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

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Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

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



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : October | Volume : 16 | Issue : 10 | Page : OC01 - OC06 Full Version

Predictors of Duration of Hospital Stay in COVID-19 Disease: A Retrospective Study


Published: October 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/57264.16853
KP Vijayalakshmi, AK Srikanth, Rikita Ramesh Mudhol, Vrushali Mohite, JG Ravindra, Sagar Sadanand, Yadur Srinidhi

1. Assistant Professor, Department of General Medicine, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara University, Dharwad, Karnataka, India. 2. Assistant Professor, Department of General Medicine, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara University, Dharwad, Karnataka, India. 3. Assistant Professor, Department of General Medicine, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara University, Dharwad, Karnataka, India. 4. Junior Resident, Department of General Medicine, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara University, Dharwad, Karnataka, India. 5. Junior Resident, Department of General Medicine, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara University, Dharwad, Karnataka, India. 6. Junior Resident, Department of General Medicine, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjuna

Correspondence Address :
Dr. AK Srikanth,
Assistant Professor, Department of General Medicine, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara University,
Dharwad, Karnataka, India.
E-mail: srikanth.ak.241@gmail.com

Abstract

Introduction: A cluster of pneumonia cases were recognised at the end of the year 2019, and later designated as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It was declared as pandemic in early 2020. Coronavirus Disease 2019 (COVID-19) caused considerable morbidity and mortality. Further, it was discovered that presence of co-morbidities like diabetes mellitus, ischaemic heart disease and appearance of cytokine storm caused increased mortality.

Aim: To identify co-morbidities and laboratory parameters associated with prolonged hospitalisation in COVID-19 disease.

Materials and Methods: This retrospective study was conducted in Department of General Medicine at SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara University, Dharwad, Karnataka, India (tertiary care hospital). Data between 1st July 2020 to 30th September 2020 was collected, and analysis and interpretation was done from November 2020 to March 2021 from data obtained from medical records. Data of 402 participants was analysed for baseline characteristics like demographic distribution (age and gender), presence of co-morbidities like diabetes mellitus, hypertension, ischaemic heart disease. Patients were divided as per level of oxygen requirements, duration of hospitalisation and usage of remdesivir or steroid or both. Laboratory parameters studied were complete blood count, platelet count, serum sodium, parameters of hyperinflammation like C-reactive Protein (CRP), Lactate dehydrogenase (LDH), ferritin. Markers of COVID-19 associated with high mortality like Neutrophil to Lymphocyte Ratio (NLR) and D-dimer were also taken. Mean hospital stay was associated with all the parameters. Data was analysed by one way Analysis of Variance (ANOVA) and Independent t-test.

Results: Maximum patients seen were in the age group of 40-60 years (45.52%). Common co-morbidities observed were diabetes mellitus (48.26%) and hypertension (45.27%). Presence of co-morbidities like diabetes mellitus (p-value=0.0171), hypertension (p-value =0.0238), ischaemic heart disease (p-value=0.0024) was associated with prolonged hospitalisation. Among laboratory markers higher level of parameters of inflammation like NLR >2 (p-value=0.0183), CRP >6 mg/L (p-value=0.004), ferritin >300 ng/mL (p-value=0.05) and indicators of hypercoagulable state {D-dimer >500 ng/mL (p-value=0.0014)} were associated with significantly prolonged stay. patient who received both remdesivir and steroids stayed longer compared to either remdesivir alone or only steroids (p-value=0.0001).

Conclusion: State of hyperinflammation and presence of co-morbidity especially uncontrolled diabetes mellitus and usage of steroids were associated with prolonged hospitalisation. Periodic assessment of these patients until recovery may help reducing mortality and morbidity.

Keywords

Coronavirus disease-2019, Cytokine storm, High neutrophil-lymphocyte ratio, Hyperinflammation, Hyperferritenaemia, Uncontrolled hyperglycaemia

In December 2019, a cluster of pneumonia cases were recognised. Later it was named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). and declared as pandemic by World Health Organisation (WHO) in early 2020. It led to widespread morbidity and mortality across the globe. It further added burden on healthcare with acute shortage of resources and manpower. It still remains a devastating and re-emerging pandemic. It is well known that older age (>65) and diabetes increases severity of pneumonia (1). However, there is limited data on effect of other co-morbidities like hypertension and ischaemic heart disease in Coronavirus Disease 2019 (COVID-19). This is especially important since the binding of SARS-CoV-2 is mediated by Angiotensin Converting Enzyme-2 (ACE-2) receptor. Studies done so far have given risk factors for fatal outcome in COVID-19 disease (1),(2). A study on predictors of mortality in COVID-19 was also published by the authors of this study (3). However, factors affecting duration of hospitalisation are not well characterised.

