Int J App Pharm, Vol 12, Issue 5, 2020, 16-28Review Article

COVID-19: EPIDEMIOLOGY, PATHOGENICITY AND GLOBAL UPDATES

MANJINDER SINGH1, MANJU NAGPAL1, VARINDER SINGH1, AMEYA SHARMA1,2, GITIKA ARORA DHINGRA3, PARAMJOT MAMAN4, VIVEK PURI1,2*

1Chitkara College of Pharmacy, Chitkara University, Punjab, India, 2Chitkara University School of Pharmacy, Chitkara University, Himachal Pradesh, India, 3NCRD’s Sterling Institute of Pharmacy, Nerul, Navi Mumbai, India, 4Paraxel International Ltd, Mohali, Punjab, India
Email: vivek.puri@chitkara.edu.in

Received: 25 May 2020, Revised and Accepted: 03 Jul 2020

ABSTRACT

Novel coronavirus (COVID-19) is a highly contagious virus that originated from China and has become a major threat in the current time. Presently, finding an effective treatment strategy for COVID-19 is in infancy. Worldwide, numerous clinical trials employing different treatment strategies (antiviral drugs and vaccines) are in progress to develop an effective therapeutic regimen against COVID-19. Literature related to the epidemiology, mortality, pathogenicity, treatment strategies and clinical data was studied and database was collected using various search engines such as j-gate, google scholar, scihub, pubmed, sciencedirect etc. The present review systematically summarises the published information about epidemiology, various stages of pandemic, mortality, pathogenicity, modes of transmission, clinical characteristics, methods of prevention, ongoing treatment strategies and drugs under clinical trials associated with COVID-19 with a hope to avoid possible threatening of the lives of millions of human beings and provide directions for future studies.

Keywords: COVID-19, Coronavirus, Epidemiology, Pathology, Zoonotic, Prevention and Treatment

© 2020 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
DOI: http://dx.doi.org/10.22159/ijap.2020v12i5.38439. Journal homepage: https://innovareacademics.in/journals/index.php/ijap

Speedy peer review was done as the subject of the manuscript was related with pandemic.

INTRODUCTION

Over the past two decades, coronaviruses (CoVs) have been associated with 99 significant disease outbreaks in East Asia and the Middle East. The MERS (Middle East respiratory syndrome) and SARS (Severe acute respiratory syndrome) and began to emerge in 2002 and 2012. Fig. 1 deliberates the spread of various viral infections with its minimum and maximum rate [1, 2].

Fig. 1: Percentage range of various viral infections spread (self-made)

A novel CoV has become prominent in late 2019 and continued till today. It may impose health threat globally and has become influential in giving the evolved epidemic in China and other areas. Currently, health care professionals and workers are putting efforts worldwide to control the disease outbreaks caused by the novel CoV (originally named 2019-nCoV). It was first identified in Wuhan City, Hubei Province, China, on December 12th 2019 [2-4]. On February 11th 2020, the World Health Organization (WHO) announced the official designation for this current CoV associated disease to be “COVID-19”. Corona means crown, the well-known virus acquired this name from a sharp (spiny) crown of glycoproteins on its surface [5, 6]. The various mammals and birds were typically infected by this RNA virus. The primary cluster of patients were found to be connected with the Wuhan’s huanan South China seafood market [7, 8]. CoVs belong to the family Coronaviridae (subfamily Coronavirinae), the members of which infect a broad range of hosts, producing symptoms and diseases ranging from a common cold to severe and ultimately fatal illnesses such as SARS, MERS, and as of present, COVID-19 breakthrough to respiratory diseases such as ARDS (acute respiratory distress syndrome), pneumonia and multi-organ failure. Countless people did not show any symptoms [9, 10]. Till now, globally 55,00,679 total cases of COVID-19 were reported, out of which 28,51,888 (52%) were found to be active, 3,46,721 (6%) patients were died and 23,02,070 (42%) were recovered as depicted in fig. 2. Favourably, infants have been intermittently affected without any death loss. COVID-19 has represented a high negative impact on the economy of China as well as a few other nations. The lessons from such earlier threats of SARS, MERS and of the current COVID-19 situations need to be kept in mind for active strategy planning to counter such emerging and zoonotic pathogens that could pose pandemic threats while putting human lives at bay [11, 12].

Fig. 2: COVID-19 cases, recoveries, deaths worldwide as of May 24, 2020 (self-made)

The SARS-CoV-2 is an envelope, spherical shape, single-stranded plus sense RNA (Ribonucleic acid) virus with helical symmetry belonging to beta coronaviruses of Coronaviridae. 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. 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 (Severe acute respiratory syndrome coronavirus-2) producing COVID-19 in humans has its origin from bats as it acted as natural ancestral host. Fig. 3 shows various strains of coronaviruses affecting human population till date [13-16].

