Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : January | Volume : 16 | Issue : 1 | Page : EC05 - EC09 Full Version

High Resolution Computed Tomography Findings of Pulmonary Fibrosis in COVID-19 Survivors and its Association with Inflammatory Markers- A Retrospective Study


Published: January 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/51211.15874
Tarang Patel , Virendrakumar Meena , Swati JIndal , Anjana Verma , Ashish Sharma , Rishi Sharma

1. Assistant Professor, Department of Pathology, All India Institute of Medical Sciences, Rajkot, Gujarat, India. 2. Assistant Professor, Department of Radiology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India. 3. Assistant Professor, Department of Pathology, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India. 4. Associate Professor, Department of Community Medicine, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India. 5. Professor, Department of Biochemistry, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India. 6. Professor, Department of Respiratory Medicine, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India.

Correspondence Address :
Dr. Tarang Patel,
Assistant Professor, Department of Pathology, All India Institute of Medical Sciences,
Temporary Campus, Civil Hospital, Rajkot-360001, Gujarat, India.
E-mail: tarangpatelmddnb@outlook.com

Abstract

Introduction: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection enters human body through respiratory tract and then rapidly spread to involve lungs and multiply swiftly leading to severe hypoxic pneumonia. Clinically, Coronavirus Disease-2019 (COVID-19) infection is identified by three stages based on viral infection, lung involvement with inflammation and pulmonary fibrosis. High resolution Computed Tomography (HRCT) lung play an important role in diagnosis and management of lung fibrosis in coronavirus disease patients.

Aim: To study association between inflammatory markers and development of lung fibrosis in post COVID-19 patients. Study also aimed at assessment of chest Computed Tomography (CT) Involvement Score (CT-IS) and COVID-19 Reporting and Data System (CO-RADS) for chest CT in post COVID patients presented with lung fibrosis.

Materials and Methods: This retrospective study included elaborate evaluation of HRCT findings and inflammatory markers of 54 patients presented with pulmonary fibrosis at tertiary care centre for duration of six months from 1st June to 30th November 2020. Only those patients were included in which both HRCT findings and clinical laboratory parameters were available. Interleukin-6 (IL-6), C-Reactive Protein (CRP), serum ferritin, Lactate Dehydrogenase (LDH), Erythrocyte Sedimentation Rate (ESR) and Procalcitonin (PCT) markers were studied. Statistical analysis was conducted using Chi-square test to compare the inflammatory markers with CT-IS score with p-value <0.05 was considered significant.

Results: Total 536 COVID positive patients were admitted in hospital and underwent HRCT lung from June 2020 to November 2020. Out of 536, 54 (10.07%) patients showed findings of lung fibrosis on follow-up CT scan. Among 54 patients with lung fibrosis, CRP, serum ferritin and IL-6 levels were high in 46 (85.19%), 42 (77.77%) and 48 (88.89%) patients respectively. Lactate dehydrogenase, ESR and PCT were increased in 12 (22.22%), 15 (27.78%) and 06 (11.11%) patients respectively. These levels were higher in fibrotic phase compared to prefibrotic phase. Erythrocyte sedimentation rate was significantly associated with the severity of lung fibrosis, having significant p-value=0.004.

Conclusion: Among all inflammatory markers, ESR value may be useful as a surrogate marker to predict the pulmonary fibrosis in COVID-19 patients. C-reactive protein, IL-6, LDH, serum ferritin and PCT levels do not show significant association with lung fibrosis on HRCT scan.

Keywords

Acute respiratory syndrome, Coronavirus disease 2019, C-reactive protein, Ferritin, Ground-glass opacity, Inflammatory biomarkers, Interleukin-6

Coronavirus Disease-2019 (COVID-19) is a pandemic that started in 2019. It is an acute respiratory illness caused by a novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The disease was first identified in Wuhan city of Hubei Province, China and then spread to other provinces of China. From China it outspread globally to involve countries all over the world (1). Millions of people have been infected by this virus throughout the world. The SARS-COV-2 is the seventh member of viruses, which are known to cause human respiratory tract infections. Four of these pathogenic viruses cause mild infections of upper respiratory tract, whereas three coronaviruses cause lower respiratory tract infections and also responsible for lung complications (2).

