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 Table of Contents  
REVIEW ARTICLE
Year : 2022  |  Volume : 13  |  Issue : 4  |  Page : 179-184

Elucidating the pathogenicity, diagnosis, treatment, and prevention of COVID-19 – Part II


Department of Conservative Dentistry and Endodontics, SRM Institute of Science and Technology, SRM Dental College, Chennai, Tamil Nadu, India

Date of Submission29-Aug-2022
Date of Decision15-Oct-2022
Date of Acceptance18-Oct-2022
Date of Web Publication15-Dec-2022

Correspondence Address:
Dr. Monisha Parshotam Khatri
Department of Conservative Dentistry and Endodontics, SRM Institute of Science and Technology, SRM Dental College, Bharathi Salai, Ramapuram, Chennai - 600 089, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/srmjrds.srmjrds_112_22

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  Abstract 

Introduction: After throwing light on COVID-19 infection, its transmission, available treatment options in Part I, this article has focused on various preventive measures proposed to deal with the disease. Aim: The Part II of this review article aimed to provide the different measures advocated to prevent COVID-19. Methods: An electronic search was performed in PubMed and Google Scholar databases with the keywords "Corona virus, COVID-19, World Health Organization, Severe Acute Respiratory Syndrome, SARS-CoV-2, Prevention, Vaccines" from January 2017 to August 2022. Results: A total of 42 articles were included in the current review. Conclusion: The theoretical evidence does advocate the use of vaccines to be good candidates, but practically, no guarantee can be given that an individual will never be infected. One needs to take personal precautions such as hand sanitizing, wearing a mask in public places, and maintaining social distancing till a permanent cure is procured.

Keywords: Coronavirus, COVID-19, Prevention, SARS-CoV-2, Vaccines, World Health Organization


How to cite this article:
Khatri MP, Mahalaxmi S. Elucidating the pathogenicity, diagnosis, treatment, and prevention of COVID-19 – Part II. SRM J Res Dent Sci 2022;13:179-84

How to cite this URL:
Khatri MP, Mahalaxmi S. Elucidating the pathogenicity, diagnosis, treatment, and prevention of COVID-19 – Part II. SRM J Res Dent Sci [serial online] 2022 [cited 2023 Feb 6];13:179-84. Available from: https://www.srmjrds.in/text.asp?2022/13/4/179/363796


  Introduction Top


There is no doubt that as COVID-19 has become a disease difficult to comprehend, the best measure to deal with it is to prevent it. There have been a number of deaths in COVID-19 patients, especially the elderly and patients with comorbidities and/or immune suppression. Moreover, unless a permanent solution is sorted, preventive measures including social distancing and diet modifications need to be included in the new normal. The Part II of this review highlights the various measures introduced and practiced to prevent COVID-19.


  Methods Top


An electronic search was performed in PubMed and Google Scholar databases with the keywords "Corona Virus, COVID 19, World Health Organization, Severe Acute Respiratory Syndrome, SARS-CoV-2, Prevention, Vaccines" from January 2017 to August 2022.


  Results Top


A total of 42 articles were included in the current review.


  Discussion Top


Prevention

In order to boost one's immune system, the Academy of Nutrition and Dietetics recommends a clinically credible diet that is rich in Vitamin A (beta-carotene), C, D, and zinc (Zn).[1] It is a known fact that micronutrients impact the functioning of the immune system. They enhance resistance against infections and can redirect the inflammatory response to the benefit of the individual.[2] The preventive measures are categorized as vitamins, minerals, and vaccines [Figure 1].
Figure 1: COVID-19 preventive strategies. LAV: Live attenuated vaccine

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Vitamins

The antioxidant effects of various vitamins that help combat the harmful free radicals are given below:

Retinol (Vitamin A) regulates the innate and cell-mediated immunity, and is shown to improve antibody titers in the body after vaccinations such as measles and anti-rabies. It also helps resist infections by enhancing white blood cells' functions.[3],[4]

