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

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On Sep 2018




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



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On Aug 2018




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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.
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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.
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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.
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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 : February | Volume : 16 | Issue : 2 | Page : BC01 - BC04 Full Version

Association of Serum Lactate Dehydrogenase and Qualitative C-Reactive Protein with the Severity of COVID-19 Disease


Published: February 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/52186.15939
Barnali Thakur, Keshab Bora, Manidip Chakraborty

1. Associate Professor, Department of Biochemistry, Silchar Medical College and Hospital, Silchar, Assam, India. 2. Assistant Professor, Department of Biochemistry, Silchar Medical College and Hospital, Silchar, Assam, India. 3. Postgraduate Trainee, Department of Biochemistry, Silchar Medical College and Hospital, Silchar, Assam, India.

Correspondence Address :
Dr. Manidip Chakraborty,
Postgraduate Trainee, Department of Biochemistry, Silchar Medical College, Silchar, Assam, India.
E-mail: dr_mchak@yahoo.co.in

Abstract

Introduction: After December 2019, the word “COVID” became the nightmare to the civilisation. As per the nomenclature laid by World Health Organisation (WHO), the disease is called Coronavirus Disease-2019 (COVID-19) and the causative virus is Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). By August 11th 2021, the virus caused around 43 lac deaths with an infection burden of approximately 20.3 crore cases worldwide. Many studies are published from most of the corners of the world regarding clinical features, laboratory parameters and radiological features of the disease to identify the infection at an early stage. Serum Lactate Dehydrogenase (LDH) and C-Reactive Protein (CRP) are among the most commonly studied parameters in COVID-19, though in India, a smaller number of studies were done in this regard. As the disease itself is new to the medical fraternity, maximum studies were done with small sample size which requires more studies to confirm the findings.

Aim: To find out the association of on-admission serum LDH and qualitative CRP with the severity of COVID-19 disease.

Materials and Methods: The present study was a retrospective observational study conducted for three months from May to July 2021. A 114 Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) positive COVID-19 patients were included as per the inclusion-exclusion criteria of which 57 were from Intensive Care Unit (ICU), considered as ‘severe’ patients and 57 from ward, taken as ‘non severe’ patients. Required blood parameters including LDH and CRP values were obtained from Laboratory Information System (LIS) and clinical data was obtained from hospital database. The values were analysed using statistical software.

Results: Present study showed significant difference in values of LDH among ICU and ward patients (p=0.0001), also significant difference of CRP positive percentage between these two groups (p=0.0003) was observed.

Conclusion: On the basis of the findings of the present study, it can be concluded that on-admission LDH and CRP can be used as a marker of severity in COVID-19 disease.

Keywords

Coronavirus disease-2019, Multiorgan dysfunction syndrome, Severe acute respiratory syndrome coronavirus-2

Since more than a year, the whole world is fighting a pandemic of COVID-19. It was first observed in Wuhan, China in December 2019 as a contagious respiratory tract infection which in severe form causes atypical pneumonia and subsequently Acute Respiratory Distress Syndrome (ARDS) and lastly Multiorgan Dysfunction Syndrome (MODS) and death (1). Later, the culprit virus was identified as SARS-CoV-2 (2). As per WHO nomenclature, the disease was named as COVID-19 (3). The disease spread to the rest of the world within a short span of time. On 30th January 2020, WHO declared it as a ‘public health emergency of international concern (4) as the disease was spreading to rest of the world at a jet speed and ultimately on 11th March 2020, WHO announced COVID-19 disease as a global pandemic (3). India is also fighting since January 30, 2020 when the first case of COVID-19 disease was identified in Kerala, India (5). Presently, India has a total number of 3.2 crore cases with a death toll of 4.28 lacs (6),(7). The state of Assam is having a disease burden of 580,657 with number of deaths 5,502 (8). (All data as on 11th August, 2021).

The most studied haematological parameters in COVID-19 infection are serum LDH, CRP, ferritin, D-dimer, lymphocyte count, Interleukin-6 (IL-6) etc. LDH is an enzyme which causes reversible conversion of pyruvate to lactate (9). LDH is found in almost all the major organ tissues in abundance in the form of five different iso-enzymes like LDH1 is mostly found in heart, LDH2 in reticulo-endothelial system, LDH3 in lung, LDH4 in kidney and pancreas and LDH5 is abundantly found in liver and skeletal muscle. So, any tissue injury of these organs causes cell death and subsequent rise in serum LDH level (10).

The SARS-CoV-2 virus has higher affinity for Angiotensin Converting Enzyme 2 (ACE-2) receptors which are highly expressed on alveolar cell type 1 and type 2. The virus enters first through lung as a result of interaction between S protein of virus and ACE-2 receptor (11). Gradually, it stimulates the macrophages in alveoli and then there is a stimulation of innate immunity which later becomes uncontrolled due to release of excessive pro-inflammatory cytokines (12), there is loss of alveolar-capillary barrier and pneumonia develops which turns to ARDS. As a result of lung tissue damage, LDH3 rises initially which reflects an increase in serum LDH level. In advance stage of the disease, further serum LDH rise occurs due to the injury of myocardium, kidney, liver etc., by the virus as a part of cytokine storm which causes MODS (13).

