criteria Any patients who had inconstant with inclusion criteria. Any patients with a history of severe restrictive or obstructive lung disease before Covid-19 infection. Any patients with an initial severe course of COVID-19 disease that required prolonged hospitalization or intensive care treatment. Any patients with an alternative diagnosis for reported symptoms.  Any patient with acute respiratory distress syndrome and/or required intubation/mechanical ventilation. Immune compromised patient and patient with malignancy. Patients who did not complete the entire information sheet for this investigation. 3.1.3 Ethical Consideration The scientific and Ethics Committee in the Thi-Qar University / College of Medicine reviewed and approved the protocol. The proposal was accepted by Thi-Qar Governorate authorities in Iraq. Oral and written consent was obtained from the patients after a thorough explanation of the purpose of the investigation and verification of the accuracy of the acquired data. 3.1.4 Study Design This observational, prospective, randomized, and cohort study was conducted to assess chest CT scans of patients with post- COVID-19 syndrome after a mild or moderate acute infection to investigate if there were objective long-term damages on lung parenchyma and evaluated the association with persisting respiratory symptoms. 3.2 Symptoms and Clinical Parameters Systematically documented medical reports extracted demographics (sex, age, BMI, and smoking status), symptoms during acute infection, and post-COVID-19 symptoms. Record symptoms as absent only if they are documented in the medical record as "absent." The Modified Medical Research Council Dyspnea Scale (mMRC) grades dyspnea according to severity. Researchers evaluated chest CT scan indications to determine if patients exhibited abnormal clinical findings. Patients with persisting respiratory symptoms and no relevant abnormal clinical findings discussed the pros and cons of a chest CT scan to increase the certainty of excluding relevant lung damage, and they underwent a chest CT scan if requested. Comorbidities that existed before the acute COVID-19 infection were recorded. Our team conducted standard pulmonary functional testing following ATS/ERS guidelines, which included measuring forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), diffusion capacity of the lung for monoxide (TLco), and carbon monoxide transfer factor (Kco). 3.3 CT Image Acquisition Single-energy CT was performed in all patients on Revolution EVO (GE Healthcare, Japan), which is a computed tomography (CT) scanner, with or without the application of an intravenous contrast agent in supine position at full inspiration. Revolution EVO uses volume CT technology, which uses a single source of X-rays at a variable angle, can improve image quality, reduce radiation dose, and shorten scan time. No specific post-COVID-19 protocol was applied. The protocol depends on the referral question. In a subset of patients where expiratory CT in the prone position was available, the scans were additionally analyzed. CT scans were performed at 80 to 120 kVp with varying tube currents and a pitch of 1–1.2. Images were reconstructed at a slice thickness of 0.75–2 mm using iterative reconstruction algorithms. 3.4 Statically Analysis Using Microsoft 365 Excel 2024 and SPSS (IBM version 26.0), the data were analysed. In this study, results were provided as mean ± SD and frequencies as percentages. We did not perform an a priori sample size calculation due to the explanatory study design. The Chi-square test, multivariable logistic regression, and ANOVA test were used to analyse the variables. All statistical tests were two-tailed, probability levels less than 0.05 were deemed physiologically significant, and p- values less than 0.01 were deemed extremely significant. 4 Results and Discussion 4.1 Patient Population As presented in the Table 4-1 and Figure 4-1, most of the patients in this study were male (62%), aged between 26 and 50 years (66.67%), whose weight ranged between 55 and 75 kg (59.33%), college students (68.67%), and non-smokers (78.67%). Table 4-1 The sociodemographic characteristics of patients Variables Parameters Frequency Percent Male 93 62.00% Gender Female 57 38.00% ≤25yrs 8 5.33% 26-50yrs 100 66.67% Age Categories 51-75yrs 37 24.67% >75yrs 5 3.33% 55-75kg 89 59.33% Weight 76-95kg 58 38.67% >95kg 3 2.00% Illiterate 6 4.00% Primary 18 12.00% Education Level Secondary 23 15.33% College 103 68.67% Current 3 2.00% Smoking Former 29 19.33% Never 118 78.67% Total 150 100.00%  90% 80% 70% 60% 50% 40% 30% 20% 10% 0% ≤25yrs Secondary Current Never Male Female 26-50yrs 51-75yrs >75yrs 55-75kg 76-95kg >95kg Primary Former Illiterate College Gender Age Categories Weight Education Level Smoking Figure 4-1 The sociodemographic characteristics of patients As presented in the Figure 4-2, most of the patients in this study needed both treatments, medical and O2, (65%). 