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.
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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 : May | Volume : 16 | Issue : 5 | Page : OC17 - OC23 Full Version

Clinical Course and Outcome of COVID-19 in Kidney Transplant Recipients: A Single-centre Retrospective Observational Study


Published: May 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/52091.16340
Shiva Kumar Ammayappan, Arul Rajagopalan, Jegan Arunachalam, Arun Prasath, Rakesh Durai, Manorajan Rajendran, Benoy Varghese, Shanmuganathan Velu

1. Resident, Department of Nephrology, Madurai Medical College, Madurai, Tamil Nadu, India. 2. Associate Professor, Department of Nephrology, Madurai Medical College, Madurai, Tamil Nadu, India. 3. Assistant Professor, Department of Nephrology, Madurai Medical College, Madurai, Tamil Nadu, India. 4. Assistant Professor, Department of Nephrology, Madurai Medical College, Madurai, Tamil Nadu, India. 5. Assistant Professor, Department of Nephrology, Madurai Medical College, Madurai, Tamil Nadu, India. 6. Professor, Department of Nephrology, Madurai Medical College, Madurai, Tamil Nadu, India. 7. Resident, Department of Nephrology, Madurai Medical College, Madurai, Tamil Nadu, India. 8. Resident, Department of Nephrology, Madurai Medical College, Madurai, Tamil Nadu, India.

Correspondence Address :
Shiva Kumar Ammayappan,
Department of Nephrology, Government Rajaji Hospital, Madurai Medical College, Madurai, Tamil Nadu, India.
E-mail: shiv.dr.0508@gmail.com

Abstract

Introduction: Solid Organ Transplants (SOT) is at increased risk of Coronavirus Disease 2019 (COVID-19) infection, which may result in acute graft dysfunction and even death. While the disease has been well studied in the general population, it is not the case in renal transplant recipients. The poor immunological response of the vaccine in postrenal transplant patients, the emergence of newer strains, and the possibility of a third wave in India, makes it even more important to know more about the course and outcome of the disease in post renal transplant patients.

Aim: To evaluate the demographics, clinical presentation, biochemical profile, course of hospitalisation in post kidney transplant patients with COVID-19.

Materials and Methods: This retrospective observational study study with 18 patients was conducted in Madurai Medical College, Tamil Nadu, India for duration of four months, from May 2021 to August 2021 and data collection from May 2021 to July 2021 and data analysis in August 2021. All post kidney transplant patients having evidence of COVID-19 were included. Detailed clinical history, biochemical profile, radiological findings, treatment, and final outcomes were collected and compared. Non parametric statistical tests were used, in addition to Chi-square test and odds ratio. Kaplan-Meier plot was used for survival analysis.

Results: The most common presentation was fever 15 (83.3%), followed by cough 10 (55.6%). C-reactive Protein (CRP) {65 mg/L (11.48-94.48)}, D-dimer {0.72 mcg/mL (0.59-1.1)}, serum creatinine {3.5 mg/dL (2.12-5.93)}, and platelet count {200,000 cells/cu.mm (1.75-2.22)} and showed statistically significant (p<0.05) association with the outcome. About 15 (83.3%) patients developed Acute Kidney Injury (AKI). Seven patients (38.9%) had stage three AKI necessitating haemodialysis, of which six did not survive. The median survival time was 22 days, with 95% confidence interval (19.792-24.208), with case fatality rate of 33.3%

Conclusion: Postkidney transplant patients are at high risk of contracting COVID-19. CRP, D-dimer, serum creatinine, platelet counts, and arterial oxygen saturation may serve as prognostic markers. Dialysis may be required in view of high incidence of AKI and acute graft dysfunction, though the outcome seems dismal in such patients. Hence, the need for early hospitalisation and more effective treatment protocol is essential to improve outcome.

Keywords

Acute graft dysfunction, Biopsy, Coronavirus disease 2019, Dialysis, Immunosuppressives, Rejection

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19, is responsible for an everlasting worldwide pandemic. The country has witnessed two horrendous waves of the disease and is standing at the brink of a third one. The high rate of transmissibility in the asymptomatic phase has facilitated the virus to spread globally with catastrophic outcomes (1). It has posed as a great challenge for clinicians all over the world. Though, it may cause a mild disease in some, it has led to millions of deaths worldwide (1).

