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- DOI 10.18231/j.ijohd.2021.032
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COVID-19 An update on oral symptoms, newer variants, second wave and vaccination drive in India — A Review
- Author Details:
-
Srilekha Jayakumar *
-
Chakravarthy Srinivas Vineetha
-
Bindu Meera John
-
Karthikeyan Arumugam
-
Dinesh Sridhar
Srilekha Jayakumar *
Introduction
The disease caused by corona virus has been termed as COVID-19 (Corona Virus disease -2019) and is a new virus that has not been previously identified in humans.[1] Following the first wave, due to its rapid spread and numerous mutant strains that are developing, the second wave has totally wobbled many countries in the world and India had faced tragedy of second wave were the single day spike of COVID -19 case was above 3.5 – 4 lakhs. There has been a change in pattern of signs and symptoms and a variation in range of the affected age groups due to the development of newer strains of the virus. Apart from restrictions of gatherings and personal protective aids, researchers are now focussing on mass immunisation programs by vaccination.[2], [3]
Mechanism of corona virus entry into human cell
Corona viruses are spherical enveloped particles containing single-stranded RNA with a nucleoprotein present within a capsid consisting of matrix protein. The envelope has club-shaped glycoprotein surface projections.[4] The genome of corona virus encodes five structural proteins such as, Spike protien, Membrane protein, Nucleocapsid protein, Hemagglutinin esterase (HE), and Small envelope protein. [5], [6] Several mutations have been occurring in corona virus especially in its spike protein, that has resulted in numerous variants arousal in different parts of the world (Table 1, 2). Now a striking threat to the world is arousal of “Delta plus” variant.[7], [8]
The entry of corona virus in the host cell is mediated by spike proteins. Corona viruses mostly recognize amino-peptidases or carbohydrates as an important receptor for entering into human cells. The spike protein contains a 3-dimensional structure in the receptor binding region to maintain the vander Waals forces. The 394 glutamine residues in the receptor binding region of SARS-CoV-2 is recognized by the lysine 31 residue on the human angiotensin converting enzyme receptor (ACE 2). This interaction between the virus and ACE receptor on human cell facilitate the virus to enter into the host cell.[9]
The outbreak and symptoms of COVID-19
The outbreak of novel corona virus and second wave hit is rapidly alarmed the world and resulted in a global health emergency. India experienced massive second wave of COVID -19 which was threatening the entire nation. This disease mainly affects the lung’s efficiency to exchange oxygen and resulting in difficulty to breathe. Patients infected with SARS-CoV-2 have mainly shown pneumonia like symptoms that include fever, cough, shortness of breath, sputum production and myalgia or fatigue, indicating that corona virus affects the respiratory tract and causes acute respiratory disease. Apart from the respiratory symptoms, patients have developed other symptoms which appears within 2 to 14 days after exposure to the virus.[10], [11]
Gastrointestinal[10], [11] — Diarrhea, poor appetite, nausea, vomiting
Central nervous system[10], [11] — Headache and confusion
Cardio vascular system[10], [11] — Palmus, chest distress
Other symptoms[10], [11] — Loss of smell and taste
Oral Symptoms — loss of taste and COVID tongue (Table 3)
Preventive measures and treament modalities in india
Routes of transmission of corona virus includes, Direct transmission (through cough, sneeze, or droplet inhalation), Contact transmission (through oro‑nasal‑ocular route) and Aerosol transmission. Following the outbreak of second wave Centers for Disease Control and Prevention (CDC) has updated its guidelines for the use of masks.[12]
Doubling your mask[12], [13] — wearing a cloth mask over a surgical mask provides more protection.
Knotting the ear loops[12], [13] — Knotting the ends of the ear loops is another way to ensure that the mask covers your mouth and nose completely and thus reducing the exposure by more than 95 per cent
Using mask fitter[12], [13]- to improve the fitting of the mask, use a mask fitter or nylon covering over the mask is recommended and this will also prevent from inhaling the aerosol particles.