53, 35% Treatment Medical Treatment Treatment Both (Medical 97, 65% and O2) Figure 4-2 The distribution of patients based on treatment 4.2 Symptoms and Clinical Parameters As presented in the Table 4-2 and Figure 4-3, most of the patients in this study had dry cough (52.67%), and dyspnea (63.33%), while most of those did not have thoracic pain (63.67%).  Table 4-2 The persistent respiratory symptoms Variables Parameters Frequency Percent None 63 42.00% Cough Dry cough 79 52.67% Cough with sputum 8 5.33% None 95 63.33% Thoracic Pain Yes 55 36.67% None 55 36.67% Dyspnea Yes 95 63.33% Total 150 100.00% 70.0% 60.0% 50.0% 40.0% 30.0% 20.0% 10.0% 0.0% None Dry cough Cough None Yes None Yes with sputum Cough Thoracic Pain Dyspnea Figure 4-3 The symptoms and clinical parameters of patients As presented in the Table 4-3, most of the patients in this study had at least a pre-existing comorbidity (68%); 47.33% had hypertension (HTN); 28% had cardiovascular disease (CVD); 2% had stoke; and 32.67% had asthma. Table 4-3 Pre-existing comorbidities of patients in this study. Co-morbidity Frequency Percent without any disease 48 32.00% HTN 71 47.33% CVD 42 28.00% Stroke 3 2.00% Asthma 49 32.67% Total 150 100.00% 4.3 Chest CT Scan Findings As presented in the Table 4-4 and Figure 4-4, most of the patients in this study had normal chest CT scan findings (58.67%), and only 41.33% had abnormal chest CT scan findings, distributed as unilateral and bilateral findings (16.67% and 24.67%, respectively). Only 17.33% of patients had interlobular septal thinning; 21.33% had ground glass opacities (GGO); 12.67% had fibrotic-like changes; 7.33% had reticulation; 4% had consolidation; 3.33% had pleural effusion; 2% had honeycombing; 4% had emphysema; and 4% had bronchiectasis. Table 4-4 Chest CT scan findings of patients Abnormal CT findings Variables Parameters Total Unilateral Bilateral n 36 None % 24.00% Interlobular Septal Thickening n 11 15 26 Yes % 7.33% 10.00% 17.33% n 32 None % 21.33% Ground glass opacities (GGO) n 18 12 30 Yes % 12.00% 8.00% 20.00% n 43 None % 28.67% Fibrotic like changes n 3 16 19 Yes % 2.00% 10.67% 12.67% n 51 None % 34.00% Reticulation n 5 6 11 Yes % 3.33% 4.00% 7.33% n 56 None % 37.33% Consolidation n 4 2 6 Yes % 2.67% 1.33% 4.00% n 57 None Pleural Effusion % 38.00% Yes n 5 0 5  % 3.33% 0.00% 3.33% n 59 None % 39.33% Honey Combing n 3 0 3 Yes % 2.00% 0.00% 2.00% n 56 None % 37.33% Emphysema n 3 3 6 Yes % 2.00% 2.00% 4.00% n 56 None % 37.33% Bronchiectasis n 3 3 6 Yes % 2.00% 2.00% 4.00% n 25 37 62 Total Abnormal CT findings % 16.67% 24.67% 41.33% n 88 Normal CT findings % 58.67% n 150 Total % 100.00% Abnormal Bilateral Findings, 37, 25% Normal, 88, Abnormal 58% Unilateral Findings, 25, 17% Figure 4-4 The distribution of patients based on chest CT findings 4.4 Correlation of Clinical Parameters and Chest CT Scan Findings As presented in the Table 4-5, the interlobular septal thickening, Fibrotic-like changes and emphysema were significantly related to cough and dyspnea, and GGO was significantly related to chest pain, while reticulation and bronchiectasis were significantly related to cough and chest pain, while consolidation related significantly to chest pain. Table 4-5 Correlation of Clinical Parameters and Chest CT Scan Findings Variables Cough Chest Pain Dyspnea X2 0.247 0.017 0.202 Interlobular Septal Thickening Sig. 0.002 0.836 0.013 X2 0.155 0.311 0.138 Ground glass opacities (GGO) Sig. 0.058 0.000 0.091 X2 0.243 -0.123 -0.209 Fibrotic like changes Sig. 0.003 0.132 0.010 X2 0.239 0.211 0.055 Reticulation Sig. 0.003 0.010 0.505 X2 0.036 0.268 0.014 Consolidation Sig. 0.663 0.001 0.864 X2 0.008 0.013 -0.013 Pleural Effusion Sig. 0.927 0.876 0.876 X2 0.122 -0.109 0.109 Honey Combing Sig. 0.138 0.185 0.185 X2 0.174 0.056 -0.268 Emphysema Sig. 0.034 0.492 0.001 X2 0.174 0.268 -0.056 Bronchiectasis Sig. 0.034 0.001 0.492 As presented in the Table 4-6, multivariable logistic regression analyses showed evidences of an association between the radiological chest CT findings and persisting respiratory symptoms such as cough, and thoracic pain, while there was no evidence with dyspnea. Table 4-6 Multivariable regression models between radiological findings and persisting symptoms. Symptoms Sig. Exp(B) 95% C.I. for EXP(B) Cough 0.000 7.054 (16.711 - 2.978) Chest Pain 0.002 3.651 (8.226 - 1.62) Dyspnea 0.224 1.619 (3.523 - 0.744) 4.5 Discussion People diagnosed with COVID-19 commonly have symptoms such as respiratory distress, head pain, elevated body temperature, reduced