The SOT recipients are vulnerable to many respiratory viral infections due to a weakened T-cell mediated immune response (2). SOT recipients have been classified as having high risk for severe illness due to SARS-CoV-2 by the Centers for Disease Control and Prevention (CDC) (3). There is still paucity of data on the natural course of the disease, the treatment regime to be used, the effect of the immunosuppressive drugs, the risk factors and many more in the SOT recipients. Interestingly, an immunocompromised state has yet not been proven to have a worse clinical outcome (4). A Chinese meta-analysis proposed that risk factors such as hypertension, chronic respiratory disorders, cardiovascular diseases, older age, but not immunosuppression as predictors of severe COVID-19 disease (5). Another study pointed out that viruses that belong to the same corona virus family, as Middle East Respiratory Syndrome (MERS) and SARS-CoV-2 have not been shown to have an increased risk or worse outcome in immunocompromised patients (6). Immunosuppression on the background of hyperinflammation may prove to be even beneficial, by blunting down the cytokine release, as postulated by Mehta P et al., (7). In contrast, a review article by Lai Qet al.,found a mortality of 23.1% and a need for invasive ventilation in 23.9% of SOT recipients (8). The expert American Association of the Study of Liver Disorder (AASLD) consensus also pointed out that immunosuppressed patients are at higher risk for severe illness from COVID-19 (9).

There have been numerous case series on COVID-19 in SOT recipients from all over the world. But the evolving variants of corona viruses are still posing a danger to the community. The Centre for Disease Control and Prevention (CDC) has declared the recent omicron variant (B.1.1.529) as a variant of concern (10). The recent surge of Omicron cases is worrisome and may present as the third wave in the Indian subcontinent. The effectiveness of full vaccination in SOT recipients is also dismal. A study done in Israel showed seroconversion after vaccination in only 37.5 % in kidney transplant recipients, as compared to 100% in the controls (11).

The treatment protocol of COVID-19 among these transplant patients is also different from the general population. Complex decisions regarding the tapering of immunosuppressives have to be taken. The immunosuppressives used in renal transplant recipients were found to have anti-viral properties. Corticosteroids may be beneficial in the treatment (12). Mycophenolate Mofetil (MMF) was shown to have antiviral properties against MERS, but in SARS-CoV-2, it has been shown to do more harm than benefit in in vivo studies (13). Therefore, its use is not recommended. Calcineurin inhibitorshave been shown to have anti-viral properties, but still needs more research (14). There are limited data on the clinical courses and outcome of COVID-19 in renal transplant recipients from South India.

This study presents an analysis of the data on COVID-19 in renal transplant patients. It aimed to evaluate the demographics, clinical presentation, biochemical profile, and course of hospitalisation in renal transplant patients with COVID-19.

Material and Methods

This was a retrospective observational study. conducted at Madurai Medical College, Tamil Nadu, India for a duration of four months, from May 2021 to August 2021 and data collection from May 2021 to July 2021 and data analysis in August 2021. This study was approved from the Institutional Ethics Committee (CDSCO: Reg no. ECR/1365/Inst/TN2020). A written informed consent was obtained from all the participants of this study.

Inclusion criteria: The inclusion criteria comprised all post kidney transplant patients (both live and deceased donor) having evidence of COVID-19 (either Reverse Transcription Polymerase Chain Reaction (RT-PCR) positive or evidence of COVID-19 pneumonia on Computed Tomography (CT) chest).

Exclusion criteria: The exclusion criteria included all patients with chronic graft dysfunction.

Study Procedure

A total of 18 patients were evaluated in this study. Data regarding the clinical history, routine blood investigations complete blood count, renal function tests, liver function tests, serum ferritin, d-dimer), radiological findings- Ground Glass Opacities (GGO), lobar consolidation, oxygen requirement, treatment and final outcomes were collected and compared.

Lymphopenia was defined as Absolute Lymphocyte Count(ALC) <1000 cells/cumm (15). Oxygen requirement was classified as: no oxygen needs; low oxygen requirement (nasal cannula, venturi mask with FiO2 of 0.5); high oxygen requirement (venturi mask with FiO2 of >0.5, reservoir mask with oxygen at 15 L/min and high -flow nasal ventilation); non invasive ventilation; and mechanical ventilation (16).