Fig. 3: Various strains of corona virus (self-made)

Epidemiology

The novel coronavirus (2019-nCov) has 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). The virus, SARS-CoV-2 was named by the ICTV (International Committee on Taxonomy of Viruses), and the disease was mentioned as COVID-19 (Coronavirus Disease-19) [17, 18]. In December 2019, many pneumonia cases clustered in Wuhan city were reported and searches for the source have shown Huanan Seafood Market as the origin [19, 20]. The first case of the COVID-19 epidemic was discovered with unexplained pneumonia on December 12, 2019, and 27 viral pneumonia cases with seven being severe, were officially announced on December 31, 2019 [21]. The 515 environment samples were collected from the patients related to businesses and their neighbours on January 1st of 2020 and delivered immediately for testing to medical laboratory centers such as IVD (Institute of Viral Disease), CCDC (Chinese Center for Disease Control and Prevention). Furthermore, 70 more samples were collected on January 12th 2020 from the seafood market (wildlife shops) for evaluation. These tests indicated that out of 585 samples, 33 samples contained 2019-nCoV, suggesting that virus was initiated from animals vended in the market of seafood. On 22nd January, 2020, novel CoV has been declared to be originated from bats and belonged to group 2 of β-coronavirus that contains SARS-CoV. Though SARS-CoV and COVID-19 are of the same β-coronavirus subgroup family. Their similarity at genome level is 70%, and the novel group has been found to show genetic differences from SARS-CoV. This virus outbreak has been raised during the Spring Festival in China as SARS epidemic occurred. Traditionally, spring festival is the most famous festival in China and approximately 3 billion people travel country widely. These conditions begun favourable circumstances for the spread of this extremely contagious virus and severe difficulties in prevention and control of the epidemic [22, 23]. This virus can infect all age individuals. As per Bin Cao, the Executive Vice President of the Institute of Respiratory Medicine, CAMS (Chinese Academy of Medical Sciences), around 72% confirmed infectious patients are of more than 40 y old among them 64% are only males. Around 40% of the patients also suffering from diabetes and high blood pressure.

Early detection, diagnose, quarantine and treatment are effective preventive measurements which inhibit human-to-human transmission and reduces secondary infections that develops amidst close contacts and health professionals [24, 25].

Besides affecting China (mainly), SARS-CoV-2 (COVID-19) has now spread in the whole world. Out of cumulative 28,51,888 active cases, 3,46,721 human deaths and 23,02,070 recovered have been documented as of May 24, 2020. Currently, the virus has been spread to more than 200 countries and territories with a number of confirmed cases. There are top 10 countries which are highly affected by stage-IV (epidemic) namely USA (16,86,436), Brazil (3,65,213), Russia (3,44,481), Spain (2,82,852), UK (2,59,559), Italy (2,29,858), France (1,82,584), Germany (1,80,328), Turkey (1,56,827) and India (1,38,917). Fig. 4 depicts the worldwide spread of novel coronavirus. In spite of various strategies issued by numerous health agencies to combat the transmission of COVID-19, the growing number of infected patients globally remains the matter of concern as shown in fig. 5.

Fig. 4: Diagrammatic representation of worldwide novel corona virus spread (self-made)

Stages of COVID-19

There are four stages of COVID includes one who has travelled to foreign countries, which is already virus-hit and return to his/her origin country. In the second, the person has been in contact with the patient having travel history. After that, the transmission occurs when a patient was not exposed to corona infected person or the one who has no travel history to any virus hit country. The larger areas are affected when this transmission occurs. Last stage is the worst stage in which the disease grabs an epidemic shape with no endpoint.

Table 1: Worldwide novel coronavirus spread, recoveries, deaths as of May 24, 2020

