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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
Original article / research
Full Version
Association of Serum Calcium and Serum Uric Acid Level with Inflammatory Markers to Predict the Outcome of COVID-19 Infection: A Retrospective Study
Correspondence Address :
Dr. D Namitha,
Assistant Professor, Department of Biochemistry, Adichunchanagiri Institute of Medical Sciences, Mandya, Karnataka, India.
E-mail: namitha25.nami@gmail.com
Introduction: Novel Coronavirus Disease 2019 (COVID-19) is an acute respiratory disease and the severity of COVID-19 is highly variable, ranging from asymptomatic infection to life-threatening disease. Therefore, biomarkers are required to assess the prognosis of the disease at the earliest.
Aim: To determine the correlation of serum calcium and serum uric acid levels with inflammatory markers of COVID-19 infection and also to assess serum calcium and serum uric acid levels in predicting the outcome of COVID-19 infection.
Materials and Methods: A retrospective study was conducted in Adichunchanagiri Institute of Medical Sciences, B.G Nagara, Karnataka, India from 1st April 2021 to 30th June 2021. Out of 483 COVID-19 infected patients admitted during the study period, data of 136 patients, investigated for serum calcium and serum uric acid levels were collected from medical records. Patients were categorised into survived and non survived group based on the outcome. Descriptive statistics, Analysis of Variance (ANOVA) test, Student’s t-test were applied. Receiver Operating Characteristic (ROC) curve was used in predicting the outcome of COVID-19 infection.
Results: Of the 136 COVID-19 positive patients, 87 were male and 49 were female patients. Mean age of non survived was significantly higher (59.19±12.6 years) as compared to survived patients (44.44±13.35 years). Further, Random Blood Sugar (RBS), C-Reactive Protein (CRP), Lactate Dehydrogenase (LDH) and D-dimer values were significantly higher among non survived patients (233±135.37 mg/dL, 9.92±3.93 mg/L, 422.88±191.51 IU/L and 586.19±258.9 ng/mL, respectively) as compared to survived patients. Significant positive correlation was found between serum uric acid levels with LDH (r-value=0.231; p-value=0.007). Whereas, serum calcium showed negative correlation with CRP (r-value=-0.55; p-value=0.526) and D-dimer (r-value=-0.052; p-value=0.551). The ROC curve analysis showed that area under curve for serum uric acid level (0.530) was more as compared to serum calcium (0.460).
Conclusion: Serum uric acid is emerged as a better biomarker towards the prediction of outcome of patients. Early evaluation of serum calcium levels and serum uric acids could aid in predicting the outcome of the disease.
Biomarkers, Coronavirus disease 2019, Receiver operating characteristic, Severity
Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) predominantly affects respiratory system and may manifest from asymptomatic to mild symptoms or severe respiratory disease (1). In early December 2019, the first case of pneumonia of unknown origin was identified in Wuhan, the capital city of Hubei province (2). From then COVID-19 quickly spread throughout the world and World Health Organisation (WHO) has declared it as a pandemic (3). In India, from 3rd January 2020 to 7th June 2021, there have been 28,909,975 confirmed cases of COVID-19 with 349,186 deaths reported (4).
During the first wave of COVID-19 pandemic many studies were undertaken to investigate the clinical and laboratory characteristics (5),(6),(7). The commonly investigated parameters were routine biochemical and pathological investigation, inflammatory markers, organ injury biomarkers and CT scan of thorax (1),(8). However, very few studies are conducted on serum calcium levels in COVID-19 infection (9),(10).
Many theories have been put across to explain the clinical manifestations and severity of COVID-19 infection. However, the pathogenesis of COVID-19 is not clear and also there is currently no effective antiviral treatment (11). During the second wave, the altered serum calcium level and serum uric acid levels in severely infected hospitalised COVID-19 patients were observed by the researchers (9),(11).