The AKI was defined and classified according to Acute Kidney Injury Network (AKIN) criteria (17). An institutional protocol was devised for managing immunosuppression in post-transplant COVID-19 patients after referring the European Renal Association-European Dialysis and Transplantation Association Developing Education Science and Care for Renal Transplantation in European States (ERA-EDTA DESCARTES) expert opinion (18). Antiproliferative agents (MMF and Azathioprine) were reduced. Of the patients taking Calcineurin inhibitors cyclosporin A was continued at the same dose and Tacrolimus dose was reduced. The dose of prednisolone was increased to 20 mg once daily. For patients with severe COVID-19 pneumonia, all immunosuppressants except low dose steroids were withdrawn.

The CRP was checked for all patients and patients were divided into having mild, moderate, or severe inflammatory reaction {CRP (mg/L) 10-50-mild; 50-100-moderate; >100-severe}.

Patients were treated with Intravenous (IV) steroids (either dexamethasone 6 mg BD or methyl prednisolone 40 mg twice a day (BD) depending on their inflammatory status (19),(20). In such patients, oral steroids were withheld.Underlying procoagulant risk was determined according to D-dimer values {D-dimer (mcg/mL) <0.5-mild; 0.5-1.0-moderate; >1.0-severe}. All patients with mild risk were started on once daily, and all patients with moderate to severe risk were started on twice daily subcutaneous enoxaparin.

All patients were treated with hydroxychloroquine, vitamin C, zinc and ivermectin. Remdesivir was started for patients who had SpO2 level <85%. It was administered as an intravenous infusion of 200 mg on day one followed by 100 mg as infusion once daily for four more days (21). Final outcome was classified as either recovery, death or recovery from the illness, but still on dialysis (graft loss).

Statistical Analysis

All data was compiled in Microsoft Excel, and statistical analysis done using Statistical Package for the Social Sciences (SPSS) v16. Normality tests (Shapiro Wilk, assessment of skewness and kurtosis) revealed non parametric data. Non parametric statistical tests were used, in addition to Chi-square test and odds ratio. Kaplan-Meier plot was used for survival analysis. The p-value <0.05 was considered statistically significant, and 95% confidence intervals were used.

Results

Total of 18 patients were studied (14 male and four female). The mean age was 40.389±11.3 years. Most of the patients had associated co-morbidities, the most common of which were diabetes and systemic hypertension (8 out of 18 each). Two patients had chronic Hepatitis C Virus (HCV) infection, one had chronic Hepatitis B Virus (HCB) infection, two had a history of coronary artery disease, and one had a recent history of acute graft dysfunction. The demographic variables and co-morbidities of the study population are shown in (Table/Fig 1).

The median time since transplant was 37 (IQR 23.5-111.25) months. The median duration of hospital admission was around 13.5 (IQR 7-20.25) days {10 (IQR 7-15.75) days in survivors vs 20.5 (IQR 11.75-22.5) days in non survivors, p-0.004}. The baseline creatinine was 1.45 (IQR 1.3-1.88) mg/dL. The baseline immunosuppressive used was calcineurin inhibitors in 15 patients, Mycophenolate Mofetil (MMF) in 16 patients, Azathioprine in one patient and mTOR inhibitors in one patient. Five patients were on double immunosuppression and 13 patients were on triple immunosuppression.

The symptomatology, laboratory investigations and radiographic findings of the patients are shown in (Table/Fig 2). The most common symptom was fever. One patient presented with an acute anterior wall myocardial infarction. During further evaluation, two patients had diabetic ketoacidosis, one patient had emphysematous pyelonephritis. Three patients showed rejection (Table/Fig 3).

The median WBC count was 7650 cells/cu.mm. The incidence of lymphopenia was 66.67 %. The median Absolute Leukocyte Count (ALC) was less in non survivors. Similarly, the median platelet count was also low in non survivors. Though the baseline creatinine was almost same in both survivors (1.4 mg/dL) and non survivors (1.5 mg/dL), the peak creatinine during in hospital admission was higher in non survivors, which also had a prognostic effect on the survival (p-0.001). The median CRP in survivors was low in comparison to non survivors. Quite similarly, D-Dimer was also low in survivors. Both CRP and D-Dimer were statistically significant with respect to the outcome

Total 12 out of 18 patients had nasopharyngeal swab RT-PCR positivity.Fourteen patients had multifocal/bilateral GGOs and the average GGO involvement was 22.5%. Two patients had lobar opacities and two had no acute radiographic findings. (Table/Fig 4) represents the Box and Whisker plot of the quantum of GGOs of survivors and non survivors. Non survivors had a relatively poor oxygenation status {SpO2-79 % vs 96 % in survivors, p-0.001]. Box and Whisker plot of oxygen saturation of survivors and non survivors is shown in (Table/Fig 5).