The popularity of Vitamin C stems from Nobel Laureate Linus Pauling's publication "Vitamin C and the Common Cold" (1976). Vitamin C is a potent antioxidant that protects proteins, lipids, carbohydrates, and nucleic acids from the ill effects of reactive oxygen species produced during metabolic activity. It enhances neutrophil and monocyte chemotaxis and proliferation of T-lymphocytes and increases synthesis of immunoglobulins and cytokines in response to infections.[2] Due to this, Vitamin C levels get depleted during infections and need to be supplemented through diet or as supplements. Human trials have reported a lower incidence of pneumonia in Vitamin C-supplemented groups.[5] It is said that Vitamin C reduces the level of pro-inflammatory cytokines and thus helps fight against COVID-19.[6]

Vitamin D is both a nutrient and a hormone that modulates cellular and adaptive immunities. It plays an important role as an immunosuppressant, thus preventing and/or suppressing autoimmune diseases.[2] Vitamin D supplementation improves clinical outcomes of COVID-19 patients according to a retrospective multicenter study.[6],[7]

Minerals

Zinc enhances both innate and adaptive immune functions such as antibody response, and infectious disease resistance.[1] Unbound form of Zn ion has been found to be having an antiviral effect against replication of rhinovirus.[2] In addition, it also has anti-inflammatory properties, decreased production of inflammatory cytokines, and oxidative stress biomarkers.[8] With all the above properties correlated to be beneficial in the current scenario, its direct effect on SARS-CoV-2 virus is yet to be elucidated.

Copper (Cu) is involved in the functions of T-helper cells, neutrophils, natural killer cells, and macrophages. These cells are involved in the killing of infectious microbes, cell-mediated immunity, and production of specific antibodies. Cu also functions as a co-factor for oxidation-reduction reactions, as enzymes for iron metabolism, connective tissue maturation, and neurotransmission.[1] In vitro studies have shown that Cu has antiviral properties. Cu ion blocks papain-like protease-2, a protein required for replication of SARS-CoV-1.[9] Although there is not enough evidence on the therapeutic effects of Cu supplements on susceptibility of COVID-19 infections, dietary Cu supplementation may improve host immune system and the metabolism of other micronutrients, thereby preventing the severity of the viral infection.[10]

Similar to Zn and Cu, selenium also influences the innate and adaptive immune functions, being the single most important nutrient for AIDS patients. It prevents the formation of free radicals and oxidative damage to the cells and tissues along with a combination of enzymes.[11] In a study by Im et al., patients suffering from COVID-19 showed deficiency in levels of Selenium to up to 42%. Although a clear relation between the two was shown, it could not be concluded that supplementation of Se could help in decreasing the severity of the disease.[12]

Iron, like Cu, is essential for many immunological functions such as immune cell (specifically lymphocytes) proliferation and maturation.[2] Iron deficiency is reported to decrease host immunity predisposing to recurrent acute respiratory tract infections.[13] Although iron supplementation has been associated with immune-enhancing capacity, its presence can also worsen the infection and inflammation due to its increased oxidative stress capacity.[9] Therefore, the status of iron is an area of interest for further research, to evaluate its pros and cons in the current situation.

It is well evidenced that a balance of the above and many more such vitamins and minerals offer some protection against inflammatory and infectious diseases. A healthy immune system may well be a good defense against the COVID-19 infection, which does not have a clinically credible preventive and curative treatment so far.

On the contrary, unwarranted use of vitamins and minerals could lead to adverse reactions such as allergies, side effects, drug interactions, and dependency which could lead to undue expenditure and overuse.[14] Therefore, until definitive evidence is procured, overuse of these should be avoided.

Vaccines

Vaccines are viral preparations administered to an individual in order to stimulate the body's self-specific immunity by producing antibodies to help fight against the virus. SARS-CoV-2 vaccines are classified as molecular, particular, and cell based.