Country Active cases Recovered Deaths Total cases Reference
Afghanistan 9,289 1,075 218 10,582 [11, 12]
Albania 177 789 32 998 [11, 12]
Algeria 2,922 4,784 600 8,306 [11, 12]
Andorra 58 653 51 762 [11, 12]
Angola 47 18 4 69 [11, 12]
Anguilla 0 3 3 [11, 12]
Antigua and Barbuda 3 19 3 25 [11, 12]
Argentina 7,892 3,732 452 12,076 [11, 12]
Armenia 3,516 3,064 81 6,661 [11, 12]
Aruba 3 95 3 101 [11, 12]
Australia 481 6,531 102 7,114 [11, 12]
Austria 800 15,063 640 16,503 [11, 12]
Azerbaijan 1,466 2,607 49 4,122 [11, 12]
Bahamas 43 46 11 100 [11, 12]
Bahrain 4,537 4,587 14 9,138 [11, 12]
Bangladesh 26,229 6,901 480 33,610 [11, 12]
Barbados 15 70 7 92 [11, 12]
Belarus 21,844 14,155 199 36,198 [11, 12]
Belgium 32,540 15,272 9,280 57,092 [11, 12]
Belize 0 16 2 18 [11, 12]
Benin 106 82 3 191 [11, 12]
Bermuda 43 81 9 133 [11, 12]
Bhutan 21 6 27 [11, 12]
Bolivia 5,384 629 250 6,263 [11, 12]
Bosnia and Herzegovina 577 1,680 144 2,401 [11, 12]
Botswana 15 19 1 35 [11, 12]
Brazil 1,92,556 1,49,911 22,746 3,65,213 [11, 12]
British Virgin Islands 1 6 1 8 [11, 12]
Brunei 3 137 1 141 [11, 12]
Bulgaria 1,457 840 130 2,427 [11, 12]
Burkina Faso 90 672 52 814 [11, 12]
Burundi 21 20 1 42 [11, 12]
Cabo Verde 222 155 3 380 [11, 12]
Cambodia 2 122 124 [11, 12]
Cameroon 2,860 1,865 165 4,890 [11, 12]
Canada 34,290 43,985 6,424 84,699 [11, 12]
CAR 581 22 1 604 [11, 12]
Caribbean Netherlands 0 6 6 [11, 12]
Cayman Islands 67 61 1 129 [11, 12]
Chad 400 215 60 675 [11, 12]
Channel Islands -4 517 45 558 [11, 12]
Chile 40,236 28,148 718 69,102 [11, 12]
China 83 78,268 4,634 82,985 [11, 12]
Colombia 15,432 5,016 727 21,175 [11, 12]
Comoros 65 21 1 87 [11, 12]
Congo 324 147 16 487 [11, 12]
Costa Rica 300 620 10 930 [11, 12]
Croatia 118 2,027 99 2,244 [11, 12]
Cuba 170 1,689 82 1,941 [11, 12]
Curaçao 2 14 1 17 [11, 12]
Cyprus 324 594 17 935 [11, 12]
Czechia 2,562 6,078 315 8,955 [11, 12]
Denmark 898 9,900 562 11,360 [11, 12]
Diamond Princess 48 651 13 712 [11, 12]
Djibouti 1,196 1,064 10 2,270 [11, 12]
Dominica 0 16 16 [11, 12]
Dominican Republic 6,210 8,133 458 14,801 [11, 12]
DRC 1,761 317 63 2,141 [11, 12]
Ecuador 30,088 3,560 3,108 36,756 [11, 12]
Egypt 11,694 4,807 764 17,265 [11, 12]
El Salvador 1,247 633 35 1,915 [11, 12]
Equatorial Guinea 784 165 11 960 [11, 12]
Eritrea 0 39 39 [11, 12]
Estonia 227 1,532 64 1,823 [11, 12]
Eswatini 92 156 2 250 [11, 12]
Ethiopia 425 152 5 582 [11, 12]
Faeroe Islands 0 187 187 [11, 12]
Falkland Islands 0 13 13 [11, 12]
Fiji 3 15 18 [11, 12]
Finland 1,472 4,800 307 6,579 [11, 12]
France 89,600 64,617 28,367 1,82,584 [11, 12]
French Guiana 182 145 1 328 [11, 12]
French Polynesia 0 60 60 [11, 12]
Gabon 1,463 459 12 1,934 [11, 12]
Gambia 11 13 1 25 [11, 12]
Georgia 196 522 12 730 [11, 12]
Germany 11,657 1,60,300 8,371 1,80,328 [11, 12]
Ghana 4,653 1,998 32 6,683 [11, 12]
Gibraltar 7 147 154 [11, 12]
Greece 1,333 1,374 171 2,878 [11, 12]
Greenland 1 11 12 [11, 12]
Grenada 5 17 22 [11, 12]
Guadeloupe 32 115 14 161 [11, 12]
Guatemala 3,108 258 58 3,424 [11, 12]
Guinea 1,582 1,673 20 3,275 [11, 12]
Guinea-Bissau 1,066 42 6 1,114 [11, 12]
Guyana 63 62 10 135 [11, 12]
Haiti 909 22 27 958 [11, 12]
Honduras 3,302 468 180 3,950 [11, 12]
Hong Kong 32 1,030 4 1,066 [11, 12]
Hungary 1,565 1,690 486 3,741 [11, 12]
Iceland 3 1,791 10 1,804 [11, 12]
India 77,172 57,721 4,024 1,38,917 [11, 12]
Indonesia 15,497 5,402 1,372 22,271 [11, 12]
Iran 22,483 1,05,801 7,417 1,35,701 [11, 12]
Iraq 1,571 2,738 160 4,469 [11, 12]
Ireland 1,971 21,060 1,608 24,639 [11, 12]
Isle of Man 9 303 24 336 [11, 12]
Israel 2,285 14,153 279 16,717 [11, 12]
Italy 56,594 1,40,479 32,785 2,29,858 [11, 12]
Ivory Coast 1,127 1,219 30 2,376 [11, 12]
Jamaica 332 211 9 552 [11, 12]
Japan 2,317 13,413 820 16,550 [11, 12]
Jordan 228 471 9 708 [11, 12]
Kazakhstan 4,144 4,352 35 8,531 [11, 12]
Kenya 780 383 51 1,214 [11, 12]
