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

Users Online : 97749

AbstractMaterial and MethodsResultsDiscussionConclusionReferencesDOI and Others
Article in PDF How to Cite Citation Manager Readers' Comments (0) Audio Visual Article Statistics Link to PUBMED Print this Article Send to a Friend
Advertisers Access Statistics Resources

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 : May | Volume : 16 | Issue : 5 | Page : SC06 - SC10 Full Version

Association of Multisystem Inflammatory Syndrome Temporally Associated with COVID-19 (MIS-C) with Coinfections: A Retrospective Cross Sectional Analytical Study from Northern India


Published: May 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/52068.16332
Afreen Khan, Aparna Chakravarty, Rizwan Naqishbandi, Rekha Harish, Faizan Kamili

1. Assistant Professor, Department of Paediatrics, HIMSR and HAHC, New Delhi, Delhi, India. 2. Associate Professor, Department of Paediatrics, HIMSR and HAHC, Delhi, Delhi, India. 3. Senior Resident, Department of Paediatrics, HIMSR and HAHC, New-Delhi, Delhi, India. 4. Professor, Department of Paediatrics, HIMSR and HAHC, New Delhi, Delhi, India. 5. Senior Resident, Department of Paediatrics, HIMSR and HAHC, New Delhi, Delhi, India.

Correspondence Address :
Afreen Khan,
Handard Institute of Medical Science and Research, New Delhi, Delhi, India.
E-mail: afreenkhan1204@yahoo.com

Abstract

Introduction: Multisystem Inflammatory Response Syndrome in Children (MIS-C) temporally associated with Coronavirus Disease 2019 (COVID-19) is characterized by fever, raised inflammatory markers, multisystem involvement with evidence of COVID-19 infection (positive RT-PCR or serology). It occurs concurrently or after 4-6 weeks of acute COVID infection.It has wide range of clinical presentation ranging from mild asymptomatic infection to severe life-threatening illness. Clinical presentation of MIS-C has considerable overlapping features with other tropical infections. During peak wave of COVID-19, when large proportion of population has been affected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), contracting other infections during and within four weeks of active COVID-19 is inevitable. Despite of this concern, only few researchers have studied co-infection and they explained a complex interaction between COVID-19 and other infections like tuberculosis and dengue. They demonstrated how one infection augments the severity of other. To the best of our knowledge no pediatric population-based study explained the interaction of acute COVID-19 & MIS-C with other infections so far.

Aim: To determine the association of MIS-C with co-infections in SARS-CoV-2 positive children of 1 month to less than 18 years of age.

Materials and Methods: A retrospective review of the medical records of pediatric patients with SARS-CoV-2 infection, treated from September 2020 to February 2021, was performed.All the patients who fulfilled World Health Organization (WHO) criteria of MIS-C were included. Detailed demographic, clinical, laboratory parameters and associated co-infections were recorded.The severe and non severe MIS-C groups were compared. Sample ‘t’ test, Wilcoxon test and Chi-squared test were used for statistical analysis.

Results: A total of 44 children fulfilled the diagnostic criteria of MIS-C and were included in the study. Out of 44 , 20 children (45.4%) had severe disease and 24 had non severe disease. The mean age of children with severe MIS-C was 7.38±5.39 years, as compared to 4.37±4.61 years in the non severe group (p-value= 0.044). Males were predominantly affected in both the groups (Male: Female =1.22:1 in severe MIS-C and 2.4:1 in non severe MIS-C). The gastrointestinal system was most commonly affected in both groups. Associated co-infection was noted more in severe MIS-C group (11 vs 1 patient in severe vs non severe group, p-value=<0.001).Tuberculosis was found to be associated in three patients, followed by complicated enteric fever, and severe dengue in two patients each. The odds ratio for developing severe MIS-C in the presence of co-infections was 10.5(CI=2.33-47.27) while in its absence it was 0.10(0.02-0.43).

