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

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On Sep 2018

Prof. Somashekhar Nimbalkar

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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."

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Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
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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.
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Professor and Head
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Saraswati Dental College
On Sep 2018

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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.
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Best regards,
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Muzaffarnagar Medical College,
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,
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
(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)
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.
On April 2011

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
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : November | Volume : 16 | Issue : 11 | Page : PC01 - PC06 Full Version

Assessment of Potential Risk Factors, Characteristics, and Outcome of Pneumothorax and Pneumomediastinum in Patients with COVID-19: A Retrospective Case-control Study

Published: November 1, 2022 | DOI:
T Prasanna Kumar, K Madan, AS Arjun, N Monica

1. Associate Professor, Department of Respiratory Medicine, MS Ramaiah Medical College, Bangalore, Karnataka, India. 2. Assistant Professor, Department of General Surgery, MS Ramaiah Medical College, Bangalore, Karnataka, India. 3. Senior Resident, Department of Respiratory Medicine, Bangalore Medical College and Research Institute, Bangalore, Karnataka, India. 4. Junior Resident, Department of General Surgery, MS Ramaiah Medical College, Bangalore, Karnataka, India.

Correspondence Address :
Dr. T Prasanna Kumar,
Associate Professor, Department of Respiratory Medicine, MS Ramaiah Medical College, MSRIT Post, MSR Nagar, Bangalore-560054, Karnataka, India.


Introduction: Pneumothorax (PTX) and/or Pneumomediastinum (PMD) are rare complications of Coronavirus Disease-2019 (COVID-19) and are linked to high mortality. Incidence rates vary between 0.56-2.01% in the reported literature. With clinical examination being hampered in the current pandemic setting, there is a delay in the diagnosis. There is a need to identify and establish potential predictive factors, that may aid in identifying patients with a high-risk of developing PTX and/or PMD.

Aim: To identify potential risk factors and thus, explore their association with PTX and/or PMD among patients with COVID-19.

Materials and Methods: A retrospective case-control study was conducted at MS Ramaiah Medical College and Hospital, Bangalore, Karnataka, India, over a six-month period. A total of 130 patients diagnosed with COVID-19 were recruited in a 1:3 ratio as cases and controls, respectively. The study included 31 consecutive patients with PTX and/or PMD (cases) and 99 consecutive patients serving as controls, Cases were patients, diagnosed radiologically with PTX and/or PMD, and controls were, matched individuals without PTX and/or PMD. Patient’s clinical and laboratory parameters (complete blood count, renal and liver function tests, serum levels of inflammatory markers such as C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-Dimer were tested for potential association with PTX and/or PMD. Student’s t-test, Chi-square test, multivariate and univariate logistic regression analysis were performed.

Results: During the study period, there was a total of 3,251 COVID-19 admissions at the centre, with 976 patients requiring Intensive Care Unit (ICU) admission. The overall incidence of PTX and/or PMD during the study period was (31/3251) 0.95%. The previous history of COVID-19, non vaccination with COVID19 vaccine, cough as a predominant symptom, high values of baseline CRP, total bilirubin, Aspartate Transaminase (AST), and total leukocyte counts had a positive association. In-hospital mortality (54.8% vs 33.30%) and 28-day mortality (35.7% vs 7.6%) following discharge, were higher among those with PTX and/or PMD.

Conclusion: Patients with a history of previous infection with COVID-19, non vaccination/incomplete-vaccination with COVID-19 vaccines, and patients with increasing total leukocyte counts and AST levels, high baseline total serum bilirubin were at increased risk of a detrimental clinical course and may indicate, the possibility of development of PTX and/or PMD in COVID-19 disease.


Coronavirus disease-2019, Respiratory infections, Severe acute respiratory syndrome

COVID-19 is an infectious respiratory disease caused by the novel coronavirus Severe Acute Respiratory Syndrome (SARS-CoV-2) that emerged in Wuhan, China at the end of 2019, resulting in a worldwide pandemic (1). The development of PTX and/or PMD is one of the emerging respiratory complications of COVID-19 viral pneumonia. PTX is defined as the presence of air or gas in the pleural cavity (i.e., the potential space between the visceral and parietal pleura of the lung), which can impair oxygenation and/or ventilation (2), whereas, PMD also known as mediastinal emphysema is an uncommon condition characterised by the accumulation of air or gas in the mediastinum (3).

