covid -19 review article

www.wjpps.com Vol 9, Issue 6, 2020.

420

Thukral et al. World Journal of Pharmacy and Pharmaceutical Sciences

COVID -19 – REVIEW ARTICLE

Kanika Singh1, Shiva

2, Kapil Saroha

3, Swati Saroha

4, Pushpa Yadav

5, Viruj Khare

6,

Himanshu Thukral*7

1BDS, MDS(Oral and Maxillofacial Surgery), Consultant Oral and Maxillofacial Surgeon,

Noida.

2BDS, Dental Surgeon, Indore.

3MDS (Orthodontist), CEO Kapil Dental Clinic and Implant Center, Delhi.

4MDS (Periodontics), CEO Kapil Dental Clinic and Implant Center, Delhi.

5BDS; Associate Fellowship in Laser Dentistry(WCLI, USA); Certified Endodontist, Ivory

Dental Clinic and Implant Centre, Noida.

6BDS; Certified Endodontist; Certification in Oral Cancer Screening(NICPR, Noida),

KHARE DENTAL CARE, Chattarpur, MP.

7MDS (Oral and Maxillofacial Surgeon), CEO Sarita Oral and

Maxillofacial Center, New Delhi.

ABSTRACT

Corona virus causes respiratory infection including pneumonia, cold,

sneezing and coughing while in animal it causes diarrhea and upper

respiratory diseases. Corona virus transmitted human to human or

human to animal via airborne droplets. Corona virus enters in human

cell through membrane ACE-2 exopeptidase receptor. WHO and

ECDC advised to avoid public place and close contact to infected

persons and pet animals. Firstly Corona virus (2019-nCoV) was

isolated from Wuhan market China at 7 Jan. 2020.

KEYWORDS: Corona virus, COVID-19, MERS-CoV, SARS-CoV,

Wuhan.

INTRODUCTION

On December 31, 2019, the China Health Authority alerted the World Health Organization

(WHO) to several cases of pneumonia of unknown aetiology in Wuhan City in Hubei

Province in central China. The cases had been reported since December 8, 2019, and many

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.632

Volume 9, Issue 6, 420-433 Review Article ISSN 2278 – 4357

*Corresponding Author

Dr. Himanshu Thukral

MDS (Oral and

Maxillofacial Surgeon),

CEO Sarita Oral and

Maxillofacial Center, New

Delhi.

Article Received on

29 March 2020,

Revised on 19 April 2020,

Accepted on 10 May 2020

DOI: 10.20959/wjpps20206-16267


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patients worked at or lived around the local Wuhan Sea food Wholesale Market although

other early cases had no expo-sure to this market.[1]

On January 7, a novel coronavirus originally abbreviated as 2019-nCoV by WHO, was

identified from the throat swab sample of a patient.[2]

This pathogen was later renamed as

severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study

Group[3]

and the disease was named coronavirus disease 2019 (COVID-19) by the WHO.

As of January 30, 7736 confirmed and 12,167 suspected cases had been reported in China

and 82 confirmed cases had been detected in 18 other countries.[4]

In the same day, WHO

declared the SARS-CoV-2 outbreak as a Public Health Emergency of International Concern

(PHEIC).[4]

According to the National Health Commission of China, the mor-tality rate among confirmed

cased in China was 2.1% as of February4[5]

and the mortality rate was 0.2% among cases

outside China.[6]

Among patients admitted to hospitals, the mortality rate ranged between

11% and 15%. COVID-19 is moderately infectious with a relatively high mortality rate, but

the information available in public reports and published literature is rapidly increasing. The

aim of this review is to summarize the current understanding of COVID-19 including

causative agent, pathogenesis of the disease, diagnosis and treatment of the cases, as well as

control and prevention strategies.