olfactory function, and an overall decline in gastrointestinal health (Balachandar, Vellingiri, et al., 2020). This study investigated the chest CT findings after 12 months of follow-up in patients with persistent respiratory symptoms from previous mild-to-moderate COVID-19 infections. Some patients who initially had a mild or moderate COVID-19 infection may continue to experience respiratory symptoms such as difficulty breathing or chest pain. Currently, the causes behind these persistent symptoms remain unidentified, and standard diagnostic tests in clinical practice do not reveal any significant abnormal results. The findings of the Watanabe, Atsuyuki, et al.’s study closely resembled those of the SARS-CoV-1 outbreak in 2003. Approximately 30% to 40% of individuals who survived the infection exhibited aberrant radiological findings within 6 months to 1 year after their recovery. Patients who still showed CT abnormalities at the 12 months follow-up continued to exhibit comparable results at the 15-year follow-up (Zhang, Peixun, et al., 2020; Hui, et al., 2005). Applying this time course to COVID-19 reveals a significant increase in the number of people impacted, which raises severe concerns. Several prospective studies have examined the long-term effects on the lungs one year after COVID-19 (Shang, Luorui, et al., 2021; Zhao, Yumiao, et al., 2021; Zhan, Yan, et al., 2021; Zangrillo, Alberto, et al., 2022), specifically after a meta-analysis that focused on a 90-day follow-up period (So, Matsuo, et al., 2021). Identifying persistent morbidity or disability in individuals with severe COVID-19 throughout follow-up is typically straightforward using pulmonary function tests and/or imaging. Nevertheless, evaluating the progression of CT abnormalities has proven to be difficult because of the absence of numerous subsequent examinations and the varying degrees of severity. Some studies have included both asymptomatic patients and those who needed mechanical ventilation, thus complicating the analysis (Watanabe, Atsuyuki, et al., 2022).  The long-term alterations in chest CT scans have been extensively assessed in patients who originally experienced a severe infection necessitating hospitalization and, in certain instances, intensive care intervention. (Pan, Feng, et al., 2022; Solomon, Joshua, et al., 2021; Martini, et al., 2021) After the acute infection, 61% of patients had their chest CT abnormalities resolved within 3 months, and 75% of patients had them resolved within 12 months (Pan, Feng, et al., 2022). Patients who still have anomalies may see a decrease in their diffusing capacity (Lerum, Tøri Vigeland, et al., 2021). In exceptional cases, prolonged lung injury might lead to irreversible fibrotic alterations (Malesevic, Stefan, et al., 2023). In the study by Zhao, Yu-miao, et al., (2020) reported that people who have fully recovered from a severe virus infection may experience long-term lung damage and pulmonary function impairment after 3 months of discharge. Patients with abnormal high-resolution chest CT (HRCT) imaging of the Lungs generally had a higher age compared to those with normal chest HRCT scores, indicating that older patients typically had higher chest radiological scores (Das, Karuna, et al., 2017). Patients in the abnormal CT group had a prolonged incubation period and a higher CXR peak score compared to those in the normal CT group. This suggests that patients who had remaining abnormalities in their chest radiology after being discharged experienced more severe side effects (Zhao, Yu-miao, et al., 2020). A study conducted on deceased COVID-19 patients revealed that the examination of lung tissue revealed significant changes at a microscopic level, such as the collapse of air sacs and the development of fibrous tissue (Ochs, Matthias, et al., 2021; Bharat, Ankit, et al., 2020). Furthermore, single-cell RNA sequencing revealed similarities in gene expression between idiopathic pulmonary fibrosis and COVID-19 in the explanted lungs of patients undergoing lung transplantations or postmortem analysis. This includes the presence of Keratin-17-expressing epithelial cells, profibrotic macrophages, and myofibroblasts (Bharat, Ankit, et al., 2020). Therefore, examining CT scans during the early stages could potentially provide valuable insights into the prognosis of patients.  