Kuwait 15,029 6,117 156 21,302 [11, 12]
Kyrgyzstan 425 992 16 1,433 [11, 12]
Laos 5 14 19 [11, 12]
Latvia 313 712 22 1,047 [11, 12]
Lebanon 400 688 26 1,114 [11, 12]
Lesotho 2 2 [11, 12]
Liberia 100 139 26 265 [11, 12]
Libya 33 39 3 75 [11, 12]
Liechtenstein 26 55 1 82 [11, 12]
Lithuania 422 1,138 63 1,623 [11, 12]
Luxembourg 115 3,767 110 3,992 [11, 12]
Macao 0 45 45 [11, 12]
Madagascar 383 142 2 527 [11, 12]
Malawi 46 33 4 83 [11, 12]
Malaysia 1,185 5,945 115 7,245 [11, 12]
Maldives 1,223 144 4 1,371 [11, 12]
Mali 368 597 65 1,030 [11, 12]
Malta 128 476 6 610 [11, 12]
Martinique 92 91 14 197 [11, 12]
Mauritania 216 15 6 237 [11, 12]
Mauritius 2 322 10 334 [11, 12]
Mayotte 673 894 20 1,587 [11, 12]
Mexico 13,802 47,424 7,394 68,620 [11, 12]
Moldova 3,130 3,713 250 7,093 [11, 12]
Monaco 4 90 4 98 [11, 12]
Mongolia 108 33 141 [11, 12]
Montenegro 0 315 9 324 [11, 12]
Montserrat 0 10 1 11 [11, 12]
Morocco 2,531 4,703 199 7,433 [11, 12]
Mozambique 143 51 194 [11, 12]
MS Zaandam 7 2 9 [11, 12]
Myanmar 73 122 6 201 [11, 12]
Namibia 7 14 21 [11, 12]
Nepal 513 87 3 603 [11, 12]
Netherlands N/A N/A 5,822 45,236 [11, 12]
New Caledonia 0 18 18 [11, 12]
New Zealand 27 1,456 21 1,504 [11, 12]
Nicaragua 63 199 17 279 [11, 12]
Niger 101 783 61 945 [11, 12]
Nigeria 5,350 2,263 226 7,839 [11, 12]
North Macedonia 443 1,422 113 1,978 [11, 12]
Norway 390 7,727 235 8,352 [11, 12]
Oman 5,800 1,933 37 7,770 [11, 12]
Pakistan 36,270 17,198 1,133 54,601 [11, 12]
Palestine 63 357 3 423 [11, 12]
Panama 4,341 6,279 306 10,926 [11, 12]
Papua New Guinea 0 8 8 [11, 12]
Paraguay 544 307 11 862 [11, 12]
Peru 66,708 49,795 3,456 1,19,959 [11, 12]
Philippines 9,918 3,249 868 14,035 [11, 12]
Poland 11,136 9,194 996 21,326 [11, 12]
Portugal 11,758 17,549 1,316 30,623 [11, 12]
Qatar 34,521 9,170 23 43,714 [11, 12]
Réunion 5,486 11,399 1,185 18,070 [11, 12]
Romania 2,27,641 1,13,299 3,541 3,44,481 [11, 12]
Russia 90 237 327 [11, 12]
Rwanda 40 411 1 452 [11, 12]
S. Korea 713 10,226 267 11,206 [11, 12]
Saint Kitts and Nevis 0 15 15 [11, 12]
Saint Lucia 0 18 18 [11, 12]
Saint Martin 4 33 3 40 [11, 12]
Saint Pierre Miquelon 0 1 1 [11, 12]
San Marino 357 266 42 665 [11, 12]
Sao Tome and Principe 239 4 8 251 [11, 12]
Saudi Arabia 28,650 43,520 390 72,560 [11, 12]
Senegal 1,556 1,456 35 3,047 [11, 12]
Serbia 5,064 5,857 238 11,159 [11, 12]
Seychelles 0 11 11 [11, 12]
Sierra Leone 426 241 40 707 [11, 12]
Singapore 16,717 14,876 23 31,616 [11, 12]
Sint Maarten 3 59 15 77 [11, 12]
Slovakia 180 1,301 28 1,509 [11, 12]
Slovenia 21 1,340 107 1,468 [11, 12]
Somalia 1,329 204 61 1,594 [11, 12]
South Africa 11,054 11,100 429 22,583 [11, 12]
South Sudan 641 6 8 655 [11, 12]
Spain 57,142 1,96,958 28,752 2,82,852 [11, 12]
Sri Lanka 458 674 9 1,141 [11, 12]
St. Barth 0 6 6 [11, 12]
St. Vincent Grenadines 4 14 18 [11, 12]
Sudan 3,197 458 165 3,820 [11, 12]
Suriname 1 9 1 11 [11, 12]
Sweden 24,490 4,971 3,998 33,459 [11, 12]
Switzerland 730 28,100 1,906 30,736 [11, 12]
Syria 41 41 4 86 [11, 12]
Taiwan 20 414 7 441 [11, 12]
Tajikistan 1,582 1,301 46 2,929 [11, 12]
Tanzania 305 183 21 509 [11, 12]
Thailand 63 2,921 56 3,040 [11, 12]
Timor-Leste 0 24 24 [11, 12]
Togo 228 141 12 381 [11, 12]
Trinidad and Tobago 0 108 8 116 [11, 12]
Tunisia 86 917 48 1,051 [11, 12]
Turkey 33,793 1,18,694 4,340 1,56,827 [11, 12]
Turks and Caicos 1 10 1 12 [11, 12]
UAE 14,184 15,056 245 29,485 [11, 12]
Uganda 130 68 198 [11, 12]
UK N/A N/A 36,793 2,59,559 [11, 12]
Ukraine 13,261 7,108 617 20,986 [11, 12]
Uruguay 129 618 22 769 [11, 12]
USA 11,35,434 4,51,702 99,300 16,86,436 [11, 12]
Uzbekistan 586 2,565 13 3,164 [11, 12]
Vatican City 10 2 12 [11, 12]
Venezuela 849 262 10 1,121 [11, 12]
Vietnam 58 267 325 [11, 12]
Western Sahara 3 6 9 [11, 12]
Yemen 170 10 42 222 [11, 12]
Zambia 577 336 7 920 [11, 12]
Zimbabwe 27 25 4 56 [11, 12]