HISTORY AND ORIGIN

First case of corona virus was notified as cold in 1960. According to the Canadian study

2001, approximately 500 patients were identified as Flu-like system. 17-18 cases of them

were confirmed as infected with corona virus strain by polymerase chain reaction.[4]

Corona

was treated as simple non fatal virus till 2002. In 2003, various reports published with the

proofs of spreading the corona to many countries such as United States America, Hong Kong,

Singapore, Thailand, Vietnam and in Taiwan. Several case of severe acute respiratory

syndrome caused by corona and their mortally more than 1000 patient was reported in 2003.

This was the black year for microbiologist.[5]

When microbiologist was started focus to

understand these problems. After a deep exercise they conclude and understand the

pathogenesis of disease and discovered as corona virus. But till total 8096 patient was

confirmed as infected with corona virus. So in 2004, World health organization and centers

for disease control and prevention declared as “state emergency”. Another study report of


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Hong Kong was confirmed 50 patient of severe acute respiratory syndrome while 30 of them

were confirmed as corona virus infected. In 2012, Saudi Arabian reports were presented

several infected patient and deaths.[5]

COVID-19 was first identified and isolated from

pneumonia patent belongs to Wuhan, china. Microbiology Corona virus is spherical or

pleomorphic, single stranded, enveloped RNA and covered with club shaped glycoprotein.

Corona viruses are four sub types such as alpha, beta, gamma and delta corona virus. Each of

sub type corona viruses has many serotypes. Some of them were affect human of other

affected animals such as pigs, birds, cats, mice and dogs.[7]

MODE OF SPREADING

Peoples can get the infection through close contact with a person who has symptoms from the

virus includes cough and sneezing. Generally corona virus was spread via airborne zoonotic

droplets. Virus was replicated in ciliated epithelium that caused cellular damage and infection

at infection site. According to a study published in 2019, Angiotensin converting enzyme 2

(ACE.2), a membrane exopeptidase in the receptor used by corona virus in entry to human

cells.[8]

Virus transmission routes were represented in figure 1. Characteristics According to a

report published on 24 Jan 2020, corona virus infected patient have many common features

such as fever, cough, and fatigue while diarrhea and dyspnea were found to be as uncommon

feature. Many of them patient reported bilateral abnormalities. Corona virus was isolated

from bronchoalvelor lavage fluid in china in 2020. It is also detected in blood samples. Till

now, corona virus was not confirmed in feaces and urine sample of patent.

Figure 1: Trasnission of Corona Virus via Airborne Droplets.


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Risk factors

The incidence of SARS-CoV-2 infection is seen most often in adult male patients with the

median age of the patients was between 34 and 59 years. SARS-CoV-2 is also more likely to

infect people with chronic comorbidities such as cardio-vascular and cerebrovascular diseases

and diabetes. The highest proportion of severe cases occurs in adults ≥60 years of age, and in

those with certain underlying conditions, such as cardiovascular and cerebrovascular diseases

and diabetes.[9]

Severe manifestations maybe also associated with coinfections of bacteria and fungi.[9]

Fewer

COVID-19 cases have been reported in children less than 15 years. In a study of 425

COVID-19 patients in Wuhan, published on January 29, there were no cases in children

under 15 years of age. Nevertheless, 28 paediatric patients have been reported by January

2020.[10]

The clinical features of infected paediatric patients vary, but most have had mild symptoms

with no fever or pneumonia, and have a good prognosis. Another study found that although a

child had radiological ground-glass lung opacities, the patient was asymptomatic. In

summary, children might be less likely to be infected or, if infected, present milder

manifestations than adults; therefore, it is possible that their parents will not seek out

treatment leading to underes-timates of COVID-19 incidence in this age group.[11]

Pathogenesis and immune response

Like most other members of the coronavirus family, Beta-coronavirus exhibit high species

specificity, but subtle genetic changes can significantly alter their tissue tropism, host range,

and pathogen city. A striking example of the adaptability of these viruses these viruses is the

emergence of deadly zoonotic diseases in human history caused by SARS-CoV and MERS-

