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

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Dr Mohan Z Mani

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

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

Prof. Somashekhar Nimbalkar

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

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

Dr. Kalyani R

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

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

Dr. Saumya Navit

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

Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
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,
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,
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
(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)
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.
On April 2011

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
On Jan 2020

Important Notice

Year : 2021 | Month : August | Volume : 15 | Issue : 8 | Page : ZE06 - ZE10 Full Version

Oral and Periodontal Manifestations of COVID-19 and its Plausible Association with Periodontal Disease

Published: August 1, 2021 | DOI:
Narayane Ramkumar, Hanumanth Sankar

1. Senior Lecturer, Department of Periodontics, Indira Gandhi Institute of Dental Sciences, Puducherry, India. 2. Reader, Department of Orthodontics, Indira Gandhi Institute of Dental Sciences, Puducherry, India.

Correspondence Address :
Dr. Narayane Ramkumar,
Senior Lecturer, Department of Peridontics, IGIDS MGMCRI Campus,
Puducherry, India.


The coronavirus disease 2019 (COVID-19), has caused a significant and urgent threat to the global health. It has markedly affected the delivery of healthcare services all over the world. Early diagnosis of the disease is imperative to contain the spread of the viral infection. The virus can also lead to potential systemic complications such as lungs involvement, skin, and oral manifestations. The presence of oral lesions is emerging evidence that may indicates the presence of COVID-19 infection. Since, the virus has affinity for Angiotensin Converting Enzyme (ACE2) receptors present in the respiratory tract, oral mucosa, tongue and salivary glands; therefore, the oral cavity serves as a major habitat for invasion of the virus. This review aimed to discuss the oral and periodontal manifestations of COVID-19. Articles between December 2019 and April 2021 were searched for this narrative review in Pub Med, Scopus, Science Direct related to COVID-19 and its oral manifestations, using the following terms: “Corona virus,” “COVID-19,” and “SARS-CoV-2” in combination with “Stomatognathic diseases,” “Oral manifestation,” and “Mouth diseases” and “Periodontal diseases”. The oral manifestations commonly associated with COVID-19 are salivary gland disorders, xerostomia, alteration of taste and smell and lesions in oral mucosa. The appearance of these oral manifestations during the asymptomatic phase of disease helps in early identification of the disease. The recent COVID-19 infection has been strongly associated with the appearance and establishment of cytokine storm. It is found that many components of the cytokine storm are common with the cytokine expression found in periodontitis. This narrative review aims at exploring the association between COVID-19 and periodontal disease through their cytokine profiles.


Angiotensin converting enzyme-2 receptors, Coronavirus disease 2019, Cytokine, Early diagnosis

The coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is an infectious disease affecting the respiratory tract. The SARS-CoV-2 is mainly transmitted through respiratory droplets and close contact with the infected routes. Most of the infected people present with fever, cough and difficulty in breathing; some develop severe pneumonia, renal and multiorgan failure and some may remain asymptomatic (1).

The novel coronavirus disease 2019 (2019-nCoV) has been found to be a serious threat to global health. Current researches showed that coronavirus invades human cells via the receptor ACE2 through single-cell RNA sequencing (scRNA-seq) data analysis (2). Hence, it is found that cells with ACE2 receptor may become the host cell for the coronavirus. Studies have identified the organs that are at risk and are vulnerable to COVID-19 infection (e.g., lung; Zou X et al., 2020) (3), tongue mucosa (Wang W et al., 2020) (4), salivary gland mucosa (Xu J et al., 2020) (5), epithelial cells of oral mucosa (Xu H et al., 2020) (6). The SARS-CoV-2 interaction with ACE2 receptors may also impair taste bud sensitivity, which could induce dysfunctional gustatory responses (7).