Several potential factors play an important role in causing hypocalcaemia in COVID-19. One could be a direct effect of SARS-CoV-2 viral E gene entry into host cells (12),(13),(14). SARS-CoV-2 viral E gene encodes a small transmembrane protein that functions as a calcium ion channel and causes alteration in calcium homeostasis within the host cell leading to the activation of inflammatory pathways resulting in lung cell damage. As a whole formation of virus structure, its entry into host cell, replication and their virion release, requires calcium (15). Serum uric acid is a strong reactive oxygen species and being an antioxidant plays important role in defence mechanism (16),(17). Schuler CF et al., showed that when the virus enters the body it invades the respiratory system and causes inflammation that results in increase in serum uric acid level (18).
Kelly A and Levine MA reported that acutely ill patients had decreased levels of serum calcium which is associated with a poor prognosis (10). A retrospective analysis by Zheng T et al., reported that the serum uric acid level was positively associated with inflammatory markers (19). In contrary, Hu F et al., in their study on association of serum uric acid levels with COVID-19 severity reported that serum uric acid and serum uric acid/creatinine levels at admission were lower in patients with severe COVID- 19 as compared to moderately infected patients (11).
The relation between serum uric acid levels with severity of COVID-19 infection is inconsistent. Further no studies have compared the serum calcium and serum uric acid level with outcome of COVID-19 infection. Early initiation of therapy according to alterations in serum calcium level and serum uric acid level may decrease the mortality of COVID-19 infection. Hence, the aim of the present study was to check the correlation between serum calcium and serum uric acid level with inflammatory makers among COVID-19 patients and to assess serum calcium and serum uric acid levels in predicting the outcome of COVID-19 infections.
This retrospective study was conducted in Adichunchanagiri Institute of Medical Sciences (AIMS), B.G Nagara, Karnataka, India. The data of COVID-19 patients admitted at AIMS from 1st April 2021 to 30th June 2021 was collected from medical records for a period of two months and was analysed between October 2021 to November 2021. Study was initiated after obtaining ethical clearance from Institutional Ethical Committee [No. AIMS/IEC/261/2021 Dated18/06/2021].
Inclusion criteria: COVID-19 patients, confirmed with Rapid Antigen Test (RAT) and/or Real Time Polymerase Chain Reaction (RT-PCR), aged >18 years, who were investigated for calcium and serum uric acid level either on the day of admission or during their stay in the hospital were included in the study.
Exclusion criteria: Patients who had history of parathyroid disease, bone disease, chronic liver disease, kidney dysfunction and malignant tumours were excluded from the study.
During the study period, 483 COVID-19 infected patients were admitted at AIMS, out of which, 136 COVID-19 patients, investigated for calcium and serum uric acid level were enrolled in the study by convenient sampling method.
Data Collection
The data required for the present study was obtained from the medical records. Data included baseline clinical characteristics like age, gender, co-morbid status, duration of hospital stay and investigations such as Random Blood Sugar (RBS), blood urea, serum creatinine, serum albumin, Aspartate Amino Transferase (AST), Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), serum calcium, serum uric acid, C-Reactive Protein (CRP), Lactate Dehydrogenase (LDH) was analysed by various methods using Vitros-250 dry chemistry and D-dimer was analysed using XL 1000i operan, done on the day of admission and or during the stay were included. Above mentioned biochemical investigations were analysed for COVID-19 infected patients as these are inflammatory markers and are associated with severity and mortality of COVID-19 disease (5),(6),(7).
All the COVID-19 patients were categorised into survived and non survived group, based on their serum calcium levels patients were grouped into normal (8.5-11 mg/dL) or decreased (<8.5 mg/dL) and based on their serum uric acid level patients were divided into three groups normal (2.5-6 mg/dL), decreased (<2.4 mg/dL) or increased (>6 mg/dL) (Table/Fig 1) (20).
Statistical Analysis
The collected data was entered in Microsoft excel sheet and analysed using Epi data software. Descriptive statistics like frequency and proportion was calculated. Student’s t-test was used and p-value <0.05 was considered as statistically significant. Analysis of Variance (ANOVA) test was used to compare the parameters with different levels of serum uric acid. Pearson’s correlation was employed to examine the correlation between serum calcium level and serum uric acid level with outcome of COVID-19 admitted patients. Receiver Operating Characteristic (ROC) curve was used to assess serum calcium and serum uric acid in predicting the development of outcome of COVID-19 infection.