Fig. 5: Cumulative cases of COVID-19 worldwide from december 31, 2019 to May 24, 2020 (self made)

COVID-19 cases worldwide

As of May 24, 2020, the outbreak of the coronavirus disease (COVID-19) has been confirmed in around 203 countries or territories. The virus had infected 55,00,679 people worldwide, and around 3,46,721 people were died because of this viral infection. The most severely affected countries include the USA (16,86,436), Brazil (3,65,213), Russia (3,44,481), Spain (2,82,852) and UK (2,59,559) [11, 12]. Complete worldwide country wise data of total coronavirus (COVID-19) active cases, recoveries and deaths till May 24, 2020 is illustrated in table 1.

Pathogenicity of COVID-19

Structure of coronavirus

Most common viruses can be genetically divided into two types. One type of viruses has DNA (Deoxyribonucleic acid) as genetic material and the other type have RNA as genetic material. The RNA viruses can further divided into two types: first type contains ssRNA (Single stranded ribonucleic acid) and other type contains dsRNA (Double-stranded ribonucleic acid) as genetic material [26-28].

In current scenario, the most dangerous and recently discovered virus (2019 origin) is Coronavirus, which is one such example of ssRNA viruses. The RNA present in these Coronoavirus mainly consists of RNA Synthesis materials, nanostructural polyproteins, viral polymerase and the genome. The genome of this RNA virus mainly consists of four basic structural proteins like envelop, spike, nucleocapsid and membrane. Such coronavirus may also contain some other types of helper proteins. The length of these coronaviruses is highly dependent on the nanostructuralpolyproteins, viral polymerase and the genome present in the virus [29, 30]. There are two most widely known strains, named as SARS and MERS, which have caused more than 800 deaths. The size of the virus varies as per the diameter between 80-120 nm. The structure of SARS CoV-2 is shown in fig. 6.

Fig. 6: Structure of novel SARS-Cov2 (self-made)

Basically, coronaviruses are divided into four categories α-coronavirus (α-COV), β-coronavirus (β-COV), δ-coronavirus (δ-COV), γ-coronavirus (γ-COV) [8, 31, 32]. Alpha and Beta coronavirus are mainly related with infections in mammals, whereas Gamma-and Delta coronavirus predominantly (not entirely) infect birds [33]. The examples of alpha coronaviruses are human coronavirus-229E and virus-NL63 and of beta coronaviruses are human coronavirus-OC43 and virus-HKU1 and these are recognized human pathogens and are accountable for the worldwide occurrence of the common cold in humans [34, 35]. It is evident from the study that up to 20% of tests in humans accompanied with respiratory disease have an acute infection with these viruses. Human Corona Virus-229E was first to extricate in 1967 and only 65% nucleotide identity was shared with another human alpha coronavirus, Human Corona Virus-NL63 was first isolated in 2003 from a child (7 mo) suffering from respiratory diseases (bronchiolitis and conjunctivitis) [36]. However, the majority of infections with Human Corona Viruses cause only mild respiratory tract illness. Human Corona Viruses are responsible for onset of disease, especially, but not completely in infants and immune-suppressed patients. Coronavirus not only occurs in the respiratory tract but can be detected in stool [22, 37].

Multiplication/replication of virus in host body

When the coronavirus enters the host body then it gradually multiply and shows its genomic adaptation and hence is able to survive in the host body. Each viral cell shows the different types of genomic adaptation as compared to other virus. Various steps by which the virus expands in the body are mentioned below [38-44].

Firstly, there is an interaction between sensitive human cells with spike protein of the virus takes place. Afterward, it enters into sensitive human cells and Corona virus Genome encoding occurs. This accelerates gene expression in the virus; these genes encodes functional proteins, which helps in accommodating Corona Viruses to their human host. Such type of genome changes resulting from recombination, gene exchange, gene insertion, or deletion are very frequent among CoronaViruses and this further will take place in future outbreaks as in past epidemics. As a result of the studies, the Corona Virus subfamily is rapidly expanding with new generation sequencing applications that improves the detection and definition of novel Corona Virus species. In conclusion, Corona Virus classification is continually changing. According to the most recent classification of The International Committee on Taxonomy of Viruses (ICTV), there are four genera of thirty eight unique species of this virus as given in fig. 7.

Fig. 7: Replication of corona virus (self made)

After entering the cell, the viral RNA manifests itself in the cytoplasm. Genomic RNA in the coronavirus is encapsulated and polyadenylated. This RNA encodes various structural and non-structural polypeptide genes. These polyproteins are split by proteases that exhibit chymotrypsin-like activity. The resulting complex drives/increases more RNA production by both the processes (replication and transcription). Full-length RNA copies of the genomes are massively produced during process of replication. Additionally, it is used as a template for RNA genomes of full length. A subset of 7-9 sub-genomic RNAs are produced during transcription and encoding of all structural proteins occursby discontinuous transcription. Viral nucleo-capsids are combined from RNA (genomic) and in the cytoplasm (R-protein) and then are budded into endoplasmic reticulum (ER) lumen, by the process of exocytosis, the new virions are escaped out from the diseased cell and can contaminate various organs like liver, kidney intestines, T lymphocytes etc., as well as the respiratory system.

Risk factors of novel coronavirus

Risk factors for COVID-19 (Human Corona Virus-2019) are still largely unknown; however, it is believed that the virus is transmitted to humans via contaminated live animals (snakes, civet cats). All three β-coronaviruses were developed via zoonotic communication. Risk factors for zoonotic transmission of MERS and SARS was direct contact through infectious animals. The suspected reservoir hosts are currently believed to be bats, similar to the SARS epidemic [45-53].