The COVID-19 presents with a wide range of oral signs and symptoms that includes taste disorders, unspecific oral ulcerations, desquamative gingivitis, petechiae, and co-infections such as candidiasis (8). There is uncertainty in these oral manifestations whether they are following a typical clinical pattern resulting from the direct SARS-CoV-2 infection or due to systemic deterioration, given the possibility of co-infections, impaired immune system, and adverse reactions of medical treatment (9),(10). Since, there is lack of clarity in the prevalence of clinical manifestations, the range of COVID-19 oral manifestations has been considered of broad and current interest. Hence, the present review focused on oral and periodontal manifestations in COVID-19 and its assosciation with periodontal disease.


The most relevant contributions related to oral and periodontal manifestations of COVID-19 were chosen based on the nature, in this narrative review article. The search was conducted using six MeSH keywords including, “Corona virus,” “COVID-19,” “SARS-CoV-2”, “Stomatognathic diseases,” “Oral manifestation,” and “Mouth disease”, “Periodontal manifestation” in Pub Med, Scopus, and Science Direct databases among articles between December 2019 and April 2021.

The review of literature showed that most of the studies were on systemic manifestations, therefore we focused more on oral related symptoms and periodontal health and possible disease mechanisms which may provide new clinical information and new vistas for early diagnosis of COVID-19.


COVID-19 shows varied clinical presentation, ranging from asymptomatic state to acute respiratory distress syndrome along with multiorgan dysfunction. The clinical presentation of COVID-19 includes fever, cough, sore throat, fatigue, headache, myalgia, breathlessness and conjunctivitis (11). It is found that COVID-19 is associated with increase in inflammatory cytokines such as Interleukin (IL)-IL2, IL7, IL10, Interferon-gamma inducible protein 10 kD (IP-10),Granulocyte colony-stimulating factor (G-CSF or GCSF), Monocyte chemotactic protein-1 (MCP-1), Macrophage inflammatory protein-1 alpha (MIP-1α/CCL3); Tumor Necrosis Factor alpha (TNFα) which can progress to pneumonia, respiratory failure and death in some cases by the end of first week (12). Acute lung injury, Acute Respiratory Distress Syndrome (ARDS) , shock and acute kidney injury are the complications associated with severe COVID-19 disease. Elderly and those with underlying co-morbidities are associated with more adverse outcomes and death. The case fatality rate associated with this disease was found to be between 2% and 3% (11).

The high transmissibility of SARS-CoV-2 may be attributed to the unique virological features of SARS-CoV-2. Transmission of SARS-CoV-2 occurred mainly after illness onset and peaked following disease severity. However, the SARS-CoV-2 viral load in upper respiratory tract samples was already highest during the first week of symptoms, and thus the risk of pharyngeal virus shedding was very high at the beginning of infection. Transmission of COVID-19 takes place through viruses in liquid droplets during speech from COVID carrier (13). However, much smaller particles, aerosols are also attributed to the spread of the virus (14). Coronavirus pose a risk of prolonged infection such as the case of SARS-CoV-2 due to their persistence on inanimate surfaces for days. These findings explain the rapid geographic spread of COVID-19, and to reduce the risk of transmission of this disease, a public health intervention provides benefits to mitigate the pandemic (15).


The oral manifestations commonly associated with COVID-19 are salivary gland disease, xerostomia, dry mouth and burning sensations, oral ulcerations and blisters, taste and smell alterations, and oral mucosal lesions. In addition to the above symptoms erosion, bulla, vesicle, pustule, fissured/depapillated tongue, macule, papule, plaque, pigmentation, halitosis, whitish areas, haemorrhagic crust, necrosis, petechiae, swelling, erythema, and spontaneous bleeding were also noted in patients with COVID-19 (4),(5),(8),(16),(17),(18),(19),(20),(21),(22),(23),(24),(25),(26),(27). The sites of involvement of these oral manifestations were tongue, labial mucosa, palate, gingival, buccal mucosa, oropharynx and tonsil (16),(17),(18),(19),(20),(21),(22),(23),(24),(25),(26),(27). Most of the oral lesions were symptomatic. The oral lesions had a latency time of 4 to 12 weeks with the onset of systemic symptoms (16),(17),(18),(19),(20),(21),(22),(23),(24),(25),(25),(26),(27). These oral manifestations could be due to the direct viral infection or they are aggravated by COVID-19, linked to immunocompromised system or long term pharmacotherapy (28).