Two patients were treated with i.v. Remdesivir and 16 patients were treated with oral antivirals (Oseltamivir in 12 and Favipiravir in 4 patients).

Immunosuppressives were tapered on a case to case basis. For three patients MMF, Tacrolimus were decreased, and Prednisolone was increased. All immunosuppressives, except low dose steroids were stopped for one patient. All these four patients did not survive irrespective of these drastic measures. Six patients did not need any change in the immunosuppressive regimen, all of whom survived. Details regarding the treatment (including tapering of immunosuppressive drugs and ventilation requirement) are shown in (Table/Fig 6).

Four patients needed invasive ventilation, two needed non invasive ventilation, and three needed low flow nasal oxygen, while nine patients were oxygen independent.

The incidence of AKI was remarkably high 15 (83.3%) with stage 3 AKIN being the most common finding 6 (38.9%) (Table/Fig 7), (Table/Fig 8). All these six patients underwent haemodialysis, out of which 5 patients died, and one had a graft loss and is still on haemodialysis. The median time of initiation of haemodialysis in non survivors was five days with 95% confidence interval (2.841-7.159). All patients with AKIN 1 and 2 survived without the need of haemodialysis.

Six patients died (case fatality rate- 33.3%). One patient recovered from the illness but had graft loss and is continuing dialysis (Table/Fig 8), at the time of reporting the study. The most common cause of death was respiratory failure 3 (50%), followed by sepsis 2 (33.3%), and sudden cardiac arrest 1 (16.7%) (Table/Fig 8).

The Kaplan-Meier survival analysis is shown in (Table/Fig 9). It shows the probability of the event(death) at specific intervals in the study population. The median survival time was 22 days (19.792-24.208) with 95 % confidence interval. There was no difference in the type of transplant (live or deceased) on the overall survival.

Discussion

There are still many uncertainties regarding the recent COVID-19 pandemic in kidney transplant patients in terms of clinical symptomatology, patient and graft outcomes, the effect of immunosuppression and the role of anti-virals. This study has discussed the demographics, clinical presentation, biochemical profile, and course of hospitalisation in kidney transplant recipients with COVID-19.

Most of the patients presented with fever and cough, like the study done in Columbia University, in which 87% patients had fever and 60% had cough (22). An Italian study showed similar results (16). This is in contrast to another study done in the same geographical region, in which cough was the predominant symptom (23).

Three patients presented with only diarrhoea. Interestingly, diarrhoea was a common symptom in a Spanish study where four of 18 patients had diarrhoea whether post-transplant immunosuppression may modify the clinical presentation of COVID-19, making SOT recipients more prone to gastrointestinal symptoms compared to non transplant patients, remains to be confirmed (24).

One patient presented with an acute anterior wall myocardial infarction. Myocardial injury has been demonstrated to be around 7% in a review article by Uriel N et al., (25). In a case series from Italy, 24 of 28 COVID-19 patients with myocardial infarction had chest pain as their first symptom (26). Acute Coronary Syndrome (ACS) either due to plaque rupture demand ischaemia or vasospasm is certainly conceivable (27). Activated macrophages secrete collagenases that degrade collagen, a major constituent of the fibrous capon atherosclerotic plaques, which can lead to plaque rupture (28). Activated macrophages also secrete tissue factor, a potent procoagulant that triggers thrombus formation when the plaque ruptures (28). Given haemodynamic changes and exaggerated inflammatory response frequently seen with COVID-19, risk for ACS is higher.

Further evaluation revealed that two patients had diabetic ketoacidosis, one of whom also developed emphysematous pyelonephritis and succumbed. Study done in India by Par Ret al., concludes that Diabetic ketoacidosis is not uncommon in COVID-19 patients with pre-existing diabetes mellitus and portend a poor prognosis with a mortality rate of nearly 50% (29).

