INTRODUCTION:

The novel corona virus disease (COVID-19) is due to the presence of severe acute respiratory syndrome coronavirus (SARS-CoV2) in humans, that was began from Wuhan, Hubei province of China in late 2019 and spread worldwide¹. This corona virus causes severe respiratory infections as they are zoonotic pathogens, which begin from infected animals and are transmitted from animals to human being (Sahin et al., 2020). It affects large number of population and a major cause of motility (443,231 cases worldwide)².

The World Health Organisation (WHO) declared it as a pandemic and a major concern of public health emergency of international concern (PHEIC)^3,4,5. This global pandemic and to stop its transmission a we have to synchronized the strength and to maintain a strong public and health care responses^6,7.

Types of Coronaviruses:

Coronaviruses are a combination of associated viruses that may cause diseases in birds and mammals. In humans, Coronaviruses is one of the major pathogens that primarily infect the human respiratory system⁸. Coronaviruses are characterised mainly due to presence of crown like spikes on surface hence known as Coronavirus. There are four main sub-groupings of coronaviruses, named as alpha, beta, gamma, and delta. Human coronaviruses (HCoV) were first discovered in the mid-1960s. The seven coronaviruses that can transmit to human being listed as 229E (Alpha coronavirus), NL63 (Alpha coronavirus), OC43 (Beta coronavirus), HKU1 (Beta coronavirus), SARS-CoV (Beta coronavirus that causes severe acute respiratory syndrome or SARS), MERS-CoV (Beta coronavirus that causes Middle East Respiratory Syndrome or MERS) and SARS-CoV-2 (Novel coronavirus that causes coronavirus disease 2019, or COVID-19). Human being throughout the world usually get infected with human coronaviruses HKU1, OC43, NL63 and 229E^9,10. Recently the human generations are effected by the exposure of novel coronaviruses and a possible cause of morbidity and mortality¹¹. The recent corona virus are SARS-CoV, MERS-CoV, SARS-CoV19^12,13.

Transmission of COVID-19:

The zoonotic origin and its transmission were based on the huge number of infected persons that were exposed to live animal market in Wuhan, China. Preliminary report acknowledged two species of snakes could be a possible reservoir of COVID-19. However, till now no evidence noticed for coronavirus reservoir other than mammal and birds^14,15Bats genomic sequence analysis suggested that mammals are the most suitable link between COVID-19 and humans. Many studies have suggested that person-to- person transmission is a probable route for transmission of COVID-19 infection ¹⁶. This is supported by the cases that appeared within families and among who those are not exposed to the wholesale market of Wuhan city. Person-to- person spread occurs via direct contact through droplets by coughing or sneezing from an infected individual¹⁷. The transmission of the virus is not reported currently in gestational cases from mother to unborn child birth and even during delivery. It has to be ruled out because of an important aspect, whether it effects the maternal health or not; because pregnant mothers are more vulnerable to respiratory disorders¹⁸. The lung epithelial cells are the primary target of the virus because host cell is the first step of viral infection followed by the fusion with the cell membrane hence it has been reported that human to human transmission of SARS-CoV2 occurs by the binding between the receptor-binding domains of virus spikes with the cell, which has been identified as angiotensin-converting enzyme-2(ACE2) receptor. The sequence of receptor-binding domain of corona virus spikes is identical to SARS-CoV. This information extremely advocates that the migration into the host cells is via. the ACE-2 receptors^19,20. The clinical manifestation depends upon the symptoms and can be find out through polymerase chain reaction (PCR) analysis, X-ray imaging of chest (CT scan), that diagnose even the asymptomatic infection ranging from mild to severe and critical cases²¹.

