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 : 2021 | Month : August | Volume : 15 | Issue : 8 | Page : OC11 - OC14 Full Version

Predictors of Mortality in Patients of COVID-19 Pneumonia in Intensive Care Unit: An Observational Study in a Tertiary Care Hospital, Lucknow, India


Published: August 1, 2021 | DOI: https://doi.org/10.7860/JCDR/2021/49061.15189
Hemant Kumar, Preeti Gupta, Shobhit Shakya, Sumeet Dixit, Manoj Kumar Pandey, Nikhil Gupta, Amiya Pandey

1. Associate Professor, Department of Respiratory Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. 2. Associate Professor, Department of Ophthalmology, Hind Institute of Medical Sciences, Sitapur, Uttar Pradesh, India. 3. Associate Professor, Department of General Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. 4. Assistant Professor, Department of Community Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. 5. Senior Resident, Department of Respiratory Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. 6. Assistant Professor, Department of General Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. 7. Senior Resident, Department of Respiratory Medicine, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

Correspondence Address :
Dr. Sumeet Dixit,
Flat No. 905, Faculty Apartments, Dr. Ram Manohar Lohia Institute of Medical Sciences, Vibhuti Khand, Lucknow-226010, Uttar Pradesh, India.
E-mail: docdixit30@gmail.com

Abstract

Introduction: Coronavirus Disease-2019 (COVID-19) is caused by the Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) which is an enveloped positive-sense single-stranded RNA virus. Initial steps of the infection involve binding of the spike protein (S) of the virus to Angiotensin Converting Enzyme-2 (ACE-2) receptor on the mucosal surfaces of various organs like lungs, kidney, heart, intestine. Pathogenesis of complications are still poorly understood.

Aim: This study was designed to find out the baseline biochemical parameters at the time of admission which may predict outcome in COVID-19 patients.

Materials and Methods: This observational study was conducted in a dedicated COVID-19 hospital, Dr. Ram Manohar Lohia Institute of Medical Sciences (Dr. RMLIMS), Lucknow, Uttar Pradesh, India, from 1st July, 2020 to 30th November, 2020. A total of 109 moderate to severe COVID-19 pneumonia patients who required Intensive Care Unit (ICU) admission, were enrolled. Based on their outcome, patients were divided into two groups: “Survived” and “Expired”. Biochemical characteristics of patients were compared among the two groups using univariate and multivariate analysis.

Results: On Univariate analysis Coagulation profile, Prothrombin Time (PT), International Normalised Ratio (INR), Activated Partial Thromboplastin Time (APTT) and D-Dimer values were raised significantly in the expired group. Among other acute phase reactants Lactate Dehydrogenase (LDH), C-Reactive Protein (CRP), Interleukin-6 (IL-6), and Creatinine Phosphokinase-MB (CPKMB) were raised in expired group and this difference was significant statistically too. On Multivariate analysis among all acute phase reactant only IL-6 was increased significantly. All other variables were found to be non significantly associated with mortality, statistically (p-value <0.05).

Conclusion: Baseline biochemical parameters have prognostic values in COVID-19 patients. Raised IL-6 levels can be viewed as an independent predictor of mortality among COVID-19 patients at the time of admission in ICU.

Keywords

Coronavirus disease-2019, D-Dimer, Interleukin-6

Coronavirus Disease-2019 (COVID-19) is caused by a SARS-CoV-2 which is an enveloped positive-sense single-stranded RNA virus. First cluster of similar type of pneumonia cases, later named as COVID-19, were found in Wuhan city in the Hubei Province of China, in December 2019. From China, it spread widely and involved almost all the countries. The World Health Organisation (WHO) declared it a pandemic on 11th March 2020. In India, first case was reported on 30th January, 2020 in Kerala, in a student who had returned from Wuhan city of China. First death in India was reported on 10th March, 2020 from the state of Karnataka in a 76-year-old male who had returned from Saudi Arabia. He had co-morbidities-hypertension, diabetes and asthma. Since then mortalities have been increasing continuously and around 19.86 lacs deaths have occurred world-wide (1) while 1.52 lacs patient have expired in India till 16th January, 2021 (2).

The SARS-CoV-2 virus attaches to mucosal surfaces of various organs like lungs, kidney, heart, intestine by binding of its spike protein to the ACE-2 receptors (3). Most common organ involved is lungs where it manifests as pneumonia; classified according to respiratory rate and oxygen saturation as mild pneumonia {Respiratory Rate (RR) <24/min and SpO2 <94%}, moderate pneumonia (RR 24-30/min, SpO2 94-90%) and severe pneumonia (RR >30/min, SpO2 <90%) (2). Around less than 5% patients of COVID-19 get critical illness and complications like Acute Kidney Injury (AKI), myocarditis, Acute Respiratory Distress Syndrome (ARDS) etc., which increases morbidity and mortality in these patients. Risk of mortality increases in severe to critical illness (4). Pathogenesis of complications are still poorly understood. Many studies have shown downregulation of ACE-2 enzyme which prevents conversion of angiotensin-2 to angiotensin-1. Angiotensin-2 molecule is proinflammatory which leads to inflammation and tissue injury which ultimately leads to complications like myocardial injury, AKI and ARDS etc., (5). There is no positive association between severity of disease and level of ACE-2 receptors. These receptors are more in males as compared to females and this may be the cause of higher complication rate in male patients (6). The complications of COVID-19 pneumonia and mortality is largely dependent on age, co-morbidities and severity of disease (3). Advanced age, elevated Lactate Dehydrogenase (LDH) and D-Dimer are also found to be risk factor for ARDS and mortality (7).