Most of the patients in this study were male (62%), aged between 26 and 50 years (66.67%), and those had at least a pre-existing comorbidity (68%). These results were similar to others by Yin, Xi, et al., (2021) who reported that most COVID-19 patients with dyspnea were elderly males. Prior research on SARS has indicated that males and older patients who have survived the disease are more prone to developing fibrosis. In the past, a significant number of patients who were in the early stage of rehabilitation after recovering from SARS reported experiencing restrictions in their overall physical abilities and/or difficulty breathing (Chan, et al., 2003). Collectively, while individuals who have recuperated from COVID-19 have been observed to exhibit radiological, functional, and psychological irregularities to different extents, they experienced moderate to severe hindrances in carrying out household chores or regular employment. Therefore, it is crucial to provide continued care and monitoring for these patients (Zhao, Yu-miao, et al., 2020). Likewise, the analysis by Yin, Xi, et al., (2021) reveals that survivors experiencing dyspnea exhibit a higher presence of reticulations, which may be the underlying reason for their breathing difficulties (Antonio, Gregory E., et al., 2003). A previous study found that 83% of patients showed radiological abnormalities within 7 days of being admitted (Xiong, Ying, et al., 2020; Han, Xiaoyu, et al., 2020b), indicating that radiological abnormalities produced by SARS-CoV-2 may improve as time progresses. Additionally, scientists found that survivors of other viral pneumonias, such as SARS, H1N1, and H7N9, also experienced a similar rate of residual radiographic alterations (Ng, et al., 2004; Mineo, Giangaspare, et al., 2012; Wang, Qingle, et al., 2013). The second iteration of SARS-CoV differs from the previous iteration by 380 amino acids. This means that five of the six essential amino acids in the part of the viral spike protein (S) that binds to the receptor are different from those in ACE2 (Wu, Aiping, et al., 2020). SARS-CoV-2 demonstrates a higher affinity for ACE2 compared to SARS-CoV-1, resulting in increased ease of transmission. This could elucidate the reason for the significantly greater impact of COVID-19 on the global scale compared to the initial outbreak of SARS (Gheblawi, Mahmoud, et al., 2020). COVID-19 may not be comparable to other diseases due to its distinct and unique characteristics. Only 41.33% of the patients in this study had abnormal chest CT scan findings, they distributed as unilateral and bilateral findings (16.67% and 24.67%, respectively). Only 17.33% of patients had interlobular septal thinning; 21.33% had ground glass opacities (GGO); 12.67% had fibrotic-like changes; 7.33% had reticulation; 4% had consolidation; 3.33% had pleural effusion; 2% had honeycombing; 4% had emphysema; and 4% had bronchiectasis. A recent systematic study has shown that the histological results of diffuse alveolar damage caused by COVID-19 cannot be distinguished from those caused by other factors. Ultimately, a chronic/fibrotic phase was observed, characterized by the presence of a honeycomb lung with collagen fibrosis in the alveolar gaps and interstitium. Additionally, there was a thickening of the alveolar wall and squamous metaplasia of the alveoli (Satturwar, Swati, et al., 2021). These alterations have been documented in 43% of 30 COVID-19 corpses and were linked to a prolonged period of sickness and hospitalization, as well as the requirement for mechanical ventilation (Li, Yan, et al., 2021). Based on a prior report by Hui, et al., (2005), 33 patients (30%) exhibited aberrant CT findings, while 17 patients (15.5%) experienced impaired DLCO six months after recovering from SARS. David et al., analyzed 97 patients who had recovered from SARS. They discovered that even after 1 year, there were still aberrant CT results and DLCO anomalies present (Hui, David, et al., 2005). The results of our research align with earlier studies which indicate that dry cough and shortness of breath are the prevailing lingering symptoms experienced by individuals who have recovered from COVID-19 (Logue, Jennifer, et al., 2021; Havervall, Sebastian, et al., 2021; Morin, Luc, et al., 2021; Townsend, Liam, et al., 2021; Davis, Hannah, et al., 2021; Smet, Jelle, et al., 2021; Daher, Ayham, et al., 2020; Trinkmann, Frederik, et al., 2021; Huang, Chaolin, et al., 2023; Abdallah, Sara, et al., 2021). Recurrent symptoms are highly prevalent, especially among patients with minor acute illness. The bulk of COVID-19-infected patients belong to this group, with a significant proportion being outpatients (Darawshy, Fares, et al., 2022). Abdallah et al. found that 81.6% of non-hospitalized COVID-19 survivors experienced ongoing fatigue and dyspnea after physical activity. However, their lung function and performance on cardiopulmonary exercise tests were not affected (Abdallah, Sara, et al., 2021). Logue et al. found that 65.3% of 150 outpatients with moderate illness experienced chronic symptoms (Logue, Jennifer, et al., 2021). Other