Incidence rates of PTX vary between 0.56-2.01% in reported literature so far largely comprising of case series with the majority of the cases linked to those on mechanical ventilation (4),(5),(6),(7),(8). A case-control multicentre study found a higher incidence of PTX in patients with COVID-19, when compared to that in non COVID-19 infected patients despite excluding those due to invasive and non invasive ventilation (8).

The majority of secondary spontaneous PTX cases are due to Chronic Obstructive Pulmonary Disease (COPD), although most lung diseases have been reported to cause PTX including lung infections (2). Existing studies on COVID-19 with PTX show a low representation of COPD, thus implicating the SARS-CoV-2 virus itself as the causative factor. Most viral epidemics affecting the respiratory system have demonstrated PTX as a complication and they are associated with worse patient outcomes including mortality (9),(10). Among others, Pneumocystis jirovecii has been frequently associated with the occurrence of PTX (11).

The pathogenetic basis of PTX in COVID-19 has been linked to the breakdown of alveolar membrane integrity due to direct invasion and necrosis of lung tissue including the pleura by the microorganism itself. An increase in alveolar pressure due to violent coughing can cause alveolar damage. Selective over distention of the alveoli due to mucus impaction, inflammation and consolidation can lead to alveolar rupture even in the absence of mechanical ventilation (8),(12),(13).

In a pandemic setting, eliciting important clinical signs that enable a diagnosis of PTX is hampered for want of safety. In addition, the threshold to perform chest imaging among physicians is highly variable leading to a missed or delayed diagnosis. In such a setting, the identification of factors that are strongly associated with the development of PTX would play a critical role in improving patient management, yet there is scant literature on the same.

Knowledge of the potential risk factors could play an important role in the development of potential lung protective strategies in the management of COVID-19, thus present study was conducted to explore the association between risk factors for PTX and PMD among patients with COVID-19 and to determine the early outcome at 28 days discharge in patients developing PTX and/or PMD.

Potential hypotheses to be generated for the study was:

a. Patients with a high inflammatory response to SARS-CoV-2 infection are at a higher risk of developing lung damage favouring spontaneous PTX.

b. High total bilirubin is a predictor for subsequent PTX.

Material and Methods

This retrospective case-control study was conducted at MS Ramaiah Medical College and Hospital, Bangalore, Karnataka, India, from July 2021 to December 2021. A total of 130 patients satisfying study criteria were enrolled consecutively, for every case of PTX included, three matched controls were recruited. The present study was approved by the Institutional Medical Ethics Committee (Approval Number-MSRMC/EC/AP-05/07-2021) and informed consent was obtained from study participants or their immediate relatives, as deemed necessary.


Inclusion criteria:

• Adults diagnosed with COVID-19 infection as per Ministry of Health and Family Welfare (MOHFW) guidelines, Government of India (14).

• Radiological evidence of PTX and/or PMD on the chest radiograph or computed tomography of the thorax.

a. PTX- The presence of hyperlucency with no lung or vascular markings in an area corresponding to the pleural space with visible visceral pleural line and partial or completely collapsed underlying lung.

b. PMD- The presence of lucency adjacent to the mediastinal structures such as trachea, aorta, and heart.

Exclusion criteria:

• Secondary spontaneous PTX due to chronic lung disease (such as COPD, bronchial asthma, interstitial lung disease, sequelae to pulmonary tuberculosis, etc.)

• PTX due to chest trauma

• PTX due to interventions such as central venous access, pleurocentesis, etc.


Inclusion criteria:

• Adults diagnosed with COVID-19 disease as per Ministry of Health and Family Welfare (MOHFW) guidelines, Government of India (14).

Exclusion criteria:

• Evidence of PTX or PMD during and/or after hospital stay for COVID-19 management.