Therefore, the range of oral manifestations of SARS-CoV-2 has been considered of broad and modern day interest. COVID-19 additionally could also jeopardise the oral health leading to a variety of opportunistic fungal infections, recurrent oral Herpes Simplex Virus (HSV-1) infection, oral unspecific ulcerations, fixed drug eruptions, dysgeusia, xerostomia, ulcerations (29).

Salivary Gland Disease

The SARS-CoV-2 expression has been detected in the oral epithelium and sputum, swabs of human saliva. This expression in saliva is being considered a tool for diagnostic strategies. Patients with COVID-19 infection are found to have salivary gland involvement. ACE2 has been reported as an important receptor for COVID-19. Xu J ., demonstrated that ACE2 expression in minor salivary glands compared to lungs was higher, thereby suggesting that COVID-19 could potentially target salivary glands (5). In accordance to these findings, Chen N et al., evaluated the expression of ACE2 receptor of 2019-nCoV in the epithelial cells of salivary gland and demonstrated the possibility of 2019-nCoV infection of the salivary glands (12).They also mentioned that higher positive saliva detection rate of 75% in critically ill patients was due to virus invasion caused by high viral loads or infected salivary glands in the last stage of the disease. The same results have been also reported by Wang W et al., and Kotfis K and Skonieczna-Z????ydecka K (4),(17). It is important to know that only salivary detection of COVID-19 was seen and the presence of it in the nasopharynx had no evidence. Additionally, analysis of ACE2 in human organs showed a high expression of ACE2 in minor salivary glands (5).


A relatively high number of COVID-19 patients presented with dry mouth (30). The factor that controls salivary gland secretion includes temperature, circadian rhythm and intensity, type of taste (31). It is noted that hyposalivation in COVID-19 patients is attributed to the use of medication and psychological processes such as depression, anxiety, stress through pathways in the amygdala, hypothalamus and brainstem (20).

It was also noted that in patients with hyposalivation, there is an increased risk of getting COVID-19. The possible explanation is that the proteins with antiviral properties such as Cathelcidin (LL-37), lactoferrin, lysozyme, mucins, peroxidase, salivary agglutinin (gp340, DMBT1), sIgA SLPI, α, β-defensins, cystatins in saliva are found to be decreased (32). The severity of SARS-CoV-2 infection is higher in middle aged population and in patients with co-morbidities. Dry mouth has been attributed to the psychological changes in the patient, poor oral hygiene, or adverse reactions due to medications. According to Dos Santos JA, xerostomia occurring in COVID-19 patients and decreased salivary flow are interlinked (8).

Taste and Smell Alterations

The two genes, namely ACE2 and Transmembrane Serine Protease 2 (TMPRSS2) expressed in the olfactory epithelial support cells, stem cells, and nasal respiratory epithelium are mainly involved in the transport of SARS-CoV-2 into the cell, and these may be potential mechanisms whereby this infection can lead to anosmia. The virus penetrates into the CNS through peripheral trigeminal and olfactory nerves following intranasal inoculation. Keyhan SO et al., described that the damage of the olfactory nerve and trigeminal nerve causes dysosmia and dysgeusia due to virus invasion or excessive exposure to chemicals and disinfectant agents that are used by people due to the viral epidemic (20). A previous study also suggested that complications of demyelination and T-cell mediated autoimmune reactions were noticed in the path of the infection which causes nerve injuries leading to the occurrence of dysosmia and dysguesia (20). Recently, another mechanism has been proposed which states that the sustentacular cells, the supporting cells of olfactory neurons, have the highest number of ACE2 receptors. These cells transfer odour from air to neurons. The mature olfactory neurons do not express ACE2 while sustentacular cells do. The sense of scent in these patients appears to be lost, due to the fact that these cells aid neurons in sensing odours, possibly by processing odour binding proteins (29).

