COVID-19, an Emerging Coronavirus Infection: Current Scenario and Recent Developments-An Overview

During December 2019, a novel coronavirus virus (2019-nCov) emerged in China, which posed an International Public Health Emergency in a couple of weeks, and very recently attained the position of a very high-risk category by World Health Organization (WHO). This virus was named the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses (ICTV), and the disease referred to as Coronavirus Disease-19 (COVID-19). Till March 8, 2020, the virus has claimed the lives of nearly 3,600 humans out a total of approximately 110,000 confirmed cases affected by this infection. The present editorial is a brief overview highlighting the most salient features and facts with regards to COVID-19, an emerging coronavirus infection, its causative virus (SARS-CoV-2), the current worldwide scenario, recent developments and currently ongoing progresses to contain and control this disease which have now spread to more than 100 countries across the globe. Of note, worldwide researchers and various health agencies are all together doing their best to halt the spread of this virus and avoid any possible pandemic situation to be faced, which otherwise would threaten the lives of millions of human beings.


INTRODUCTION
Coronaviruses are continually evolving. Examples include the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS) that caused fatal outbreaks earlier, and now the present emerging Coronavirus Diseases 2019 , caused by the SARS-2 Coronavirus (SARS-CoV-2), initially expressed as pneumonia of unknown origin, thus posing a significant threat to public health across the globe [1][2][3] . COVID-19 has represented a high negative impact on the economy of China as well as a few other nations 4,5 . The lessons from such earlier threats of SARS, MERS and of the current COVID-19 situations need to be kept in mind for formulating plans for countering such and other emerging and zoonotic pathogens that could pose pandemic threats while putting human lives at bay 6 .

Current Scenario
After its initial emergence in Wuhan, China,during December month of the year 2019, this novel emerging CoV was included under the Public Health International Emergency category on January 30, 2020 7,8 . Besides affecting mainly China, SARS-CoV-2/COVID-19 has now spread to more than 100 countries (9). Out of cumulative 111,354 confirmed cases, 3,892 human deaths have been documented as of March 9, 2020 10,11 . Due to such a quick jump with regards to the total number of confirmed SARS-CoV-2 infected persons as well as affecting several countries in a short time interval, the WHO designated it under a very high-risk category. Few of the reports have mentioned the possibility of probable pandemic risks and threats with the bloom. They loom in rapidly increasing cases of COVID-19, alarming us to put very high efforts to check the spread of this widely circulating virus among world population by following appropriate prevention and control measures along with formulating global solutions and modified strategies with future perspectives [12][13][14][15][16][17][18][19] .

The Virus (SARS-CoV-2 )
The SARS-CoV-2 is an enveloped, spherical shape, single-stranded plus sense RNA virus with helical symmetry belonging to beta coronaviruses of Coronaviridae 20 . The virus has peplomers made up of glycoprotein projected over the envelope in a manner of crown (hence named corona), and these spike proteins help in binding with receptors present in the body of animals (bats, rodents, civets, cats, Malayan pangolins, camels, among other potentially competent hosts) and humans [21][22][23] . Modifications at the level of spikes on receptor binding ligands are responsible for zoonotic spillover and crossing of the species barrier. As per high genomic similarities, it is suggested that SARS-CoV-2 producing COVID-19 in humans has its origin from bats as bats acted as natural ancestral host [24][25][26][27][28] . Scanning electron microscopy, transmission electron microscopy, and cryo-electron microscopic images of the structure of the SARS-CoV-2 confirmed the change in spike glycoprotein of SARS coronavirus-2 29 . In the Coronaviridae family, seven viruses affect mainly human beings, four producing mild respiratory illness, while three including-SARS-CoV-1, MERS, and current SARS-CoV-2 were dangerous as produced epidemics. ICTV named this pneumonia-causing virus as SARS-CoV-2 instead of 2019-nCoV as genetic studies revealed the similarity between SARS (2002-2003 severe acute respiratory syndrome outbreak) coronavirus and COVID-19 producing coronavirus 30 . Genomic studies indicated that there is a difference of merely five nucleotides in between SARS coronavirus and SARS-CoV-2 and emphasized that 2019-nCoV has emerged from SARS CoV 31 . SARS-CoV-2 can be transmitted from animal to person or person to person via airborne particles/ drops. The virus infects type 2 pneumocytes and ciliated bronchial epithelial cells through ACE2 receptors 18,32 . The virus can be transmitted through respiratory droplets, tears, and body fluids if exposed to the mucous membranes of the eyes, mouth, or nose. Other transmission modes are yet to be further elucidated if so.