The main component of the COVID vaccines is the spike proteins (example: mRNA-1273, BNT162b2, Ad26.COV2.S, AZD1222, Ad5-nCoV, and Sputnik V) or their receptor binding domain (RBD) (example: ZF2001, BNT162b1, and ARcoVax) which blocks the SARS-CoV-2 entry by producing antibodies against them.[15] They may be in the form of SARS-CoV-2 proteins and subunits, nucleic acids encoding a viral antigen, live-attenuated and inactivated viruses, replicating and nonreplicating viral vectors, virus-like particles, and cell-based vaccines.[16]

Nucleic acid vaccine

*There are 21 mRNA and 15 DNA base COVID vaccines in various stages of clinical trials.[17] Among the mRNA, the earliest vaccines to be approved by the Food and Drug Administration (FDA) for emergency use were the Pfizer and Moderna vaccines.[15] Pfizer or BNT162 or Comirnaty vaccine was the first vaccine to receive emergency use listing from the World Health Organization (WHO) in December 2020 and is administered as two doses with an interval of 3 days. The BNT162 vaccine trials were initiated in Germany which later spread to the USA. This vaccine generates a CD8+ and CD4+ T-lymphocyte activation and neutralizing antibodies against the SARS-CoV-2 virus.[18],[19] Pfizer on October 12, 2020, became the first US/European-based COVID-19 vaccine that included people under the age group of 18 years in their Phase III clinical trial. As of now, FDA has approved the use of Pfizer vaccine for adolescents (12–15 years), young adults (>15 years), and the elderly.[18],[19] On November 18, 2020, the Phase III trial was officially said to be completed with an efficacy of 95% and is claimed to be safe for people across various races and genders.[20]

Moderna vaccine also known as Spikevax or mRNA-1273 is administered in two doses with an interval of 4 weeks and is developed by Moderna, in Cambridge, Massachusetts, and funded by the National Institute of Allergy and Infectious Diseases. A lipid nanoparticle vector carries the prefusion form of the S protein and, when injected, translates and transcripts the mRNA to produce viral antigens. These viral antigens are then recognized by the body's immune system which in turn activates the adaptive immune response against the S protein of SARS-CoV-2.[18],[19] Moderna's mRNA-1273 on November 16, 2020, became the second vaccine to release results of its Phase III interim clinical trial stating it to be 94.5% effective with maximum safety and no side effects.[20] Although few reports have shown the associated risk of myocarditis with Pfizer and Moderna vaccines, the Advisory Committee on Immunization Practices (ACPI) review concluded that the benefit exceeds the risk.[21] They have also been shown to be effective against the new variants of SARS-CoV-2, i.e., the B.1.1.7 and the 501Y.V2.[22]

Advantages of these mRNA vaccines include prevention of genome integration by translation occurring in the cytoplasm, activation of both T-cell and antibody response, rapid development, and large-scale production whereas disadvantages include that they have never been licensed in humans, requirement of delivery system for the entry of mRNA into the cell, and storage in low- and ultra-low temperatures.[15],[17]

Another type of nucleic acid vaccine is the DNA vaccine. INO-4800 developed by INOVIO Pharmaceuticals, USA, is in its Phase 3 clinical trial that is given in two doses with an interval of 4 weeks and acts by inducing specific immune response in the host when a full-length S protein sequence is inserted into the host via a pGX0001 plasmid vector.[15],[17] Although a risk of gene integration always exists with the DNA vaccine, its advantages include safe and high immune response, simultaneous cloning and screening of S protein from multiple SARS-CoV-2 strain, and storage of synthetic DNA for a year or more at room temperature.[15],[16] As of August 26, 2021, INOVIO's global Phase 3 trial to assess the efficacy of INO-4800 has been authorized to be conducted in men and nonpregnant women, aged 18 years and above in countries which include Latin America, Asia, and Africa.[23]

Viral vectored vaccine

Adenovirus vectored vaccines are the most commonly used vaccines with an advantage that adenovirus, a nonenveloped dsDNA virus does not integrate into the human genome when administered, hence warranting its safety.[24]

