DOI:10.30919/es8d1009

Received: 11 May 2020
Revised: 24 May 2020
Accepted: 26 May 2020
Published online: 26 May 2020

 A Recapitulation of Virology, Modes of Dissemination, Diagnosis, Treatment, and Preventive measures of COVID-19: A Review

Viquar S. Shaikh,1 Gulam M. Nazeruddin,2 Yaseen I. Shaikh,2,* Samir H. Bloukh,3 Zehra Edis3 and Habib M. Pathan4

1Department of Chemistry, Nowrosjee Wadia College, Pune - 411 001, India

2Department of Chemistry, AbedaInamdar Sr. College, Pune - 411 001, India

3College of Pharmacy and Health Science, Ajman University, PO Box 346, Ajman, United Arab Emirates

4Advanced Physics Laboratory, Department of Physics, SavitribaiPhule Pune University, Pune – 411007, India

Email: sheray2k@gmail.com  (Y. I. Shaikh)

Abstract

COVID‐19, which is instigated by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused the pandemic. This disease provoked with its epicenter in China. Belonging to the Coronaviridae family of viruses, it is a new strain of β type of coronavirus. The World Health Organization (WHO) declared its name as ‘SARS‐CoV‐2’. In January 2020, the WHO declared COVID‐19 as the sixth public‐health emergency of international suffering. Lack of etymology, precautionary measures, specified drug or vaccination for this viral infection was the main reason for the epidemic. Hence, there was an extensive need for the scientists throughout the globe to work on it. Some potential inhibitors have been reported to possibly treat COVID‐19 affected patients. Likewise, a new technique, which is the Plasma Therapy, is used in the treatment. In this context, this review aims to summarize the epidemiology, virology, mode of dissemination, diagnosis, treatment, and prevention measures of COVID‐19.

Table of Content

In this review, the key points related to this COVID-19 disease, the most infuriating disease of the 21st century, were discussed.

 

 

 

Keywords: COVID-19; SARS-CoV-2; Virology.


1. Introduction

The family Coronaviridae within the order of Nidovirales comprises the Coronaviruses. The viral coat of those viruses features a spike or S protein. As these viruses showed crown-like structure, they are named as Coronaviruses. Coronaviruses size is around 65-125 nm, this is often the diameter size, and the genetic material is a single-stranded RNA having 26 to 32 kbs.[1] The Coronavirus family is split into 4 subgroups viz., alpha (α), beta (β), gamma (γ), and delta (δ) coronavirus.[2] The viruses cause Severe Acute Respiratory Syndrome (SARS), pathogenic Influenza, and the Middle East Respiratory Syndrome (MERS), which can further cause acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) that results in renal failure and ends up in death.[3] Earlier it has been thought that these viruses only infect animals until the globe noticed the SARS outbreak caused by SARS-CoV in 2002 in Guangdong, China.[4] After a decade, another pathogenic coronavirus, called Middle East respiratory syndrome coronavirus (MERS- CoV),[5] caused the plague in Middle East countries.[6]

During December 2019, they reported many pneumonia patients with unidentified reasons behind the disease in Wuhan. After analyzing the sequence, the unidentified pneumonia was identified as a mutated strain of SARS-CoV, i.e., a unique coronavirus (CoV), which was named as nCoV-2019. Novel Coronavirus 2019 caused the coronavirus disease 2019 (COVID-19).[7-9] The virus may be a member of the β subgroup of the family Coronaviridae. The nomenclature of the virus was done by the International Committee on Taxonomy of Viruses (ICTV) and was named as SARS-CoV-2 and the disease as COVID-19.[10] Within the history, SARS-CoV (2003) had infected about 8098 individuals with a fatality rate of 9% across 26 countries throughout the globe. On the opposite hand, coronavirus (2019) infected 4618821 individuals till the date of this writing. It shows that the transmission rate of SARS-CoV-2 is on top of SARS-CoV. The genetic recombination event at S protein within the Receptor Binding Domain(RBD) region of SARS-CoV-2 may be responsible for the enhanced transference ability of this virus.[11] Further in this paper, we introduce the epidemiology, virology, transmission, pathogenicity, diagnosis, treatment of this infection, and the COVID-19.