The CRP is used in the clinical practice from a long time as a marker of some pro-inflammatory conditions like sepsis. It is an acute phase protein in the pentraxin family of ligand-binding plasma proteins which are also calcium dependent (14). Site of production is usually liver and it grossly responds to the tissue damage secondary to inflammation while stimulated by some pro-inflammatory cytokines like IL-6. In pro-inflammatory conditions it starts to rise within 4-6 hours and reaches its peak in 36-50 hours (15).

In COVID-19 disease, it is the cytokine storm which makes the disease complicated and severe. In cytokine storm, there is uncontrolled release of pro-inflammatory cytokines like IL-6 which ultimately leads to tissue damage and MODS. Keeping pace with the extent of inflammatory process and tissue damage, CRP also rises in proportion. This makes CRP an important parameter to assess the disease prognosis and severity in COVID-19 disease as described in many studies in regard to COVID-19 disease (16),(17).

The sheer number of patients being admitted with COVID-19 infection overwhelms the capacity to test for multiple parameters and risk stratify them. Many hospitals in India do not have the facility of conducting IL-6, ferritin or D-dimer tests. With this view, in present study, authors have included serum LDH and CRP, measured on admission, as a main variable with an aim to observe any association of these two parameters with the severity of the disease as in India comparatively less number of studies was being conducted in this regard. This will verify the early positive results of other countries and also will help to identify potentially high risk patients for developing severe disease so that timely intervention can reduce the mortality too.

Material and Methods

The present study was a retrospective observational study conducted for three months, in the Department of Biochemistry; Silchar Medical College, Assam, India. Data was collected from May 2021 to July 2021, and was analysed in August 2021. The study was done abiding all the ethical norms of the Institute. None of the identifications of the patients were disclosed. As it was a retrospective study, no patient was examined by the authors. Though, all the procedures were done as per the guidelines of the Ethical Committee of the Institute, but during the peak of the COVID-19 second wave here, ethical committee clearance could not be obtained, however considering importance of the situation and the need of the study, the study was proceeded further.

Inclusion criteria: Patients with age more than 18 years, patients diagnosed with COVID-19 infection by RT-PCR method and admitted in either the ward or the ICU were included.

Exclusion criteria: Patients diagnosed with haematological malignancies or solid tumours, patients taking immunosuppressive drugs for another disease, patients with a recent history of solid organ transplant or bone marrow transplant, patients with any known chronic disease of liver, kidney and heart, patients with disease of musculoskeletal system, patients with chronic systemic inflammatory disease.

Sample size calculation: The population was around 160 (since during the study period approximately 160 on an average COVID-19 patients were admitted daily) So, with 5% marginal errors and 95% Confidence Interval (CI), the sample size was calculated using online sample size calculator and it came around 113 (18). The final sample size was taken as 114 for present study.

Data Collection

Total of 114 patients, who fulfilled inclusion-exclusion criteria; diagnosed for COVID-19 disease by RT-PCR method were included in the study. Among them 57 patients were included from COVID ward and 57 other patients were included from COVID ICU. As per the hospital protocol, clinically non severe patients (asymptomatic, mild symptomatic or patients who required less than 5 litre/min oxygen only and without any co-morbidity) were kept in COVID ward and in the present study, this group of patients was considered as non severe group. Clinically, severe patients (symptomatic with oxygen requirement more than 5 litre/min and with co-morbidities, patients who required invasive or non invasive respiratory assistance etc.,) were kept in ICU and this group was considered as severe group. Data regarding their biochemical parameters were extracted from the LIS of the Institute.

The values of serum LDH and CRP on admission to ward/ICU were collected for each patient. Cut-off CRP level was taken as 10 mg/dL (15). Relevant history of the patient was collected from hospital database.

Statistical Analysis

Microsoft excel version 14.0.4734.1000 with add-ons and Graph pad online free version were used for statistical analysis. Mean and Standard Deviation (SD) was used to represent continuous variables whereas percentage used for categorical variables. Analysis regarding any association of serum LDH and CRP with the severity of disease was done by comparing serum LDH level and qualitative CRP in both the groups. Among statistical tests, Chi-square statistics were used where p<0.05 was taken as significant and unpaired t-test with CI of 95% was also used.

Results

Data of 114 COVID patients were analysed (57 from ICU and 57 from ward). Distribution of study participants according to the age showed around 43.9% of the patients falls in the age group of 40-59 years. In ward and ICU also, this age group 40-59 years had the maximum number of patients with percentage of 42.1% and 45.6%, respectively. The mean age of the ward patients was 51.5 years where as in ICU patients, mean age was 58.73 years (Table/Fig 1).

Gender wise distribution shows male patients were 64.9% of total. The sex distribution was not significant statistically between ICU and ward patients (severe and non severe patients) with p-value of 0.6946 (Table/Fig 2).