studies have reported comparable results (Havervall, Sebastian, et al., 2021; Townsend, Liam, et al., 2021; Davis, Hannah, et al., 2021; Trinkmann, Frederik, et al., 2021). Another study by Yin, Xi, et al., (2021) demonstrated that around 50% of the reticulations identified on CT scans upon discharge, suggesting that not all reticulations appropriately indicate fibrosis. That difference might be because some abnormalities are easy to hide, leaving only reticulations visible. On the other hand, for some COVID-19 patients who have survived, reticulations may show that their lesions are in their later stages. Prior investigations with limited duration have indicated that reticulations are a sign of fibrosis (Liu, Ruxiu, et al., 2020; Liang, Ting, et al., 2020; Zhou, Yongxia, et al., 2020). This finding aligns with the long-term follow-up findings in patients with severe acute respiratory syndrome (SARS) (Antonio, Gregory E., et al., 2003; Hsu, Hsian-He, et al., 2004). A separate investigation conducted by Darawshy, Fares, et al., (2022) revealed that individuals who have survived COVID-19 experience ongoing impairment in their overall well-being and persistent symptoms, specifically including difficulty breathing and exhaustion, for 3 months following the first onset of the disease. Persistent symptoms are present irrespective of the initial severity of the disease. Individuals who initially experience a severe case of COVID-19 exhibit more significant deterioration in lung function and a higher occurrence of aberrant imaging results after 12 weeks, in comparison to individuals with mild or moderate cases of the illness (Darawshy, Fares, et al., 2022).  In this study, bronchiectasis were shown in only 4% of the patients. Another study by Yin, Xi, et al., (2021) demonstrated that the survivors experienced bronchiolectasis both during the peak period and at the time of discharge was around 25% and fell significantly to roughly 12.5% over the follow-up period. A minority of patients exhibited pleural effusion and increased mediastinal lymph nodes, following prior findings (Chung, Michael, et al., 2020). The rate of subpleural distribution and the rate of residual lesion showed a significant drop after 6 months compared to the first 6 months after discharge in the study by Yin, Xi, et al., (2021). Furthermore, it was shown that 30% of the individuals who survived displayed GGOs on CT images for a period exceeding 6 months after being discharged. The observed outcomes could be attributed to the fact that individuals who experience shortness of breath had larger lesions that are not fully resolved upon discharge and follow-up. This indicates that these abnormalities may persist and gradually diminish over time. In the study cohort conducted by Tarraso, Julia, et al., (2022), it was shown that 27% of patients continued to have radiological abnormalities at the 12-month. Pan et al. achieved a comparable proportion of 53 out of 209 cases (Pan, Feng, et al., 2022), whereas Wu et al. recently reported a slightly higher rate of 24%, after eliminating patients receiving invasive mechanical ventilation from their study group (Wu, Xiaojun, et al., 2021). Fibrotic-like alterations are characterized by the presence of traction bronchiectasis, parenchymal bands, and/or reticular patterns (Antonio, Gregory, et al., 2003; Martínez-Jiménez, et al., 2017) In this study, fibrotic-like alterations were shown in 12.67% of the patients. This result was lower than others by Tarraso, Julia, et al., (2022), Fabbri, Laura, et al., (2023), and Watanabe, Atsuyuki, et al., (2022) which they reported was 23%, 21%, and 29% respectively. Another study by Han et al. found that 114 patients had radiological changes after being discharged, with just four of them having needed invasive mechanical ventilation (Han, Xiaoyu, et al., 2021a). Mechanical ventilation is an acknowledged contributor to the development of fibrosis (Cabrera-Benitez, Nuria, et al., 2014), which is triggered by mechanical strain and an induced inflammatory response known as "biotrauma." This reaction involves the production of cytokines, chemokines, and growth factors. However, excluding the consideration of mechanical ventilation, the evaluation of fibrotic consequences following COVID-19 infections could uncover alterations that are directly caused by the virus. According to a recent study, 4.8% of patients with moderate symptoms developed inflammatory interstitial lung disease after 3 months (Myall, Katherine Jane, et al., 2021). Biomedical research suggests that viral infection in the lung can lead to fibrosis through many pathways. As previously stated, the increased levels of fibrogenesis-related biomarkers observed in these individuals