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 : April | Volume : 16 | Issue : 4 | Page : LC10 - LC15 Full Version

Diurnal Variation in the Mortality of Patients with COVID-19 Pneumonia: A Retrospective Study


Published: April 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/54837.16205
Jenita Baruah, Anshul Shakya, Mukul Sarma, Giriraj Kusre

1. Associate Professor, Department of Community Medicine, Assam Medical College, Dibrugarh, Assam, India. 2. Assistant Professor, Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam, India. 3. Associate Professor, Department of Anatomy, Assam Medical College, Dibrugarh, Assam, India. 4. Professor, Department of Anatomy, Assam Medical College, Dibrugarh, Assam, India.

Correspondence Address :
Giriraj Kusre,
Professor, Department of Anatomy, Assam Medical College, Dibrugarh, Assam, India.
E-mail: kusregiriraj@gmail.com

Abstract

Introduction: Coronavirus Disease 2019 (COVID-19), the new contagious novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), pandemic in 2020-21 has had a devastating impact on human race. The most common cause of death among hospitalised patient was COVID-19 pneumonia or lung injury. Various studies have shown diurnal variation in human mortality due to all causes with or without intervention.

Aim: To identify existence of diurnal variations for mortality among the hospitalised patients with COVID-19 pneumonia.

Materials and Methods: This hospital-record based, retrospective study was conducted in a tertiary referral centre of north-east India (Assam Medical College, Dibrugarh, Assam, India) which was a dedicated COVID-19 hospital during the pandemic. The study was conducted from September 2021 to December 2021 and the data was collected and recorded from the Cadaver slips issued to families of patient dying of COVID-19 pneumonia during the period January 2021 to August 2021. The data were generated by plotting the number of deaths of COVID-19 cases for each two hour interval as a percent of the mean number of deaths per two-hour interval and as a percentage of cumulative deaths per two-hour interval on a 24 hour scale. The deaths were sub grouped according to gender, age, and reported co-morbid causes of death along with pneumonia. Comparisons of data i.e., mean deaths/2 hour interval (mean±SD) were performed by one-way Analysis of Variance (ANOVA), followed by Bartlett’s test for equal variances. The p-value <0.05 was considered as statistically significant.

Results: Total 743 deaths, with 537 males and 206 females were included in the study. Mean age of the deaths was 56.01 years. There was rise of deaths during 4 PM-6 PM (16:00-18:00) interval for all deaths due to COVID-19 pneumonia. The increase in deaths during this period mainly accounted for males equal or above 65 years and females below age 65 years. However, the deaths of females equal or above the age of 65 years did not show significant diurnal variation. Only 26.51% (n=197) of pneumonia deaths were without co-morbidity.

Conclusion: There exists a diurnal variation in mortality among COVID-19 pneumonia patients with evening rise of deaths. Diurnal variation is significantly more among males rather than females above 65 years.

Keywords

Circadian rhythm, Coronavirus disease 2019, Severe acute respiratory syndrome coronavirus 2, Time of death

Coronavirus Disease 2019 (COVID-19) pandemic in 2020-21 had a devastating impact on human race resulting in large numbers of death in a very short period of time. The most common cause of death among hospitalised patient was COVID-19 pneumonia (1),(2). Age ≥65 years, existing co-morbidities, increased blood pressure, increased White Blood Cell (WBC) count, elevation in levels of cardiac troponin, myoglobin, creatinine, D dimer and IL-2R, IL-6 were associated with death in COVID-19 pneumonia, whereas Partial pressure of O2 (PaO2) ≥80 mmHg was the only protective factor (3),(4),(5).

Mortality and morbidity due to cardiovascular events, hypertensive diseases and asthma show an increase in morning hours (6),(7). Human mortality due to all causes show diurnal variation with maximum death during 6 AM-8 AM interval, one of the probable reason being circadian rhythm (8). Circadian rhythms have been observed in several human organs (9). In healthy individuals increase in airway resistance, and decrease in peak respiratory flow, Forced Expiratory Volume in 1 second (FEV1), Forced Vital Capacity (FVC), Peak Expiratory Flow (PEF) and FEV1/FVC values are seen in morning hours, Adrenocorticotropic Hormone (ACTH) secretion and levels of cytokines and cytokine receptors also show diurnal variation. These variations have profound impact on disease processes (10),(11),(12),(13).