The IL-6 is a cytokine which has multiple mechanisms. It regulates immune cells by transmitting cell signals, it also has strong proinflammatory effect which causes inflammation, tissue injury, ARDS, sepsis, septic shock, multi organ failure and eventually death (8). Considering the novelty of the disease and health impacts of the COVID-19, this study was an attempt to find out baseline biochemical parameters at the time of admission which may predict poor outcome in COVID-19 patients.

Material and Methods

A prospective observational study was carried out at Dr. Ram Manohar Lohia Institute of Medical Sciences (Dr. RMLIMS), Lucknow, Uttar Pradesh, India from 1st July, 2020 to 30th November, 2020. The COVID-19 facility at Dr. RMLIMS was a designated Level-3 treatment facility to provide healthcare to moderate to severe COVID-19 pneumonia patients. The Institutional Ethical Clearance was obtained by Ethical Committee (IEC NO.63/20).

Inclusion criteria:

• Patient of moderate (RR 24-30/min, SpO2 94-90%) to severe COVID-19 pneumonia (RR >30/min, SpO2 <90%) confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and admitted to Intensive Care Unit (ICU) (9).
• Consent to participate in the research study, received either from the patient or attendant.

Exclusion criteria:

• Patient age <18 years
• Patient suffering from other moribund non COVID-19 disease which could cause death of patient like end stage renal disease, terminal cancer, end stage liver disease, pre-existing chronic lung disease etc.,
• Pregnant females.

Study Procedure

All moderate to severe COVID-19 pneumonia patients requiring admission from 1st July, 2020 to 30th November, 2020 were included in the study. A total of 140 patients confirmed by RT-PCR test who required admission in ICU, were recruited for the study and 31 patients had to be excluded as they did not fulfil the inclusion criteria. So, a total of 109 patients were included in the study and their data was analysed. During hospitalisation, patients were treated in ICU with a standard institutional protocol consisting of intravenous Remdesivir, Dexamethasone, Enoxaparin, appropriate antibiotics and other necessary treatment. Patients were given other support like ventilator, dialysis, blood transfusion etc., whenever required.

All eligible patients underwent detailed clinical examination, and relevant investigations such as Complete Blood Count (CBC), Renal and Liver Function Tests (RFT and LFT), Random Blood Sugar (RBS), Serum Ferritin, IL-6, Procalcitonin, PT-INR, APTT, Fibrinogen, D-Dimers. Based on outcome after hospital stay, patients were divided into two groups.

Group 1 (non-survivor or expired)- This group included patients who died during the hospital stay.
Group 2 (survived)- This group included patients who survived during the hospital stay and were discharged after recovery.

All demographic (age and sex), clinical and laboratory parameters were compared between Survivor and Non survivor groups.

Statistical Analysis

Discrete data were analysed by cross tables using descriptive method. Continuous data was represented as mean and Standard Deviation (SD). Continuous variables were compared between the two groups using student’s t-test. Biochemical characteristics of patients among survived and non survived groups were compared using univariate and multivariate methods. The p-value<0.05 was considered as statistically significant.

Results

A total of 109 moderate to severe COVID-19 pneumonia patients who required ICU care, were enrolled in the research study. Out of 109 patients, 79 patients survived while 30 patients expired during the hospital course. Maximum patients were in the age group of 51-60 years while only one patient was in age group of less than 20 years (Table/Fig 1).

The COVID-19 pneumonia was almost three times more common in males as compared to females. Mean respiratory rate was higher in expired group and mean SpO2 levels were lower in patients with adverse outcome (Table/Fig 2).

Routine blood investigations were done in both the groups and compared between the two using student’s t-test. Mean values of haemoglobin and lymphocyte count were lesser in expired group as compared to survived group. Mean values of Total Leucocyte Counts (TLC), Neutrophilic count, blood urea, AST and Alkaline Phosphatase (ALP) were more in expired group as compared to the survived group (Table/Fig 3).

Acute phase reactants were compared between two groups by Univariate logistic regression analysis. Coagulation profile (PT, INR, and APTT) were raised significantly in expired group while fibrinogen was not changed significantly. Among other acute phase reactants, D-Dimer, LDH, C-CRP, IL-6, and Creatinine Phosphokinase-MB (CPKMB) were raised in expired group and this difference was significant statistically (Table/Fig 4).