At the time of writing this article, globally infected cases are 55,946,862 with 13,44,557 global deaths and overall case fatality rate 2.40% (3). SARS-CoV-2 swiftly spread throughout the world in 2002. The SARS-CoV-2 has been more infective than SARS-CoV, showing doubling time of 2.3-3.3 days and basic reproductive number (R0) of 5.7 (4). The Angiotensin Converting Enzyme 2 (ACE 2) is receptor for the SARS-CoV-2 plays a crucial role in human infections (5). Drugs increasing the ACE2 expression may enhance the infection, such as Angiotensin-Converting Enzyme Inhibitors (ACEI) and Angiotensin II Receptor Blockers (ARB) (6). Smoking could be a risk factor for SARS-CoV-2 because it can enhance ACE2 expression (7).

Both innate and adaptive immunity play a pivotal role to fight against COVID-19 infection (8). One theory suggest that severe COVID-19 progression could be due to insufficient adaptive immunity and imprudent innate immunity response leading to increased proinflammatory cytokines and chemokines (9),(10). Varied inflammatory markers such as C-Reactive Protein (CRP), Interleukin-6 (IL-6), serum ferritin and Procalcitonin (PCT) have been reported to be remarkably associated with the escalating risks of severe COVID-19 progression (11),(12). Initial studies indicated vascular aetiology induced by activation of proinflammatory cytokines and complement pathway, is accountable for underlying organ damage in seriously sick COVID-19 patients (13),(14).

High resolution Computed Tomography (HRCT) lung plays a pivotal role in the diagnosis and treatment of COVID-19 pneumonia (15). Some studies demonstrated the varied HRCT findings, with the prime features being ground-glass opacities and pulmonary consolidation (16),(17). COVID-19 Reporting and Data System (CO-RADS) is an assessment system based on chest Computed Tomography (CT) and used to evaluate suspicion for lung involvement by COVID-19. The CO-RADS was introduced by Dutch Radiological Society (18). Study of clinical, radiological and autopsy findings in COVID-19 patients suggest lung fibrosis being a common occurrence following infection, and current evidence suggests that lung fibrosis might complicate the SARS-CoV-2 infection (19).

It is the need of hour to identify important inflammatory biomarkers which may be helpful in identifying patients in early clinical stage and proper clinical management may be provided to decrease the likelihood of clinical deterioration. The aim of this study was to analyse HRCT lung findings in COVID-19 patients with attention on development of pulmonary fibrosis and recognising those biomarkers with the help of understanding of progression of CT findings.

Material and Methods

This retrospective study of COVID-19 cases, showing pulmonary fibrosis on HRCT scan (admitted between 1st June 2020 to 30th November 2020) was conducted in month of February 2021 at Geetanjali Medical College and Hospital, Udaipur, a tertiary care centre in Udaipur, Rajasthan, India. A total of 536 COVID patients were admitted during the study period and were confirmed cases with at least one positive Reverse Transcription Polymerase Chain Reaction (RT-PCR) report. Out of 536 cases, 54 patients (10.07%) had fibrosis on HRCT scan. The laboratory reports of these patients were retrieved from their medical records and analysed. Inflammatory biomarkers utilised in this study were IL-6, CRP, serum ferritin, Lactate Dehydrogenase (LDH), Erythrocyte Sedimentation Rate (ESR) and PCT. Measurements during lung fibrosis on scan were compared with prefibrotic measurements of inflammatory markers.

Ethical Committee approval was obtained (no.1949) dated 01-02-2021. All data was anonymised before the analyses. No informed consent was required due to the characteristics of the design.

Inclusion criteria

1. Patients with at least one positive RT-PCR for SARS-CoV-2.
2. Patients admitted at our hospital who had undergone testing for inflammatory markers and CT scan findings.
3. Patients who developed lung fibrosis on subsequent follow-up radiology.

Exclusion criteria: Patients with negative RT-PCR for SARS-CoV-2 or patients without follow-up CT scan findings or patients with incomplete investigation profile were excluded from the study.

CT Scan Protocol

The HRCT chest was done on 64 slice CT scanner (Siemens Somatom sensation, Germany) in supine position by using standard HRCT protocol. The scans were obtained by utilising 120 kvp and final images were reconstructed in axial, sagittal and in coronal sections. Scans were performed for both prefibrotic and fibrotic stages.

Prefibrotic phase is characterised by ground-glass opacity and consolidation patches, whereas fibrotic phase is defined by reticular opacities, fibrotic strands and traction bronchiectasis. Prefibrotic phase was considered for 0-4 days from clinical onset and fibrotic phase was considered for 7-10 days after onset of symptoms (15).