*There are currently 3 vaccines under this category which are in the Phase 4 clinical trial, namely AZD1222 (AstraZeneca/Oxford vaccine (Vaxzevria®)/ChAdOx1 nCoV-19 recombinant adenovirus vaccine, Ad5-nCoV (CanSino/CanSinoBIO), and Sputnik V (Gam-COVID-Vac/Gamaleya), and the most commonly known Ad26.COV2.S (Johnson and Johnson/Janssen) is in Phase 3, all of which express the full-length S protein. While Johnson and Johnson and Casino vaccines require single dose, the other two vaccines are given as 2 doses with AstraZeneca administered in a gap of 4–12 weeks having shown that increased time interval up to 12 weeks increases efficacy and binding antibody response. And Sputnik V is given in time interval of 3 weeks.[24] They can be stored at 2°C–8°C while Sputnik V requires either frozen (−18°C) or lyophilized storage (2°C–8°C). The main advantage of these adenovirus vector vaccines apart from being safe is that they induce good humoral and cellular response with disadvantage of preexisting immunity against a human viral vector that can weaken the host immune response.[15],[19]

On March 22, 2021, the Phase III trial of AZD1222 by AstraZeneca, US, showed 79% efficacy at preventing symptomatic COVID-19 disease, 100% efficacy against severe disease and hospitalization, and consistent efficacy between ethnicity and age with 80% efficacy in participants aged 65 years and above.[25] According to the WHO, the vaccine shows a 63.09% efficacy against symptomatic SARS-CoV-2 infection.[26] Similarly, the results obtained by interim Phase III clinical trial after recruiting 4000 participants from Pakistan, Mexico, Russia, Chile, and Argentina showed 65.28% and 68.83% efficacy after 14 and 28 days of single-dose vaccination, respectively, against all symptomatic SARS-CoV-2 infection and an efficacy of 95.47% and 90.07% after 14 and 28 days of single-dose vaccination respectively.[27]

When it comes to Sputnik V, a large double-blind Phase III clinical trial in Moscow, Russia, including 21,977 adults, showed 91·6% efficacy against COVID-19 when evaluated on the 21st day after administration of the first dose.[28] On February 2021, Johnson and Johnson announced that the vaccine showed 85% efficacy against severe COVID-19 disease in people 18 years and older according to results from the phase 3 ENSEMBLE study design that included 43,783 participants across eight countries including a variety of ethnic groups.[29] Although higher efficacy was shown, a report by Rosenblum et al. enumerates the cases of Guillain–Barré syndrome in males aged 50–64 years and thrombosis with thrombocytopenia syndrome in females aged 30–49 years with Janssen vaccine, and mentions that although according to the ACPI the benefit surpasses the risk, this information regarding the adverse effects associated should be put across the providers, vaccine recipients, and the public under the right to information. This has also been shared by the FDA in the fact sheets and added to the CDC guidelines as well.[21]

Inactivated vaccines

This is a conventional method of vaccine development that involves growing viruses in cell culture such as Vero cells followed by inactivation by heat or chemicals like formaldehyde or beta-propiolactone.[16],[24] *There are currently 17 inactivated vaccines under clinical trials.[17] CoronaVac by Sinovac Biotech, China, is in phase IV and is given as two doses intramuscularly (IM) at a time interval of 14 days. Associated adverse effects include pain at injection site with mild local reactions and low immunogenicity.[30] Two vaccines BBIBP-CorV and WIBP-CorV from Sinopharm along with the China National Pharmaceutical Group in collaboration with the Beijing Institute of Biological Products and Wuhan Institute of Biological Products, respectively, are given IM as two doses, 3 weeks apart with minimum adverse effects like pain and fever.[19] *According to a large multi-country Phase 3 trial, 14 or more days after the second dose, an efficacy of 79% was shown against symptomatic COVID-19 disease as well as against hospitalization in patients administered with 2 doses of BBIBP vaccine.[31] Covaxin/BBV152, a purified inactivated whole virion, by Bharat Biotech and Indian Council of Medical Research is given as two doses with an interval of 14 days, with associated side effects associated after first dose such as pain at the site of injection, fever, fatigue, nausea, and vomiting.