All acute phase reactants which were significant in univariate analysis were analysed by multivariate logistic regression analysis. Among all of these acute phase reactants, only IL-6 was increased significantly in expired group as compared to patients who survived. All other variables were non significant statistically (Table/Fig 5).

Discussion

The SARS-CoV-2 virus is a lesser virulent virus as compared to that of other past recent outbreaks like MERS-CoV, Ebola etc. Mortality rate of COVID-19 globally is 2.16% (1), while in India; mortality is lesser, around 1.44 % (2). Mortality in COVID-19 patients who required ICU care is higher as in present study where it is 27.5%. Mortality rate in ICU patients is reducing over time due to better understanding of the disease and its management. This trend was shown by Dennis JM et al., who showed the change in mortality from 42-19.6% in ICU patients (10).

Acute phase reactants increase in COVID-19 disease, especially in patients who require ICU care. Mechanism of this phenomena is cytokine storm which causes increment in inflammatory markers like LDH, C-reactive Protein CRP, Ferritin, IL-6, Amylase, Lipase etc. Other mechanism is coagulation abnormalities which causes so markers of coagulation abnormalities like PT, INR, APTT, Fibrinogen, D-Dimer etc., also increase. Other markers like CPKMB shows cardiac injury and Procalcitonin shows secondary bacterial infection which leads to morbidity and mortality. All above acute phase reactants were compared in survived and expired group to find out predictor of mortality.

In univariate analysis, among coagulation profile PT, INR, APTT and D-dimer were more elevated in expired group as compared to survived group and this elevation was significant statistically. Other coagulation marker fibrinogen was decreased in expired group but this difference was not significant statistically. Among inflammatory markers, Serum LDH, Serum C-reactive protein, IL-6, and CPKMB were elevated in expired group as compared to survived group. These elevations in markers were significant statistically. Other inflammatory markers like serum ferritin and procalcitonin were also increased in expired group as compared to survived group but this difference was not significant statistically.

All parameters which were significant in univariate analysis were compared by multivariate analysis. Only IL-6 was elevated significantly in expired group as compared to survived group (p-value=0.023). This finding has been supported and refuted by many studies. Trecarichi EM et al., in his study of 50 elderly patients showed higher serum IL-6 levels in expired group and it was identified as an independent predictor of in-hospital mortality. This finding of his study supports our findings (11).

In a prospective, cohort study by Du RH et al., 179 patients were recruited to see predictor of mortality (12). Only two factors CD3+ CD8+ T cells and cardiac troponin I came as significant predictor while none of acute phase reactants came out as significant predictor of mortality. This was in contrast to our study as we didn’t analyse both of factors as predictors of mortality. In a systematic review and meta-analysis done by Tian W et al., authors analysed 4659 patients of 14 studies, they concluded that cardiac troponin, C-reactive protein, IL-6 and D-dimer were predictors of mortality (13). Similar to these studies, our study also showed IL-6 as predictor of mortality. Others markers like CRP, D-Dimer were also increased in expired group in our study in univariate analysis.

The IL-6 is one of the important markers of cytokine storm so high levels of IL-6 predict severity in COVID-19 patients. Han H et al., enrolled 102 patients and classified them according to severity. IL-6 was significantly elevated in more severe groups which expired later on (14). Authors concluded IL-6 as a predictor of severity and mortality of disease. Henry BM et al., conducted a meta-analysis with 18 studies and included 2984 patients (15). They concluded that IL-6 and 10 (IL-10) and serum ferritin were strong predictor of severe and fatal COVID-19 pneumonia.

Liu F et al., studied prognostic value of inflammatory markers in patients with COVID-19 pneumonia (8). In their retrospective cohort study of 140 patients, they concluded that CRP and IL-6 were independent predictor of severity and outcome of COVID-19 disease. They also suggested IL-6 > 32.1 pg/mL as cut-off value which predict severity of disease.

Limitation(s)

This was a single centre study. A multicentric study with a larger sample size was needed to more accurately predict the mortality factors.

Conclusion

Biochemical parameters like IL-6 are helpful in predicting mortality in moderate to severe COVID-19 pneumonia patients. IL-6 levels should be routinely measured in all these patients at the time of admission.

References

1.
Coronavirus disease (COVID-19) Pandemic https://www.who.int/emergencies/diseases/novel-coronavirus-2019 (last accessed on 17/01/2021).
2.
COVID-19 INDIA as on 17/01/2021 Available at: https://www.mohfw.gov.in/ (last accessed on 17/01/2021).
3.
Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE 2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020;14:185-92. [crossref] [PubMed]
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DOI and Others

10.7860/JCDR/2021/49061.15189

Date of Submission: Feb 18, 2021
Date of Peer Review: May 17, 2021
Date of Acceptance: Jun 02, 2021
Date of Publishing: Aug 01, 2021

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 CHECKING METHODS:
• Plagiarism X-checker: Feb 19, 2021
• Manual Googling: Jun 02, 2021
• iThenticate Software: Jun 22, 2021 (13%)

ETYMOLOGY: Author Origin

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