Conclusion: The findings of this study support that concurrent infections in COVID-19 can exacerbate the severity of COVID-19 illness and may lead to severe MIS-C.

Keywords

Dengue, Enteric fever, Multisystem inflammatory syndrome, Severe acute respiratory syndrome coronavirus 2 related, Tuberculosis

The emergence of the second wave has hit hard the low and middle-income (LMI) countries like India with daily case counts exceeding 2 00,000 during the peak of second wave (1). In the year 2020, during the initial stage of the pandemic, the studies on COVID-19 mostly represented adult data. Children were reported to have mild symptoms until April 2020 when reports from United Kingdom described incomplete Kawasaki disease and toxic shock syndrome in association with COVID-19 infection (2),(3). Similar cases were reported across the world which subsequently was termed as multisystem inflammatory response syndrome in children temporally associated with COVID-19 (MIS-C). In May 2020, Centers for Disease Control and Prevention (CDC) and WHO published the case definition for MIS-C (4),(5). The criterion includes fever, elevated inflammatory markers, and signs of multisystem involvement, evidence of SARS-CoV-2 infection or exposure, and exclusion of other potential causes. An increased incidence of such cases usually occurs 4-6 weeks after a peak wave of COVID-19. With the availability of more studies, it is seen that the spectrum of clinical manifestation of COVID-19 is wide and ranges from mild illness to severe life-threatening conditions, causing multiorgan failure leading to significant morbidity and mortality (6),(7).

The LMICs are already overburdened with infections like dengue, typhoid, malaria and tuberculosis. Moreover, multiple factors like disruption of routine and preventive healthcare services, overwhelmed healthcare facilities, social stigma, fear, delay in seeking treatment, poor nutrition, and lockdown restrictions causing overcrowding at home may lead to increase in burden of endemic infections (8). With emergence of COVID-19 pandemic affecting large proportion of population during its peak, it is reasonable to anticipate the increase rate of co-infections and superinfections (SARS-CoV-2 and endemic infections) and they are inevitable. The literature review by Visca D et al., explained a complex interaction between COVID -19 and tuberculosis in adults, and how it increases the severity and progression of one another; but no study so far has explained the co-existence of these conditions in the pediatric population(9). So, this study aimed to evaluate the association between MIS-C and other infections and to evaluate if their co-existence augments the severity of MIS-C.

Material and Methods

A retrospective cross-sectional analytical study was conducted at the Department of Pediatrics, Hamdard Institute of Medical Sciences and Research, Delhi. The study duration was from 1st September 2020 to 28th February 2021. Ethical approval was taken from Jamia Hamdard Institutional Ethics Committee (JHIEC) for conducting the study.

Inclusion criteria: All children, admitted during the study period, who fulfilled criteria for MIS-C including children having co-infections were included in the study (4),(5).

Case Definition

According to WHO all the following 6 criteria must be met to diagnose a child with MIS-C:

1. Children and adolescents 0–19 years of age
2. Fever ≥3 days
3. Clinical signs of multisystem involvement (at least 2 of the following):
a. Rash or bilateral non purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet).
b. Hypotension or shock.
c. Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities {including an Echocardiogram (ECHO) findings or elevated Troponin/N-terminal, protein B-type natriuretic peptide (NT-proBNP)},
d. Evidence of coagulopathy {by Prothrombin time (PT) test, Partial Thromboplastin Time (PTT), elevated d-Dimers}.
e. Acute gastrointestinal problems (diarrhoea, vomiting, or abdominal pain).
4. Elevated markers of inflammation such as Erythrocyte Sedimentation Rate (ESR), C-reactive protein, or procalcitonin.
5. No other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes.
6. Evidence of COVID-19 {Reverse transcriptase polymerase chain reaction (RT PCR), antigen test or serology positive}, or likely contact with patients with COVID-19.

Exclusion criteria: Children with chronic co-morbidities i.e. immunodeficiency syndrome, cerebral palsy, bronchopulmonary dysplasia, inborn error of metabolism, hematological malignancy, congenital heart disease & connective tissue disorders were excluded from the study.