COVID-19 Reporting and Data System (CO-RADS)

• CO-RADS 0 imply incomplete scan or insufficient quantity.
• CO-RADS 1 and CO-RADS 2 implies chosen in case of very low level and low level of suspicion for COVID-19 infection respectively.
• CO-RADS 3 implies in case of equivocal findings of lung involvement by COVID-19.
• CO-RADS 4 and 5 correspond to high level and very high level of suspicion.
• CO-RADS 6 is given in case of positive COVID-19 case confirmed by RT-PCR test (18).

All the patients were categorised according to Computed Tomography- Involvement Score (CT-IS) developed by Chung M et al., (20). CT-IS was calculated using number of involved lung lobes and percentage of involvement (18),(20).

Statistical Analysis

Data were analysed using Statistical Package for the Social Sciences version 16.0 (IBM Corp. Released 2012, IBM SPSS statistics for Windows, Armonk, NY). Quantitative variables were presented as mean values. Frequency distribution was done for categorical variables and determined as proportions. Chi-square test or Fisher’s-exact test was used to compare the laboratory parameters with CT-IS on CT scan. The p-value <0.05 was considered as significant.

Results

Total 536 patients were confirmed as COVID-19 positive by RT-PCR test and had undergone HRCT scan procedure. Out of 536 patients, 54 patients developed pulmonary fibrosis on follow-up CT scan findings (Table/Fig 1),(Table/Fig 2).

Inflammatory biomarkers were studied in 54 patients of lung fibrosis. CRP, Ferritin and IL-6 levels were high in 46 (85.18%), 42 (77.78%) and 48 (88.89%) patients out of 54 patients. LDH, ESR and PCT were increased in 12 (22.22%), 15 (27.78%) and 6 (11.11%) patients out of 54 patients (Table/Fig 3).

The CT-IS was associated with laboratory parameters. Evaluation of the inflammatory markers in severe category (severe CT-IS) patients revealed that 94.2% patients had raised IL-6 levels, 82.9% had raised CRP levels, 77% had raised Ferritin levels, 14.3% had raised ESR levels, 11.4% had raised PCT levels and 17.1% had raised LDH levels. About 80% of patients with moderate CT-IS, showed raised IL-6 levels, 73.3% had raised Ferritin levels, 60% had raised ESR levels, 13.3% had raised PCT levels and 33.3% had raised LDH levels. All patients with moderate CT-IS had raised CRP levels. Amongst all the inflammatory markers, only ESR value was found to be significantly associated with CT-IS, with p-value of 0.004 (Table/Fig 3).

Out of 54 patients of lung fibrosis, 42 (77.78%) patients had bilateral lung lesions on HRCT lung. Bilateral lower lobes were the most common site to be involved, followed by upper lobes and middle lobes. Peripheral region or sub pleural ground glass opacities were the most common form of lesion distribution on HRCT scan in prefibrotic stage. Reticular opacities, parenchymal bands and traction bronchiectasis findings are seen in lung parenchyma of post COVID fibrosis patients. Initial changes of pulmonary ground glass opacities were present at 0-4 days from clinical onset. Maximum involvement of lung on CT was seen at 7-10 days from symptoms onset (Table/Fig 4),(Table/Fig 5),(Table/Fig 6),(Table/Fig 7).

Discussion

The COVID-19 pandemic, caused by SARS-CoV-2, is rapidly expanding throughout the world. Albeit it is widely known that most cases have mild symptoms with a good prognosis, COVID-19 disease may develop into Acute Respiratory Distress Syndrome (ARDS) or may culminate in death. Till date, there is no efficacious treatment for COVID-19 (21),(22). Several studies have demonstrated increased serum levels of proinflammatory cytokines in COVID-19 patients. Even, anti-inflammatory reagents therapy among COVID-19 patients also focusses on the scathing role of inflammation in the progressive pathogenesis of COVID-19 (23),(24).

In the present study, all the patients were categorised according to CT-IS score (20). CT-IS was assessed using each of the five lobes of the lung (three right lobes and two left lobes) and percentages of involvement. Lobe score 1 equals to less than 5% involvement, Lobe score 2 equals to 5-25% involvement, Lobe score 3 equals to 26-49% involvement, Lobe score 4 equals to 50-75% involvement and Lobe score 5 equals to 76-100% involvement (20). Whereas, CO-RADS system is used to categorised patients radiologically, depending upon degree of suspicion for COVID-19 lung involvement. CO-RADS system has a significant role in COVID-19 pneumonia diagnosis (18). As per the classification, patients with very high suspicion for COVID-19 are categorised into CO-RADS 5. In our study, we included only COVID-19 positive patients confirmed by RT-PCR test, corresponding to CO-RADS 6 category.