suggest that bilateral COVID-19 pneumonia can activate specific biological pathways (Safont, Belen, et al., 2022). The SARS-CoV-2 infection damages the alveolar epithelium and triggers the release of cytokines. Macrophages are drawn to this, causing harm to the basement membrane, and triggering the activation of fibroblasts. Moreover, hemorrhage caused by endothelial injury triggers a series of reactions in the coagulation system that ultimately leads to the formation of fibrin. These factors collectively lead to fibrosis of the alveolar space (John, Alison, et al., 2021). The results of our research were inconsistent with prior studies that indicate there is no correlation between the severity of the initial COVID-19 infection and the presence of chronic symptoms and poor health (Havervall, Sebastian, et al., 2021; Townsend, Liam, et al., 2021). The precise cause of residual symptoms is not completely understood; however, it is believed that chronic inflammation, immune- mediated vascular dysfunction, and thromboembolism are significant contributing factors (Myall, Katherine Jane, et al., 2021). In their study by Havervall, Sebastian, et al., (2021) found that 26% of participants who tested positive for anti-spike IgG antibodies experienced moderate-to-severe symptoms lasting for a minimum of 2 months, compared to just 9% of participants who tested negative for these antibodies. These data indicate that the presence of positive anti-spike IgG antibodies may contribute to the persistence of symptoms.  Zhou et al. evaluated the long-term consequences of 120 individuals, who generally had mild cases of COVID-19, 12 months after their initial infection. Among the non-severe cases, 56.6% of the 83 chest CTs conducted at the 12-month follow-up revealed abnormal findings. These abnormalities included 13.3% GGOs and 16.9% fibrotic-like alterations. While the majority of mild to severe instances did not have persistent symptoms, our study sample with continued post-COVID-19 symptoms had a slightly higher prevalence of GGOs (20% compared to 13.3%). The incidence of fibrosis-like patterns (16.9%) was marginally higher than the 12.67% prevalence of fibrotic-like alterations observed in our population (Zhou, Zhiming, et al., 2020). Furthermore, research involving individuals with severe COVID-19 has indicated that parenchymal abnormalities are likely to resolve within 12 months following recovery (Martini, et al., 2021). Mosaic attenuation is an ambiguous observation that can be linked to conditions affecting the tiny airways, circulatory system, or lung tissue. Frequently, it occurs due to the entrapment of air in certain areas of the lungs upon exhalation. Still, mosaic attenuation and air trapping can be seen in people whose lung function tests are normal, so they do not always mean that something is wrong (Hashimoto, et al., 2006). According to a prior investigation, 21% of chest CT scans of healthy adults (with a median age of 44 years and 64% being female) exhibited mosaic lung attenuation (Pan, Feng, et al., 2022). Because of this, it is important to tell the difference between substantial mosaic attenuation and minor physiological differences in attenuation that affect less than four secondary pulmonary lobules, since people with asthma and healthy people have both seen this appearance around the same number of times (Park, Chan Sup, et al., 1997). Consistent with prior research, the meta-analysis by Watanabe, Atsuyuki, et al., (2022) assessed the presence of CT abnormalities in patients who had recovered from COVID-19, both at 12 months follow-up and across time, and they determined that the occurrence of CT abnormalities remains elevated one year after infection, particularly among patients with severe or critical conditions, indicating the presence of fibrotic alterations. Moreover, the decrease in the diffusing capacity of the lungs for carbon monoxide (DLCO) continued even after 1 year following COVID-19, indicating the presence of fibrotic alterations. They found that although patients showed a gradual recovery over time, many of them still had CT abnormalities that remained at the 1-year follow-up. They showed fibrotic-like alterations, interstitial septal thickening, and bronchiectasis. These findings may suggest the development of pulmonary fibrosis following COVID-19 (Pan, Feng, et al., 2022; Han, Xiaoyu, et al., 2021a; Chen, Yanfei, et al., 2021; Chen, Yanfei, et al., 2021; Xie, Lixin, et al., 2005; Nöbauer-Huhmann, Antonio, Gregory E., et al., 2003; Iris-M., et al., 2001). The severity of the condition appeared to have an impact on the scope of the CT findings (Chen, Yanfei, et al., 2021; Gamberini, Lorenzo, et al., 2021). A comprehensive review and meta-analysis