The radiological findings were variable with the most common finding being bilateral/multifocal GGOs (77.8%), two patients had lobar consolidation and two patients had normal CT findings. This finding was comparable to the study done in Columbia university, where about half of the patients had bilateral/multifocal opacities, 13% had lobar opacities and 33 % had unremarkable radiographs (22). Another study done in Wuhan, China showed a similar finding, with GGOs being the most common radiological abnormality (30).

The incidence of lymphopenia was more in non survivors (83.3% vs 58.3% in survivors). The median ALC was also lower in non survivors, though not statistically significant. This is in contrast with the study done in New York, where the lowest lymphocyte count had a prognostic significance on the outcome (31). However, the median platelet count which was also lower in non survivors had a statistical correlation with the outcome, similar to the New York study (31). This could be explained by the possible occurrence of Disseminated Intravascular Coagulation (DIC) with COVID-19, which is more common in non survivors (32).

Many patients also had elevated D-dimer level, which in the absence of any obvious thromboembolic events, also favours the occurrence of microvascular thrombosis or DIC. A study done in China postulated that higher d-dimer levels are associated with a severe infection (33).

The median CRP value was also comparatively higher in non survivors which could reflect an exaggerated inflammatory response. Both CRP and D-dimer were significantly associated with the overall survival.

AKI was described in 57 % transplant patients as compared to 29% in general population in a Chinese study (34). In another study, 40% post-transplant patients developed AKI (22). In this study, fifteen (83.3%) patients developed AKI, out of which 7(38.9%) patients had AKIN stage 3. Around 6 (33.3%) patients needed renal replacement therapy in the form of haemodialysis. In the study done in New York by Azzi Y et al., 23% needed RRT (31). Angiotensin- Converting Enzyme (ACE-2) and dipeptidyl peptidase, which are expressed in proximal tubule cells, have been identified as receptors for corona virus (35),(36). Uptake of SARS-CoV-2 virus into the proximal tubular epithelium is a possible explanation for AKI. In addition, microangiopathy mediated by complex inflammatory processes has also been suggested (37).

Three patients underwent biopsy for acute graft dysfunction, out of which two had TCMR and one had coexistent ABMR and TCMR (Table/Fig 3). They were treated with high dose steroids (including plasmapheresis for the patient with co-existent ABMR and TCMR). In a study by Kudose S et al., on biopsy findings in COVID-19, out of three allograft biopsies, one patient had TCMR, one had cortical necrosis and one had Acute Tubular Injury (ATI) (38). Out of these three, two patients recovered and one continued to be dialysis dependent. In contrast, in this study, all the three patients had a poor outcome. Two of these patients did not survive. One had a graft loss and is continuing dialysis. In addition to the above described mechanisms for AKI in COVID-19, other mechanisms like acute rejection from under suppression, or CNI toxicity through drug-drug interaction may play a role in transplant kidneys (39). Also, the inflammatory milieu surrounding COVID-19 may trigger or exacerbate immune-mediated processes in transplant patients like development of acute T-cell mediated rejection in a patient with preformed donor-specific antibodies (38). Supporting this hypothesis is the fact that all the 3 patients who had graft rejection had markedly high CRP.

Regarding ventilation requirements, 4 (22.2%) patients were intubated and mechanically ventilated. All those who were required mechanical ventilation did not survive. This is similar to the finding in an American study where 23 out of 28 intubated patients did not survive and the need for intubation was thus, concluded as a marker of poor prognosis (31).All the intubated patients had severe disease, thus the high mortality in them. A Korean study compared mortality between early intubated patients and patients managed conservatively (40). Early intubation was not found to offer any survival benefit.

