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 : June | Volume : 16 | Issue : 6 | Page : BC12 - BC16 Full Version

Markers of Coagulation Dysfunction and Inflammation in Diabetic and Non Diabetic COVID-19 Patients- A Retrospective Study


Published: June 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/55998.16424
Firdushi Begum, Malavika Barman, Elteza Tahjiba Jahir

1. Associate Professor, Department of Biochemistry, Gauhati Medical College and Hospital, Guwahati, Assam, India. 2. Associate Professor, Department of Biochemistry, Gauhati Medical College and Hospital, Guwahati, Assam, India. 3. Demonstrator, Department of Biochemistry, Gauhati Medical College and Hospital, Guwahati, Assam, India.

Correspondence Address :
Dr. Firdushi Begum,
Associate Professor, Department of Biochemistry, Gauhati Medical College and Hospital, Guwahati, Assam, India.
E-mail : firdushi72@gmail.com

Abstract

Introduction: Since the end of 2019, a novel Coronavirus Disease 2019 (COVID-19), declared a pandemic by World Health Organization (WHO) has ravaged the world. Diabetic patients have been reported to be more susceptible to intensive care admissions, and deaths due to COVID-19. Diabetes Mellitus (DM) and COVID-19, both associated with chronic and acute inflammation respectively can impact each other in terms of clinical progression and outcome. Given the novelty of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pathogen, there is need to update and increase the limited evidence on the probability of DM acting as a risk factor and influencing disease severity and progression.

Aim: To compare the markers of inflammation and coagulation dysfunction between COVID-19 patients with and without DM as co-morbidity and thereby to study the effect DM has on the prognosis of COVID-19.

Materials and Methods: This was a retrospective, observational, single-centre study, conducted Department of Biochemistry at Gauhati Medical College and Hospital, Guwahati, Assam, India, from January 2021 to June 2021. Clinical and laboratory data of 500 laboratory confirmed COVID-19 patients were reviewed in this study. The patients were grouped as diabetic case group and non diabetic control group. Data was presented as percentages for categorical variables and median (interquartile range) for continuous variables. Chi-square test was used to see the association of different qualitative information and Mann-Whitney U test was used to see the association of quantitative data and all p-values were given for justification. A p-value <0.05 was considered statistically significant.

Results: The sample included 300 diabetic and 200 non diabetic COVID-19 patients. The mean age non diabetic patients (47.5 years) was significantly less as compared to the diabetic group (54.5 years), p-value <0.001. The serum level of inflammatory biomarkers, C-Reactive Protein (CRP), ferritin, and markers of hypercoagulable state, D-dimer, was found to be significantly high (p-value <0.001) in diabetic patients as compared to non diabetic patients. Diabetics had a poor prognosis with 231 (77%) receiving oxygen as compared to 51 (25.5%) of non diabetic patients. Total 173 (57.7%) of diabetic COVID-19 patients had to be shifted to ICU, 201 (67%) suffered from post COVID-19 complications and the mortality rate was higher at 18% in diabetics as compared to 1.5% in non diabetic subjects.

Conclusion: Diabetic patients are at higher risk of uncontrolled inflammation and hypercoagulable state which eventually leads to deterioration of COVID-19 infection status.

Keywords

Co-morbidity, Coronavirus Disease 2019, Glycaemic control, Hypercoagulable state, Prothrombin time

Towards the end of 2019, a new virus named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was first identified in Wuhan province of China (1). The disease caused by infection with the virus was named Coronavirus Disease 2019 (COVID-19) and declared a pandemic by World Health Organization (WHO) (2). Since 2019 the virus has spread across continents and has affected 382.3 million people worldwide and resulted in the death of 5.7 million as of 2nd February 2022 (3). Spread via respiratory droplets, the main clinical manifestation is lung injury (4),(5). SARS-CoV-2 pathophysiology remains incompletely understood, but research evidence has suggested that exaggerated inflammation play a critical role in its pathogenesis. Inflammatory responses triggered by a rapid viral replication and cellular destruction, can induce the release of cytokines by macrophages and monocytes leading to cytokine storm (6). Inflammatory markers like ferritin, C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Interleukin-6 (IL-6), have been reported to be significantly associated with a high risk of development of severe COVID-19. The increased likelihood of thromboembolic events in COVID-19 is another factor of grave concern as reflected by high levels of D-dimer, elevated activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT). The SARS-CoV-2 can enter the endothelial cells via the Angiotensin Converting Enzyme 2 (ACE2) receptor, with viral replication causing inflammatory cell infiltration, endothelial cell apoptosis and microvascular prothrombotic effects (7),(8).