The data was extracted from records, which included demographic profile, detailed clinical presentation, presence of other co-infections (tuberculosis, dengue, enteric fever etc.).The following laboratory parameters were recorded - complete blood count, absolute lymphocyte count, hepatic function tests, renal function tests, CRP (C-reactive protein), ESR (Erythrocyte sedimentation rate), serum ferritin, D-dimer, coagulation profile, creatinine phosphokinase-MB(CPK-MB) and lactate dehydrogenase (LDH). Any clinically significant finding on Chest X-ray and other radiological imaging were recorded. Qualitative COVID-19 RT PCR was performed by using COVIWOK COVID-19 test kit and SARS-CoV-2 quantitative antibodies were detected in serum by the LIAISON® SARS-CoV-2 S1/S2 IgG test which uses indirect Chemiluminescence Immunoassay (CLIA) technology for the quantitative determination of anti S1 and anti S2 specific IgG antibodies.

These patients were further divided into two groups on the basis of severity(10),(11) (Table/Fig 1).

• Severe MIS-C: Patients with shock, cardiac dysfunction, severe respiratory distress, respiratory failure, altered sensorium, thromboembolism, markedly raised inflammatory markers (CRP>10 mg/dL, Serum Ferritin >500 mcg/L, raised cardiac Troponin I >0.5 ng/mL)
• Non severe MIS-C:Children with persistent fevers and mild symptoms(Diarrhoea,headache, fatigue etc). Inflammatory markers may be elevated but without signs of severe multisystem involvement.

Both the groups (Severe MIS-C and Non severe MIS-C) were further subdivided into two, on the basis of presence or absence of co-infections (Table/Fig 1) and were compared. Further patients within severe MIS-C group, with and without co-infections were compared, to determine if presence of co-infections affects the disease severity.

Statistical Analysis

Data were coded and recorded in MS Excel spreadsheet and transferred to Statistical Package for Social Sciences (SPSS) software version 23.0 (IBM Corp.). Group comparisons for continuously distributed data were made using Independent sample‘t’ test when comparing two groups. If data were found to be non normally distributed, appropriate non parametric tests in the form of Wilcoxon test were used. Chi-squared test was used for group comparisons for categorical data. In case the expected frequency in the contingency tables were found to be <5 for >25% of the cells, Fisher’s exact test was used instead. Statistical significance was kept at p≤0.05.

Results

Total of 44 pediatric patients fulfilled the inclusion criteria (MIS-C), and were included in the study. Out of them, 20 patients were found to have severe MIS-C (45.4%), and the remaining 24 (54.5%) were classified in the non severe MIS-C group. Among 20, 11 patients (55%) in severe MIS-C group had co-infections as compared to only 1 patient in non severe MIS-C. (Table/Fig 1).

Severe MISC v/s Non severe MISC (Table/Fig 2), (Table/Fig 3): The children in the severe MIS-C group were relatively older (7.38±5.39 years in MIS-C v/s 4.37±4.61 years in non severe, p-value<0.05). There was no difference in age distribution in the severe MIS-C group. In the non severe MIS-C group, majority (70.8%) were less than five years of age. Males were predominantly affected in both the groups (Male: Female =1.22:1 in severe MIS-C & 2.4:1 in non severe MIS-C).

The most commonly involved system in both the groups was gastrointestinal (80% in severe and 83% in non severe), followed by the respiratory system (75%) in severe MIS-C and central nervous system including non specific signs like irritability and confusion (62%) in non severe MIS-C group. All the patients in severe MIS-C group, and majority in non severe MIS-C group (91.7%) had fever. Respiratory symptoms, mucous membrane changes, swollen hands and feet, shock and oliguria were found to be significantly higher in severe MIS-C group (p-value<0.05), whereas diarrhoea was more common in non severe MIS-C population (p-value=0.008).

