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

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Dr Mohan Z Mani

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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 : August | Volume : 16 | Issue : 8 | Page : BC19 - BC23 Full Version

Correlation of Lipid Profile with Inflammatory Markers among COVID-19 Positive Patients: A Retrospective Study


Published: August 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/55477.16744
Asha Kumari, Yuthika Agarwal, Sangeeta Bhattacharya Singh, Shikhaa Mahajan, Vivek Sharma

1. Assistant Professor, Department of Biochemistry, Shaheed Hasan Khan Mewati Government Medical College, Nalhar, Nuh, Mewat, Haryana, India. 2. Assistant Professor, Department of Biochemistry, Shaheed Hasan Khan Mewati Government Medical College, Nalhar, Nuh, Mewat, Haryana, India. 3. Professor and Head, Department of Biochemistry, Shaheed Hasan Khan Mewati Government Medical College, Nalhar, Nuh, Mewat, Haryana, India. 4. Associate Professor, Department of Biochemistry, Shaheed Hasan Khan Mewati Government Medical College, Nalhar, Nuh, Mewat, Haryana, India. 5. Demonstrator, Department of Biochemistry, Shaheed Hasan Khan Mewati Government Medical College, Nalhar, Nuh, Mewat, Haryana, India.

Correspondence Address :
Dr. Asha Kumari,
House No. 504, C-2 Block, Shaheed Hasan Khan Mewati Government Medical College,
Nalhar, Nuh, Mewat-122107, Haryana, India.
E-mail: drashatigraniya@gmail.com

Abstract

Introduction: Lipids are fundamental biomolecules of the body. Infections like Coronavirus Disease-2019 (COVID-19) with intricate immune response in some patient’s leads to acute complications by affecting metabolic pathways at multiple levels. Metabolism of cholesterol, triglyceride and High Density Lipoprotein-Cholesterol (HDL-C) is deranged by cytokines and multiple inflammatory mediators. The sex differences in lipid metabolism may contribute in susceptibility, severity and outcome COVID-19. Performing lipid profile in COVID-19 patient may help in assessing severity and prognosis of disease.

Aim: To assess the relationship between lipid profile and inflammatory markers in COVID-19 patients and also to evaluate the gender-wise differences in lipid parameters and their correlations with inflammatory markers.

Materials and Methods: This retrospective study was conducted in Department of Biochemistry at SHKM, GMC, Mewat, Haryana, India (tertiary care health centre) on COVID-19 positive patients attending Outpatient Department (OPD) and Inpatient Department (IPD), from October 2020 to December 2020. The data of 85 patients with COVID-19 positive, confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and who were prescribed for lipid profile along with C-Reactive Protein (CRP) and serum ferritin were included in the study. Serum total cholesterol, triglyceride, HDL-C, CRP and ferritin were measured in the subjects. Data was statistically analysed using Student’s t-test and Pearson’s correlation coefficient.

Results: Total 85 (46 males and 39 females) COVID-19 patients were included in the study. Mean age in male and female patients were 43.02±15.52 years and 42.02±15.25 years, respectively with a range of 5-82 years. Mean value of Serum triglycerides, HDL-C and total cholesterol was 204.94±141.27 mg/dL, 42.97±13.38 mg/dL and 187.058±45.75 mg/dL, respectively. Serum triglycerides were statistically significantly higher in males than females (p-value=0.0413). The HDL-C, however, was significantly higher in females than males (p-value=0.0006). In male patients, r-value between cholesterol and CRP was -0.3538, and p-value was 0.016. Ferritin had a significant negative correlation with HDL-C (r-value=-0.3578, p-value=0.00079). Weakly positive correlation was noted between triglyceride and ferritin (r-value=0.2285, p-value=0.035).

Conclusion: High levels of serum triglycerides, low total cholesterol, and low HDL-C correlates with inflammatory markers like CRP and ferritin in COVID-19 patients. Lipid profile may be used as a potential marker in all COVID-19 patients in assessing prognosis of disease.

Keywords

Cholesterol, Coronavirus disease 2019, Ferritin, Triglyceride

It has been almost two years since the outbreak of COVID-19 from Wuhan, China. The world seems to be struggling in the claws of this pandemic (1). The clinical spectrum of COVID-19 ranged from mild asymptomatic cases to severe pneumonia which along with intense systemic inflammation, resulted in acute respiratory distress syndrome, organ failures and death (2). Other causes of fatalities implicated were acute cardiac injury, venous thromboembolism, acute kidney injury, coagulopathy and shock (3).