incorporated seven studies, including a total of 231 individuals who were diagnosed with COVID-19 but did not exhibit any symptoms during the initial phase of the infection. The average number of positive chest CT abnormalities in people with an infection who did not have any symptoms was 62% (Vafea, Tsikala, et al., 2020). These abnormalities included ground-glass opacities (GGO), stripe shadows, and interlobular septal thickening. Another study by Malesevic, Stefan, et al., (2023) reported that although more than half of the patients showed findings on imaging that might be attributed to post- COVID-19 features, the majority of chest CT findings were only subtle and discrete, mostly in the subpleural parts of the lung, and the reported respiratory symptoms were not related to the chest CT abnormalities. The presence of SARS-CoV-2 infection did not have a direct impact on the chest CT scan results. Additionally, there was no correlation between the chest CT findings, lung function testing, and the persistence of respiratory symptoms such as difficulty breathing, cough, and chest pain. These findings endorse the careful examination of CT imaging in individuals experiencing persistent symptoms after a mild or moderate COVID-19 infection while having normal lung function testing and oxygen saturation levels. In another study by Uysal et al., 64 asymptomatic COVID-19 patients underwent examination during the acute phase of infection. The participants had a mean age of 59.6±12.3 years, with 65% being female. Despite having no aberrant clinical or laboratory findings, 75% of the COVID-19 patients had lung involvement. GGOs were the predominant observation in 63% of the subjects (Uysal, Emine, et al., 2021). In addition, chest CT scans conducted on individuals who were recuperating from the SARS-CoV-1 pandemic in 2003 revealed the presence of persistent GGO and reticular opacities, together with mild traction bronchiectasis. These findings resembled fibrotic-like alterations in the lung (Ketai, et al., 2006). Another study by Darawshy, Fares, et al., (2022) indicates that most patients with lingering pulmonary injury after COVID-19 exhibited signs of inflammatory lung illness, such as organizing pneumonia or GGO, as shown on CT scans. Another study by Malesevic, Stefan, et al., (2023) found that 39.6% of the patients had distinct mosaic attenuation without any significant radiologic distribution. However, they cannot determine whether the lung abnormalities are a result of the SARS-CoV-2 infection or pre-existing diseases because of the absence of pre-infection chest CT scans, as in our study. As a result, conducting additional radiological examinations on these patients appears superfluous, morally questionable due to the risks associated with radiation exposure, and not cost-effective. While further validation in a larger, prospective trial is necessary, the outcomes of our investigation appear to have significant clinical consequences and should guide healthcare professionals in monitoring post-COVID-19 individuals following a mild or moderate acute infection. Furthermore, we believe that this favorable pattern is also present in less severe cases, as the progression of a serious infection typically results in the resolution of tissue alterations within a span of 12 months (Pan, Feng, et al., 2022). We suggest that chest CTs should only be used when there are clear signs during a clinical exam, such as low oxygen levels in the blood (hypoxemia) or signs of obstructive or restrictive lung disease from lung function tests, or when other doctors ask for more imaging. There was a link between having pulmonary restriction and the amount of lung parenchymal involvement seen on CT scans in people with acute COVID-19 in the study by Steinbeis, Fridolin, et al., (2022). This correlation indicates the presence of inflammation and fibrotic changes resulting from SARS-CoV-2 infection. There is growing evidence that SARS-CoV-2 infection leads to the development of a profibrotic phenotype, which is consistent with other viral causes of pneumonia-like SARS, MERS, and influenza infections. A study on SARS-CoV-1 revealed that 30% of survivors had abnormal chest radiographs during the 6-month follow-up (Hui, et al., 2005). The study also found a significant occurrence (62%) of pulmonary fibrosis, which is worth mentioning (Antonio, Gregory E., et al., 2003). A research team conducted a preliminary investigation using hyperpolarized Xenon MRIs on 11 nonhospitalized patients who were experiencing chronic difficulty breathing but had normal chest CT scans. The results of these patients were then compared to those of 12 COVID-19 patients who were admitted to the hospital. Similar changes in