Co-infections (Table/Fig 4): Total of 12 (34.1%) patients among cohort had other co-infections. Further 11 (55%) patients in severe MIS-C group had non SARS-CoV-2 infections which was significantly higher than the non severe MIS-C group (4.2 %) (p-value<0.001). The 11 patients in the MIS-C group with co-infections included tuberculosis in three patients, two with dengue fever, two with complicated enteric fever, one each with viral hepatitis A, viral hepatitis E, measles and amoebic dysentry. In the non severe MIS-C group only one patient was diagnosed with co-infection who had tuberculosis. The odds ratio for developing severe MIS-C in the presence of co-infections, was 10.5 (CI=2.33-47.27).

On comparing the patients with and without co-infections within severe MIS-C cohort, no significant difference was found in terms of clinical presentation, severity of illness (requirement of oxygen, ionotropic, ventilator support etc.), laboratory parameters and duration of stay.

Discussion

Since the emergence of COVID-19 pandemic, the deleterious effect of co-morbidities like diabetes, hypertension and congenital heart diseases on the severity of the infection have been explained. Limited studies have explored the association of SARS-CoV-2 with non SARS-CoV-2 infections, especially prevalent in LMIC like tuberculosis (TB) and other tropical infections including dengue and malaria. (8),(12),(13). Though many researchers have tried to provide a vision to foresee the increased burden of co-infections (concurrent infections with SARS-CoV-2 and other organisms), yet no population-based study described them in detail (14),(15),(16). Some authors attempted to estimate the effect of COVID-19 pandemic on HIV, tuberculosis and malaria in LMIC (8). With the aid of a modelling study researchers have raised concerns that due to disruption of routine health services, there could be a significant increase in mortality over next 5 years due to non SARS-CoV-2 infections (13).

Preliminary studies have shown that SARS-CoV-2 infected patients with latent TB have increased risk of disease progression and TB patients are at 2.1-fold increased risk of developing severe disease (17),(18). In addition to the socio-economic factors and logistic issues, a complex interplay of various pathophysiological mechanisms has been responsible. Impaired lung function due to pre-existing respiratory infection and shared immune dysregulation are contributory. (9),(18). They are presumed to augment the severity of each other. This hypothesis could explain the development of MIS-C and progression to severe disease in these patients. In the present cohort, four patients had TB co-infection, of which three had disseminated TB and MIS-C; all were adolescents and received Bacille Calmette-Guerin (BCG) vaccine. Few adult population-based studies have been published on TB and COVID-19 co-infection, but there is no pediatric data, except three cases reports by Gupta S et al. (19). To understand the interaction between tuberculosis and COVID-19, a global study coordinated by Global Tuberculosis Network (GTN) and supported by WHO is ongoing (20). Preliminary results that suggest that COVID-19 is contributory in TB pathogenesis cannot be ruled out or confirmed at present and larger studies are required (21).

Tropical infections like dengue, malaria and scrub typhus occur in post monsoon period (22). If an epidemic of COVID-19 hits a tropical country like India during this time then there can be an increase rate of these co-infections. Moreover, tropical infections and COVID-19 have similar clinical presentation; Yan et al has shown that the presentation of COVID-19 can overlap with dengue leading to misdiagnosis (22). Increased mortality and morbidity have been seen in adults infected with COVID-19 and dengue co-infection. Few cases of dengue and scrub typhus with COVID-19 in children have been reported. All had associated MIS-C and were critically ill (24),(25),(26),(27). An adolescent with scrub typhus was reported to develop macrophage activation syndrome (MAS) (27). Similar findings were observed in this study. Two critically ill patients were diagnosed with MIS-C & dengue co-infection (diagnosed by NS1 antigen detection) of which one developed secondary hemophagocytosislymphohistiocytosis (HLH). Though dengue virus is a known etiological agent, studies have also suggested SARS-CoV-2 as potential trigger for causing HLH but here the role of either could not be confirmed. One recent study has recommended HLH investigation in severe COVID-19 patients with suggestive laboratory parameters. (28). The increased severity in such co-infections could be explained with cross reactivity of immune responses. Certain studies have suggested that SARS-CoV-2 and dengue virus (DENV) interaction could lead to antibody dependent enhancement in SARS-CoV-2 infection (29),(30). However, detailed studies are required to draw conclusion on their exact pathogenesis and to determine if their role is bidirectional in disease progression or amplification.