First evidence-animals to human

It is based on the numerous infected people that were barren to market of animals in Wuhan. In the market, the alive animals are sold daily; and was found that this was a zoonotic origin of the COVID-19. WMHC (Wuhan Municipal Health Commission) recorded the 27 positive cases of pneumonia on 12th December, 2019 and out of them, 7 cases were critical. Most of the patients were having recent history of Seafood Wholesale Market in Wuhan. In this market, various animals and reptiles such as bats, snake and poultry animals were also traded. This was known to be main cause of origin of new type of coronavirus, this pandemic is growing very faster and provisionally called as COVID-19 by WHO (World Health Organization).

Second evidence-snakes to humans

Various efforts were made in search of intermediate carriers and reservoir host. Initial reports were resulted that two species of snakes are reservoir of the COVID-19 possibly. Although, no evidence was found of coronavirus reservoirs other than bird and mammals.

Third evidence-mammals (bats) to humans

The genomic sequence of this COVID-19 is 88% identical with SARS, which is a bat originated disease indicates that the mammals are mostly linked between COVID-19 and humans.

Fourth evidence-human to human

Many cases have been reported and suggested that transmission between people (person to person) spreads COVID-19 infection. It is anticipated by the cases occurred within families and among the people who did not explore animal market in Wuhan. Primarily, person-to-person transmission takes place through direct contact or by coughing or sneezing (droplet spreading) from an infected individual.

Fifth evidence-human mother to child

A small study was conducted on a pregnant women (third trimester) who was infected with coronavirus. There was no evidence that the transmission occurred from mother to child. Although all pregnant mothers went through surgery (caesarean), it remains unclear whether transmission can takes place during normal vaginal delivery. Pregnant mothers are comparatively more susceptible to this infection so this study is important.

Modes of transmission

Initially, it was presumed that COVID-19 got transmitted from the bat (due to similar genome sequence) to humans via an unknown intermediate [54, 55]. However, subsequent cases showed that human to human transmission of COVID-19 is more viable [56]. Since COVID-19 has become a pandemic and international health emergency, clearly, it is evident that there is a lack of understanding the various means of COVID-19 transmission [57, 58]. Although, the COVID-19 transmission modes have already been discussed by various national and international agencies such as WHO and National Centre for Disease Control, Directorate General of Health Services Ministry of Health and Family Welfare, Government of India, the increasing number of COVID-19 patients showed that people are finding hard to understand this information and difficult to adhere. To control the further spread of COVID-19, people should be informed about various methods by which this contagious disease can transmit [59, 60]. Besides common people, it is very important for health care providers to know COVID-19 dissemination routes as they are constantly dealing with COVID-19 infected patients [61]. Fig. 8 shows potential transmission routes for novel coronavirus (COVID-19). A person may develop COVID-19 infection by:

Fig. 8: Potential transmission route for novel coronavirus (COVID-19) (self-made)

Contact transmission

By making a direct contact with contaminated animate (human or animals) and/or inanimate objects (water, food, stethoscope or thermometer) COVID-19 can spread [55, 59]. It can also be indirectly transmitted via an intermediate person or object e.g. without maintaining proper hand hygiene in between touching an infected body site of a patient and then a normal person [62, 63]. Sometimes, it may spread by contacting asymptomatic carriers as the infected person may not be aware of harbouring the virus [64, 65]. The direct transmission was reported in an observational study from Zhejiang province, where 62 patients were reported to develop laboratory positive COV-2 infection via direct exposure to already confirm COVID-19 infected individuals [66].

Droplet transmission

Chances of COVID-19 infection are more likely to occur in people who are in the vicinity of 1 metre to infected individual as droplets (containing virus) released by an infected person via coughing and sneezing (excretions/secretions of the gastrointestinal tract, respiratory tract, blood or any other body fluid) may be inhaled by healthy individuals [67]. Even talking with an infected person may spread the CVOID-19 [68].

Airborne dissemination

Very small airborne particles (containing virus) that can travel via air currents which can be inhaled by susceptible individuals and thus may contribute to COVID-19 transmission. Transmission under specific settings such as bronchoscopy, cardio pulmonary resuscitation, manual ventilation before intubation, endotracheal intubation and tracheostomy which lead to the production of aerosols may also possible (WHO report dated 27 March, 2020). A person with compromised immunity such as aged people, pregnant women, and persons taking immunosuppressive and chemotherapeutic agents may have higher chances to develop COVID-19 infection [69].

Sign and symptoms

COVID-19 is a respiratory viral infection which leads to the development of mild to moderate clinically diagnosed symptoms after 2-14 d of its exposure [70]. As suggested by WHO, usually, the symptoms get resolve without any special treatment; however, person above the age of 60 frequently requires hospitalization and special care [71]. WHO has reported the development of fever, dry cough and tiredness as common diagnostic characters along with other symptoms including aches, breathlessness, runny nose, sore throat and diarrhoea for COVID-19 infection. The clinical characteristics varied from patient to patient and 138 hospitalized patients showed the development of fever, fatigue, dry cough, anorexia, myalgia, dyspnea, expectoration, pharyngalgia, diarrhea, nausea, dizziness, vomiting and abdominal pain [72]. These symptoms were consistent with another COVID-19 patients [18, 73, 74]. Also, the computed tomography scans showed bilateral lung ground-glass opacity in the majority of the cases [75]. The various symptoms are shown diagrammatically in fig. 9.