The Disease (COVID-19)
COVID-19 is the third CoV outbreak in humans that occurred in last two decades, causing clinical manifestations of respiratory, digestive, and systematic affections, mainly expressed by pnemonia 33,34 . The case fatality rate is around 2-3%, but severely affected patients may die due to excessive alveolar damage, which leads to progressive respiratory failure as evident from many countries including Italy and China 35 . Due to close contact, few persons may remain as asymptomatic carriers without manifesting any clinical symptoms of cold, fever, fatigue or lung pathology. As competent carrier they can shed virus till 21 days of period to other persons who will come in contact to them 36 . Initial symptoms include fever, mild chills, dry cough, fatigue and shortness of breath, severe respiratory distress, pulmonary pneumonia, which worsen if timely not diagnosed and not appropriately medicated 37 . As lung inflammation advances hypoxemia triggers and to compensate shortness of breath, sometimes cardiac arrest takes place, and hence patient sinks. Therefore, it is advised as soon as symptoms of dry cough and fever begin to appear, consult a medical practitioner to prevent further pathology within the body 38 . Histological examination performed over biopsy tissues obtained from lung, liver, and heart tissue elaborated detailed picture of desquamation of pneumocytes, the formation of hyaline membrane, bilateral diffused alveolar damage, presence of cellular fibromyxoidexudate. As marked cytopathic effects, multi nucleated syncytial cells along with atypical enlarged pneumocytes and interstitial mononuclear inflammatory infiltrates with the majority of lymphocytes in the affected lungs are prominent features 39 .

Zoonotic links
Recently, few of the reports have highlighted the role of animals, veterinary, crossspecies jumping, zoonotic links and spillover events of SARS-CoV-2 and its transmission to humans, before acquiring human to human transmission, as have been implicated with SARS and MERS 2,6,40-46 . Atypical exposure point of SARS-CoV-2 has pointed out towards the implication of seafood market in Wuhan, China 47 , as a wet-market that sells different kinds of poultry, bats, snakes, marmots and other wildlife animals for human consumption at a single place, that can act as hot spot acting as a human-animal interphase/ interaction event, where zoonotic viruses can jump to cross-species barrier-or spillover to humans through seafood tanks, presence of live-dead animals body fluids, blood, excretion or air born mode of transmission leading to the emergence of novel pathogens such as SARS-COV-2 and others 48 . Still in some parts of world, western medicines are not much popular or in practice and people yet rely on using traditional medicines which uses not only various herbs but bat saliva, dung and other body parts are also used. As bats are employed as materia medica, so we can not deny the probability of zoonotic spillover through bats 24,28 . By involving intermediate hosts (bridge hosts), SARS-CoV-2/ 2019-nCoV attained altered pathogenicity and enhanced transmissibility through modified receptor binding domain (RBD) 2,18,26,49-57 .

Diagnosis
For prompt diagnosis of SARS-CoV-2, molecular tools are widely preferred [58][59][60][61][62] . Serological diagnosis is not of much help at the peak of the epidemic, though serum samples of recovered patients can be tested to know the titer of IgG. In severely infected patients, computed tomography technique (CT) and X-Ray can be of help to observe the lesions of pulmonary pneumonia in the lungs in correlation with clinical symptoms to depict the picture of COVID-19 37 . For the diagnosis of exposed but asymptomatic carriers, detection of viral nucleic acid (RNA) is of pertinent help, and by using pharyngeal swab the viral RNA can be detected, such carriers should be kept in isolation to prevent the transmission and spread risk 25,36 . Most popularly, real-time RT-PCR (rRT-qPCR) is performed over respiratory secretions so that within a short period, viral RNA can be detected 63 . Researchers have also developed a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic technique for rapid and colorimetric detection of COVID-19 coronavirus. This isothermal LAMPbased method for COVID-19 detection is referred to as iLACO. In this technique, a fragment of the ORF1ab gene was amplified by using six primers, and phenol red are used as a pH indicator when amplification takes place color changes from pink to light yellow. At the same time, in negative cases, it remains pink 64 . In addition to that, multiple reference laboratories are progressing sequencing the complete genome from the rRT-PCR positive isolates.