Among 136 COVID-19 positive patients, 87 (76 survived and 11 non survived) were male patients with mean age of 47.10±14.48 years and 49 (34 survived and 15 non survived) were female patients with mean age of 47.53±14.4 years and there was no significant difference between the gender with p-value of 0.86.
The mean age of non survived was significantly higher as compared to survived patients. Further, RBS (p-value=0.013), CRP (p-value=0.023), LDH (p-value=0.010) and D-Dimer (p-value=0.043) values were higher among non survived patients as compared to survived patients and it was found be significant. Whereas mean values of albumin (p-value=0.014) were higher among survived patients as compared to non survived with significant difference between them (Table/Fig 2).
As seen in (Table/Fig 3), out of 136 COVID-19 positive patients, 94 (69.12%) had normal serum calcium level with mean value of 9.30±0.56 mg/dL and 42 (30.88%) patients had decreased serum calcium level with mean value of 7.81±0.72 mg/dL and it was found to be statistically significant (p-value <0.0001).
D-dimer level was significantly higher among patients with decreased calcium level as compared to patients with normal calcium level. However, other parameters like RBS, urea, creatinine, AST, ALT, ALP, CRP and LDH values were higher among patients with decreased calcium level. Whereas, Albumin and serum uric acid level was lower among patients with decreased calcium level (Table/Fig 4).
Study subjects were compared based on serum uric acid level as shown in (Table/Fig 5) majority 110 (80.88%) patients had normal serum uric acid level. However, 11 (8.09%) had decreased and 15 (11.03%) had increased serum uric acid level.
The mean value of RBS was significantly higher among patients with increased serum uric acid. Further, mean value of urea and creatinine was higher among patients with increased uric acid as compared to patients with normal and decreased level of uric acid and it was found to be significant. Similarly, mean value of serum calcium and LDH was significantly higher among patients with increased uric acid (Table/Fig 6).
Among 110 survived COVID-19 patients majority 83 (75.45%) had normal serum calcium level. Similarly, 91 (82.73%) had normal serum uric acid level, as compared to 9 (8.18%) of decreased and 10 (9.09%) of increased serum uric acid level (Table/Fig 7).
Out of 26 non survived COVID-19 patients 15 (57.69%) had decreased serum calcium level. However majority of non survived patients had normal serum uric acid level, only 5 (19.23%) patients had increased uric acid and 2 (7.69%) patients were having low serum uric acid level (Table/Fig 8).
A significant positive correlation was found between serum uric acid levels with LDH (r-value=0.231; p-value=0.007). Whereas, Serum calcium showed negative correlation with CRP (r-value=-0.55; p-value=0.526) and D-dimer (r-value=-0.052; p-value=0.551) but it was not found statistically significant (Table/Fig 9).
The ROC analysis was done to predict the prognostic performance of serum calcium and uric acid to predict the development of poor outcome (Table/Fig 10). It found that, the Area Under the Curve (AUC) for serum uric acid (0.530) was higher as compared to serum calcium (0.460). Therefore serum uric acid with higher AUC emerged as a better biomarker towards the prediction of poor outcome with COVID-19 infection.
In the present clinical retrospective study, the correlations between serum calcium and serum uric acid with outcome of COVID-19 infection was investigated. Out of 136 study participants, the incidence of hypocalcaemia was seen in 42 (30.88%) cases and hyperuricaemia was in 15 (11.03%) cases. Decreased serum calcium was observed significantly higher among non survived COVID-19 patients.