Major pathophysiological pathways have been hypothesised which can predict varied clinical presentation but other potential factors needs to be identified for better patient care (4). Severity of COVID-19 increases with age, male gender and co-morbidities like diabetes mellitus and hypertension. The associations are multifactorial. Scavenger Receptor class B type 1 (SRB1), an important protein for High Density Lipoprotein (HDL) cholestrol trafficking helps in binding for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) proteins (4).

Lipids are fundamental structural components of bio membranes and participate in various processes of infection. The binding of SARS-CoV-2 to host cell membrane, activation, cell entry and spread to other cells is affected by lipid composition of membrane especially cholesterol-enriched lipid rafts (5). Mass Spectrometry (MS)-based proteomics analysis suggested that the derangements in lipid metabolism may favour the progression of COVID-19 (6). After replication inside the cytoplasm, virus is released from cell membrane. A cell culture based study has shown that cellular SARS-CoV-2 infectivity is increased by cholesterol present inside the cell (7). Virus modifies the lipid and carbohydrate metabolic pathways of host cell. A specific lipidomic fingerprint has been observed in COVID-19 patients by a metabolomics study (8). Apart from forming bio membranes and providing energy, lipids are important cell signaling molecules. The metabolic derivatives of cholesterol may have immunomodulatory properties like affecting the regulatory T-cell proliferation (9) (Table/Fig 1).

Viral infections hamper these biological functions of lipids and promote cell apoptosis and death (4). Inflammatory mediators synthesised during the infection derange lipid metabolism by lowering cholesterol synthesis and absorption, reducing clearance of triglyceride-rich lipoprotein and decreasing production of Apolipoprotein A1. Earlier a study noticed a fall in HDL-C and Low Density Lipoprotein (LDL)-Cholesterol (sometimes) levels along with maintained or raised Triglyceride levels during infections (10). In COVID-19, low LDL-C, HDL-C and Triglyceride (TG) levels have strong correlations with disease severity. Another factor linked with severity is Sterol Regulatory Element-Binding Protein 2 (SREBP-2) C-terminal fragment activated by COVID-19 in patient’s blood which may become a therapeutic target for preventing cytokine storm (11).

Lipid profile of populations of various countries showed considerable ethnic differences in a study. Asian Indians were reported to have higher adverse lipid pattern due to low HDL-C and high TG as compared to other countries, making them more prone to high prevalence of Cardiovascular Disease (CVD) and diabetes mellitus. Decreased HDL-C was more common in Asian Indians even with desirable LDL-C levels, irrespective of their diabetic status. Factors responsible for this included genetic, environmental, psychosocial, cultural and unexplained causes (12).

Taking into account the high prevalence of lipid disorders and their cardinal role in COVID-19, differences of lipid profile in Indian population from other countries, this study was planned to evaluate the levels of total cholesterol, triglyceride and HDL-C along with C-Reactive Protein (CRP) and ferritin in COVID-19 patients in rural district of Haryana, India where no such study has been conducted so far.

Hence, the present study was performed to assess the relationship between serum total cholesterol, triglyceride and HDL-C with serum CRP and serum ferritin which are markers of inflammation in COVID-19 patients. Also to evaluate any differences in male and female patients in lipid parameters and their correlation with inflammatory markers i.e, serum CRP and ferritin.

Material and Methods

This retrospective study was conducted in Department of Biochemistry at SHKM, GMC, Mewat, Haryana, India (tertiary care health centre) on COVID-19 positive patients attending Outpatient Department (OPD) and Inpatient Department (IPD), from October 2020 to December 2020. Data were analysed in February 2021. The study was approved by the Ethics Committee of the Institution (EC/OA-26/2020).

Inclusion criteria: All COVID-19 positive patients, confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and who were prescribed for lipid profile laboratory examination along with C-Reactive Protein (CRP) and serum ferritin were included in the study.

Exclusion criteria: Children younger than five years were excluded from the study.

Sample size calculation: The sample size was calculated using confidence interval 95%, margin of error 5% and population proportion 5%, i.e, N=73. But for final sample size, the retrospective data of 85 COVID-19 positive patients including 46 males and 39 females were collected in the study.

Data Collection

Values of all the parameters were recorded from patient files along with other demographic details (age and gender) available in Medical Record Department (MRD). The values of serum Triglycerides (TG), total cholesterol, High Density Lipoprotein (HDL), serum CRP and serum ferritin values were entered in patient performa and a masterchart for statistical analysis was made in Apple MacBook Air Numbers App. Very Low Density Lipoprotein (VLDL) is a calculated parameter from TG in the machine and no separate kit is used. So, the results of VLDL are actually same as TG. Tests were performed on Roche auto analyser C501 using methods and reference intervals as mentioned in (Table/Fig 2) (13),(14),(15).