CDC does not recommend the use of N95 respirators for protection against COVID-19 in non-healthcare settings. N95 (filter up to 95% of particles in the air) respirators should be prioritized for healthcare personnel.[12], [13]
|
S.no |
Corona virus variants |
First reported country |
|
1. |
B.1.1.7 (Alpha) |
United Kingdom, UK variant |
|
2. |
P.1 (Gamma) |
Japan and Brazil |
|
3. |
P.2 |
Brazil |
|
4. |
B.1.351 (Beta) |
South Africa |
|
5. |
B.1.427 |
United States (California) |
|
6. |
B.1.429 |
United States-(California) |
|
7. |
B.1.1.7 + B.1.429 (US-UK variant ) |
United States-(California) |
|
8. |
B.1.525 |
United kingdom |
|
9. |
B.1.617 |
India (double mutant) |
|
10. |
B.1.617.2 (Delta), |
Delta variant - India |
|
11. |
B.1.617.2.1 |
Delta plus variant - Europe |
|
S.no |
Variants |
Features |
|
1. |
B.1.1.7 B.1.427 B.1.1.7 + B.1.429 (US-UK variant ) |
Increased transmissibility rate |
|
2. |
P.1 B.1.351 B.1.427 B.1.429 |
Decrease in susceptibility to the combination of bamlanivimab and etesevimab monoclonal antibody treatment. |
|
3. |
P.2 |
Escape the antibodies for other variants |
|
4. |
B.1.617 B.1.525 |
Evade host immune responses |
|
5. |
B.1.1.7 + B.1.429 (US-UK variant ) B.1.429 |
Escape antibodies which is produced post vaccination. |
|
6. |
B.1.617.2 |
40-60% more contagious or transmissible than the Alpha variant (U.K./B.1.1.7) |
|
7. |
B.1.617.2.1 |
Evading immunity that people developed from vaccination well as natural immunity after recovering from COVID |
|
Oral manifestations |
Pathophysiology |
|
ACE2 is expressed in human oral tissues, especially enriched in dorsal tongue. SARS-CoV-2 would cause direct damage to ACE2-expressing cells of taste buds during the cellular entering process, resulting in gustatory dysfunction. Patients presented a prevalence of 45% for taste disorders, 38% for dysgeusia, 35% for hypogeusia, and 24% for ageusia. Zinc deficiency is considered as one of causative factors for gustatory dysfunction associated with COVID-19. A decreased zinc level favours the interaction of zinc-dependent metalloenzyme ACE2 with spike proteins of SARS-CoV-2 but an increased zinc level inhibits ACE2 expression. |
|
|
Hyposalivation – reduced secretion of saliva[15] |
Human salivary glands express ACE2 and TMPRSS2, salivary gland infection with SARS-CoV-2 affects saliva secretion, thereby disrupting the taste sensation. |
|
Sialadenitis and Xerostomia[8] |
SARS-CoV-2 could cause acute sialadenitis by binding to ACE2 receptors in the epithelia of salivary glands, resulting cell lysis. Zinc deficiency also an added factor for sialadenitis The SARS-CoV-2 enters the peripheral nervous system (supplying the salivary gland) and damage it during their neuroinvasion, affecting the function of salivary glands. Viral invasion by trans-synaptic pathway. |
|
Reports shows COVID-19 patients developed ulcers on hard palate, tongue and buccal mucosa, erosions of lips and buccal mucosa. The most common site of lesions is tongue (38%), followed by labial mucosa (26%) and palate (22%). Hyper-inflammatory response secondary to the viral infection are linked to oral mucosal lesions associated with COVID-19. Expression of higher inflammatory cytokines IL-6 may contribute to mucosal lesions. |
|
|
COVID tongue 18 - Association between geographic tongue (GT) and SARS-CoV-2 infection |
Presents with irregular areas of depapillation on the dorsal surface of the tongue. Few literatures shows evidence suggesting that Geographic tongue might be associated with elevated levels of the infammatory cytokine interleukin-6 (IL-6). This is the cytokine that is upregulated in severe COVID-19 disease. |
|
ACE 2 and furin are expressed in sulcular and periodontal pocket epithelium which aid in viral invasion. Therefore, SARS-CoV-2 infects these epithelial cells resulting in periodontal diseases. Literature shows Prevotella intermedia is frequently detected in COVID-19 patients, SARS-CoV-2 could predispose individuals to a periodontal disease through bacterial co-infection by Prevotella intermedia. |
Vaccination Drive in India
Government of India ensure to take all necessary steps to face the challenge and threat posed by COVID-19. At present, the priority of the government is to make COVID -19 vaccine available to all. COVID-19 vaccination drive has been initiated to cover healthcare and frontline workers from January 16th 2021, for citizens — above 60 years of age from March 1st 2021, above 45 years of age from April 1st 2021, above 18 years of age from May 1st 2021.