Several factors like advanced age, male sex, presence of comorbidities like Diabetes Mellitus (DM), hypertension, coronary vascular disease, chronic kidney disease, cancer, predisposes COVID-19 infected patients to more severe infection with long hospital stay and fatal outcome (9),(10). Mankind has been struggling with the diabetes mellitus pandemic when it confronted this new COVID-19 pandemic (11). The physiology of both DM and COVID-19 are quite similar though the inflammatory responses, hyperglycemia and resultant tissue damage in COVID-19 is intensely acute as compared to DM, which is characterized by chronic low grade inflammation, impaired glycaemic control, and slowly progressive multi tissue injury (11). With similar pathological injury inflicted by both these diseases on the body organs, it is highly likely that the acute inflammation brought about by COVID-19 adversely affects the glycaemic control in DM patients and aggravates the multi tissue injury resulting in adverse outcomes.

Given the novelty of SARS-CoV-2 pathogen, there is need to update and increase the limited evidence on the probability of DM acting as a risk factor and influencing disease severity and progression (4),(12). This study was thus designed to compare the inflammatory and coagulability status of COVID-19 patients with and without diabetes and find out whether a diabetic patient was at a greater risk of adverse prognosis compared to a non diabetic patient.

Material and Methods

This retrospective observational study was conducted in Gauhati Medical College and Hospital, Assam, India. For the study purpose, the records of patients admitted to the COVID-19 wards from May 2020 to October 2020 were scanned. Analysis of collected data was done in the months of May 2021 and June 2021. Total patients enrolled for the study was 500 based on the inclusion and exclusion criteria, 300 diabetic patients (cases) and 200 non diabetic patients (controls). The study was done only after obtaining approval of Institutional Ethics Committee (Ref No: MC/190/2007/Pt-II/DEC-2020/10).

Inclusion criteria:

• COVID-19 positive patients admitted to the COVID-19 wards, irrespective of severity.
• Age ≥15 years
• Already diagnosed diabetic cases with COVID-19 were taken as case group and COVID-19 patients without any co-morbidity were taken as control group.

Exclusion criteria:

• Patients with liver disorders, coagulopathies, and other co-morbidities other than Diabetes Mellitus.
• Pregnant women
• Age <15 years.

Data collection: Infection by SARS-CoV-2 was diagnosed either by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) or Rapid Antigen Test (RAT). The COVID-19 positive patients were either admitted to Corona Wards or Intensive Care Units (ICU) depending on the severity of the cases. The patients were classified into mild, moderate and severe based on WHO guidelines on clinical management of COVID-19 (13).

Mild disease: Symptomatic patients meeting the case definition for COVID-19 without evidence of pneumonia or hypoxia.

Moderate disease: Adults with clinical signs of pneumonia (fever, cough, dyspnoea, fast breathing), SpO2 ≥90% on room air.

Severe disease: Adults with clinical signs of pneumonia and one of the following:

• Respiratory rate > 30 breaths/min;
• or SpO2 < 90% on room air.

The COVID-19 patients who were categorised as mild and moderate at the time of admission and admitted to COVID-19 wards were chosen as study subjects.

• Diabetic case group: (n=300) Has diabetic COVID-19 cases (223- mild and 77-moderate).
• Non diabetic patients group: (n=200) Has non diabetic controls (149-mild and 51-moderate)

But 173 diabetic cases and 16 non diabetic controls progressively became severe after admission and had to be shifted to COVID-19 ICU.

Procedure

Demographic and clinical data as regards to signs and symptoms, duration of hospital stay, treatment protocol followed which included administration of medicines and oxygen, post COVID-19 complications transfer to ICU, and final prognosis records were collected from Medical Records Department and noted down in a proforma prepared for the purpose. Laboratory data was collected from the Central Clinical Laboratory. On admission of the patients, Random Blood Glucose (RBG), urea, creatinine, Liver Function tests (LFT), C-Reactive Protein (CRP), ferritin, Lactate Dehydrogenase (LDH), D-dimer, Complete Blood Count (CBC) were done to collect the baseline data. Urea, Creatinine, LFT, along with other parameters was estimated at the time of admission in all COVID-19 patients. For the purpose of this study Urea, Creatinine, LFT (except AST, ALT, TP, Albumin) were not compared. Data of AST, ALT, TP, Albumin, LDH, Lymphocyte, Neutrophil, CRP, Ferritin, D-Dimer, APTT, PT, was collected and compared.