Diagnosis of Human coronaviruses (HCoV):

Most of the countries are employing and sharing numerous type of clinical and epidemiological information to decide accurate methods for rapid and precise diagnosis. In United State of America (USA), standards have been established for persons under investigation (PUI) for COVID-19. As per U.S. Centres for Disease Control and Prevention (CDC), patients with positive COVID-19 has developed fever and/or symptoms of acute respiratory disorders such as cough and difficulty in breathing but some patients don’t have any symptoms i.e. asymptomatic^22,23. If a person is a PUI, it is recommended to the practitioners that immediately put that individual in isolation. Initially, they suggested for testing of all other sources of respiratory infection. Furthermore, they suggested for using epidemiologic factors to help in decision making for a better treatment plan. This comprises anyone who hadin close contact with the patient of COVID-19²⁴. The WHO recommended collecting specimens from both the upper respiratory tract (URT) and lower respiratory tract (LRT) such as expectorated sputum, endotracheal aspirate, or broncho alveolar lavage (BAL). The collection of BAL samples should only be executed in mechanically ventilated patients as LRT samples seem to remain positive for a more extended period²⁵. The sample should be stored in laboratory for the amplification of the genetic material extracted from the mucus or saliva sample is through a reverse transcription polymerase chain reaction (RT-PCR), which involves the synthesis of a double-stranded (ds) DNA molecule from an RNA. When the genetic material is adequate, the search is for those portions of the genetic code of the CoV that are conserved²⁶. The probes are taken on the initial gene sequence released by the Shanghai Public Health Clinical Centre & School of Public Health, Fudan University, Shanghai, China on Virological.org, and subsequent confirmatory evaluation by other labs. If the test result is positive, it is recommended that the test is repeated for verification²⁷. In patients with confirmed COVID-19 diagnosis, the laboratory assessment should be repeated to assess for viral clearance prior to being free from observation²⁸. The accessibility of tests is based on which country a person lives in with increasing obtainability occurring nearly daily. Regarding laboratory examinations, in the early stage of the sickness, a normal or decreased total white blood cell (WBC) count and a decreased lymphocyte count can be revealed. Lymphopenia seems to be a negative prognostic factor²⁹. Increased values of hepatic enzymes, LDH, muscular enzymes, and C-reactive protein can be found. There is a normal pro-calcitonin value. In critical patients, D-dimer value is elevated, blood lymphocytes decreased persistently, and laboratory alterations of multi-organ imbalance (high amylase, coagulation disorders, etc.) are found³⁰.

Epidemiology:

The corona outbreak first identified in Wuhan city of china in the month of December 2019 and declared as a pandemic by WHO on 11 March 2020³¹. The preponderance of the cases has been reported from Hubei and surrounding area, but large number of cases also observed in other part of the China. Initially it was assumed that this virus was spread through the people of China or those who used to travel from China to other countries³². But now the things are worsening day by day due to the infection that is due to SARS-CoV-2 that resembles with the bat coronavirus, pangolin coronavirus and SARS-CoV^33,34. Globally more than 8,128,490 confirmed cases of COVID-19 has been reported on 16June, 2020 in over 213 countries and territories which resulting in more than 443,231death and 4,272,860recoveries^35,36. There may be significant unreported cases with milder symptoms and some time they are also noticed as asymptomatic³⁷.

Prevalence of COVID-19 worldwide:

We can't fight this pandemic if we don't know who is infected. Coronavirus disease (COVID-19) represents global public health concern and WHO declares public health emergency. The outbreak started in the late 2019 and spread around the globe by March 2020 and effects around 213 countries around the globe. The European Centre for the Disease Control and Prevention (ECDC) publishes daily updates of confirmed deaths due to COVID-19³⁸. The most gravely affected nations include United State of America (U.S.A), Brazil, Russia, India, United Kingdom, Spain, Italy, China, Iran, , and France. Thousands of new cases are being reported each day³⁹. The number of death increase above 443,231, with several countries reporting sobering increases. Among the different countries of the world U.S.A having maximum number of infected people. The figure 1 showed countries, territories or areas with reported confirmed cases of COVID-19, 19 March 2020. It is important to note that risk assessment of COVID-19 is very high globally as per WHO. The table 1 shows the situation in numbers total (new) cases in last 24 hours (As of 19^th March 2020)⁴⁰.