Co-WIN application is the digital platform for the vaccination drive in India. The CO-WIN application will help the citizen with an option to register and schedule the vaccination session online in centers of their choice. Covishield and Covaxin received first Emergency use Authorisation by National Regulator on January 16th 2021. Vaccination drive to be expanded with Sputnik V, Pfizer and Moderna in India in upcoming days.[21]
Covaxin (BBV152)[22], [23]
Development
By Bharat Biotech in collaboration with the Indian Council of Medical Research (ICMR) — National Institute of Virology (NIV).
Technology
Inactivated vaccine developed using Whole-Virion Inactivated Vero Cell. Advantage of inactivated vaccines is that they do not replicate and are therefore unlikely to revert and cause pathological effects. They contain dead virus, incapable of infecting people but still able to trigger the immune response. Covaxin is able to induce both Th1 T-cell responses and humoral response in the host.
Special features
COVAXIN has immune-potentiators, also known as vaccine adjuvants – Algel – IMDG (Chemosorbed imidazoquinoline onto the aluminium hydroxide gel) that boost immunogenicity.
Dosage
Vaccine given in two doses, 4 to 6 weeks apart (28 to 48 days)
Storage temperature
2 to 8 degree Celcius.
Efficacy
Covaxin demonstrated efficacy of 81 percent in Phase 3 clinical trials. Effective against united kingdom, Brazil and Indian variants of corona virus.
Side effects
Pain at the injection site, Headache, fatigue and fever. No severe or life-threatening (i.e grade 4 and 5) adverse events were reported.
Covishield[24], [25]
2 to 8 degree celcius
Development
developed by Oxford University in collaboration with AstraZeneca and manufactured in India by Pune's Serum Institute of India.
Technology
ChAdOx1 nCoV-19 vaccine (AZD1222) is a chimpanzee adenoviral vectored vaccine with full length SARS-CoV-2 spike insert. A viral vector vaccine uses a harmless version of a different virus, called a “vector,” to deliver information to the body that helps it protect and trigger the immune response.
Special features
Vector technology, previously the same technology used for preparation of vaccine for EBOLA virus, other incredients in covishield are L-Histidine, L-Histidine hydrochloride monohydrate, Magnesium chloride hexahydrate, Polysorbate 80, Ethanol, Sucrose, Sodium chloride, Disodium edetate dihydrate (EDTA) and Water.
Dosage
Two doses, 6 to 8 weeks (42 to 56 days).
Storage temperature
To 8 degree Celcius
Efficacy
Trial shows when doses were given one month apart, efficacy was 60-70 percent. Another trial shows when two doses given 2-3 months apart, efficacy was 90 per cent.
Side effects
Pain or tenderness at the injection site, Headache, Tiredness, Muscle or joint aches, Fever, Chills, Nausea, enlarged lymph nodes, excessive sweating, itchy skin or rash.
Sputnik V[26]
Development
developed by Gamaleya Research Institute and the Russian defence ministry partnered with Dr Reddy's in September 2020 to conduct clinical trials of Sputnik V in India.
Technology
Two-dose adenoviral vector vaccine using two different adenoviruses for each dose.
Special feature
A vector vaccine based on adenovirus DNA (adenovirus serotypes 5 and 26 are used), in which the SARS-CoV-2 coronavirus gene is integrated. Adenovirus is used as a “container” to deliver the coronavirus gene (the antigen insert is an unmodified full-length S-protein) to cells and start the synthesis of the new coronavirus's envelope proteins triggering the immune system.
Dosage
Days to three months
Storage temperature
2-8 degree Celcius.
Efficacy
Clinical trials reported 91.6% efficacy rate.
Side effects
Slight body temperature rise and pain around the injection site.
Pfizer (BNT162b2)[27]
-73 degree celcius
Development
By Pfizer and BioNTech
Technology
mRNA vaccine, consist of genetic information (spike protein) from the virus in the form of messenger RNA.