The blood tests were repeated according to the clinical progression of the cases. For the purpose of this study CRP, ferritin, D-dimer, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Total Protein (TP), albumin, Lactate Dehydrogenase (LDH) levels, neutrophil count, lymphocyte count, activated Partial Thromboplastin time (aPTT) and Prothrombin Time (PT) between diabetic case group and non diabetic control group were compared. The CRP, ferritin, D-dimer, AST, ALT, TP, albumin, LDH were done in the Vitros 5600 Integrated System (Ortho Clinical Diagnostics, New Jersey, USA). Neutrophil and lymphocyte count were done in Sysmex Haematology Analyzer and aPTT and PT on ERBA ECL 105 Coagulation Analyser. For the parameters showing an increasing trend, the highest reported level was chosen for the purpose of the study.

Statistical Analysis

Data collected were scrutinized thoroughly and baseline information was presented by standard statistics. Categorical values were expressed as percentages (%) and continuous variables as median, Interquartile Range (IQR) as the data was found to be dispersed and did not follow normal distribution. All the statistics have been calculated and computed using IBM, Statistical Package for Social Sciences (SPSS), version 20.0 and graph prepared using Microsoft Excel. To see the association of different qualitative data Chi-square test was administered and all p-values were given for justification. Similarly to test the equality of medians for quantitative data Mann Whitney U test was used. A p-value <0.05 was considered statistically significant at 5% level.

Results

The median age of non diabetic patients (47.5 years) was significantly less as compared to the diabetic group (54.5 years), p-value <0.001. Males were two times more infected by SARS-CoV-2 than females. For all the patients the most common presenting symptoms were fever, chill, cough and fatigue (Table/Fig 1). Maximum number of diabetic COVID-19 cases was in the age group of 36-45 years (131/300, 43.67%) (Table/Fig 2). There was significant difference in CRP, ferritin, neutrophil and lymphocyte count and D-dimer levels between the diabetic case group and non diabetic control group (Table/Fig 3).

On comparison of the prognosis it was found that diabetics had a poor prognosis with 231 (77%) receiving oxygen as compared to 51 (25.5%) of non diabetics. Total 173 (57.7%) of diabetic COVID-19 patients and 16 (8%) non diabetic controls progressively became severe and had to be shifted to ICU, 201(67%) suffered from post COVID-19 complications and the mortality rate was higher at 54 (18%) in diabetics as compared to 3 (1.5%) in non diabetics (Table/Fig 4).

Finally high levels of the inflammatory markers and markers of coagulation dysfunction were found to be associated with a worse prognosis. There were 98 (54.75%) of patients with a D-dimer level between 0.5 to 2 μg/mL and 75 (88.24%) of patients with D-dimer level >2 μg/mL required to be shifted to ICU. The ICU admissions and mortality also rose with the rise in ferritin levels with 75 (78.13%) of patients with a ferritin level of more than 1000 ng/mL needing ICU admission. CRP also showed a positive association with worse prognosis as reflected by the increasing percentages of ICU admissions and death with increasing CRP levels (Table/Fig 5). Higher percentage of diabetic COVID-19 patients were found to suffer from Acute Respiratory Distress Syndrome (ARDS) 146 (48.7%) and acute kidney injury 41 (13.7%) as compared to non diabetics (Table/Fig 6).

Discussion

Mankind has been trying hard to deal with DM, a chronic metabolic disorder that currently affects about 422 million persons worldwide particularly in the low and medium income countries (14). With the emergence of COVID-19 infection, the diabetic population which is vulnerable to any infectious condition due to compromised immunity is exposed to another severe acute respiratory viral disease. Characterisation of COVID-19 patients in India showed that 28.6% of the patients have co-morbidities like Hypertension (HTN) or DM (15). It became clear as COVID-19 evolved, that associated co-morbidities, most important being Cardiovascular Disease (CVD) and DM predisposed patients to adverse outcomes (16). For a better understanding of this novel COVID-19 disease and its early diagnosis laboratory medicine plays a very important role (17). Biochemical monitoring of COVID-19 patients through testing is critical for assessing disease severity and progression, as well as monitoring of therapeutic intervention (18). This study was planned to compare the inflammatory and coagulation markers between diabetic and non diabetic COVID-19 patients, to document that presence of DM increased the risk of coagulation disorders in COVID-19 patients resulting in increased adverse outcomes.