 

2. Epidemiology

Transmission of virion depends on the source of the infection, the route by which it transmits, and the host of interest. The SARS and MERS are transmitted by animal intervened hosts (Paradoxurus hermaphrodites and Camelus dromedaries).[12] Studies suggest that the primary host is pangolin[13] and also bat.[14,15] Earlier cases suggest the viral transmission from the seafood market in Wuhan, China.[16] The secondary mode of transmission is person-to-person transmission as the major one. According to National health center (N.H.C.) of China, the disease COVID-19 can be transmited by inhaling droplets of saliva, by contact, through feces or by aerosol droplets too.[17] Lack of data was responsible for the increase in the disease. Before the quarantine strategy was regulated and used, the disease was on a surge of massive destruction of mankind throughout China and the entire globe. Then it comes to the study of the Basic Reproductive rate (R0), whose definition states the mean several secondary cases ascribed by the first case after the case is introduced in a susceptible population. This R0 is very important in predicting the pharmaceuticals and non-pharmaceuticals arbitrations. The threshold essential to get rid of the disease is calculated by 1-1/R0. From this, we can conclude that if the threshold value is lower than eliminating, the disease becomes easy to be controlled by following the measures like quarantine, self-isolation, and lockdown. Social distancing can eradicate the influence of transmission. But if the threshold is high, then the population has to be subjected to medication or vaccination.[18]

As of May 18th, 2020 (Fig. 1), 4618821 cases of COVID-19 are confirmed according to the WHO report.[19] The risk worldwide is high according to WHO. The top five countries (Table 1) are arranged based on their descending order of maximum infected cases and their mortality rates which have been calculated considering the population from the worldometer.[20] As the pandemic originally observed in China, a controlled province is observed there. When the virus started spreading throughout the world, lack of knowledge regarding its diagnosis, its prevention, and its treatment led to a boost in the infected individuals in these top five countries as well as throughout the world. Delay in taking the precautionary steps is also one of the major reasons for the increase in infected individuals. China was successful in overcoming the rise of the epidemic by starting the anti-epidemic campaign. Quick quarantining was ordered for Wuhan and all the possible required resources were supported. As the epicenter of the epidemic was Wuhan, it was lockdown immediately, and no person was allowed to go out or come in.[21] This quarantine step expanded from Wuhan to Hubei and then throughout the country. This immediate response strategy, which was successfully followed by each citizen in China, was the reason that China successfully came out of this devastating situation. The highest mortality rate per the given data is in Spain with 27650 death cases.

 

Table 1. Top 5 countries with a maximum confirmed case with
deaths (Till 18th, May 2020).

Country

Confirmed
Cases

Total
Deaths

Mortality Rate

(per1000/year)

United States of America

1432265

87180

0.0007

Russian Federation

290678

2722

0.0001

United Kingdom

243699

34636

0.0014

Brazil

233142

15633

0.0002

Spain

231350

27650

0.0016

 

3. Manifestation of COVID-19

After clinical studies, we can state that various signs and symptoms of COVID-19 are:[22]

Maximum patients show a decrease in their white blood cell (WBC) count and many show lymphocytopenia.

Table 2. Symptoms of COVID-19.

Initial symptoms

Fever

Coughing

Muscle pain or fatigue

Sore throat

Lower frequency
initial symptoms

Heart palpitation

Diarrhea

Headache

Loss of smell and taste

Serious symptoms

Shortness of breath and difficulty in breathing

Loss of speech

Chest pain

 

4. Gender and age group

After analyzing various cases related to the patients of COVID-19, it is seen that the patients who are infected are adult patients.[23,24] If we consider age, people of all ages can get infected by COVID-19. But mainly patients aged 70 and above get easily infected, as there is a decrease in immunity with an increase in age.[25] Except elderly people, kids are also vulnerable to the infection of COVID-19.[26]

 

Fig. 1: Global distribution of COVID-19 cases, from WHO Coronavirus Disease (COVID-19) situation reports. [19]

 

The infected patient’s mean or median ages were 56, 55.5, and 49.0 as per distinct case studies.[23,24] This similarity in the results was also seen in two reports. The first study was of 1099 patients from 552 hospitals in 31 provinces of China, where the median age came to be 47.0 years and 51.1% of the infected individuals were between 15-49 years of age. The second study included 4021 cases in 30 provinces of China where the mean age came to be 49 years and 50.7% of the infected individuals were between 20-50 years. In both cases, the patients were suffering acute respiratory distress (ARD) and pneumonia.[27,28] The infection of the virus shows no gender specificity. In some countries, infected men are high while in some countries infected women are high. But there is a gender gap seen in the mortality rate. As per various articles, it can be stated that men face a higher risk of death in comparison with women.[29-31Answer for this may be immune or hormonal factors, but the actual reason is still unclear.[32,33] In comparison with the SARS mortality rate, COVID-19 shows no uniqueness, as a similar case has been seen in the earlier SARS outbreak too.[34]

 

5. Virology

The COVID-19 is caused by novel type coronavirus (nCoV-19), which was named as Severe Acute Respiratory Syndrome Coronavirus Two (SARS-CoV-2) later on. Coronaviruses belong to a family within the order of Nidovirales, i.e. viruses that replicate forming a nested set of mRNAs (“Nido-” for “nest”). Alpha Coronaviruses (HCoV- 229E and HCoV-NL63) and beta Coronaviruses (HCoV- HKU1, HCoV-OC43) are the two genera, in which the human Coronaviruses exist and cause Middle East respiratory syndrome coronavirus [MERS-CoV], and the severe acute respiratory syndrome coronavirus [SARS-CoV].