CoV. In both viruses, bats served as the natural reservoir and humans were the terminal host,

with the palm civet and dromedary camel the intermediary host for SARS-CoV and MERS-

CoV, respectively. Intermediate hosts clearly play a critical role in cross species transmission

as they can facilitate increased contact between a virus and a new host and enable further

adaptation necessary for an effective replication in the new host.[12]

Because of the pandemic potential of SARS-CoV-2, careful surveillance is immensely

important to monitor its future host adaptation, viral evolution, infectivity, transmissibility,

and pathogenicity. The host range of a virus is governed by multiple molecular interactions,


424


including receptor interaction. The envelope spike (S) protein receptor binding domain of

SARS-CoV-2 was shown structurally similar to that of SARS-CoV, despite amino acid

variation at some key residues. Further extensive structural analysis strongly suggests that

SARS-CoV-2 may use host receptor angiotensin-converting enzyme 2 (ACE2) to enter the

cells, the same receptor facilitating SARS-CoV to infect the airway epithelium and alveolar

type 2 (AT2) pneumocytes, pulmonary cells that synthesize pulmonary surfactant. In general,

the spike protein of coronavirus is divided into the S1 and S2 domain, in which S1 is

responsible for receptor binding and S2 domain is responsible for cell membrane fusion.[13]

The S1 domain of SARS-CoV and SARS-CoV-2 share around 50 conserved amino acids,

whereas most of the bat-derived viruses showed more variation. In addition, identification of

several key residues (Gln493 and Asn501) that govern the binding of SARS-CoV-2 receptor

binding domain with ACE2further support that SARS-CoV-2 has acquired capacity for

person-to-person transmission. Although, the spike protein sequence of receptor binding

SARS-CoV-2 is more similar to that of SARS-CoV, at the whole genome level SARS-CoV-2

is more closely related to bat-SL-CoVZC45 and bat-SL-CoVZXC21.[14]

However, receptor recognition is not the only determinant of species specificity. Immediately

after binding to their receptive receptor, SARS-CoV-2 enters host cells where they encounter

the innate immune response. In order to productively infect the new host, SARS-CoV-2 must

be able to inhibit or evade host innateimmune signalling. However, it is largely unknown how

SARS-CoV-2 manages to evade immune response and drive pathogenesis.[15]

Given that COVID-19 and SARS have similar clinical features, SARS-CoV-2 may have a

similar pathogenesis mechanism as SARS-CoV. In response to SARS-CoV infections, the

type I interferon (IFN) system induces the expression of IFN-stimulated genes (ISGs)

toinhibit viral replication. To overcome this antiviral activity, SARS-CoV encodes at least 8

viral antagonists that modulate induction of IFN and cytokines and evade ISG effector

function.[16]

The host immune system response to viral infection by mediating inflammation and cellular

antiviral activity is critical to inhibitviral replication and dissemination. However, excessive

immune responses together with lytic effects of the virus on host cells will result in

pathogenesis. Studies have shown patients suffering from severe pneumonia, with fever and

dry cough as common symptoms at onset of illness.[17]


425


Some patients progressed rapidly with Acute Respiratory Stress Syndrome (ARDS) and

septic shock, which was eventually followed by multiple organ failure and about 10% of

patients have died. ARDS progression and extensive lung dam-age in COVID-19 are further

indications that ACE2 might be a route of entry for the SARS-CoV-2 as ACE2 is known

abundantly present on ciliated cells of the airway epithelium and alveolar type II

(cells(pulmonary cells that synthesize pulmonary surfactant) in humans.[18]

DIAGNOSIS

The COVID-19 usually presents as an acute viral respiratory tract infection and many

differential diagnoses related to common viral pneumonia should be considered, such as

influenza, parainfluenza, adenovirus infection, respiratory syncytial virus infection,

metapneumovirus infection, and atypical pathogens, such as Mycoplasma pneumoniae and

Clamydophila pneumonia infections etc.[1,8]

Therefore, it is crucial to trace the travel and exposure history when approaching a suspected

patient back from an epidemic area. In addition, commercial respiratory syndromic diagnostic

kits that detect multiple etiological agents (such as Filmarray Respiratory Panel) may help

timely differential diagnosis.