Chronic Obstructive Airways Diseases (COPD) and asthma which involves lung, show severity during morning hours due to exacerbation of the physiological variations in various lung parameters (14) and since the major organ involved in COVID-19 pneumonia was lung, it was imperative to expect that the diurnal variation of lung parameters must have affected mortality due to the disease. Thus, in the present study, we sought to identify existence of diurnal variations for mortality among the hospitalised patients with COVID-19 pneumonia.

Material and Methods

This hospital-record based, retrospective study was conducted in a tertiary referral centre of north-east India (Assam Medical College, Dibrugarh, Assam, India) which was a dedicated COVID-19 hospital during the pandemic. The study was conducted from September 2021 to December 2021 and the data was collected and recorded from the Cadaver slips issued to families of patient dying of COVID-19 pneumonia during the period January 2021 to August 2021.

Ethical clearance was taken from the Institutional Ethics Committee (vide letter no EC 8393 dated 22nd September 2021). Due permission from the hospital authority was taken to access the data available in the Medical Record Department.

Inclusion and Exclusion criteria: Deaths due to COVID-19 pneumonia with or without co-morbid conditions were included in the study. COVID-19 pneumonia deaths associated with accidents, pregnancy and poisoning were excluded from the study.

All deaths occurring during the study period, where COVID-19 pneumonia was the primary cause of death were selected. Total 743 deaths were included as per the inclusion and exclusion criteria.

COVID-19 positive cases: As per hospital protocol COVID-19 positive was defined as all cases showing positive Rapid Antigen Test (RAT) and or Reverse Transcription-Polymerase Chain Reaction (RT-PCR) test for COVID-19 done under supervision of the Department of Microbiology of the Institute (15).

COVID-19 pneumonia: It was defined as patients with clinical symptom of pneumonia and bilateral ground glass opacity with peripheral distribution and lower lobe preference on chest X-ray (16).

Data Collection

Information regarding time of death, sex, age, and associated co-morbidity was entered in Excel sheet. The deaths were sub grouped according to gender, age, and reported co-morbid conditions along with pneumonia. The time of the day was represented in 24 hour format e.g., 10:00 AM was represented as 10:00 and 2:00 PM as 14:00. The 24 hour format of the day was divided into 12 temporal groups, each group of 2 hour duration. The data were generated by plotting the number of deaths of COVID-19 pneumonia for each 2 hour interval as a percent of the mean number of deaths per 2 hour interval and as a percentage of cumulative deaths per 2 hour interval on a 24 hour scale.

Statistical Analysis

Comparisons of mean deaths/2 hour interval (mean±SD) were performed by one-way Analysis of Variance (ANOVA), followed by Bartlett’s test for equal variances. The temporal distribution of percentage mean death/2 hr interval for total COVID-19 pneumonia related deaths of various subgroups were statistically analysed by two-way ANOVA, followed by Bonferroni post-tests for equal variances. GraphPad Prism-5 software (Graph Pad Software Inc., CA, USA) was used for statistical analysis. The p-value <0.05 was considered as statistically significant. Statistically analysed report of percentage cumulative death of COVID-19 pneumonia cases with respect to gender-cum-age was performed for the linear fitting by the multiple-data fit mode using OriginPro 8 statistical software.

Results

Total 743 cadavers, with 537 males and 206 females had COVID-19 pneumonia as primary cause of death. Mean age of the deaths was 56.01 years [Table Fig-1]. Mean number of deaths/2 hours interval for 12 (N) different time points among different subgroups showed that deaths among males and males below 65 years were significantly more in comparison to the other subgroups [Table Fig-2],[Table Fig-3].

On temporal distribution of total COVID-19 pneumonia deaths at two hours interval, mortality during the 4 PM-6 PM (16:00-18:00) interval was maximum, and was minimum during 8 AM-10 AM (08:00 to 10:00) [Table Fig-4],[Table Fig-5]. All other subgroups except females equal or above 65 years of age also showed diurnal variations. The overall effect of time of day was significant for temporal concentrations in deaths of the males and females under 65 years of age. The temporal distribution of percentage mean death/2 hr interval for 743 COVID-19-related deaths of various subgroups has been depicted in [Table Fig-6].

Furthermore, such gender and/or age related variation in the pattern COVID-19 deaths was also supported by the statistical analysis of the percentage cumulative death/2 hour interval of gender and/or gender-cum-age, respectively [Table Fig-7],[Table Fig-8],[Table Fig-9].

COVID-19 pneumonia deaths were commonly associated with co-morbid conditions. Only 197 (26.51%) of COVID-19 pneumonia cases had no associated co-morbidity. Hypertension, diabetes, both diabetes and hypertension, diabetes associated with other clinical conditions, hypertension associated with other clinical conditions, both diabetes and hypertension associated with other clinical conditions and other clinical conditions alone were seen in decreasing order of prevalence among these deaths [Table Fig-10].