Definitions were taken from National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) guidelines (Table/Fig 3) (16). Atherogenic dyslipidaemia: Elevated levels of TG and small-dense low-density lipoprotein and low levels of HDL-C (16).

Statistical Analysis

Data was collected in numbers application and statistically analysed using Pyscripter software. Mean and Standard deviation (SD) were calculated for continuous variables with normal distribution. Differences between groups were tested using Student’s parametric t-test for continuous variables. A p-value <0.05 was taken as significant. Pearson’s correlation coefficient was used to estimate the strength of correlation between parameters.

Results

Total 85 (46 males and 39 females) COVID-19 patients were included in the study with age of 42.56±15.31 years. Mean age in male and female patients were 43.02±15.52 and 42.02±15.25 years, respectively. Serum triglyceride levels were significantly higher in males (233.63±146.92 mg/dL) than females (171.10±127.99 mg/dL), (p-value=0.0413). The HDL-C however was significantly higher in females (48.23±12.92 mg/dL) than males (38.52±12.20 mg/dL) (p-value=0.0006). All values of lipid profile parameters and inflammatory markers between male and female are presented in (Table/Fig 4).

Nine (19.57%) male patients and 4 (10.26%) females had CRP levels >5 mg/dL. Inflammatory marker, serum ferritin in 18 (39.13%) male patients was above 400 ng/dL and 5 (10.86%) male patient had <30 ng/dL. Ferritin <15 ng/dL (lower limit) was noticed in 4 (10.26%) females while 8 (20.51%) females had ferritin >150 ng/dL (higher limit). Out of total, 3 (7.7%) females patients had serum ferritin >400 ng/dL. These results indicate more inflammation in male subjects as compared to females in COVID-19.

A statistically significant negative correlation between cholesterol and CRP was found in male patients (r-value=-0.3538, p-value=0.016). The correlation between cholesterol and ferritin was a very weak negative correlation (r-value=-0.1717) in total cases (Table/Fig 5).

Another significant inverse correlation was discovered between serum ferritin and HDL in male patients (r-value=-0.3917, p-value=0.0070). Females patients had no correlation between HDL and ferritin (r-value=0.0035). Weak positive correlation was noted between TG and ferritin (r-value=0.2285, p-value=0.035).

In COVID-19 positive females, triglycerides increases with age (r-value= 0.3047; p-value=0.0045). Similarly ferritin concentrations also rises with progressing age in female (r-value=0.3013) and male (r-value=0.284) subjects (Table/Fig 6).

Discussion

The present study is the first study on lipid profile in COVID-19 patients in north India. Number of cases included in the study was 2185 as lipid profile was a less requested investigation in COVID-19 patients as compared to blood glucose and inflammatory markers. Masana L et al., also highlighted the low prescription of lipid profile in COVID-19 patient care (17).

The results of present study demonstrated hypolipoproteinemia and hypertriglyceridemia in COVID-19 patients. Decrease in HDL-C concentration and elevation of triglyceride level was positively correlated with ferritin levels. CRP and ferritin levels were negatively correlated with total cholesterol level.

A meta-analysis performed on 19 studies supported the role of lipid profile in both severity and prognosis of COVID-19 (18). Significantly decreased levels of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were found in the severe group when compared with the non severe group in a random effect model. However, no significant difference was observed in the level of TG between severe and non severe groups or survivor and non survivor groups (18).

These derangements in lipid metabolism were more pronounced in male patients as compared to females. Triglycerides levels and ferritin levels were associated with progressing age in females. This gender bias has been less studied in previous studies [19-21]. Lipid profile derangements with growing inflammation may be used to assess severity and prognosis of COVID-19 and help in better patient care. Being one of the major metabolic pathway of body, the effect of alterations in lipid chemistry is going to be paramount.

The severity of COVID-19 is reflected by rise in inflammatory markers like CRP and ferritin. In COVID-19 pandemic, it was noticed that patients who were overweight and obese required more IMV and had higher peaks of CRP and ferritin than patients with normal weight (22). Few studies on effects of COVID-19 on lipid profile have been conducted (19),(20).

It was shown that the increased concentration of total cholesterol, low density lipoprotein, high density lipoprotein and triglycerides in the serum was inversely correlated with the severity of COVID-19 (4). Another study concluded, that low HDL-C levels and high triglyceride levels are important high risk markers for COVID-19 hospital admitted cases (17).