Table 1: Coronavirus disease 2019 (COVID-19) Situation Report. Data accurate as of 16^th June 2020^[39].

Region	Total Confirmed case (new case in last 24h)	Total Death case (new case in last 24h)
Globally	7 823 289 cases (132 581)	431 541 deaths (3 911)
Western Pacific Region	198 995 cases (1 131)	7 215 deaths (15)
European Region	2 416 920 cases (18 141)	188 350 deaths (349)
South-East Asia Region	471 392 cases (15 953)	12 927 deaths (401)
Eastern Mediterranean Region	778 200 cases (19 649)	17 077 deaths (437)
Region of the Americas	3 781 538 cases (69 770)	201 848 deaths (2 596)
African Region	175 503 cases (7 937)	4 111 deaths (113)

Figure: 1 Illustration of the geographical spread of confirmed COVID-19. Data accurate as of 16^th June 2020³⁹

Symptoms of corona virus infection:

It takes 2- 14 days to develop symptoms after infection from the virus the further details of this infection is discussed in Table 2. Fever, tiredness, and non-productive cough are the most common symptoms of COVID-19. Maximum victims (about 80%) get cured without requiring exceptional management. The intensity of symptoms (Table 2) can range from very mild to severe. Older aged group (> 60 years) and people having existing chronic medical conditions, like cardiovascular disease including hypertension, diabetes and other immune suppressed states and chronic lung/kidney/liver disease may be at higher risk. In severe cases, contagion can lead to death⁴¹.

Table 2: Symptoms of COVID-19.

Symptoms	More common	Less common
Fever	✔ (98%)
Cardiovascular complications
Acute respiratory distress syndrome (ARDS)
Inflammations
Headache		✔ (<10%)
Dizziness		✔ (<10%)
Fatigue	✔ (70%)
Non-productive cough	✔ (59%)
Myalgia	✔ (35%)
Shortness of breath	✔ (31%)
Sore throat	✔ (17%)
Joint or muscle pain		✔ (<15%)
Diarrhea		✔ (<10%)
Other GI symptoms		✔ (<10%)
Chills		✔ (<10%)
Runny nose		✔ (<5%)

DIAGNOSTIC METHODS OF CORONAVIRUS:

Coronavirus infections are diagnosed by a medical practitioner on the basis of symptoms and it is confirmed by the lab examination. The purpose of testing is to check the infected people and let them aware about how to maintain their health and other preventive measures. So that the contaminations should be stopped. Testing is also very important to know the proper response of the virus. Through the testing we can get the actual data about the blowout of the disease and thus to slow down the spread of the disease by taking evidence-based measures. Molecular recognition and Serology testing methods are the two main methods used to test the COVID-19. In the molecular testing method the test sample can be check through the polymerase chain reaction (PCR) along with nucleic acid tests and other innovative analytical procedures. Serology testing is based on detection of the presence of antibodies produced by the host immune system against the virus by using ELISA antibody test kits. Serology antibody testing is being used both for surveillance and investigational purposes while the molecular test methodologies are used for the diagnosis⁴². WHO recommended the PCR test and it is included in the protocol for the diagnosis for COVID-19 and is commonly used for diagnosis of this pandemic where, patient’s nose and throat swabbed samples is taken to perform this test. For the confirmation of the disease RT-PCR (reverse transcription polymerase chain reaction) will be conducted that can identify minute quantity of viral ribonucleic acid (RNA). If severe pulmonary disease is suspected, a chest CT should also be done to identify the incidence of viral pneumonia. It’s also important to look for other causes of similar symptoms by doing different test.

Safety measures and protection:

Initially the diagnosis of the cases of corona virus infection Covid-19 is conducted on the basis of clinical manifestations and exposure history, within the last 2 weeks. The person who is positive for that viral infection would be considered at high risk if he/she having any of two symptoms listed below:

1. Fever or respiratory symptoms or digestive symptoms or fatigue

2. Laboratory examination: WBCs is normal or decreased or with lymphocyte count or increased level of C-reactive protein;

3. Atypical chest X-ray.

For an infected person at intermediate or truncated risk threat, analogous investigative standards will be applied after excluding influenza and other respiratory infections. Suspected cases who met any one of the following criteria were defined as confirmed cases⁴¹.