Oral Mucosa

Oral manifestations associated with COVID-19 includes blisters in labial mucosa, recurrent herpetic stomatitis, small multiple painful ulcers in palate and desquamative gingivitis. In addition to this, other findings include geographic tongue, petechiae, recurrent oral HSV-1, candidiasis, traumatic ulcers and thrush-like ulcers (33).

Chaux Bodard AG, reported a case of 45 year old female patient with an irregular ulcer on the dorsal side of the tongue on intraoral examination. The oral lesion was followed by an erythematous plane lesion on the big toe on the third day. Further on day 8, the patient tested positive for COVID-19 (27). The irregular ulcer was found to occur after the expression of the macular erythematous lesion, which could be attributed to vasculitis. The vascular inflammation is due to variable inflammatory response associated with COVID-19. The occurrence of the erythematous rash could be due to inflammatory reaction. Thereby the acute, irregular, solitary oral ulcer could be considered as an inaugural symptom of 2019-nCoV infection (29). In another case report by CM Carreras-Presas et al., they showcased three cases where oral vesiculobullous lesions were seen associated with SARS-CoV-2 infection. In the first case, the lesions resembled a herpetic recurrent stomatitis on the hard palate in a 56-year-old healthy male. The second case was a diabetic, 58-year-old male with multiple small ulcers on his palate with unilateral affection and the last case was a 65-year-old female with blisters in her internal lip mucosa as well as desquamative gingivitis (9). It was interesting to note that all the three cases had pain with oral ulcers and blisters before seeking medical advice. In less than 2% of the case, stomatitis, oral ulcers, and dry mouth were seen which was due to side effects of antiviral drugs such as interferon-alpha and beta. Treatment of these conditions included hyaluronic acid and chlorhexidine mouth wash. Thus, it was encouraged that intraoral examinations should be performed in patients with suspected SARS-CoV-2 (34). As the oral findings are still relatively new in the literature, their occurrence and presentation may vary significantly among COVID-19 patients. Therefore, the associated systemic diseases and/or poor oral health may act as a contributory factor to the oral symptoms (10).


The detection of SARS-CoV-2 is mandatory for managing COVID-19 which is enabled by real-time Reverse Transcription–Polymerase Chain Reaction (RT-PCR). The RT-PCR detects SARS-CoV-2 nucleic acids. SARS-CoV-2 is found to spread through respiratory droplets, aerosols or fomites. Nasal or oropharyngeal samples are helpful in detection of SARS-CoV-2. It is also noted that samples from bronchoalveolar lavage, tracheal aspirates and pleural fluids and/or urine, blood and faeces contain virus. Saliva is considered as an alternative source for SARS-CoV-2 and virus specific antibodies (35).

Saliva can be used as a viable diagnostic fluid for the detection of COVID-19. The sensitivity of saliva for SARS-CoV-2 detection in COVID-19 patients was higher in comparison to nasopharyngeal swabs. Due to the plethora in disease biomarkers, saliva is considered as a potential diagnostic tool for monitoring general health and disease (29). It has added advantages of being an easy, safe, economic and non invasive diagnostic approach (36). Greater than 90% of nasopharyngeal specimens detected respiratory viruses, including coronavirus genera. It was found that ACE2 expressing cells were higher in number in minor salivary glands than that in lungs (36). The limitations of nasopharyngeal or oropharyngeal swab includes a risk to healthcare workers through sneeze or cough and transmission of virus particles by aerosols. The presence of coagulation disorders or thrombocytopenia can precipitate bleeding which is also one of the limitations of nasopharyngeal swabs (35). Saliva collection being a non invasive procedure extensively minimises the exposure of healthcare workers to COVID-19. It is noteworthy that the saliva of infected patients was identified with and saliva as a diagnostic fluid adds value to be a potential diagnostic tool for early detection of coronavirus and minimising its spread (29).


Currently, host and microbial signature states are being examined and studied to possibly identify any potential correlations. Recently, the correlation between periodontitis and COVID-19 has been studied (37).