There literature is scarce regarding factors affecting length of hospitalisation from India. Prolonged hospitalisation carries risk of complications like healthcare associated infections, malnutrition, psychosocial insecurity (4),(5). With vast crowding of current health infrastructure, routine screening of patients for these complications is difficult and may not be effective. Hence, applying screening protocols to a subset of patients with risk factors for prolonged hospital stay will help in early identification of complications, thus improving the overall outcome. The aim of this study was to study the effect of co-morbidities and to identify laboratory parameters associated with prolonged hospital stay in COVID-19 disease.

Material and Methods

This retrospective study was conducted in Department of General Medicine at SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara University, Dharwad, Karnataka, India (tertiary care hospital). Data between 1st July 2020 to 30th September 2020 was collected, and analysis and interpretation was done from November 2020 to March 2021. Permission was taken from Institutional Ethics Committee and Medical Records Department (ref: SDMIEC/2021/12, date: 15/07/2021). Total 402 patients were included by using consecutive sampling method.

Inclusion and Exclusion criteria: All patients who were positive for COVID-19 infection by RT-PCR and symptomatic for severe acute respiratory illness/infection with positive rapid antigen test for COVID-19 were included in the study. Patients <18 years of age were excluded from the study.

Data Collection

Data was compared for baseline characteristics like demographic distribution (age and gender), presence of co-morbidities like diabetes mellitus, hypertension, ischaemic heart disease. Patients were divided as per level of oxygen requirements, duration of hospitalisation and usage of remdesivir or steroid or both. Laboratory parameters studied were complete blood count, platelet count, serum sodium, parameters of hyperinflammation like C-reactive Protein (CRP), Lactate Dehydrogenase (LDH), ferritin, Neutrophil to Lymphocyte Ratio (NLR) and D-dimer.

Statistical Analysis

One-way Analysis of Variance (ANOVA) and Independent t-test were used for data analysis. Software used for analysis was Statistical Package for Social Sciences (SPSS) version 20.0. A significance was set at 5% level (p-value <0.05).

Results

Data from 402 patients were collected. Demographic profile of patients is shown in (Table/Fig 1). Out of 402 patients, 183 patients (45.52%) were in the age group of 40-60 year, 64 patients (15.92%) were between 18-39 years, 155 patients (38.56%) above 60 years. There were 111 female patients (27.61%) and 291 (72.39%) male patients in this study.

Out of 402 patients 135 patients did not have any co-morbidity and 194 patients (48.26%) had diabetes mellitus, 182 patients (45.27%) had hypertension, 32 patients (7.96%) had chronic kidney disease, 24 patients (5.97%) had ischaemic heart disease.

Out of total 402, 141 patients (35.07%) needed supplemental oxygen, among which 68 patients (48.22%) were on low flow oxygen by face mask, 7 patients (4.96%) required non rebreathing mask, 3 patients (2.12%) required Non Invasive Ventilation (NIV), 63 patients (44.68%) required intubation and mechanical ventilation. Distribution of patients based on laboratory parameters are shown in (Table/Fig 2) (6),(7),(8),(9),(10),(11),(12),(13). A total of 57 patients (14.18%) had HbA1C ≥10%, 156 patients (38.81%) had hyponatraemia, 12 patients had hypernatraemia (2.99%), 206 patients (51.24%) had hyperferritinaemia, 303 patients (75.37%) had CRP ≥6 mg/dL and 319 patients (79.35%) had NLR ≥2, 311 patients (77.36%) had elevated LDH. Out of 402 patients, reports of quantitative D-dimer levels were available for 119 patients, among the available reports 73 patients (61.34%) had elevated D-dimer levels of >500. 201 patients (50%) received both steroids and remdesivir, 71 patients (17.66%) received only remdesivir, 37 patients (9.20%) received only steroids, 93 patients (23.13%) received neither.

Comparison of various factors with mean duration of hospital stay (in days) is shown in (Table/Fig 3). Patients with diabetes mellitus had longer stay in hospital compared to patients without diabetes mellitus with p-value=0.0171, which was statistically significant. Patients with uncontrolled diabetes had longer stay in hospital compared to patients with controlled diabetes with p-value=0.0005 which was statistically significant. Patients with hypertension had longer stay in hospital compared to patients without hypertension with p-value=0.0238 which was statistically significant. Patients with Ischaemic heart disease had longer stay in hospital compared to patients without ischaemic heart disease with p-value=0.0024, which was statistically significant. Patients with hyperferritenaemia (p-value=0.050), raised CRP (p-value=0.0024), D-dimer (p-value=0.0014) and NLR (p-value=0.0183) had longer stay in hospital compared to the rest of the patients. Patients who received remdesivir alone have shorter stay compared to patients who received steroids alone or both steroids and remdesivir (p-value=0.0001).