Managing immunosuppression in these patients is challenging and should be decided after considering the patient age, severity of COVID-19 infection, associated co-morbidities, and time post-transplant. In milder forms of disease, the usual practice is to continue the same dose of immunosuppression, but this approach might favour high mortality in COVID-19 infection. It has been suggested in a study by Banerjee D et al., that antiproliferative agents (MMF or Azathioprine) should be stopped, the dose of prednisolone be increased, and the dose of Tacrolimus be reduced (41). An evident risk with such an approach is rejection but given the high mortality risk, the clinician’s main goal should be to focus on keeping the patient alive, with a careful assessment of risks versus benefits of continuing immunosuppression. Regarding adjustment of immunosuppression, 6 (33.3%) patients with milder form of the disease were managed on the same immunosuppressive dosage, all of whom survived with normal graft functions. One patient, who was on azathioprine developed severe persistent leukopenia and thus, azathioprine was stopped. He was suspected to have CMV viremia, but his WBC count improved with mere stoppage of azathioprine. Patients on cyclosporine A were continued on the same dose, since it has been shown to have an inhibitory effect on proliferation of corona viruses through its impact on cyclophilin A and B (14).

The optimal timing of the reintroduction of the original immunosuppressive is also still questionable. There are reports that viral shedding can occur for up to 2 weeks, but a maximum period of 37 days has also been observed (42),(43). There is also an association between the severity of the infection and the peak viral loads, which may influence the duration of subsequent viral shedding (44). Thus, given the uncertainty, the protocol followed, was to start the immunosuppressive dosage to preinfection level at either the time of discharge or to delay to a maximum of two weeks, given the risk that prolonged reduction of immunosuppression may trigger an episode of rejection.

All the patients received either oral antivirals (Oseltamivir or Favipiravir) or i.v. Remdesivir. Reports have suggested a role for Hydroxychloroquine (HCQ) in reducing the viral load (45). Invariably, all patients were treated with HCQ, in the absence of QT prolongation. Patients, who had high TC, were also treated with i.v. antibiotics and oral doxycycline. All except one patient who had severe thrombocytopenia due to underlying TMA, were treated with subcutaneous enoxaparin. The RECOVERY trial demonstrated mortality benefit in treatment with dexamethasone (19). In steroids-SARI (Glucocorticoid Therapy for Novel Coronavirus Critically Ill Patients with Severe Acute Respiratory Failure), i.v. methyl prednisolone was used, which also had a mortality benefit (20). The WHO subsequently recommended the use of systemic corticosteroids in severe cases (46). In this study, 12 out of 18 patients received iv steroids in the form of either dexamethasone (five patients) or methylprednisolone (seven patients), though their use did not have any mortality benefits.

Nine patients recovered, six patients died (case fatality rate 33.3 %) and one patient is still on dialysis. The mortality rate is comparable to other studies done in post-transplant COVID-19 patients (24),(31).

The cause of death was extrapulmonary in 50% of the patients (Table/Fig 8). Similar finding was observed in another study, where one of the seven patients studied, expired of a possible bowel infarction or intraabdominal sepsis. They concluded that mortality in critically ill patients with COVID-19 infection could be due to extrapulmonary causes like myocarditis or bowel involvement (41). As described earlier, the median platelet count, peak creatinine value, CRP value and the D-dimer value had a statistical correlation with the mortality.

Limitation(s)

The sample size was small, long term follow-up was not done and proteinuria was not evaluated. Biopsy could also not be done in all patients due to logistic reasons.

Conclusion

All transplant patients are at a higher risk of getting COVID-19 owing to their underlying immunosuppressed state. Varied presentation may occur with significant chest radiograph findings. The CRP, D-dimer, admission creatinine and platelet, arterial oxygen saturation are overall prognostic markers. They are also at a remarkably high risk of developing AKI, including acute graft rejection and a significant proportion may even need renal replacement therapy. In addition to anti-virals, the treatment also includes careful alteration of immunosuppression. The case fatality rate is also higher suggesting the need of stringent management, early hospitalisation, and more effective treatment protocol.

More studies are needed to know better about the course and outcomes of COVID-19 in transplant patients. It is therefore suggested, all countries should start maintaining a record of COVID-19 infections in kidney transplant patients. Analysis of this data may help clinicians make informed decisions about the management of these patients in these uncertain and rapidly evolving times.

Acknowledgement

The authors are thankful to Dr A Rathinavel, Dean, Madurai medical college for his immense support. The authors are also thankful to Dr Gayatri Lekshmi Madhavan for helping us with the statistical analysis.

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DOI and Others

DOI: 10.7860/JCDR/2022/52091.16340

Date of Submission: Sep 09, 2021
Date of Peer Review: Nov 26, 2021
Date of Acceptance: Mar 25, 2022
Date of Publishing: May 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? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

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