• Previous history of PTX and/or PMD due to any cause. All controls were matched with cases by all of the following criteria-age, sex, disease severity and predominant method of oxygenation. They were recruited on a 3:1 basis (three controls per case).

Study Procedure

Baseline demographic data and other independent variables such as presenting complaints, co-morbidities, time from onset of symptoms to admission, disease severity (as defined in the guidelines for management of COVID-19 disease issued by the MOHFW, Government of India (14)), time to development of PTX and/or PMD from the onset of symptoms, length of hospitalisation, need for non invasive or invasive ventilation, time from intercostal tube placement to the radiological resolution of PTX, patient progress and survival, radiological features (presence/absence and persistence/resolution of PTX and/or PMD) and data on other relevant investigative tests done as per standard work-up were recorded from existing patient records. Serum levels of inflammatory markers (such as CRP, D-Dimer, and LDH at admission and their trend in serial measurements, till the time of development of PTX, were recorded from existing patient records.

Diagnosis of PTX and/or PMD was made, based on chest radiography and or computed tomography of the thorax. High Resolution Computed Tomography (HRCT) thorax for COVID-19 disease was reported using a 25-point CT severity score with a maximum score being 25. They were graded as mild, moderate, and severe based on the score. A total score of <8 was mild, 8-15 was moderate and >15 was considered severe (15).

Outcome measures for cases and controls were length of hospitalisation, in hospital-mortality and 28-day mortality.

Statistical analysis

Descriptive statistics comprising mean±SD for continuous variables and percentage (proportions) for discontinuous variables was used to describe the data. The results were analysed using Statistical Package for the Social Sciences (SPSS) version 22.0 (SPSS Inc., Chicago, IL, USA). Student’s t-test, Chi-square test, multivariate and univariate logistic regression analysis were performed. Receiver Operating Characteristic (ROC) curve was plotted to identify the optimum sensitivity and specificity. Statistical significance was considered at p <0.05 (95% confidence interval was taken).


During the study period, there was a total of 3,251 COVID-19 admissions at our centre with 976 patients requiring ICU admission. Present study included 31 consecutive patients with PTX and/or PMD (cases) and 99 consecutive patients serving as controls, all of whom satisfied the study criteria.


The difference in distribution between the two groups was not statistically different (Table/Fig 1). The mean age of patients among cases was 51.10±18.55 years, with the majority being above the age of 60 years (35.5%, n=11/31). Among controls, the mean age was 53.91±15.55 years with the majority being above the age of 60 years (37.4%, n=37/99) (Table/Fig 2).


Males formed the majority in both groups, accounting for 71% (n=22/31) among cases and 50.5% (n=50/99) among controls, their distribution was not statistically significant (p=0.06), (Table/Fig 1).

Presenting Symptoms

Patients were managed as per standard practice, outlined by the MoHFW, Government of India (14), for the clinical management of COVID-19. The mean time period from onset of symptoms to admission was 6.32±2.66 days among cases, whereas, it was 5.46±2.26 days among controls, the difference was not statistically significant, p=0.227. Cough was the predominant symptom among cases, whereas fever was the predominant symptom among controls (Table/Fig 2).


Atleast 17 (54.8%) among cases and 40 (40.4%) among controls had no co-morbidities. Diabetes mellitus was the predominant comorbidity in the two groups (Table/Fig 2). Among those with comorbidities, the majority in both groups had a single co-morbid disease, this difference was statistically significant (p=0.005) (Table/Fig 2). The mean duration between the two episodes of COVID-19 disease as documented in case records was 110.66±45.96 days among cases and 124.09±46.19 days among controls.


All patients with moderate to severe COVID-19 disease were subjected to HRCT of the thorax. The mean CT severity score reported was 15.55±4.40 among cases and 14.80±3.64 among controls, this difference was not statistically significant p=0.81 (Table/Fig 1). The distribution of subjects by CT severity score is depicted in (Table/Fig 3). The mean time for the occurrence of PTX from the day of admission was 10.26 ±14.86 days with a median of five days. The right lung was affected in 18 (58.1%) cases, the left lung in 10 (32.2%), and both lungs in the remaining 3 (9.7%) cases. Among these cases, 16.1% (n=5/31) had evidence of PMD and 25.8% (n=8/31) had evidence of subcutaneous emphysema.