Laboratory diagnosis for COVID-19 should be performed in a well-equipped laboratory with

up to biosafety level 3 facilities for the viral culture. In Taiwan, COVID-19 is a fifth-category

notifiable communicable disease and should be reported to Taiwan Centers of Disease

Control (CDC) within 24 hours.[19]

TREATMENT

Currently, there is no validated treatment for COVID-19. The main strategies are

symptomatic and supportive care, such as keeping vital signs, maintaining oxygen saturation

and blood pressure, and treating complications, such as secondary infections or organs

failure.

Because of the potential mortality of COVID-19, many investigational treatments are

underway:

1. Remdesivir: The experimental drug is a novel nucleotide analogue prodrug in

development by Gilead Sciences, Inc. It is an unapproved antiviral drug being developed for

Ebola and SARS. In a case report on the first case of 2019-nCoV in the United States


426


administering remdesivir for compassionate use on day 11 after illness resulted in decreasing

viral loads in nasopharyngeal and oropharyngeal samples and the patient’s clinical condition

improved.[9]

However, randomized controlled trials are needed to determine the safety and

efficacy of this drug for treatment of patients with 2019-nCoV infection.

2. Convalescent therapies (plasma from recovered COVID-19 patients): This strategy

had been used to support passive immunization. Based on the studies from MERS, the

therapeutic agents with potential benefits include convalescent plasma, interferon-

beta/ribavirin combination therapy, and lopinavir.[19]

However, there are no experience on

COVID-19 and no randomized controlled clinical trials for this management at present.

3. Antiviral drugs: lopinavir/ritonavir and ribavirin had been tried to treat SARS disease

with apparent favorable clinical response.[20]

In vitro antiviral activity against SARS-

associated coronavirus at 48 hours for lopinavir and ribavirin was demonstrated at

concentrations of 4 and 50 μg/mL, respectively.

A recent report found uncanny similarity of unique insertions in the 2019-nCoV spike protein

to HIV-1 gp120 and Gag.[21]

Will anti-HIV drugs affect the 2019-nCoV treatment outcome?

Further randomized controlled trials in patients with COVID-19 are mandatory.

4. Vaccine: There is currently no vaccine available for preventing 2019-nCoV infection. The

spike protein may serve as a vaccine candidate, but the effect to human requires further

evaluation.

PREVENTION

Since there are no standard treatments for COVID-19, it is important to avoid infection or

further spreading. For general population, travel to epidemic area of COVID-19 (mainly in

China, especially Wuhan, and Hong Kong and Macaw), contact, or eating wild animal is

dissuaded.

For those who had history of travel from epidemic area in recent 14 days, body temperature

monitor and self-surveillance for 14 days should be performed. If compatible symptoms

developed, designated transportation is recommended to prevent unprotected exposure. For

healthcare workers, personal protective equipment should be put on and taken off properly

while caring a probable or confirmed patients. Stringent protection procedures should be

conducted for high-risk procedures (such as endoscopy, Ambu bagging, and endotracheal

tube intubation). Once exposed to blood or body fluids of the patient unprotected, the

healthcare workers should flush thoroughly the exposure site by water or soap. Afterward,


427


body temperature should be monitored for 14 days. The confirmed case should be isolated

(prefer a negative pressure isolation room or, alternatively, a single room with good

ventilation).