both groups' MRI images raised the possibility that the COVID-19 infection's persistent microstructural abnormalities were to blame for these differences (Grist, James, et al., 2022). A total of 63.33% of the patients in this study had dyspnea during the follow-up period; this finding is compared to another by Yin, Xi, et al., (2021), which found that 27.00% of the survivors experienced dyspnea. This rate is slightly lower than the one- third rate observed in patients with severe acute respiratory syndrome (SARS), but similar to the findings of pulmonary function tests in COVID-19 survivors at 3 months after discharge, which showed that 25.4% of patients had residual pulmonary function abnormalities (Zhao, Yu-miao, et al., 2020; Chan, et al., 2003). It is possible that the ongoing symptoms in our group of individuals who have recovered from COVID-19 could be attributed to lung abnormalities that are visible on chest CT scans. It is worth considering alternative radiological techniques that may be able to identify these significant illnesses. In addition, it is important to consider that there may be other functional impairments that were not investigated in this study, that could potentially be responsible for the ongoing symptoms. To determine the underlying reasons for persistent symptoms, it is necessary to evaluate factors other than structural abnormalities in the lungs. This is because respiratory symptoms like coughing, chest pain, and difficulty breathing are non-specific and can be due to a variety of causes, including cardiac and psychological conditions. The study by Tarraso, Julia, et al., (2022) examined the long-term effects on lung function and radiological findings of 448 hospitalized patients with bilateral COVID-19 pneumonia of varying severity 12 months after discharge. They indicate that nearly 40% of patients still had reduced lung diffusion (DLCO < 80%) one year after recovering from acute COVID-19 infection. In addition, they observed radiological fibrotic-like alterations on chest CT scans in about 23% of the patients. Nevertheless, these consequences were not linked to other indicators of seriousness that have been previously identified in cases of acute respiratory distress syndrome (ARDS), such as the requirement for mechanical ventilation. Subsequent research on individuals with Middle East respiratory syndrome (MERS) revealed that 33% of those with severe symptoms exhibited lung fibrosis, characterized by reticulation and linear opacities grouped in a mesh-like pattern. (Das, Karuna, et al., 2017). Furthermore, research on SARS and MERS has highlighted older age as a possible risk factor for developing pulmonary fibrosis in the future (Das, Karuna, et al., 2017; Antonio, Gregory, et al., 2003). Possible risk factors for fibrotic alterations and their severity concerning COVID-19 include advanced age, diabetes, obesity, lymphopenia, higher levels of D-dimer, C-reactive protein, and lactate dehydrogenase (Pan, Feng, et al., 2022; Shang, Luorui, et al., 2021; Zhao, Yumiao, et al., 2021; Li, Yumin, et al., 2021; Han, Xiaoyu, et al., 2021a; Liao, Tingting, et al., 2022). The COVID-19 virus affects a sizable number of people, and the fibrotic signs seen may indicate irreversible lung injury (Nöbauer-Huhmann, Iris-M., et al., 2001; Antonio, Gregory E., et al., 2003). Therefore, although there is a debate on whether mechanical ventilation can lead to barotrauma and subsequent iatrogenic fibrosis following acute respiratory distress syndrome, the presence of fibrotic signals on CT scans should not be disregarded. Gaining knowledge about the effects and circumstances that increase the likelihood of developing pulmonary fibrosis following COVID-19 pneumonia is crucial. This understanding can help us implement preventive treatments, such as antifibrotic therapy, in patients who are suitable candidates. By doing so, we can decrease the overall impact of the repercussions of COVID-19 worldwide (George, et al., 2020).  There were certain limitations in our investigation. At the time of the acute SARS-CoV-2 infection or before it, none of our patients underwent a chest CT scan. Therefore, it is unclear whether the COVID-19 infections caused the observed alterations in the imaging or if they were present before the infection. Even so, there were connections between chest CT results and respiratory symptoms that developed after the SARS-CoV-2 infection. Therefore, the existence of a previous chest CT is significant based on our research question. And so, the sample size may have been insufficient to demonstrate statistical significance, necessitating the need for validation through larger, multicenter research. 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