Tube thoracostomy was performed in all cases, 80.6 % (n=25/31) experienced resolution of PTX followed by removal of the intercostal tube; among them, the mean time for resolution of PTX was 10.72±5.08 days.

Overall, 35.5% (n=11/31) of cases received ventilator support in the form of non invasive ventilation from the day of admission and 74.2% (n=23/31) were on ventilator support at the time of detection of pneumothorax/pneumomediastinum.

Method of Oxygenation

The patients of both groups were distributed by their predominant method of oxygenation during the hospital stay, the differences were not statistically significant (Table/Fig 2).

Haematological Parameters

The baseline panel of investigations performed in both groups were recorded, and the differences in their means were computed and are outlined in (Table/Fig 4). The multiple regression model revealed, total leukocyte count (OR=1; 95% CI=1,1; p=0.038),
AST (OR=1.013; 95% CI=1,1.026; p=0.045), D-dimer (OR=0.79; 95% CI=0.633, 0.995; p=0.046), CRP (OR=0.97; 95% CI=0.95;p=0.005), Serum albumin (OR=0.243, 95, 0.992% CI=0.085, 0.697;p=0.009) as having significant association to the development of PTX and/or PMD, (Table/Fig 5).

Cut-off Value of Total Bilirubin

Authors hypothesised the role of total bilirubin as a potential predictor, univariate Logistic regression model was employed to test the hypothesis, thus, 0.64 mg/dL of total bilirubin can be taken as a cutoff value predictive of PTX and/or PMD based on ROC curve with an area of 0.38, the sensitivity of 71%, and specificity of 25.3% with 95% CI=0.277-0.482 (Table/Fig 6).

Outcome Assessment

The difference in immediate outcomes with respect to the change in haematological parameters at baseline and at the occurrence of disease was analysed, and a fall in platelet count during the course of illness among cases, was found to have a statistically significant association with worse immediate outcome (p=0.001) (Table/Fig 7).


The second wave of the COVID-19 pandemic in India witnessed high rates of mortality and morbidity, mostly linked to the delta variant of the virus (16).

Studies conducted across the globe, have established a higher incidence of PTX with the COVID-19 compared to that observed in the general population, indicating a direct link to the occurrence of PTX, secondary to COVID-19 disease (8),(13). During the study period, the incidence of PTX and/or PMD was found to be 0.95% overall and 31/976 (3.17%) among those requiring ICU care, this was within the range of overall incidence found in similar studies (8),(13),(17),(18),(19).

Whilst studies, propose numerous causal mechanisms to the occurrence of PTX and/or PMD, none have been established with certainty, as autopsies are performed sparingly in COVID-19 patients, thereby, limiting the possibility of direct macroscopic and microscopic examination of the lungs (8),(13),(17).

In the present study, age, gender and severity matched study population, we found that subjects who had a history of previous COVID-19 disease had a higher likelihood of developing PTX/PMD (p=0.016). This opens up the possibility of another causal
mechanism of PTX, occurring in a lung already suffering from the residual damage of a previous COVID-19 infection. However, as the present study was a retrospective study, the authors were limited in their ability to analyse in depth various aspects of this association, a systematic review of case reports of COVID-19 reinfection by Wang J et al., found that 18.8% (3/16) had more severe disease during the second episode, however, there is no literature to date, depicting its association with PTX (20).

Achieving immunity either through natural infection or vaccination is important in negating adverse outcomes associated with COVID19 disease, the unvaccinated experienced worse outcomes than the vaccinated in this study (p=0.039), higher incidence of severe
COVID-19 disease in the unvaccinated has been established by a study (21), hence, the association with PTX is likely due to the predilection for severe disease, in this subgroup.