Protection from coronavirus (COVID-19):

To protect from coronavirus (COVID-19) each and every person have to gain the knowledge regarding its transmission and to understand how it can be stopped though the preventive measures.

Knowledge about its Spread:

No vaccine available in the market to prevent coronavirus disease 2019 (COVID-19). The excellent method to prevent infection is to avoid exposure to this virus. The virus spreads mainly from person-to-person between people who narrowly enclosed to each other (within about 6 feet) through sneezing or coughing droplets and transmits from an infected person's nose or mouth into eyes, nose or mouth to the healthy person. This might be from hands, objects, or from direct contact with the infected surface. Social segregation or keeping in isolation, social distancing is very significant aspect that can help to slow down the spreading of that pandemic. As a preventive measure we have to maintain a gap of 2 meters (6.5 feet) between two persons minimizing the public interaction outside the work place and house avoid common sleeping area, common rooms, crowded places market, malls, supermarkets etc. Work from home and do not shake hands or avoid close contact if possible refer figure-2^42,43.

Figure: 2 Steps to protect from COVID-19 infection⁴².

Minimize the spread of virus:

Any suspected victim who has symptoms should self-isolate for 14 days, refer figure-2, suspects should limit unnecessary social contact as much as possible, at risk groups should avoid close contact with people outside the home. Washing of the hands should be done properly, Cover the mouth and nose with a tissue or sleeve while coughing or sneezing refer figure-1, The used tissues should be kept into a bin and wash hands, Clean and disinfect frequently touched objects and surface, Avoid close contact with the people of 6.5 feet between person-to-person, crowded place should be avoided, Stay at home in case of illness to stop the spread of infection, Do not touch eyes, nose or mouth if hands are not clean. Do not share objects that touched your mouth like bottles and cup, do not shake hands.

Steps to protect from COVID-19 (Details available in figure 2)

· Wash hands properly

· Avoid close contact

· Stay home

· Cover coughs and sneezes

· Wear a facemask

· Clean and disinfect

· Keeping well and relax

Pharmacological treatment of COVID-19:

At present there are no specific antiviral drugs or vaccines available against COVID-19 infection for effective treatment of human being. The only option available is broad spectrum antiviral drug like nucleoside analogues and also HIV-protease inhibitor. On developing symptoms like Low grade fever, cough, malaise, rhinorrhoea, sore throat without shortness of breath the treatment will be done with Oseltamivir 75mg BD but for the patients having high risk with influenza suspects antibiotics like azithromycin+amoxicilline/ Clavulanic acid along with paracetamol 500mg is used for the symptomatic treatment. In moderate to severe cases (Any one of Respiratory rate >24/min, Spo₂<94% in room air, confusion, systolic BP <90 mmHg or, diastolic BP<60mmHg) admission and test will be advised, if test negative–manage according to existing protocol, if test positive Oxygen supplementation to maintain Spo2<94%. Antipyretic, antitussive, antibiotics indicated, MDI preferred over nebulization, Hydroxychloroquine (400mg BD x 1day f/b 200mg BD x 5days) may be consider, Lopinavir/ritonavir (200mg 2 tab BD) may be consider on case to case basis (within 10 days of symptom onset), Do not combine Hydroxychloroquine with Lopinavir in view of drug interaction, Corticosteroid need to be avoided. After clinical and radiological improvement if two negative samples at least 24 hours apart then patient will be discharge. If the patient condition get worsen or he/she is facing severe complications like respiratory failure, hypotension, and mental disability then these types of patients are recommended to shift into Intensive care unit (ICU) for proper ventilation and conservative fluid management (if not in shock), Standard care for ventilated patient, Closed sanction and HME filter, Prone ventilation, ECMO for refractory hypoxemia) upon improving the condition discharge. If two negative sample at least 24 hours apart, high risk for sever disease, age>60 years, cardiovascular disease including hypertension, DM, other immuno-compromised state, chronic lung/kidney/liver disease⁴⁴.