During the course of the study while going through the case reports of the admitted patients retrospectively an important initial finding was that the admitted patients with co-morbidities outnumbered those without by 4:1 and three out of five admitted patients was diabetic. Kushwaha S et al., studied the age and gender variations in Indian COVID-19 cases and found that the male COVID-19 cases (65.39%) were more than females (34.16%) (19). In another study by Mithal A et al., conducted in a COVID-19 facility in Delhi, India, it was found that people with DM were significantly older (mean age 59.9 vs 47.7 years), and had a higher proportion of men (74.6 vs 63.7 %). The mean duration of hospital stay was higher for the diabetes group (10.4 vs 9.1 days, p-value=0.016) (20). Median Length Of Stay (LOS) was found to be longer in 184 patients with diabetes and/or uncontrolled hyperglycemia compared with 386 patients without diabetes, in a study conducted by Bode B et al., in USA (21). In the present study patients in the diabetic group was significantly older than in the non diabetic group (54.5 years vs 47.5 years, p-value <0.0001). In the diabetic case group males constituted 178 (59.3%) as compared to 122 (40.67%) females. The hospital stay of the diabetic cases were higher than non diabetic controls (14±5.13 days vs 7.58±3.9 days, p-value <0.001). The stronger immune response in females attributed to hormone estrogen being immune boosting and testosterone being considered immune suppressing may be the factor bringing in more males to the hospitals (22).

Statistical analysis of the biochemistry results showed that AST and LDH was elevated in the COVID-19 patients, whereas ALT was within range as was Total protein and Albumin levels. AST and ALT levels were high in the diabetic group as compared to non diabetic group, but the difference was not found to be significant, and as such cannot be taken as indicative of liver injury. Significantly high LDH and AST levels in diabetic COVID-19 group can be taken as indicative of tissue injury. On comparison of CRP and Ferritin levels between diabetic cases and non diabetic controls they have been found to be significantly raised in diabetic patients in this study. In a retrospective study conducted by Das B et al., involving COVID-19 patients admitted to Kokilaben Dhirubhai Ambani Hospital and Medical Research Center, Mumbai a significant increase was found in mean values of AST, ALT, total billirubin, creatinine, CRP, Procalcitonin (PCT), LDH, IL6, ferritin, LDH, hsTroponin I, NT Pro BNP and decrease in mean values of albumin, oxygen saturation and partial pressure of oxygen in COVID-19 cases than control (23). In a study by Malik SUF et al., blood biomarkers notably serum ferritin, CRP, D-dimer, ALT, troponin I, were significantly (p-value <0.05) higher in COVID-19 patients. Ferritin was significantly (p-value <0.05) higher in DM than Non DM COVID-19 patients (24). In a study by Guo W et al., in Wuhan Union hospital, inflammation-related markers, such as CRP {76.4 mg/L (IQR,12.4-93) vs 7.43 mg/L (3.14-13.45)}, and serum ferritin {764.8 ng/mL (IQR: 164-1496) vs 128.9 ng/mL(IQR: 57.25-193.15)} was found to be significantly higher in COVID-19 patients with DM as compared to non diabetics in absence of other comorbidities in both the groups (25).

Ferritin induces the activation of the monocyte-macrophage system which is a crucial part of the inflammatory storm (26). In a pooled analysis aimed to compare inflammatory storm and hypercoagulability status between diabetic and non diabetic COVID-19 patients, Varikasuvu SR et al., found that the levels of serum ferritin, CRP, and D-dimer were significantly higher in diabetic COVID-19 cases as compared to non diabetic COVID-19 patients, suggesting more susceptibility of diabetic COVID-19 patients to coagulation dysfunction and inflammatory storm (27). Along with the above markers, hematological markers also play an important role in the COVID-19 prognosis. Neutrophil to Lymphocyte ratio (NLR) is considered to be of great value in indicating a patient’s inflammatory status (28). Neutrophil count was found to be significantly raised and lymphocyte count was lower in diabetic cases. In a study by Celine et al., NLR was found to be markedly raised in COVID-19 symptomatic patients with DM (29). With decreased immune response in diabetics (30), the raised levels of inflammatory markers along with uncontrolled hyperglycemia signify exacerbation of the chronic inflammation, a characteristic pathology of DM progressing to cytokine storm and rapid deterioration of endothelial function if left untreated.