Nevertheless, the role of inflammatory markers in monitoring the severity of COVID-19 is still questionable. In our study, we concluded that among inflammatory markers, only ESR was positively associated with the severity of COVID-19. Interleukin 6 has been also implicated in the H5N1 avian influenza infections and 2003 SARS outbreak (25),(26). Recent study unveiled that in COVID-19 patients, activated T-cells may secrete IL-6 and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF). Also, GM-CSF could activate monocytes (CD14 and 16 positive), which would further enhance secretion of IL-6 and other proinflammatory cytokines (27).

C-reactive protein is a crucial systemic marker of acute-phase response, which is very sensitive in tissue inflammation, tissue damage and infections. So, it can be used as a benchmark of systemic inflammation in COVID-19 patients (28). However, Chen L et al., did not reveal any statistically significant difference in CRP levels between the severe and the non severe group, the mean CRP level was higher in the severe group compared to the non severe group (29). PCT is also an important inflammatory marker measured in routine clinical practice. Chang Z et al., reported that, levels of PCT were all higher in the critical patients in comparison to the non critical group (30). Erythrocyte sedimentation rate is another non specific inflammatory marker. Essentially, it reflects the changes of plasma protein types. Zeng F et al., in their study, found a higher ESR level in the severe group compared to the non severe group (p-value=0.005). Exuberant inflammation in severe group patients could be the reason for the above results (27). Zeng F et al., also found higher levels serum ferritin in the severe group of corona patients than those in the non severe group (p-value <0.001) (27).

The present study revealed that almost all inflammatory markers were raised in patients showing fibrotic changes in HRCT lung. Inflammatory markers were predominantly increased in patients in the moderate and severe category namely IL-6 (80% and 94.2%), CRP (100% and 82.9%), ESR (60% and 14.3%), PCT (13.3% and 11.4%) and LDH (33.3% and 17.1%), respectively. This finding is similar to the results shown in a study done by Bhandari S et al., which revealed that inflammatory markers CRP, LDH, ferritin and PCT were elevated in the severely ill patients (31). The radiological findings of COVID-19 patients on HRCT lung reflected typical features of viral pneumonia, and it was characterised by a rapid change similar to that in middle-east respiratory syndrome and severe acute respiratory syndrome (32),(33)],(34). Present study shows that utmost pulmonary findings on HRCT scan were found around 7-14 days from onset of symptoms. Results were comparable to studies by Wang Y et al., and Pan F et al., (15),(35).

Follow-up studies using HRCT scans in COVID-19 patients showed fibrotic changes. Zhou S et al., revealed that fibrotic changes were seen in 21 patients (33.9%) out of total 62 patients. Moreover, his study also concluded that fibrotic changes were more likely to take place in late phase of corona disease (8-15 days after symptoms onset) than early phase of the disease (<8 days after the symptoms onset) (36). Likewise, study by Pan Y et al., showed fibrotic changes in 11 out of 63 patients on HRCT lung performed on COVID-19 confirmed patients. (16). These HRCT lung findings are reinforced further by autopsy reports. One study reported that four patients who died of COVID-19 pneumonia revealed microscopic picture of diffuse alveolar damage along with consolidation by fibroblast proliferation. ECM and fibrin deposition in the alveolar spaces was seen in postmortem core biopsy (37). Nevertheless, it is precocious in the course of the disease to figure out if this finding would undergo resolution or in the course of time or may develop pulmonary fibrosis (38).

Limitation(s)

Limitation of study includes lack of data regarding therapeutic application against inflammatory markers positively associated with severity of lung disease in COVID-19 patients. Further studies need to be conducted for new drugs invention utilising the laboratory parameter data.

Conclusion

In conclusion, among studied inflammatory markers, only ESR was positively associated with the severity of COVID-19 and changes of pulmonary fibrosis on HRCT scan. The association of serum ferritin levels with the severity of COVID-19 needs to be further clarified. Study of inflammatory biomarkers may be helpful to treating physicians in predicting the prognosis of disease. In the absence of any proven established target therapy, aim of the clinician should be at restricting the disease grievousness and prevent any major pulmonary complications.

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DOI and Others

DOI: 10.7860/JCDR/2022/51211.15874

Date of Submission: Jul 14, 2021
Date of Peer Review: Sep 02, 2021
Date of Acceptance: Nov 11, 2021
Date of Publishing: Jan 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. Yes

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jul 22, 2021
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• iThenticate Software: Dec 16, 2021 (12%)

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