Quarantine, isolation and social distancing:

As we all know Covid-19 spreads around the globe. The governments of different countries have imposed quarantines and travel bans on an exceptional scale. Firstly China locked down whole cities, and later on Italy has imposed draconian restrictions throughout the country. In the United States, thousands of people have been subjected to “self-quarantine”. Globally different countries taken steps on travel ban and even boarder seal as a measure to stop further spreading of new infectious diseases. To save the people from infection, “quarantine” means the separation of persons (or communities) exposed to an infectious disease or protect themselves to get a chance of infection by any mean. “Isolation,” in other hands is applicable to the separation of persons who already confirmed to be infected or diseased conditioned. In U.S. law, however, “quarantine” often refers to both types of interventions, as well as to limits on travel. Many countries do not require an emergency declaration in order to issue quarantine. Center for Disease Control and Prevention (CDC), USA to take into custody, detain, or issue a conditional release for the purpose to prevent the entry into the country, or the spread across state lines, of a quarantinable disease. The currently includes “severe acute respiratory syndromes,” which known as Covid-19. CDC guidelines provide the information to minimize the spread of disease by sovereign action of state, isolation, quarantine, examination or restriction on travel in the country. The guideline is also committed to provide medical facilities to the detained victim as well as establishing a multilevel internal administrative assessment procedure. The advantage of quarantine is slowing the spread of Covid-19 across space. Social distancing means keep yourself away from large gathering, if anyone having around you maintains two meter distance where ever possible. Social distancing is quit appreciable as a common sense^45,46.

Socio economic burden:

The COVID-19 pandemic is far more than a health crisis: it is affecting societies and economies at their core. While the impact of the pandemic will vary from country to country, it will most likely increase poverty and inequalities at a global scale, making achievement of sustainable development goals even more urgent. This causes a downfall in job in every sector including pharmaceuticals production and manufacturing. In many countries the basic demands for the management of this communicable disease is not fulfilled. Pharmaceutical industries are not capable of supplying the huge demands of diagnostic reagents, kits, personnel protective equipments etc. Most of the developing country of the world is under severe crisis of basic pharmaceutical products that may lead financial crisis. There may be estimate of trillion dollar loss of economy worldwide reported by United Nation. Most of the country allocated separate budget to fight for COVID 19. Not only the economic burden is a challenge for several countries around the globe but the social and political relations among the countries are also going to be weakening. The international community is to introduce a global synchronized strength to prevent the outbreak that needs a strong public health response, high level political commitment and sufficient funding⁴⁷.

Myths:

The misinformation and myths are not new to COVID 19. It has already been in the past for several life threatening diseases i.e. HIV as well. Prevalence of myths leads to propagate the misinformation by ignoring the scientific facts which ends at plaguing the scientific community and the users. The existence of myths relies on the political influence and negligence in concern. The experts also believe about the emerging public health crisis is due to untimed pandemic coronavirus (COVID 19). There might be many reasons but myths and misinformation possibilities are not liable to be ruled out. The appeals are being shouted by the scientists and researchers to come forward in the solidarity to fight against this pandemic infection and the unity over conjecture and misinformation⁴⁸.

The internet and other social media proved an inevitable source of misinformation and myths. It engaged approximately 20 million posts and writing ups per day pointing the theories of conspiracy which included the rumour of artificial manipulation of corona virus done with a set agenda of the government. But at last the genome analysis COVID 19 was done by many countries and found the real source of the strain as animal^49,50. This misconception was to be cleared up to avoid any further confrontation. Various popular myths were circulated to treat the pandemic infection with homely made herbal remedies i.e. the use of garlic and citrus fruits and various other deadly combinations of irrational compounds to generate chlorine dioxide. Though US FDA clearly mentioned regarding the use of such combinations that may lead to the vomiting, irregularities of blood pressure and hepatic failure^51,52. The transparency must be maintained to deliver the accurate information for the treatment and data analysis to avoid any misguidance and myth based executions. It is the part of duty of the government and the citizens as well⁵³.