Unlike vector-borne diseases, the transmission of water-borne infections like enteric fever, viral hepatitis and diarrhoea occurs throughout the year with seasonal outbreaks. The peak incidence of enteric fever in India occurs post monsoon period (May-October) (31). In this study, two patients each had enteric co-infection and viral hepatitis and one had amoebic dysentery. Till now only a single case of enteric co-infection has been reported in an adolescent male (32). Here, two patients of MIS-C with enteric co-infections (positive blood cultures) were reported. Both had a complicated course with one presenting as encephalopathy showing splenial changes on Contrast-Enhanced Magnetic Resonance Imaging (CE-MRI) of brain. Mild encephalopathy with reversible splenial changes (MERS) is a rare finding in Salmonella typhi infection though few cases due to SARS-CoV-2 has been reported (33),(34). Cerebrospinal fluid sample was negative for COVID RT PCR and other viral and bacterial etiology. Identifying and treating such cases keeping in mind a broad differential diagnosis is crucial for the timely management.

Limitation(s)

There are various limitations of study. Major limitation was its retrospective design and absence of detailed immunopathological markers.

Conclusion

In conclusion, this study suggests that patient with recent SARS-CoV-2 infection, if superinfected has increased susceptibility for developing MIS-C; and SARS-CoV-2 infection increases the possibility of progression of latent TB. These results are not confirmatory and well-designed prospective studies should be designed to be able to answer many questions regarding the burden of co-infections. Further questions that need answers are- whether concurrent COVID-19 infection increases the severity of other infectious diseases, do immunopathological mechanisms cause bi-directional amplification of disease and if any superinfections post COVID-19 facilitates the development of MIS-C.

Till then, a broad differential diagnosis along with well-planned out laboratory investigations can help in early diagnosis and management.