Fig. 9: Symptoms of coronavirus (self-made)

Based on the severity of the disease, the report from Chinese Center for Disease Control and Prevention [76] has divided the clinical manifestations of COVID-19 into:

Mild disease

These symptoms were found in 81% of the clinical cases (out of 72314 total cases). This included non-pneumonia and mild pneumonia symptoms.

Severe disease

These symptoms were diagnosed in 14% of the cases (out of 72314 total cases). The manifestations included were dyspnea, impaired respiration (frequency ≥30/min), lung infiltrates >50%, blood oxygen saturation ≤93% and partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300 within 24 to 48 h.

Critical disease

These symptoms include septic shock, respiratory failure, and multiple organ dysfunction constitutes only 5% of the total COVID-19 cases (out of 72314 total cases).

Treatment of corona virus-2019

There is no antiviral treatment specifically recommended for COVID-19 till date and there is no vaccine available currently. The preventive treatment available is symptomatic and oxygenated therapy which possesses a major treatment effects in patients with severe infection. Ventilation (mechanical) is an important respiratory failure while hemodynamic support system is an important for the management of septic shock. 

On January 28, 2020, the WHO released a document summarizing WHO guidelines and scientific evidences were derived from the treatment of previous epidemics from (Human coronavirus) HCoVs. This document addresses measure for recognizing and sorting patients with severe acute respiratory disease, strategies for infection prevention and control, early supportive therapy and monitoring, a guideline for laboratory diagnosis, management of respiratory failure and ARDS, management of septic shock, prevention of complications, treatments, and considerations for pregnant patients.

Amidst other therapeutic tactics, the systemic corticosteroids are not recommended for the treatment of pneumonia (viral) and respiratory disease such as acute respiratory distress syndrome (ARDS). Additionally, unselective antibiotic administration should be avoided, whilst some centers proposed it for treating Covid-19. As per WHO, FDA and Centers for Disease Control and Prevention (CDC), there is no specific vaccine or medication that is approved or proven to treat COVID-19 infection. For individuals having mild symptoms are suggested to stay home quarantine. As of 30th March 2020, due to lack of specific treatment, the major focus for treating the hospitalised COVID-19 patients is based on their clinical manifestation. Based on the invitro and/or preclinical studies, several clinical trials are under progress to evaluate the efficacy of anti-viral drugs in COVID-19 infected patients. Some guidelines have been provided for Covid-19 related to Prevention, Diagnosis and Treatment issued and approved by the National Health Commission (NHC) of the People’s Republic of China for the treatment (tentative) of COVID-19 suggests the use of different drugs with their dose strengths against COVID 19 as shown in table 2 [77-79].

Table 2: List of anti-viral drugs to treat COVID-19 (as per the National Health Commission (NHC) of the People’s Republic of China)

S. No. Drug Route of administration Dose Treatment duration Reference
Lopinavir/Ritonavir Oral 200 mg/50 mg/capsule, 2 capsules twice daily Maximum 10 d [79]
IFN-α Vapour inhalation 5 million U twice daily Maximum 10 d [79]
Chloroquine phosphate Oral 500 mg twice a day Maximum 10 d [79]
Ribavirin Intravenous 500 mg twice or thrice a day in combination with lopinavir/ritonavir or IFN-α Maximum 10 d [79]
Arbidol Oral 200 mg 3 times a day Maximum 10 d [79]

As of 3rd May, 2020, on the basis of subsequent uncontrolled clinical trials, Ministry of Health and Family Welfare, Directorate General of Health Services, Government of India issued some important guidelines (clinical) for the management of COVID-19. It recommends the use of hydroxychloroquine (200 mg twice a day for 4 d) and azithromycin (500 mg once a day for 5 d) combination for the treatment of patients with severe COVID19 clinical manifestation. These guidelines were revised on 31st March, 2020. Earlier The Ministry of Health and family Welfare recommended the use of combination (Lopinavir/ritonavir) at same doses as mentioned in table 1 for 7 or 14 d against COVID-19 in laboratory-confirmed severe cases. However, this drug combination poses side-effects that sometimes lead to its discontinuation and, thus, limits the usage [80].

So far reports has evidenced the use of some antiviral drugs that may have potential thus may play an important role in managing COVID-19 infection [22]. A brief about the mode of action of these drugs is given below:

Chloroquine

An anti-malarial and autoimmune disease drug (Chloroquine), which is recently reported as a potential broad-spectrum antiviral drug. It was found that chloroquine effectively suppresses and clinically applicable against recently emerged novel coronavirus (COVID-19) [22, 81-84].

Lopinavir-ritonavir

A protease inhibitor, the combination of these drugs easily interfere with replication and HIV synthesis (Human immunodeficiency virus). It is highly responsible for the production of virus particles (immature and non-infectious). It is evident that the combination of Lopinavir-Ritonavir easily binds to the enzyme (endopeptidase C30) of SARS-CoV2 protease. Several reports are evident that lopinavir-ritonavir alone treated or in combination with other antiviral drugs improved the results of severe patients with SARS or MERS [22, 85-90].

Remdesivir

A nucleoside analogue GS-5734 named remdesivir was first revealed to inhibit SARS-CoV and MERS-CoV. Recently, in vitro study reported that remdesivir at low-micromolar concentration; it potently blocked SARS-CoV2 infection and high selectivity index (SI). Moreover, it is beneficial for the treatment of COVID-19 pneumonia [22, 91, 92].