Under the circumstances of resolved symptoms for 24 hours and consecutive two negative

results, isolation could be released. Corpses should be burned or buried deep. Treatments

effective against coronavirus include steam and heat. The virus is susceptible to many active

ingredients (AI), such as sodium hypochlorite (0.1%–0.5%), 70% ethyl alcohol, povidone-

iodine (1% iodine), chloroxylenol (0.24%), 50% isopropanol, 0.05% benzalkonium chloride,

1% cresol soap, or hydrogen peroxide (0.5%–7.0%), etc.22 Just like the WHO

recommendations for Ebola virus (RG4) disinfection, the environment with spills of blood or

body fluids could be cleaned up with 1:10 dilution of 5.25% household bleach for 10

minutes.[23-25]

Indian Dental Association’s Preventive Guidelines for Dental Professionals on the

Coronavirus Threat

In the light of WHO declaring the COVID-19 virus to be a pandemic, the Indian Dental

Association (IDA) recommends preventative measures for dental professionals to minimize

transmission through contact and dental procedures --- as scientific information leads to

improvements in infection control, risk assessment, and disease management.

Possible transmission routes of 2019-nCoV in dental clinics

Direct or Indirect Transmission: The virus can be passed directly from person to person by

respiratory droplets; emerging evidence suggested that it may also be transmitted through

contact and fomites. Dental patients and professionals can be exposed to pathogenic

microorganisms, including viruses and bacteria that infect the oral cavity and respiratory

tract. Dental care settings invariably carry the risk of infection due to the specificity of its

procedures, which involves face-to-face communication or direct transmission (cough,

sneeze, and droplet inhalation transmission) and contact transmission (contact with oral,

nasal, and eye mucous membranes). In addition, studies have shown that respiratory viruses

can be transmitted from person to person through direct or indirect contact, or through coarse

or small droplets, and 2019-nCoV can also be transmitted directly or indirectly through

saliva.


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Dental care settings invariably carry the risk of 2019-nCoV infection due to the specificity of

its procedures, which involves face-to-face communication with patients, and frequent

exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. The

pathogenic microorganisms can be transmitted in dental settings through inhalation of

airborne microorganisms that can remain suspended in the air for long periods, direct contact

with blood, oral fluids, or other patient materials, contact of conjunctival, nasal, or oral

mucosa with droplets and aerosols containing microorganisms generated from an infected

individual and propelled a short distance by coughing and talking without a mask, and

indirect contact with contaminated instruments and/or environmental surfaces.

Minimize Chance for Exposures

Post a sign at the entrance to the dental practice which instructs patients having

symptoms of a respiratory infection (e.g., cough, sore throat, fever, sneezing, or shortness

of breath) to please reschedule their dental appointment and call their physician. The

same thing applies if they have had any of these symptoms in the last 48 hours.

Reschedule appointments if your patients have traveled outside India in the last two

weeks to an area affected by the coronavirus disease. This includes China, Hong Kong,

Iran, Italy, France, Spain, Germany, Japan, Singapore, South Korea, Taiwan, Thailand,

Vietnam or any other COVID19 affected country.

Take a detailed travel and health history when confirming and scheduling patients. Do

not provide non-emergent or cosmetic treatment to the above patients and report them to

the health department immediately. Screen patients for travel and signs and symptoms of

infection when they update their medical histories.

Incorporate questions about new onset of respiratory symptoms into daily

assessments of all patients.

Take temperature readings as part of the routine assessment of patients before

performing dental procedures.

Take the contact details and address of all patients treated.

Install physical barriers (e.g., glass or plastic windows) at reception areas to limit close

contact with potentially infectious patients.

Make sure the personal protective equipment being used is appropriate for the

procedures being performed.

Use a rubber dam when appropriate to decrease possible exposure to infectious agents.


429


Use high-speed evacuation for dental procedures producing an aerosol.

Autoclave hand-pieces after each patient.

Have patients rinse with a 1% hydrogen peroxide solution before each appointment.

Clean and disinfect public areas frequently, including door handles, chairs and bathrooms.

Post visual alerts icon (e.g., signs, posters) at the entrance and in strategic places (e.g.,waiting

areas, elevators, cafeterias) to provide patients with instructions (in appropriate languages)

about hand hygiene, respiratory hygiene, and cough etiquette.