Most of the studies analysed lipid results of patients after becoming COVID-19 positive, but Barman HA et al., reported that the temporal changes in lipid parameters before and after COVID-19 may be associated with mortality and in-hospital adverse outcomes (19),(20),(23).

Review article by Surma S et al., found a similar potential link between the incidence of lipid disorders and the prognosis of COVID-19 patients along with a role of statins in the treatment (24). Lowering of serum lipid concentrations probably leads to worsening of inflammation, hypercoagulation and impairment of oxygen which results in multiorgan failure (6).

Multiple hypotheses have emerged by accruing research on mechanisms underlying the link between lipids and COVID-19. Earlier, it was thought that a hypercatabolic state and poor nutritional status of patient during infection is the reason for lower lipids values (25). Patients infected with a virus strain which is more evolved presents with significantly raised triglyceride and decreased HDL-C levels (26). Robust scientific proofs are available to support the changes in lipid pathways, in presence of inflammation or infections (27).

It is well known that numerous cytokines and inflammatory markers are released during infections. These molecules interacts with Lipoprotein lipase (LPL) and its regulatory proteins. The LPL is also inhibited by bacterial products and modified lipoproteins (28). The LPL is a chief enzyme involved in lipid abnormalities during infections. When LPL activity is hampered, triglyceride rich lipoproteins are less converted into LDL, resulting in hypertriglyceridemia and low HDL levels. Other causes of low HDL levels are decreased Cholesteryl Ester Transfer Protein (CETP) activity, poor app A1 synthesis and faster HDL clearance (28).

Lipoproteins enriched with triglycerides can bind toxins, thus play a role in innate immune response. HDL is also a key molecule in inflammation that binds toxins and help in its clearance from liver. So another player of innate immunity, the HDL when lowered may affect the course of disease. Drug-induced effects of statins and corticosteroids could not explain the atherogenic dyslipidaemia seen in COVID-19 (29).

A substantial difference in severity of COVID-19 has been suggested between men and women, with women having better prognosis and outcome than men. Prevalence of COVID-19 infection in male and female was 53.3% and 46.7%, respectively in a study done in 2020 and the death rate was also higher in males (58.3%) than females (41.7%) (30). Sex hormone testosterone in male was hypothesised to be a risk factor and oestrogen in female subjects was assumed to be protective in COVID-19 (31). Bhatia V et al., noted that inflammatory mediators continue to remain elevated in men having lower levels of testosterone (31).

Klein SL and Flanagan KL, studied the sex differences in immune responses and found that in men, severity of COVID-19 is more due to enhanced Angiotensin-Converting Enzyme 2 (ACE2) expression in lungs and stimulation of Transmembrane Protease, Serine 2 (TMPRSS2) expression. TMPRSS2 is a protein present on endothelial cell surface protein that participates in viral entry and spread of SARS-CoV-2. In females, on the other hand less severity of COVID-19 was probably due to two reasons, one is decreased ACE2 expression in lung and second is inhibition of TMPRSS2 expression by oestrogen (32).

As per scientific data, females have less risk factors for cardiovascular diseases than males. Factors like protein, lipidome, insulin resistance and messenger Ribonucleic Acid (mRNA) expression are comparatively favourable in females than males (33). Accumulation of more visceral fat in males as compared to females is an important hypothesis to explain more severe COVID-19 in males (34). Adipose tissue in men have greater number of macrophages and immune cells which can secrete more cytokines for longer duration than female adipose tissue. So, visceral fat can function as a source for flaring up cytokine levels in men (35).

Limitation(s)

Due to retrospective design of study, it was difficult to derive causal relationships. It was not ascertained that the lipid profile was always fasting. Another limitation was that the severity of COVID-19 disease was not taken into account. The kit for LDL was not available in the department.

Conclusion

Lipid profile is a basic investigations available in even small laboratory setups where inflammatory markers like ferritin and CRP may not be available. Lipids are important biomarkers of inflammation and infection and will be helpful in COVID-19 patient care. Lipids participate in immune response and also modulate course of disease. Triglyceride, cholesterol and HDL-C are associated with inflammatory markers and hence, may be used for assessing severity and prognosis of COVID-19. Studies with large sample size needs to be explored in India.

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DOI and Others

DOI: 10.7860/JCDR/2022/55477.16744

Date of Submission: Feb 05, 2022
Date of Peer Review: Mar 01, 2022
Date of Acceptance: May 27, 2022
Date of Publishing: Aug 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:
• Plagiarism X-checker: Feb 22, 2022
• Manual Googling: May 17, 2022
• iThenticate Software: Jul 19, 2022 (14%)

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