Special feature
Uses lipid nanoparticles that encase the RNA, protect it and helps it to slide inside the cell. Active incredients are nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2, lipids, salts and sucrose.
Dosage
Two doses, 21 days apart.
Storage temperature:
Degree celcius
Efficacy
Phase 3 trial of the BNT162b2 vaccine showed 95% efficacy
Side effects
Pain at injection-site, headache, fatigue.
Drugs Used For COVID -19 in India
Remdesivir
Remdesivir recommended candidate for the treatment of Covid-19. Remdesivir formerly known as GS-5734, is a monophosphoramidate prodrug of an adenosine analog that was developed in response to the Ebola virus outbreak in West Africa in 2014. Mechanism of action is a viral RNA-dependent RNA polymerase (RdRp) inhibitor, targeting the viral genome replication process thus halting the replication of virus.[28], [29]
Baricitinib is an oral selective inhibitor of Janus kinase (JAK) 1 and JAK 2 (used to treat moderate to severe active rheumatoid arthritis) is now recommended for COVID-19 treatment because of its inhibitory effect on SARS-CoV-2 endocytosis and on the intracellular signaling pathway of cytokines that is responsible for the hyperinflammatory state that results in severe illness. Remdesivir in combination with baricitinib has been granted a Emergency Use Authorization by the FDA for clinical use in adult and pediatric patients two years of age or older hospitalized with COVID-19 requiring supplemental oxygen (SpO2</= 94%).[30], [31]
Virafin
Virafin, the antiviral drug by Zydus Cadila, has received emergency use authorization by the Drugs Controller General of India (DCGI) for treatment of moderate cases of COVID-19. It was originally used for treating Hepatitis C virus infection.Virafin is Pegylated Interferon alpha - 2b can be used in moderate cases of COVID-19, studies reported its use reduced the need for supplemental oxygen therapy, thus preventing severe respiratory distress and failure.[32], [33], [34]
Conclusion
Corona virus has massively striked the entire world and various clinical studies has reported arousal of newer symptoms, of which oral symptoms also plays important role in identification of the diseases. Dentist should take the responsibility to screen and identify the oral symptoms of COVID- 19, that is likely occur as co-infection or secondary manifestation of COVID-19. India is now in serious thrive to come out of this second wave of COVID-19. Health care professionals are working hard to bring back the nation to a normal pace. Government of India is taking necessary steps to vaccinate each and every citizen of India.
Source of Funding
None.
Conflict of Interest
None.
References
- X Peng, X Xu, Y Li, L Cheng, X Zhou, B Ren. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci 2020. [Google Scholar] [Crossref]
- . For Information on COVID-19 Vaccine. 2021. [Google Scholar]
- . Website of Ministry of Health and Family Welfare. 2019. [Google Scholar]
- A Wu, Y Peng, B Huang. Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell Host Microbe 2020. [Google Scholar] [Crossref]
- Y Wan, J Shang, R Graham, R S Baric, F Li. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. J Virol 2020. [Google Scholar]
- R Lu, X Zhao, J Li. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020. [Google Scholar] [Crossref]
- . SARS-CoV-2 Variant Classifications and Definitions. 2021. [Google Scholar]
- M D S Pedrosa, C R Sipert, F N Nogueira. Altered taste in patients with COVID-19: The potential role of salivary glands. Oral Dis 2021. [Google Scholar] [Crossref]
- X Xu, P Chen, J Wang. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci 2020. [Google Scholar] [Crossref]
- N Chen, M Zhou, X Dong, J Qu, F Gong, Y Han. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020. [Google Scholar] [Crossref]
- C Huang, Y Wang, X Li, L Ren, J Zhao, Y Hu. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. Lancet 2020. [Google Scholar] [Crossref]