Hydroxychloroquine

Hydroxychloroquine sulfate, a Chloroquine derivative, was first synthesized in 1946 by attaching a hydroxyl group into Chloroquine. It was experimentally demonstrated in 4 animals and resulted to be much less toxic (~40%) as compared to Chloroquine. Hydroxychloroquine is widely available for the treatment of autoimmune diseases (systemic lupus erythematosus and rheumatoid arthritis). Clinically, it was investigated and found that the higher concentrations of cytokines were observed in the plasma of critically infected patients with SARS-CoV-2. It was suggesting that cytokines were associated with disease extremity. Hydroxychloroquine is a safer and an effective anti-inflammatory drug as compared to direct antiviral activity as it decreases the cytokines production [22, 93-95].

Tocilizumab

It can bind interleukins (sIL-6R) which are soluble and membrane bound (IL-6R), which further inhibits signal transduction. Currently, it used in rheumatoid arthritis and immune-modulating agents are used in some protocols. An interleukins (IL-6) blocker; Tocilizumab is used to treat patients with severe and critical COVID-19. Clinical data exhibited that symptoms and changes in CT opacity were immediately improved with administration of tocilizumab. Therefore, it could be a suitable and efficient therapeutic treatment of COVID-19 [22, 96].

Simultaneously various major pharmaceutical companies are working on the development of vaccines to combat current COVID-19.

Drugs under clinical trials

Various companies have initiated the clinical trials of possible drug candidates, which would be effective in managing COVID-19 infection, as shown in table 3 [97].

Table 3: Drugs or vaccines against COVID-19 under clinical trials

Organization Target Clinical trial phase Reference
Sanofi Plaquenil Preclinical [97]
Pfizer New mRNA vaccine Preclinical [97]
GohnsonandGohnson Covid-19 vaccine Preclinical [97]
Regeneron Monoclonal antibody therapy Preclinical [97]
Takeda Polyclonal antibody therapy Preclinical [97]
Hoth therapeutics Self-assembling vaccine (SAV) Preclinical [97]
Arcturus therapeutics Covid-19 vaccine Preclinical [97]
GSK Covid-19 vaccine Preclinical [97]
Inovio Covid-19 vaccine Preclinical [97]
CanSinoBIO Covid-19 vaccine Phase-I [97]
Moderna mRNA-1273 Phase-I [97]
Vaccitech Iopinavir/ritonavir combination Phase-IIb [97]
Gilead Remdesivir Phase-III [97]

Preventive measures for novel coronavirus

Till date there is no vaccination available against COVID-19. For now, the most common term used by the various Government Health Authorities is “Prevention Is Better than Cure”. Some preventive measures have been suggested by the WHO which will help in diminishing the spread of coronavirus. Some of these preventive advisory methods are mentioned which includes social distancing, abstain a close contact with a person who is suffering from fever and cough, maintain a distance of at least 1 meter from a person who is coughing or sneezing, refrain touching body cavities such as eyes, nose, mouth, use N95 masks, eye-protective (goggles), disposable gown raincoat (long sleeved), disposable socks and gloves, dispose tissue safely after coughing or sneezing, frequently cleaning and sanitizing the touched objects and surfaces with the help of spray or wipe. The Centers for Disease Control (CDC) states that wearing a mask is not important unless the healthy individual is caring an infected person. It also recommended that only infected person should wear masks to prevent the spread, washing hands frequently with soap and water for 20 seconds, use of sanitizer (alcohol based) if soap and water is not available., immediately seek medical surveillance, if one is suffering from fever and cough, travel advisory is surely set out by the advisory, during incubation period, preoxygenation for 5 min should be executed with the help of continuous positive airway pressure method [98, 99]. Till now there is no vaccine against COVID-19 but social distancing is the only method to break the transmission chain of this virus (fig. 10).

Fig. 10: Diagrammatic representation of social distancing and its effectiveness (self made)

Future prospectives

Based on the experience of COVID-19 pandemic, effective measures should be developed to counter the possible future zoonotic CoV epidemic. In this context, extensive studies including screening, isolation and identification on viruses, which may be associated with such outbreaks, are required. Advanced studies in development of antiviral agents against such emerging viral infections are certainly required. Till date, various control measures as notified by National and International health agencies should be taken by the public to further prevent the spread of COVID-19.

CONCLUSION

As of now, due to lack of proven effective treatment, social distancing is the only appropriate mean to avoid the spread of COVID-19 infection. Developing an effective treatment for COVID-19 is primarily important and the research strategies focusing on the designing and evaluating such therapeutic regimens should be conducted at earliest. Even the various Clinical Trial authorities should consider these studies under fast-track program wherever applicable to develop the drug and subsequently halt the COVID-19 pandemic.

ACKNOWLEDGEMENT

The authors are thankful to Dr. Madhu Chitkara, Vice-Chancellor, Chitkara University; Dr. Ashok Chitkara, Chancellor, Chitkara University; Dr. Sandeep Arora, Director, Chitkara College of Pharmacy for providing necessary facilities and support.

FUNDING

Nil

AUTHORS CONTRIBUTIONS

All the authors have contributed equally.

CONFLICT OF INTERESTS

The authors declared no conflicts of interest.

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