SARS-CoV-2 results in periodontal manifestations such as inflammation of oral tissues resulting in gingival bleeding. Elevation of the cytokine and interleukin levels is attributed to these manifestations. The periodontal manifestation also included generalised erythematous and edematous gingiva with necrosis of interdental papilla without significant clinical attachment loss (34).

Periodontitis is a chronic inflammatory disease with increase in local and systemic cytokines and chemokines. Presence of bacterial pathogen in the oral cavity acts as a potent risk factor for COVID-19 due to the possibility of bacterial super infection (12). Pathogenic bacteria present in the oral cavity are Prevotella, staphylococcus and periodonthopathic bacteria such as Prevotella intermedia, fusobacterium, treponema, and vellionella were also noted in patients with severe COVID-19 infections (12).

It was found that SARS-CoV-2 infection might occur as a co-infection of P.intermedia which is a major pathogenic bacteria leading to periodontal disease along with fusobacterium and treponema species (38). It is also noteworthy that P.intermedia along with fusobacterium species constitutes a large proportion of microbiota present on necrotising periodontal diseases (39). The SARS-CoV-2 can predispose to necrotising ulcerative periodontitis through co-infection propagated by P.intermedia (40). Immunocompromised patients such as HIV and those with autoimmune disease were found to be prone to these co-infections (34). Apart from this, diabetes, hypertension and cardiovascular disease are three main co-morbidities associated with increased risk of complication of COVID-19. These comorbidities are also associated with altered biofilms and periodontitis (40).

Oral microbiota is diverse and complex. In health, it consists of mainly streptococci and viridans group and in periodontal disease state, it consists of gram negative anaerobic bacteria including the red complex bacteria namely Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia (41). These bacteria are organised into complex community called dental biofilm which is a survival strategy for most of the bacteria, viruses and fungi. The initiation and progression of periodontal disease occurs due to a dysbiosis of commensal oral bacteria with host immune response (42).

It is also noted that apart from viral pathogenesis, periodontal dysbiosis also plays a significant role in the severity of COVID-19. Studies by Kiedrowski MR et al., and Bellinghausen C et al., have also shown that there is an exacerbation of release of pro-inflammatory cytokines in response to viral infection with pre-exposure of airway epithelial cells to common respiratory bacteria such as Haemophilus influenzae, Pseudomonas aeruginosa and Streptococcus pneumonia (43),(44). This is suggestive of microbial interactions on pulmonary inflammation with pleiotropic effects (34). Taking this into consideration, the bacteriologic status of patients with severe viral infections helps the clinicians to categorize the risk status of the patients (45).

It was also shown that 80% of patients with severe COVID-19 had high bacterial load. Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes are most commonly isolated bacteria (5),(40). It has also been noted that the COVID-19 affected patients with higher severity had increased levels of inflammatory markers. These patients reported in higher neutrophil count and lower lymphocyte count, it is common for a bacterial super infection that implies in severe activity disease of COVID-19 (34).

It has been found that host immune response plays an important role in COVID-19 patients (46). It was found that COVID-19 and periodontal disease have a two way relationship. Studies by (Ruan Q et al., 2020; Zhou F et al., 2020) have shown that periodontitis shares common risk factors with most chronic inflammatory diseases known to influence COVID-19 severity (47), (48). Periodontitis, in association with Cardiovascular Diseases (CVD), cancer, Coronary Heart Diseases (CHD) and cerebrovascular diseases has been found to have high mortality rates (Scannapieco FA et al., 2003) (49). These associations are attributed to genetic and environmental risk factors, and also through common chronic inflammatory pathways (Schenkein HA et al., 2020) (50).

Systemic increase in the inflammatory responses during periodontitis shows similarity with the cytokine storm in COVID-19 patients. The SARS-CoV-2 infection results in increased inflammatory response which could possibly cause periodontitis. It is also worth, mentioning that periodontitis might be a predisposing factor for COVID-19 (33),(34).