There are several myths which are sum up by the World Health Organization (WHO)⁵⁴:

S. No.	Myth	Fact and Recommendation
1.	Hot bath and shower may prevent the infection by COVID 19	No, it wouldn’t prevent any infection to happen but it is better to clean the hands frequently to eliminate the virus.
2.	Cold weather and snow kills the virus	It is not true but the frequent washing of the hands with alcohol based liquids and cleansing with water are beneficial.
3.	Coronavirus can be transmitted through mosquito bite	There is no such evidence to support the transmittance coronavirus by mosquitoes. It is a respiratory tract virus which gets spread through droplets when the infected one coughs or sneezes, or droplets of saliva or from the nose discharge. Protection is maintained by cleaning the hands frequently with an alcoholic sanitizer or wash with soap and water.
4.	Hand dryers are capable of killing the new coronavirus	No, hand dryers are not capable to kill the COVID 19 rather it is better to wash the hand as suggested above and then dry it with cloth towel or paper.
5.	UV lamp can kill the new COVID 19	No, it cannot kill the virus and it is not advisable to expose the skin to UV lamp because of the probabilities of skin cancer.
6.	Thermal scanner are effective to detect the infection	No, it is not true always because it detects the temperature only while it takes 2 to 10 days to show the symptoms.
7.	Spraying of alcohol and chlorine on body kills all virus	No, It cannot kill the virus which has already entered in the body. And it is harmful for body to be exposed for such sprays.
8.	Vaccine against pneumonia works against new coronavirus	No, it does not work against new coronavirus. The virus is unique and it requires specific vaccine to work against it. WHO is supporting this project to develop the vaccine
9.	Rinsing of nose with saline is helpful to prevent the infection from coronavirus	No, It is not true. Rinsing of nose with saline only help to recover from the symptoms of common cold not from the corona virus.
10.	Eating garlic prevent the corona infection	No, It does not. Though it has antibacterial properties but not effective against coronavirus.
11.	Coronavirus only infect the old people not younger one	No, it can infect all age groups but the person who is already carrying diabetes, asthma or cardio vascular diseases are more susceptible.
12.	Antibiotics are effective to treat corona infection	No, It is not true. Actually the antibiotics are not functional against viral infection. For a hospitalized person the antibiotics are given to combat the co infections.
13.	It can be treated well, there are many medicines to alter to prepare the final prescription	No, There is no specific medicine or vaccine to control the infection but the work on such projects are going on and the reports are being received by WHO regularly.

Some other myths are also being summarised which don’t possess any reliable accountability. WHO also considers them as myths and these are as follows⁵⁵

· You are not infected with COVID 19 if could hold your breath for 10 seconds.

· The virus can be flushed out of your mouth with water.

· You must not use the Ibuprofen if infected with COVID 19.

· The wireless service 5 G is also a causing factor to induce COVID 19.

· Hot climate or weather is enough to get rid of COVID 19.

· Face mask can protect you from COVID 19 infection.

· Garlic or any other herb can cure the new corona infection.

· Bleaching or spraying of alcohol on your body can protect you from infection.

RECOMMENDATION:

It is clear that more research is urgently needed to identify novel chemotherapeutic drug for treating COVID-19 infection. There is crucial requirement to build an animal model to reproduce the disease presently observed in human, many groups of scientists are working hard to develop non-human model to study COVID-19 infection to established fast track novel therapeutic, testing of potential vaccines and to provide a better understanding of virus-host interaction.

CONFLICT OF INTEREST:

All authors declared there is no conflict of Interest.

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Received on 30.04.2020 Modified on 15.06.2020

Research J. Pharm. and Tech. 2021; 14(4):2308-2315.

DOI: 10.52711/0974-360X.2021.00408