Instructions should include how to use tissues to cover nose and mouth when coughing or

sneezing, to dispose of tissues and contaminated items in waste receptacles, and how and

when to perform hand hygiene.

Provide supplies for respiratory hygiene and cough etiquette, including alcohol-based hand

rub (ABHR) with 60-95% alcohol, tissues, and no-touch receptacles for disposal, at

entrances, waiting rooms, and patient check-ins.

Risk Assessment is Critical

Dental personnel should be alert and identify patients with an acute respiratory illness when

they arrive, give them a disposable surgical face mask to wear and isolate them in a single-

patient room.

Airborne Spread

The dental papers show that many dental procedures produce aerosols and droplets that are

contaminated with virus. Thus, droplet and aerosol transmission of 2019-nCoV are the most

important concerns in dental clinics and hospitals, because it is hard to avoid the generation

of large amounts of aerosol and droplet mixed with patient’s saliva and even blood during

dental practice. In addition to the infected patient’s cough and breathing, dental devices such

as high-speed dental hand-piece uses high-speed gas to drive the turbine to rotate at high

speed and work with running water. When dental devices work in the patient’s oral cavity, a

large amount of aerosol and droplets mixed with the patient’s saliva or even blood will be

generated. Particles of droplets and aerosols are small enough to stay airborne for an

extended period before they settle on environmental surfaces or enter the respiratory tract.

Thus, the 2019-nCoV has the potential to spread through droplets and aerosols from infected

individuals in dental clinics and hospitals.


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FACIAL PROTECTION

Avoid touching the eyes, nose, and mouth with unwashed hands

Wear a surgical or procedure mask and eye protection (face shield, goggles) to protect

mucous membranes of the eyes, nose, and mouth during activities that are likely to generate

splashes or sprays of blood, body fluids, secretions, and excretions.

Gown

Wear to protect skin and prevent soiling of clothing during activities that are likely to

generate splashes or sprays of blood, body fluids, secretions, or excretions.

Remove soiled gown as soon as possible, and perform hand hygiene.

Linens

Handle, transport, and process used linen in a manner which: prevents skin and mucous

membrane exposures and contamination of clothing. Avoids transfer of pathogens to other

patients and or the environment.

Respiratory Hygiene and Cough Etiquette

Persons with respiratory symptoms should: Cover their nose and mouth when

coughing/sneezing with tissue or mask, Provide tissues and no-touch receptacles to throw

away used tissues and offering face masks to patients who are coughing.

Dispose of used tissues and masks, and perform hand hygiene after contact with respiratory

secretions.

Dental personnel should use N95 respirators or respirators that offer a higher level of

protection instead of a facemask when performing or present for an aerosol-generating

procedure.

Waste Disposal

Ensure safe waste management. Treat waste contaminated with blood, body fluids, secretions

and excretions as clinical waste, in accordance with local regulations. Human tissues and

laboratory waste that is directly associated with specimen processing should also be treated as

clinical waste. Discard single use items properly.

Patient Care Equipment

Offices also should follow routine cleaning and disinfection strategies used during flu season.

Handle equipment soiled with blood, body fluids, secretions, and excretions in a manner that


431


prevents skin and mucous membrane exposures, contamination of clothing, and transfer of

pathogens to other patients or the environment.

Clean, disinfect, and reprocess reusable equipment appropriately before use with another

patient.

Train and Educate Personnel

Provide task-specific education and training on preventing transmission of infectious agents,

including refresher training.

CONCLUSION

2019-nCoV infection is a zoonotic disease with low to moderate mortality rate. Currently,

there is no standard treatment for the disease and supportive treatment was the only strategy.

Although many experimental trials are on the way, the best we can do to prevent a rampant

outbreak is stringent infection control operation. Clinicians should consider the possibility of

2019-nCoV virus infection in persons with travel or exposure history with compatible

incubation period and presenting symptoms. First-line healthcare providers should be highly

aware of appropriate infection prevention measures for suspected patients.

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covid -19 review article

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