Discussion

In this study it was found that patients with hypertension had longer hospital stay compared to patients without hypertension with p-value=0.0238 which was statistically significant. A study of 730 patients done by Thiruvengadam G et al., in the year 2020-21 in southern India showed that patients with hypertension had prolonged hospital stay (14). Kinge KV et al., conducted a study involving 2883 patients at a tertiary care hospital in Mumbai in 2020 comparing presence or absence of hypertension as predictor of fatal outcome and duration of hospital stay showed that there was statistically significant difference in hospital stay in patients with hypertension compared to patients without hypertension (15).

This difference in duration of hospitalisation in hypertension is due to multiple factors like severity of the disease itself i.e., patients with hypertension having severe COVID-19 compared to patients without hypertension (16), cardiovascular events, hypertensive crisis. Further, Immune dysregulation can be a common denominator to complications of COVID-19 (17) as well as cardiovascular events secondary to hypertension (18). The Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) trial showed that immunomodulation targeting IL-1? in hypertension reduced cardiovascular events in patients with hypertension though it did not reduce blood pressure itself (18). Few cytokine measurements on the day of admission like IL-12p (70) and IL-10 can predict progression in hypertensive patients as shown in BRACE CORONA trial (19). Future research is needed whether using immunomodulation for patients with hypertension and COVID-19 can help preventing progression to severe illness/acute renal failure/cardiovascular events which may affect severity of the disease or prolong hospital stay.

In this study it was found that, patients with ischaemic heart disease had prolonged stay compared to patients without any heart disease (p-value=0.0024). A meta-analysis done by Liang C et al., from 40 studies with total of 22,148 patients has shown that severity of COVID-19 disease increases in patients with coronary artery disease (17). Risk increases in patients with hypertension. COVID-19 disease causes many cardiovascular complications like myocardial dysfunction, myocarditis, cardiomyopathy, right ventricle dysfunction, pulmonary embolism. Also, the drugs used to treat COVID-19 might be cardiotoxic. Patients with ischaemic heart disease poses an additional risk for cardiovascular complications (17). Most of the cardiac injury begins from day five (20) and continues in post COVID phase or long COVID-19. This might explain prolonged hospitalisation in patients with ischaemic heart disease.

In this study it was found that patients with uncontrolled diabetes had prolonged hospitalisation compared to controlled hyperglycaemia (p-value=0.0005) and also patients with diabetes had significantly prolonged stay compared to patients without diabetes with COVID-19 (p-value=0.0171). A study done in Greece by Petrakis V et al., involving 133 type 2 diabetic patients showed that hospitalisation was significantly (p-value=0.004) prolonged in patients with glucose>180 mg/dL than those with lower levels on admission (21). Pre-existing hyperglycaemia is associated with poor outcome as shown in research conducted in Scotland and Swedish population (22),(23). Difference might be secondary to altered cell mediated and humoral immunity, elevated proinflammatory cytokines (24),(25), associated obesity, presence of ACE-2 receptor in adipose tissue. Severe COVID-19 disease, oxygen dependency, secondary infections, re-triaging to ICU after recovery, control of hyperglycaemia complicated by use of steroids in moderate to high-risk patients, electrolyte disturbances in diabetic patients etc. contribute to increased length of hospital stay (26). On the contrary a study done by Wu Y et al., showed no significant difference in duration of hospitalisation with respect to presence or absence of comorbidity-hypertension, diabetes mellitus, coronary artery disease (27).

In this study it was found that elevated CRP >6 mg/L (p-value=0.0025) and hyperferritinaemia (serum ferritin >300: p-value -0.05) was associated with prolonged hospitalisation. A study done by Tezcan ME at el., comprising 149 patients showed that patients with higher CRP levels (p-value=0.002) and higher ferritin level (>300 mg/mL, p-value=0.01) had prolonged hospitalisation compared to patients in short-term group (28). Severe COVID-19 disease is associated with hyperinflammation and cytokine storm (29). Rising acute phase reactants like CRP (30) and ferritin (31),(32),(33) are taken as markers of hyperinflammation in COVID-19 and reflects progression of the disease. It is imperative that patients with severe disease are also the candidates for immunomodulatory therapies and steroids. This increases the risk for secondary infections, and a challenge for euglycaemia which may add further morbidity (34),(35).

In this study it was found that high neutrophil to lymphocyte ratio is associated with prolonged hospitalisation (p-value=0.0183, for NLR>2). A study done in China by Wu Y et al., including 125 patients showed that lymphocytopaenia is associated with prolonged hospitalisation (27). Another study done in Turkey including 639 patients by Kalyon S et al., in 2020 showed that NLR was significantly higher in non survivors than survivors and non survivors had longer hospitalisation compared to survivors (36). A meta-analysis done by Henry BM et al., (37) showed that neutrophilia and lymphopenia is associated with progression to severe COVID-19 patients in hospitalised patients. This difference could be due to severity of the disease itself, need for immunomodulation and/or steroids leading to secondary infections, metabolic complications like hyperglycaemia further prolonging hospitalisation.