Therapeutics/Drugs and Vaccines
As infected individuals are hospitalized, human patients should immediately be given symptomatic and supportive treatment as per severity of symptoms 65,66 . Therapy may be comprised of supplementary oxygen or high-flow nasal cannula (HFNC) oxygen therapy through nasal route to reduce breathing stress if needed Journal of Pure and Applied Microbiology methylprednisolone intravenously to correct hypoxemia and in extreme cases adrenaline by intravenous route (IV), any repurposed drug such as lopinavir plus ritonavir as anti-viral drug by oral way, moxifloxacin or any antibiotic to prevent secondary bacterial infection by IM/IV route 37,65 . Nevertheless, multiple drugs are under study, including other antiretrovirals, such as is the case of remdesevir, but also antivirals such as oseltamivir and other therapies, including chloroquine and even indomethacin. Researchers are making high efforts to design and develop suitable vaccines for COVID-19, which may take some time 2,67-69 . In this context, efficient management of COVID-19 pneumonia by active prevention and control in a scientific manner is of utmost importance following the national and international developed guidelines 70 .

Prevention and Control
It is imperative to prevent the spark (origin at the new place) and spread (transmission between susceptible and infected) risk both to avoid the conversion of COVID-19 epidemic to pandemic and for this purpose rigorous surveillance screening should be done to know-how the pattern of emerging zoonotic epidemics 71,72 . Individual protection and community protection both need to be robust. World Health Organization (WHO), Centre for Disease Control and Prevention (CDC) and Food and Agriculture Organization (FAO) have issued instruction and COVID-19 containment strategies for the ordinary people, clinicians, travelers and for infected patients to follow so that transmission to healthy population can be prevented 11,[73][74][75][76][77][78][79] . It is advised to share awareness programs through social networking sites and platforms and follow intense epidemiological surveillance so that any new case (symptomatic and asymptomatic both) of COVID-19 can be notified to WHO [80][81][82] . Epidemiological screening of bat CoVs should be done at large global scale to have a datasheet which will be a pathfinder for newly emerging and re-emerging zoonotic pathogens 83 . The governments should encourage travelers to postpone their tours to avoid exposure to COVID-19 affected countries and those who are returning back from affected countries must be isolated and quarantined for health check-ups and evaluation of their health status 5,[54][55][56][57][84][85][86] . People should wash their hands with soap-water or prefer to use sanitizers, should remain inside home, should refrain from crowded places and avoid contacts with live-dead animals especially wild animals, children, and older adults must take precautions as they are more prone to the severe respiratory distress syndrome of COVID-19 87 . If people presents respiratory symptoms should wear face mask in order to avoid further transmission to other susceptible people. China has forced a temporary ban on the sale of wild animals in Wuhan animal market and planning to forbid the wildlife trading permanently 88 .
Indeed, considering previous experiences of edidemics and pandemics in different regions of the world, with other emerging infectious diseases, as the case of SARS, MERS 16,27 , but also swine flu and avian flu, Ebola, Nipah, Chikungunya and Zika 2,67-69,89-91 , health authorities and healthcare providers including hospitals must apply the learned experiences on previous epidemics and pandemics to frame some implementable protective strategies 14,16,[92][93][94][95] . That includes the rational use of quarantine and appropriate disease prevention, management and control procedures to be timely implemented 15,19,70,96 . Besides all the, One health approach also need due attention for prevention and control of this disease and other probable future epidemics 2,50-52, [67][68][69]97 .

CONCLUSIONS AND FUTURE PROSPECTS
Worldwide scientists, researchers, and various health agencies are working days and nights with very high efforts to stop the further transmission and spread of SARS-CoV-2 by following strict vigilance, intervention strategies, heightened prevention and control policies, and are in a race to fight COVID-19 by designing appropriate vaccines and therapeutics to keep away any pandemic situation which may arise otherwise if this virus could not be halted. Although that many aspects, derived from the research, are still to be developed, as is the case that facing the pandemic of COVID-19 many elements in certain age groups, as occurs in pediatricis not year clear 14,98 . Finally, One health approach would play an essential role in combatting COVID-19 as well as such diseases in the future. That is not a magic bullet, but yes, the world needs global solutions to prevent still or mitigate a pandemic 19 .