- . Your Guide to Masks. 2019. [Google Scholar]
- J T Brooks, D Beezhold, J D Noti. Maximizing fit for cloth and medical procedure masks to improve performance and reduce SARS-CoV-2 transmission and exposure, 2021.. MMWR Morb Mortal Wkly Rep 2021. [Google Scholar]
- J R Lechien, A Chetrit, Y C Idrissi, L Distinguin, M Circiu, S Saussez. Parotitis-Like Symptoms Associated with COVID-19. Emerg Infect Dis 2020. [Google Scholar] [Crossref]
- B Iranmanesh, M Khalili, R Amiri, H Zartab, M Aflatoonian. Oral manifestations of COVID-19 disease: A review article. Dermatol Ther 2021. [Google Scholar] [Crossref]
- R Ansari, M Gheitani, F Heidari, F Heidari. Oral cavity lesions as a manifestation of the novel virus (COVID-19). Oral Dis 2021. [Google Scholar] [Crossref]
- J Patel, J Woolley. Necrotizing periodontal disease: Oral manifestation of COVID-19. Oral Dis 2021. [Google Scholar] [Crossref]
- R Pellegrino, K W Cooper, Di Pizio, A Joseph, S Bhutani. Corona viruses and the chemical senses: past, present, and future. Chem Senses 2020. [Google Scholar] [Crossref]
- L A Vaira, G Salzano, M Petrocelli, G Deiana, F A Salzano, De Riu. Validation of a self-administered olfactory and gustatory test for the remotely evaluation of COVID-19 patients in home quarantine. Head Neck 2020. [Google Scholar] [Crossref]
- D Jothimani, E Kailasam, S Danielraj, V Ramani, H Ramachandran, P Sekar. COVID-19: Poor outcomes in patients with zinc deficiency. Int J Infect Dis 2020. [Google Scholar] [Crossref]
- . vaccination . 2021. [Google Scholar]
- R Ella, S Reddy, H Jogdand, V Sarangi, B Ganneru, S Prasad. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial. Lancet Infect Dis 2021. [Google Scholar] [Crossref]
- G N Sapkal, P D Yadav, R Ella, G R Deshpande, R R Sahay, N Gupta. Inactivated COVID-19 vaccine BBV152/COVAXIN effectively neutralizes recently emerged B 1.1.7 variant of SARS-CoV-2. J Travel Med 2021. [Google Scholar] [Crossref]
- M D Knoll, C Wonodi. Oxford-AstraZeneca COVID-19 vaccine efficacy. Lancet 2021. [Google Scholar] [Crossref]
- S P Kaur, V Gupta. COVID-19 Vaccine: A comprehensive status report. Virus Res 2020. [Google Scholar] [Crossref]
- I Jones, P Roy. Sputnik V COVID-19 vaccine candidate appears safe and effective. Lancet 2021. [Google Scholar] [Crossref]
- D M Skowronski, De Serres, G. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med 2021. [Google Scholar] [Crossref]
- J J Malin, I Suárez, V Priesner, G Fätkenheuer, J Rybniker. Remdesivir against COVID-19 and Other Viral Diseases. Clin Microbiol Rev 2020. [Google Scholar] [Crossref]
- A Al-Abdouh, A Bizanti, M Barbarawi, A Jabri, A Kumar, O E Fashanu. Remdesivir for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials. Contemp Clin Trials 2021. [Google Scholar] [Crossref]
- A C Kalil, F Thomas, M D Patterson, K Aneesh, M D Mehta, M Kay. Baricitinib plus Remdesivir for hospitalized adults with Covid-19. N Engl J Med 2021. [Google Scholar] [Crossref]
- P Sodani, L Mucci, R Girolimetti, S Tedesco, F Monaco, D Campanozzi. Successful recovery from COVID-19 pneumonia after receiving baricitinib, tocilizumab, and remdesivir. A case report: Review of treatments and clinical role of computed tomography analysis. Respir Med Case Rep 2020. [Google Scholar] [Crossref]
- . Zydus Cadila Gets DCGI Nod To Moderate Covid-19 Drug Virafin. 2021. [Google Scholar]
- R Hathway. Covid Tongue. Br Dent J 2021. [Google Scholar] [Crossref]
- A Riad, I Kassem, B Hockova, M Badrah, M Klugar. Halitosis in COVID-19 patients. Spec Care Dent 2021. [Google Scholar] [Crossref]
- Introduction
- Mechanism of corona virus entry into human cell
- The outbreak and symptoms of COVID-19
- Preventive measures and treament modalities in india
- Vaccination Drive in India
- Drugs Used For COVID -19 in India
- Conclusion
- Source of Funding
- Conflict of Interest