It was found that 58.7% patients were CRP positive of which 75.4% ICU patients had positive CRP and 42.1% ward patients had positive CRP. The difference was statistically significant with p-value of 0.0003 (Table/Fig 3).

The values of serum LDH level between severe COVID-19 patients (ICU patients) and non severe COVID-19 patients were compared (ward patients), the difference came out extremely significant with p-value of 0.0001 (Table/Fig 4).

Discussion

The clinical spectrum of COVID-19 infection can vary from asymptomatic forms to interstitial pneumonia with different lung damage and the development of ARDS (19). In COVID-19 patients, LDH and CRP might represent an expression of lung damage and might reflect the respiratory distress consequent to the abnormal inflammation status. In a small cohort of 27 patients, CRP correlated with CT findings and resulted significantly increased at the early stage of severe COVID-19 before changes in the CT score (20).

In the present study, most patients were in the age group of 40-59 years with a percentage of 43.9% and there was a male dominancy with 64.9%. Wu MY et al., in their study observed 47 patients were male out of 87 (54%) and their median age was 44 years (9). Zhang ZL et al., in their systemic review with 28 studies and meta-analysis with seven studies which comprises of 4663 patients observed that the mean age of the studies was 48.4 years with 46.7% female participants (2).

In the present study, 43 CRP positive cases were out of 57 ICU admitted patients (75.4%), and 24 CRP positive cases out of 57 non ICU patients (42.1%). The authors got the LDH mean of 551.69 U/L (with range of 182.8-2115.4 U/L) and in non severe patient group it was 441.04 U/L and in severe group 660.41 U/L. So, there was statistical significance of the difference of both CRP and LDH (p-value is 0.0003 and 0.0001, respectively) in severe group when comparing with the non severe group. Wu MY et al., got LDH level 495.1±28.22 U/L with a range 158-1482 U/L in 87 patients while in non severe group they found the level was 442±17.47 U/L and in severe group 1040±158.3 U/L. They found the difference was statistically significant with p-value of <0.01 (9). Zhang ZL et al., found both the CRP and serum LDH was high in severe group of patients in most of the study (2). Fan BE et al., in their analysis, which was done with COVID patients, ICU (n=9) and non ICU (n=58) patients got significant difference of LDH level between two groups (p-value=0.005) (4). Though this study comprised of small sample size but the finding was similar to the present study which has comparatively large sample size with COVID ICU (n=57) and non ICU (n=57) patients with statistically significant serum LDH difference (p<0.0001).

Tjahyadi RM et al., in their study with 69 COVID-19 patients found that, in 37 patients of severe group CRP value was significantly high compare to mild to moderate group and they found the association of CRP with the disease severity with p-value=0.011 (17). They also got higher serum LDH value in severe group with a mean of 1047 U/L (range 524 U/L-2239 U/L) compared to mild to moderate group which was 717.35 U/L as mean (range 270 U/L-1570 U/L). They found the difference was statistically significant with p-value<0.001 (17). The result was very similar to the finding of the present study where both the CRP and serum LDH which was measured on-admission, have statistically significant difference in values in ICU group of patients compared to ward-patient group with a p-value of 0.0003 and 0.0001, respectively. So, many studies showed positive correlations between LDH and severity of the disease and between CRP and the disease severity and support the findings of the present study.

Limitation(s)

The present study had some limitation. Firstly, larger sample size is required for the validation of the findings and secondly, the authors didn’t consider super-added infections or sepsis which may appear secondarily and can influence these two parameters.

Conclusion

Based on the findings of the present study, it can be said that as the on-admission serum LDH and CRP were found significantly higher in severe groups of COVID-19 patients (ICU patients), these two parameters can be used as markers of severity in SARS-CoV-2 infection and can be used to identify the potentially high risk patients who may develop severe form of the disease. This may help in decision making in case of high risk patients and thereby will help to reduce the mortality and morbidity. Moreover, the result of the present study has verified the findings of other studies where these two parameters were found to be clinically significant.

Acknowledgement

The authors are grateful to all the faculty members of Department of Biochemistry, Silchar Medical College, for their encouragement and support. The authors also sincerely thank to Dr. Kushal Kalvit from Tata Memorial Hospital, Mumbai, Dr. Nabiha Mayanaz Karim, Postgraduate Trainee, Department of Biochemistry, Silchar Medical College, Dr. Anjan Datta, from Tripura Medical College, Agartala, Tripura; for their selfless help and support.

References

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DOI and Others

DOI: 10.7860/JCDR/2022/52186.15939

Date of Submission: Sep 01, 2021
Date of Peer Review: Sep 20, 2021
Date of Acceptance: Dec 17, 2021
Date of Publishing: Feb 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? No
• 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: Sep 02, 2021
• Manual Googling: Nov 20, 2021
• iThenticate Software: Dec 14, 2021 (5%)

ETYMOLOGY: Author Origin

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