References

1.
World Health Organization.WHO coronavirus disease (COVID-19) dashboard [Internet]. Geneva: World Health Organization;2020. Available from: https://covid19.who.int/.(last accessed on 8rth October'2021)
2.
Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020. Epub 2020/05/11. [crossref]
3.
DeBiasi RL, Song X, Delaney M, Bell M, Smith K, Pershad J, et al. Severe COVID-19 in Children and Young Adults in the Washington, DC Metropolitan Region. J Pediatr. 2020;223:199-203.e1. doi: 10.1016/j.jpeds.2020.05.007 [crossref] [PubMed]
4.
Centers for Disease Control and Prevention Health Alert Network (HAN). Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19). https://emergency.cdc.gov/han/2020/han00432.asp (accessed on 11th April 2021)
5.
World Health Organization. Multisystem inflammatory syndrome in children and adolescents with COVID-19: Scientific Brief. 2020. https://www.who.int/publications-detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19 (accessed on 11th April 2021)
6.
Yasuhara J, Watanabe K, Takagi H, Sumitomo N, Kuno T. COVID-19 and multisystem inflammatory syndrome in children: A systematic review and meta-analysis. PediatrPulmonol2021;56:837-848. [crossref] [PubMed]
7.
Baradaran A, Malek A, Moazzen N, Shaye ZA. COVID-19 associated multisystem inflammatory syndrome: A systematic review and meta-analysis. Iran J Allergy Asthma Immunol 2020;19:570-588. [crossref] [PubMed]
8.
Hogan AB, Jewell BL, Sherrard-Smith E, Vesga JF, Watson OJ, Whittaker C, et al. Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study. Lancet Glob Health 2020;8:e1132-e1141. [crossref]
9.
Visca D, Ong CWM, Tiberi S, Centis R, D'Ambrosio L, Chen B. Tuberculosis and COVID-19 interaction: A review of biological, clinical and public health effects. Pulmonology 2021;27:151-165. [crossref] [PubMed]
10.
Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, et al; PIMS-TS Study Group and EUCLIDS and PERFORM Consortia. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA. 2020 Jul 21;324(3):259-269. [crossref] [PubMed]
11.
Center for Disease Control and Prevention, Center for Preparedness and Response: Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19), Clinician Outreach and Communication (COCA) Webinar. Available at: https://emergency.cdc.gov/coca/calls/2020/callinfo_051920.asp?deliveryName=USCDC_1052-DM28623
12.
Wu Q, Xing Y, Shi L, Li W, Gao Y, Pan S et al. Coinfection and other clinical characteristics of COVID-19 in children. Pediatrics 2020;146:e20200961. Doi: 10.1542/peds.2020-0961. [crossref] [PubMed]
13.
Garcia-Vidal C, Sanjuan G, Moreno-García E, Puerta-Alcalde P, Garcia-Pouton N, Chumbita M et al. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study. Clin Microbiol Infect 2021;27:83-88. [crossref] [PubMed]
14.
Marimuthu Y, Nagappa B, Sharma N, Basu S, Chopra KK. COVID-19 and tuberculosis: A mathematical model based forecasting in Delhi, India. Indian J Tuberc2020;67:177-181. [crossref] [PubMed]
15.
Cox MJ, Loman N, Bogaert D, O'Grady J. Co-infections: potentially lethal and unexplored in COVID-19.Lancet Microbe 2020;1:e11.https://doi.org/10.1016/S2666-5247(20)30009-4. [crossref]
16.
Gupta U, Prakash A, Sachdeva S, Pangtey GS, Khosla A, Aggarwal R et al. COVID-19 and Tuberculosis: A Meeting of Two Pandemics! J Assoc Physicians India 2020;68:69-72.
17.
Chen Y, Wang Y, Fleming J, et. al. Active or latent tuberculosis increases susceptibility to COVID-19 and disease severity. [Internet] Infectious Diseases (except HIV/AIDS) 2020 http://medrxiv.org/lookup/doi/10.1101/2020.03.10.20033795 Mar [cited 2020 May 22]. [crossref]
18.
Gao Y, Liu M, Chen Y, Shi S, Geng J, Tian J. Association between tuberculosis and COVID-19 severity and mortality: A rapid systematic review and meta-analysis. J Med Virol2021;93:194-196. [crossref] [PubMed]
19.
Gupta S, Chopra N, Singh A, Gera R, Chellani H, Pandey R et al. Unusual clinical manifestations and outcome of multisystem inflammatory syndrome in children (MIS-C) in a tertiary care hospital of North India. J Trop Pediatr. 2021;67(1):fmaa127.Doi: 10.1093/tropej/fmaa127. [crossref] [PubMed]