D-dimer level was studied as a marker of severity in COVID-19 patients by Saravanan B et al., in Tirunelveli Medical College. It was noted that the odds of patients with high levels of D-dimer being clinically symptomatic was 5.5 times more than the odds of patients with D-dimer levels <500 ng/mL (31). In the present study, the markers of coagulation, D-dimer, APTT, PT was found to be significantly raised in the diabetic group as compared to non diabetics. D-dimer level in COVID-19 patients with DM have been shown to be significantly high in studies by Varikasuvu SR et al., and Alguwaihes AM et al., (27),(32). Retrospective study by Chen X et al., conducted in Wuhan Jinyintan hospital showed that D-dimer levels in COVID-19 patients with DM were significantly increased in non survivors (33). Elevated D-dimer levels are a direct consequence of increased fibrin formation and lysis and thus an indicator of increased thrombotic activity (34). This increased thrombotic activity signified by high D-dimer levels can result in Disseminated Intravascular Coagulation (DIC) or thromboembolism leading to the development of post COVID-19 complications. High D-dimer levels have been reported as one of the risk factors for occurrence of ARDS in COVID-19 patients (35). In the present study, a higher percentage of diabetic COVID-19 patients were found to suffer from ARDS 146 (48.7%) and Acute kidney injury 41 (13.7%) as compared to non diabetics.

Zhu L et al., in a study in Hubei province of China found that subjects with DM suffered from multiple organ injury and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio: 1.49) as compared to non diabetic individuals (36). In a study by Shiv Lal et al., in a tertiary hospital in Chandigarh, India, significant association was found between severe COVID-19 disease and co-morbid conditions, DM and hypertension (37). Studying the prognosis, DM patients were found to have more adverse outcomes, in terms of more percentage of diabetic patients required oxygen therapy, ICU admissions and suffered from post COVID-19 complications. Percentage of mortality was also high among diabetics as compared to non diabetics. Similar adverse outcomes have been reported in studies by Goyal P et al., (10). Wang et al., found that patients with DM constituted 22.9% of ICU patients vs 5.9% of non ICU patients (12). Guan WJ et al., showed that 26.9% of COVID-19 patients with DM as compared to 6.1% non diabetics suffered from severe infection and met the primary composite end point of ICU admission, mechanical ventilation and death (4).

DM or uncontrolled hyperglycemia increased the length of hospital stay and mortality. However the study findings of Shi Q et al., DM (HR:1.58, 95% CI: 0.84-2.99) contradict this finding and rule out any association between DM and mortality or ICU admissions (38). But DM still remains a major co-morbidity bringing about adverse prognosis. Increased risk of ICU admissions and in-hospital mortality in diabetic COVID-19 patients can be tried to be explained by advanced age, presence of diabetic complications, and inflammation further exaggerating the Insulin resistance (39). But taking into account the COVID-19 pathophysiology other factors like hyperglycaemia associated prothrombotic state should also be considered (40). The common pathology of COVID-19 and DM suggest that acute COVID-19 induced adverse reactions may superimpose on pre-existing inflammation, glucose variability and multi tissue injury in patients with DM to aggravate adverse outcomes.

Limitation(s)

The study did not take into consideration the complications of DM in the diabetic case group at the time of admission, which may have individually contributed to the adverse outcomes in the diabetic case group. Duration of DM was also not taken into consideration.

Conclusion

This retrospective study provides direct evidence supporting the severity of COVID-19 infection in diabetic patients resulting in significantly higher mortality as compared to non diabetic patients. Keeping these findings under consideration the diabetic patients should be taken as a high risk group and vigorous monitoring as regards to glycaemic control, inflammatory markers and coagulation profile should be undertaken. This will help in early detection of cytokine storm and impending coagulation disorder so that preventive treatment can be initiated at the earliest to reduce risk of thromboembolism and DIC, thereby decreasing the morbidity and mortality of diabetic COVID-19 infected patients.

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DOI and Others

DOI: 10.7860/JCDR/2022/55998.16424


Date of Submission: Mar 03, 2022
Date of Peer Review: Mar 19, 2022
Date of Acceptance: May 16, 2022
Date of Publishing: Jun 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. No

PLAGIARISM CHECKING METHODS:
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