Gripping the genetics of viruses is essential in the production of drugs and vaccines. SARS-CoV-2 virion (Fig. 2) is a spherical containing single-stranded positive- sense RNA and 50-200 nanometers in diameter.[35] SARS- CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins. N protein comprises the RNA genome, and the S, E, and M proteins together form the viral envelope.[36] The atomic- level imaging of the spike protein has been captured using cryogenic electron microscopy[37,38] and revealed that the protein is responsible for the attachment and fusion with the membrane of a host cell. The affinity of the virus with the host is understood by performing protein modeling experiments.

 

Fig. 2. Cross-sectional view of Coronavirus. Here, SARS-CoV-2 spike homotrimer with one protein subunit is highlighted,[44] and the angiotensin-converting enzyme 2 (ACE2) binding domain (i.e. the RBD) is in magenta.

It suggests that the Spike protein binds with the receptor angiotensin-converting enzyme 2, i.e., ACE2 is the entry point of the virus in the human body.[39] Groups from China and the United States have shown the action of SARS-CoV-2 on ACE2 receptor by working on methods such as full virus genome and reverse genetic methods.[40-42] Studies show that SARS-CoV-2 has a higher affinity to human ACE2 as compared to the original SARS virus strain.[43]

 

5.1 Genome, entry, and life cycle of Coronavirus:

The s-s RNA genomes of CoV encode two large genes (i.e., the ORF1a and ORF1b genes), and encode 16 non- structural proteins (nsp1-nsp16) that are conserved in all Coronaviruses (Fig. 3). The structural genes encode the structural proteins, i.e., spike (S), envelope (E), membrane (M), and nucleocapsid (N), which are common to all Coronaviruses. Accessory genes (green colored) are unique properties of Coronaviruses in terms of number, genomic organization, sequence, and performance. Beneath genome organization comprises the structure of every S protein. S protein has the S1 and S2 subunits (named as S1 and S2 in Fig. 3). Residue numbers in each region represent their positions within the S protein of SARS and MERS. The S1/S2 cleavage sites are highlighted by the yellow line. The terms are: CP- cytoplasm domain; FP- fusion peptide; HR- heptad repeat; RBD- receptor-binding domain; RBM- receptor-binding motif; SP- signal peptide; and TM- transmembrane domain.[45]

The genome of SARS-CoV-2 is like that of typical CoVs containing at least ten open reading frames (ORFs). The first ORFs (ORF1a/b), about two-thirds of viral RNA, are translated into two large polyproteins. In SARS-CoV and MERS-CoV, two polyproteins, i.e., protein phosphatase 1 α (pp1a) and pp1ab, are processed into 16 non-structural proteins (nsp1-nsp16), which form the viral replicase transcriptase complex. The membranes start from the rough endoplasmic reticulum and it rearranges rough endoplasmic reticulam (RER) into double-membrane vesicles where the virus replicates and transcription occurs. The remaining ORFs of SARS-CoV-2, which are on the one-third of the genome, encode 4 main structural proteins (S, E, N and M proteins (Fig. 4), and several accessory proteins with unknown functions which rarely take part in the viral replication.

As discussed earlier, the SARS-CoV-2, just like SARS-CoV, requires the ACE2 as a receptor to enter cells (Fig. 5).[47] The binding of the virus to host cell receptors is a significant determinant of the pathogenesis of infection. SARS-CoV most likely originated from bats[48] and adapted to non-bat ACE2 variants as it crossed species to infect humans.[49] Dipeptidyl peptidase 4 (DPP4, also known as CD26) was identified to be a functional receptor for MERS-CoV because the receptor-binding S1 domain of the MERS-CoV spike protein was co-purified with DPP4 specifically from lysates of susceptible Huh-7 cells.[50] MERS-CoV can bind DPP4 for various species, which are able to promote the transmission to humans as well as other species, and infection of cells from varied species.[51] Understanding the related effects of receptor binding and the action of protease will help in predicting the specificity of these animals’ intervened Coronaviruses which infect humans and their possible adaptations.