In this study it was found that higher D-dimer is associated with prolonged hospitalisation with p-value=0.0014. A study done by Thiruvengadam G et al., (14) showed that patients with high D-dimer, ferritin and high neutrophil to lymphocyte ratio had prolonged hospital stay. D-dimer is a traditional marker of hypercoagulability (38). D-dimer is the product of fibrinolysis. D-dimers are the D fragments from lysis of cross-linked fibrin, not the fibrinogen or soluble fibrin. Thus, elevated D-dimers indicate active fibrinolysis in turn activation of coagulation cascade (38). D-dimer have been in use to rule out venous thromboembolism and deep vein thrombosis because of its high negative predictive value (39). Traditionally RNA viruses are associated with haemorrhagic manifestations (40). However, SARS-CoV-2 is associated with immune-thrombosis. SARS-CoV-2 induces endothelial cell damage which recruits neutrophils and monocytes, and releases cytokines (41). This along with tissue factor exposure accelerates thrombosis. There is activation of intrinsic coagulation secondary to Neutrophil Extracellular Traps (NETs) in COVID-19. This explains occurrence of thrombotic events in COVID-19 patients. Since, the COVID-19 pandemic D-dimer has been used in triaging and management of patients with COVID-19 (12),(42). Studies done till date have shown higher incidence of critical illness, thrombotic events, acute kidney injury and death in patients with elevated D-dimer levels (12),(42). Systemic anticoagulation has been included in the treatment of moderate to severe COVID-19 worldwide (43).

In this study it was found that patients with hyponatraemia and hypernatraemia had prolonged hospitalisation compared to patients with normal serum sodium. A study done by Martino M et al., in Italy with 117 patients in year 2020 showed that hypernatraemia is associated with prolonged hospitalisation and hyponatraemia with severe COVID-19 (44). A retrospective study of 642 patients done by Pillai J et al., in Johannesburg, South Africa in the year 2020 showed that serum sodium more than 145 mmol/L is associated with prolonged hospital stay (45). An analysis by HOPE registry showed that dysnatraemia was associated with mortality and sepsis in patients with COVID-19 (46). Severe disease, need for Intensive Care Units (ICU), sepsis might explain prolonged hospital stay in patients with dysnatraemia.

In this study it was found that, patients who received remdesivir alone have shorter stay compared to patients who received steroids alone or both steroids and remdesivir (p-value=0.0001). A double blinded multicentric randomised clinical trial- Adaptive COVID-19 Treatment Trial (ACTT) has shown that treatment with remdesivir will shorten the time to recovery (47). Recovery trial showed that addition of steroid lowers mortality in patients with high oxygen requirement or mechanical ventilation but not in patients requiring low flow oxygen or no oxygen (48). Another study done by Anderson M et al., showed length of hospitalisation reduced by four days in remdesivir treated group (49). A retrospective study of 450 patients in China conducted by Yiming Ma et al., showed that steroid usage resulted in longer hospitalisation (p-value=0.001) in non severe group and higher use of antibiotics (50).

Secondary infections, hyperglycaemia after steroid therapy and electrolyte disturbances in ICU patients might explain prolonged stay in patients who received remdesivir and steroids both (34),(35).

Hence, authors suggest the use of steroids only in severe cases i.e, patients requiring high flow oxygen or mechanical ventilation and use of remdesivir in all patients with lower respiratory tract involvement. Similar studies from the literature has been tabulated in (Table/Fig 4) (14),(15),(17),(21),(27),(28),(36),(37),(44),(45),(46),(47),(48),(49),(50).

Limitation(s)

Limitations of this study includes the retrospective nature of the study, heterogeneity of treatment received, lack of systematic monitoring of SARS-CoV-2 PCR and anti SARS-CoV-2 immune response. Also the present study was unable to differentiate from relapsed versus refractory disease.

Conclusion

In this study duration of stay in COVID-19 patients was prolonged among patients with underlying co-morbidities like hypertension, diabetes mellitus, ischaemic heart disease. The presence of factors like cytokine storm, hyperinflammation, dysnatraemia, uasge for steroids, contributed to prolonged stay in the present study. Further studies are needed to identify other biomarkers that can predict length of hospitalisation.

Acknowledgement

Authors would like to express heartfelt gratitude to Dr. Kiran Aithal, Head of the Department, and all the Faculty of Medicine and Statistician for their support.

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DOI and Others

DOI: 10.7860/JCDR/2022/57264.16853

Date of Submission: Apr 23, 2022
Date of Peer Review: Jun 03, 2022
Date of Acceptance: Sep 01, 2022
Date of Publishing: Oct 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. No

PLAGIARISM CHECKING METHODS:
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