In a study by Takahashi Y, 2020 it was shown that COVID -19 was aggravated by the aspiration of periodontopathic bacteria as a result of the expression of ACE2, which is a receptor for SARS-CoV-2, and inflammatory cytokines in the lower respiratory tract. It was also found that the cleaving of S glycoproteins attributed to the virulence of SARS-CoV-2 by the periodontopathic bacteria (51). In a study by Marouf N, 2021 it was found that periodontitis is associated with increased fatal outcomes of COVID-19 such as higher risk of ICU admission, assisted ventilation and increase blood concentration of D-dimer, WBC and CRP (52). Thus, it can be proposed that maintaining periodontal health might become integral for patients associated with increased adverse outcomes of COVID-19.
The association between periodontal disease, oral hygiene and COVID-19 needs further exploration (34).

(Table/Fig 1) It shows the plausible mechanism of association between periodontal disease and COVID-19 (53).

Periodontal Tissue as COVID-19 Reservoir

It is found that the risk for oral mucosa mediated SARS-CoV-2 is found to increase in patients with chronic periodontitis as it is associated with increased protease levels. Oral mucosa and gingiva and periodontal pocket act as potential reservoir for SARS-CoV-2 due the presence of ACE2 receptors. Human Virus such as human papilloma virus and Herpes Simplex Viruse (HSV) are present in the periodontal pocket. These viruses may enter systemic circulation from periodontal pocket via GCF (54). In a study by Gupta S et al., it was found that periodontal pockets may act as a potential aid in virus replication. The virus gains entry via saliva to the systemic circulation as the viral load in GCF increases. Thus, it can be speculated that GCF could represent a mode of transmission (55). Studies by (Badran Z et al., 2020, Matuck BF et al., 2020) showed that periodontal pocket epithelium could act as focal point of infection for SARS-CoV-2 (54), (56). Recently, it has been established that the spike proteins of the SARS-CoV-2 infects cells by binding to the Cluster of Differentiation 147 (CD 147) on cell membranes. (57) The distant organs were infected with viruses from PP apart from bacterial challenge generating focal infections and thus, to minimize the systemic spread of viral pathogens, periodontal therapy could benefit in such situations (55).

Chronic periodontitis exhibits higher levels of osteopontin, stimulates p38 and NF-kB, pathways and increases the level of proteases. IL-6 and caveolin 1 through JNK–AP-1 signalling pathway is induced by proteases (58). Furthermore, higher expression of CD 147 is noticed in gingival epithelial cells harvested from periodontitis patients (59). It was found that furin and cathepsin influences SARS-CoV-2 to infect the host cells. Increased proteases resulted in an increase in the expression of ACE2 and CD147 in gingival and periodontal ligament fibroblasts in rat and human tissues. Therefore, periodontitis could serve as a potential reservoir of SARS-CoV-2 infection and vice versa (34).

Inflammatory oral cavity manifestations are triggered by persistent inflammatory response. In periodontal tissue, there is increased fibrinogen degradation confirming that COVID-19 has an impact on periodontal tissue (38).


Coronavirus disease presents with various combinations of signs and symptoms. It can present with many oral manifestations such as xerostomia, oral mucosal lesions, taste and smell alterations, thus providing a new perception to the clinical prevention, diagnosis and treatment of SARS-CoV-2. Saliva have an important role as a diagnostic tool in detection of COVID-19 infection. Periodontal impact of COVID-19 infections has also been studied. The possible biological pathway evidencing two-way relationship among periodontal disease and COVID-19 has been explored. The SARS-CoV-2 infection results in increased inflammatory response which could possibly cause periodontitis. It is also worth, mentioning that periodontitis might be a predisposing factor for COVID-19.

Albeit association between periodontal findings and COVID-19 infection can be drawn, further studies are needed to establish oral and periodontal manifestations as early symptoms of COVID-19.


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Tables and Figures
[Table / Fig - 1]
DOI and Others


Date of Submission: Jan 29, 2021
Date of Peer Review: Apr 24, 2021
Date of Acceptance: Jun 27, 2021
Date of Publishing: Aug 01, 2021

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