20.
Casco N , Jorge AL , Palmero D , Alffenaar JW, Fox G , Ezz W , et al. TB and COVID-19 co-infection: rationale and aims of a global study. Int J Tuberc Lung Dis. 2021;25:78-80. Doi: 10.5588/ijtld.20.0786. PMID: 33384052. [crossref] [PubMed]
21.
Tadolini M, Codecasa LR, García-García JM, Blanc FX, Borisov S, Alffenaar JW et al. Active tuberculosis, sequelae and COVID-19 co-infection: first cohort of 49 cases. Eur Respir J 2020; 56: 2001398.https://doi.org/10.1183/ 13993003.01398-2020. [crossref] [PubMed]
22.
Susilawati TN, McBride WJ. Acute undifferentiated fever in Asia: a review of the literature. Southeast Asian J Trop Med Public Health 2014;45:719-26.
23.
Yan G, Lee CK, Lam LT, Yan B, Chua YX, Lim AY, et al. Covert COVID-19 and false-positive dengue serology in Singapore. Lancet Infect Dis 2020;20:536. [crossref]
24.
Ratageri VH, Pawar GR,Nikhil G, George SS. Co-Infection of Dengue fever with COVID-19 in a child with MIS-C. Indian J Pediatr 2021;88:485. [crossref] [PubMed] [PubMed]
25.
Alam A, Sudarwati S, Hakim DDL, Mahdiani S. Case Report: Severe COVID-19 and dengue in an Indonesian Infant. Am J Trop Med Hyg2021;104:1456-1460.
26.
Somasetia DH, Malahayati TT, Andriyani FM, Setiabudi D, Nataprawira HM. A fatal course of multiple inflammatory syndrome in children coinfection with dengue. A case report from Indonesia. IDCases 2020;22:e01002.Doi: 10.1016/j.idcr.2020.e01002 [crossref] [PubMed]
27.
Gupta A, Gill A. Multisystem Inflammatory Syndrome in a Child with Scrub Typhus and Macrophage Activation Syndrome. J Trop Pediatr 2021;67:fmab021. Doi: 10.1093/tropej/fmab021. [crossref] [PubMed]
28.
Retamozo S, Brito-Zerón P, Sisó-Almirall A, Flores-Chávez A, Soto-Cárdenas MJ, Ramos-Casals M. Haemophagocytic syndrome and COVID-19. Clin Rheumatol2021;40:1233-1244. [crossref] [PubMed]
29.
Harapan H, Ryan M, Yohan B, Abidin RS, Nainu F, Rakib A et al. Covid-19 and dengue: Double punches for dengue-endemic countries in Asia. Rev Med Virol 2021;31:e2161. Doi: 10.1002/rmv.2161. [crossref] [PubMed]
30.
Ulrich H, Pillat MM, Tárnok A. Dengue Fever, COVID-19 (SARS-CoV-2), and Antibody-Dependent Enhancement (ADE): A Perspective. Cytometry A 2020 ;97:662-667. [crossref] [PubMed]
31.
Saad NJ, Lynch VD, Antillón M, Yang C, Crump JA, Pitzer VE. Seasonal dynamics of typhoid and paratyphoid fever. Sci Rep 2018;8:6870. Doi: 10.1038/s41598-018-25234-w. [crossref] [PubMed]
32.
Ayoubzadeh SI, Isabel S, Coomes EA, Morris SK. Enteric fever and COVID-19 co-infection in a teenager returning from Pakistan. J Travel Med 2021;28:taab019. Doi:10.1093/jtm/taab019. [crossref] [PubMed]
33.
Ka A, Britton P, Troedson C, Webster R, Procopis P, Ging J et al. Mild encephalopathy with reversible splenial lesion: an important differential of encephalitis. Eur J Paediatr Neurol 2015;19:377-82. [crossref] [PubMed]
34.
Abdel-Mannan O, Eyre M, Löbel U, Bamford A, Eltze C, Hameed B et al. Neurologic and radiographic findings associated with COVID-19 infection in children. JAMA Neurol 2020;77:1440-1445. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2022/52068.16332

Date of Submission: Aug 23, 2021
Date of Peer Review: Nov 25, 2021
Date of Acceptance: Mar 04, 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? No
• For any images presented appropriate consent has been obtained from the subjects. No

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Aug 24, 2021
• Manual Googling: Feb 12, 2022
• iThenticate Software: Mar 21, 2022 (10%)

ETYMOLOGY: Author Origin

JCDR is now Monthly and more widely Indexed .
  • Emerging Sources Citation Index (Web of Science, thomsonreuters)
  • Index Copernicus ICV 2017: 134.54
  • Academic Search Complete Database
  • Directory of Open Access Journals (DOAJ)
  • Embase
  • EBSCOhost
  • Google Scholar
  • HINARI Access to Research in Health Programme
  • Indian Science Abstracts (ISA)
  • Journal seek Database
  • Google
  • Popline (reproductive health literature)
  • www.omnimedicalsearch.com