Other clinical conditions included dyselectrolytemia, alcohol withdrawal, metabolic encephalopathy, hypothyroidism, Space occupying lesion of Brain, chronic kidney disease, chronic liver disease, rheumatic heart disease, post mitral valve regurgitation, hyperkalaemia, cerebrovascular accidents, COPD, hypoxic encephalopathy, seizure, pulmonary TB, respiratory failure, decompensated chronic liver disease, renal cell carcinoma, hepatic encephalopathy, asthma, bronchial asthma, congenital heart disease, cardiac disease, shock, hepatic parenchymal disease, liver failure, acute liver failure, metabolic encephalopathy, acute pancreatitis, coagulopathy, acute hepatitis, oesophageal varices, Intestinal perforation, depression, schizophrenia, acute abdominal perforation, TB, carcinoma, anaemia, obstructive hydrocephalus, hepatic encephalopathy, Acute respiratory failure.

Discussion

In the present study, 72.3% of deaths were among males, the excess in deaths were seen irrespective of age above and below 65 years. Asirvatham ES et al., also had observed more deaths among males (71.4%) (17). Priya S et al., reported that when compared to females, males had 2.03 times higher risk of dying which was statistically significant (18). In a study from China, men were 2.4 times more vulnerable for death even though they were equally susceptible as women (19). COVID-19 virus targets the respiratory system and mainly invades alveolar epithelial cells resulting in respiratory symptoms. Three major risk factors for COVID-19 mortality were sex (male), age (≥60), and severe pneumonia (20). Decreased mortality among females is probably due to down regulation of Angiotensin II Receptor Type 1 (ATR1) and regulation of rennin activity by estrogen, due to the protective effect of X chromosome and sex hormones (21) and due to difference in response to virus and in innate or adaptive immunity (22). The higher mortality among men could be due to the behavioural risk factors such as smoking, and alcohol consumption in India (23).

Age was considered as one of the most important factors for hospitalisation and mortality in COVID-19 infection (18). In the present study the mean age of the dead patients was 56.01 year (SD-15.01). In a study from Madurai in the state of Tamil Nadu in India, the risk of death was observed to have increased with increase of age compared to the death among 18-29 years, the highest risk being among the age group ≥70 years (18), whereas in a study from Chennai, Tamil Nadu, mean age of the deceased was 62.5 years without a significant difference between male and female (17). In a study from China 83.8% of deaths were in the age range ≥65 years (19). The increasing death rate with age was expected due to the higher prevalence of co-morbidities, and less responsive innate and adaptive immune system among the elderly (24),(25). In the present study, more numbers of deaths were observed in age group below 65 years, both in males and females, which is younger than that observed by others authors, the difference may be because of the study setting.

In the present study, diurnal variation in mortality was observed among the COVID-19 pneumonia deaths. Mortality during the 4 P.M.-6 P.M. (16:00-18:00) interval was high in comparison to morning hours. The peak was mainly due to the significantly more deaths among the males and females under 65 years of age rather than females above 65 years. Human mortality due to all causes have shown a peak at 6 AM-8 AM (p<0.001) (8), diseases such as asthma, myocardial infarction, stroke, and ventricular arrhythmia also show a peak in mortality during morning hours of 6 AM-12 PM (6),(7). A common explanation for the peak is the presence of a circadian rhythm in a proarrhythmic trigger, a morning surge in sympathetic drive, b-adrenergic stimulation, delayed after depolarisations, and re-entry (26). Unlike the deaths due to the asthma, myocardial infarction, stroke, and ventricular arrhythmia, in the present study there was evening rise of mortality due to COVID-19 pneumonia, which suggests that increase in deaths due to COVID-19 pneumonia during evening hours is not due to circadian rhythm in proarrhythmic triggers.

Changes of airway caliber, airway resistance, respiratory symptoms, mucus secretion and immune-inflammatory responses during different period of day results in variation in exacerbation, frequency and occurrence of chronic obstructive pulmonary diseases and asthma (9),(14). Clock gene expression is rhythmic in the lung. Circadian rhythm within the lung is important for the immunologic control of acute lung infection and in development of chronic lung disease. Circadian rhythms is observed to be associated with susceptibility and severity of disease after infection, it also modifies its clinical presentation (27).