Likewise, the presence of cough as a predominant symptom expressed a significant statistical difference between the two groups. Miró Ã’ et al., found a complaint of dyspnoea as a strong association with the development of PTX (p=0.02) (8). Interestingly,
the presence of respiratory co-morbidities was low in present study population, just as in studies by Martinelli AW et al., (13), Miró Ã’ et al., (8), and Udwadia ZF et al., (18). One likely explanation that needs validation, is a behavioural adaptation to stronger preventive practices for COVID-19 disease, likely due to the fear of suffering severe disease, on account of the chronic lung disease.

While the majority of patients in present study, received ventilator support in the form of non invasive ventilation, 38.7% of cases with PTX received no ventilator support. The ventilator settings were not included for analysis, due to missing data in records among the majority. Present study found that in-hospital mortality was worse among controls, who received ventilator support (p=0.056), although it did not achieve statistical significance, on the other hand, there was no difference among the cases (p=0.564). Zhou C et al., (22) in their study found, that mechanically ventilated patients had a higher incidence of PTX, the incidence was higher in those with ARDS, the occurrence ranging between 14-87%, similar results were also elucidated by Gattinoni L et al., (23).

When haematological parameters were compared, CRP, D-dimer, TLC, total and direct bilirubin, and AST were significantly higher among cases than in controls, the differences express significance both statistically and clinically. Zantah M, et al., found that the presence of lymphopenia and elevated inflammatory markers including CRP, ferritin, D-dimer, and IL-6, had significant associations with spontaneous PTX (4).

Gong J et al., (24) and Wang XH et al., (7) found high total bilirubin among patients with severe COVID-19 disease, present study established a positive association of high total bilirubin with the occurrence of PTX compared to controls. Liu Z et al., (25) found elevated total bilirubin and elevated transaminases in their study, only high levels of AST established a positive association in present study. Present study found that high total bilirubin at a cut-off 0.64 mg/dL was associated with PTX, however, this value being in the normal range (0.2-1 mg/dL), holds low significance for clinical application. The high bilirubin in COVID-19 disease represents direct hepatocyte injury by the virus, due to the expression of Angiotensin Converting Enzyme-2 (ACE-2) receptors in the duct epithelial cells and hepatocytes, although at a much high concentration, than the former (26).

Immediate and late mortality was high among patients with PTX, (Table/Fig 2). Miró Ã’ et al., in their case control multicentre study (8) and Udwadia ZF et al., (18) in their retrospective study (overall mortality 74%), found similar outcomes, on the other hand, Martinelli AW et al., (13) in their multicentre retrospective case series, found that the presence of PTX did not significantly increase the rate of mortality, where survival of 63.1% was noted among such patient, however the latter being a case series with no control group for comparison is limited in its ability to make an assertion as such, yet as iterated by Martinelli AW et al., (13), PTX attributable to COVID-19 disease must not be viewed as a lost cause while prognosticating a patient.

The present study raises important questions on potential risk factors for the development of air leak syndromes in COVID-19 disease, additionally, the role of haematological parameters in prognostication and its ability to identify patients with a higher risk of developing PTX remains circumspect, inspite of the statistically significant results, authors have demonstrated as the clinical application of these parameters, is limited by numerous confounders. The presence of air leak is a marker for adverse outcomes, tube thoracostomy remains the treatment of choice in clinically significant PTX.


The limitations of present study include its retrospective nature and its relatively low sample size. A study with larger sample size and prospective design can validate the findings of present study.


Elucidating a history of previous COVID-19 disease and nil or incomplete vaccination with COVID-19 vaccines among patients with current COVID-19 infection may provide a clue towards anticipating a detrimental clinical course. In addition, high baseline serum total bilirubin levels, progressively increasing total leukocyte counts, and serum aspartate transaminase levels may be viewed with high suspicion to the possibility of developing PTX and/ or pneumomediastinum.


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DOI and Others

DOI: 10.7860/JCDR/2022/57842.17012

Date of Submission: May 17, 2022
Date of Peer Review: Jun 22, 2022
Date of Acceptance: Aug 27, 2022
Date of Publishing: Nov 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? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

• Plagiarism X-checker: May 21, 2022
• Manual Googling: Aug 23, 2022
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