These vaccines are safe as they are inactivated with disadvantage of processing of large quantities of pathogens with reduced antigenicity and antibody titers.[15],[19] According to the Phase 3 clinical trial results mentioned in the WHO interim guidelines, an overall efficacy of 78% was seen in COVID-19 with efficacy of 79% in the age group of 60 years and less, 68% in the age group of more than 60 years, and 64% in asymptomatic COVID-19 disease.[32]

Live attenuated vaccine

Exposure to inactivated or weakened form of the whole pathogen leads to the desired immune response in live attenuated vaccine (LAV). Cold adaptation, recombination, or reverse genetics are various methods of manufacturing LAV with associated risk of mutation causing reversal of virulence and reactivation in immunocompromised patients.[16] COVI-VAC by Codagenix/Serum Institute of India is in the Phase III of clinical trial and is developed by a process of codon de-optimization where the amino acid of the chemically synthesized virus is fully maintained with increased number of CpG and UpA RNA dinucleotides so as to upregulate the host responses.[17],[33]

Recombinant protein vaccines

These vaccines account for about one-third of vaccines in clinical trials and express antigens such as RBD-monomer, RBD dimer, RBD-trimer, S1 protein, full-length S protein, S-trimer, and multi-epitome vaccines. These target antigens once delivered with the help of the recombinant viral vectors induce strong T-cell responses.[15],[34] Novavax which uses the NVX-CoV2372 trimeric nanoparticle was in the Phase 3 clinical trial and used the full-length S-protein adjuvanted with matrix M and is given IM in 2 doses at a time interval of 21 days.[17],[34] Other important vaccines in Phase 3 clinical trials are mentioned in Supplementary [Table 1]. Common adverse effects of all the vaccines given IM may include pain, tenderness, swelling, redness at the site of injection, fever, fatigue, headache, chills, vomiting, diarrhea, arthralgia, myalgia, urticaria, and lymphadenopathy.[24] According to the WHO, currently there are 135 vaccines in different stages of clinical development and 194 vaccines in preclinical development. A list of the important vaccines in Phase 4 and Phase 3 clinical trials with description, type, current phase, developers, number of doses, route of administration with time interval, age group, and adverse side effects is enumerated in [Supplementary Table 1].[17],[24],[33],[35] The ever-changing strains of SARS-CoV-2 also make it necessary that these vaccines are effective against all of them and do not cause any adverse effects. In addition, a lot of factors such as host factors, demographic factors, viral variant factors, immune factors, and vaccine access factors make it difficult to develop an ideal vaccine. Among the vaccine against the alpha-strain, Pfizer shows the maximum efficacy of 90%, followed by Novavax (86%), AstraZeneca (75%), and Johnson and Johnson (70%). Similarly, the common vaccine against the Beta, B.1.351 shows an efficacy of 75% with Pfizer, 72% efficacy in the USA, 66% in Latin America, and 57% in South Africa with Johnson and Johnson, 60% with Novavax, and 10% with AstraZeneca. Although the Pfizer vaccine did not show any reduced protection against the Gamma, P. 1 (B.1.1.28.1), the Johnson and Johnson and CoronaVac vaccine showed an efficacy of 68% and 51%, respectively. All the strains showed reduced levels of neutralizing antibodies with Moderna vaccine. With ongoing studies for the delta B.1.617.2 variant and more studies required for the new Omicron strain, the need for an ideal vaccine is still of prime importance. [Table 1] enumerates the common strains of SARS-CoV-2, its mutation, transmissibility, and properties.[33],[36],[37],[38],[39],[40],[41],[42]Apart from these the variants being monitored are Epsilon (B.1.427 and B.1.429), Eta (B.1.525), Iota (B.1.526), Kappa (B.1.617.1) 1.617.3, Mu (B.1.621, B.1.621.1), and Zeta (P. 2).[42]
Table 1: Important strains and characteristics

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  Conclusion Top


The first and foremost important point to keep in mind is to avoid the possibility of contracting the virus by taking necessary precautions and building up a strong immune system. This article can be a reference to understand about the SARS-CoV-2 virus, its pathogenicity, diagnostic methods available for COVID-19, the treatment protocol followed as well as the different preventive measures taken to overcome the disease.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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