Alteration of the clock impedes the initial recognition of pathogens by lung innate defenses and negatively affects neutrophil function (10). Intra nasal inoculation of the influenza virus in mice just before the onset of their “active phase/lights off” shows significantly higher mortality and morbidity than during “rest phase/light on”, and has shown more lung injury irrespective of the rate of viral replication or viral burden (28).

Some viral infections exploit host susceptibility during the rest phase by disrupting epigenetic mechanisms, affecting the circadian clock of the host and altering the potency of the pathogenicity and the host immunity (29) some viruses either reprogram cellular metabolism or exploit host circadian variation for replication kinetics (30). Immune response and functions of T and B lymphocytes also show circadian rhythm. Melatonin suppression is associated with increased levels of specific antibodies. High levels of IL-10, an anti-inflammatory cytokine, are seen during daytime, whereas high levels of inflammatory cytokines (TNF, IL-1, and IL-6) and cytokine receptors are seen during the nighttime (13). One of the common cause of death in COVID-19 (SARS-CoV-2) was reported to be COVID-19 Pneumonia. Mal-adjusted immune responses against SARS-CoV-2 was said to be responsible for the immunopathology of the disease (1). Cellular entry of the SARS-CoV-2, triggers an inflammatory response by recruiting T-helper cells that produce interferon (IFN)-gamma (IFN-γ), interleukin (IL)-2, and IL12. The injured alveolar cells also release interferons, cytokines, and other intracellular components. The subsequent recruitment of other inflammatory cells leads to the development of a ‘cytokine storm’ which can precipitate the organ damage and multi-organ failure seen in severe disease. Tumour Necrosis Factor (TNF)-α and IL-1β are proinflammatory cytokines that cause an increase in vascular permeability, and induce recruitment of more immune cells, including neutrophils and monocytes. IL-8 recruits neutrophils, and other chemokines attract monocytes, increases vascular permeability causing leakage of fluid into the interstitial space and alveoli, resulting in interstitial and pulmonary oedema (31). Organ damage was mainly attributed to secretion of IL1β, IL-6, and TNF-α (24). The elevated inflammatory mediators the blood IL-6 level was highly correlated with the disease mortality when COVID-19 survivors and non survivors were compared (5). In the present study, the diurnal variation shown in mortality of COVID-19 pneumonia patients (evening rise) does not coincide with the physiological increase in airway resistance, and other variations in physiological functions of the lung. The evening increase in the mortality among COVID-19 pneumonia patients may have been due to the time of infection, alteration of the host circadian rhythm or abnormal immune response to the infection.

In a study from south India co-morbidities such as diabetes, hypertension and Coronary Artery Disease (CAD) were found among 62%, 49.2% and 17.5% of the deaths, respectively. The co-existence of diabetes and hypertension or diabetes, hypertension and CAD were found in 36.6% and 8.7% of the individuals respectively (17). In the present study, 546 (73.49%) of patients dying due to COVID-19 pneumonia had associated co-morbidity. Among the co-morbidities, hypertension and diabetes were the most common. Priya S et al., reported that COVID-19 patients had atleast 3 times greater risk of mortality when they had atleast one of these co-morbidity. The mortality risk was highest among those patients who had diabetes, hypertension and heart disease as co-morbidities in combination (18). In the present study, diabetes was associated in only 31.76% which was much less than the findings from studies from south India (17). The difference was probably due to selection of deaths due to COVID-19 pneumonia only rather than deaths due to all causes.

Limitation(s)

As this was a hospital record based study from a single centre, findings may not represent the deaths due to COVID-19 pneumonia at community level. It also does not reflect human intervention related reasons of death such as delay in care, deaths during shift change, death due to non availability of ICU beds, interruption of oxygen supply.

Conclusion

There exists a diurnal variation in mortality among COVID-19 Pneumonia patients during evening hours which is significantly more in males age ≥65 years and below the age of 65 years and insignificant in females above 65 years. The evening increase in the mortality among COVID-19 pneumonia patients may have been due to the time of infection, alteration of the host circadian rhythm or abnormal immune response to the infection. Further studies involving multiple centres must be carried out to validate the results of this study.

Acknowledgement

Authors acknowledge the hospital staff and administration for their role in providing us the required data.

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DOI and Others

DOI: 10.7860/JCDR/2022/54837.16205

Date of Submission: Jan 09, 2022
Date of Peer Review: Jan 21, 2022
Date of Acceptance: Mar 03, 2022
Date of Publishing: Apr 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? NA
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Jan 12, 2022
• Manual Googling: Mar 03, 2022
• iThenticate Software: Mar 09, 2022 (16%)

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