In the present study, it was observed that hyperglycaemia, hypoalbuminaemia and increased inflammatory mediator like CRP, LDH and D-dimer concentrations among non survival group COVID-19 as compared to survival of COVID-19 patients indicating higher inflammation and tissue damage among the former ones. These findings were in accordance with previously published article by Huang C et al., they reported that the median value of AST 44 U/L), ALT (49 U/L), LDH (400 U/L) and D-dimer (2.4 mg/L) were higher among patients admitted in Intensive Care Unit (ICU) as compared to non ICU patients (34 U/L, 27 U/L, 281 U/L and 0.5 mg/L, respectively) whereas median value of serum albumin level (2.79 g/L) was decreased among patients admitted in ICU (2). Elevated serum CRP and D-dimer signifies inflammatory response and coagulation disorder, further elevation of LDH detonates the tissue damage induced by COVID-19 infection (9),(19). Studies have shown significant association between hypocalcaemia and inflammatory markers that reflect severity of the disease. Present study showed a negative association of calcium levels with CRP levels and D-dimer. This is similar to the study done by Sun JK et al., (20).
In a study conducted by Liu J et al., they found that 62.6% had hypocalcaemia and patients with hypocalcaemia were presented with poor outcome (47.8% (32/67) vs 25% (10/40), p-value=0.02). In the present study it was found that among non survived COVID-19, 57.69% had decreased serum calcium level and 42.31% had normal serum calcium level (9).
Uric acid is the end product of purine metabolism and it is a potent antioxidant that alarms and initiates immune system in response to cell injury/death and thus clears the dead cells/tissues. During the process of tissue damage, intracellular uric acid is released resulting in hyperuricaemic state. A study by Schuler CF et al., showed that invasion of virus to the respiratory system could induce hyperuricsemia (18).
In the present study, it was observed elevated uric acid levels among non survived COVID-19 patients. Further, there were significant increased levels of blood sugar, urea, creatinine, calcium and LDH among the patients with hyperuricaemia. Similar to the study by Zeng T et al., a positive correlation was found between uric acid and inflammatory markers (CRP, LDH and D-dimer) in patients with COVID-19 (19).
In the present study it was found that majority of non survived (73.08%) had normal serum uric acid level however, 19.23% patients had increased uric acid as compared to 7.69% patients who had low serum uric acid level. Present study results are in concurrence with the study done by Zheng T et al., they concluded that there was a significant differences in the rates of hyperuricaemia (OR: 3.17, 95% CI: 2.13-4.70; p-value <0.001) between deceased and recovered patients (19).
In the present study, ROC analysis was done to predict the prognostic performance of serum calcium and uric acid to predict the development of poor outcome. It was found that AUC for serum uric acid level (0.530) was more compared to serum calcium (0.460). In the present study serum uric acid emerged as a better biomarker towards the prediction of prognosis of patients with COVID-19 infection. Thus, initiation of therapy based on the alterations in serum calcium and serum uric acid level will be beneficial in lessening the burden of mortality due COVID-19 infection and increases the survival rate.
The results of the present study provided the information regarding the effect of serum calcium and serum uric acid level on outcome of COVID -19 infections and survival rate. Hence, further studies are required to know the effect of calcium supplementation in treating hypocalcaemia and prognosis of COVID-19 infected patients and to know the specific relationship between admission serum uric acid lowering drug and its outcomes in hospitalised patients.
Limitation(s)
One of the potential limitations of the present study is small sample size. Secondly, referred cases with corrected/initiation of treatment for altered serum calcium and serum uric acid levels were not considered.
Present study has shown that serum calcium levels were lower and serum uric acid levels were elevated among non survived patients. Further, serum uric acid emerged as a better biomarker towards the prediction of prognosis of patients with COVID-19 infection. Findings of the present study can speculate that low calcium and elevated serum uric acid levels in COVID-19 patients could be due to viral associated cytokine and increased immune response to the damaged tissues, respectively. Therefore, early evaluation of serum calcium levels and serum uric acids could aid in predicting the outcome of the disease and helps to circumvent the damage of multiple organs.
DOI: 10.7860/JCDR/2023/58651.17209
Date of Submission: Jun 24, 2022
Date of Peer Review: Aug 25, 2022
Date of Acceptance: Oct 14, 2022
Date of Publishing: Jan 01, 2023
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? NA
• For any images presented appropriate consent has been obtained from the subjects. NA
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