Coronavirus disease-19 (a.k.a. COVID-19) is a new disease caused by a coronavirus that is still under investigation concerning how it spreads. Coronavirus is spreadable. The current form of coronavirus disease, officially known as COVID-19, is the name of the disease caused by SARS-CoV-2 virus which was first reported in late December 2019 in Wuhan, China. Coronaviruses are a large family of viruses that are commonly found in infected people and many different animal species, including camels, cattle, cats, and bats. Coronaviruses belong to a group of enveloped viruses with a positive-sense, single-stranded RNA belonging to the β genus of Coronaviridae family and viral particles resembling a shape of a crown, hence the name corona. They belong to the order of Nidovirales and subfamily of Orthocoronavirinae, characterized by having an enveloped, non-segmented RNA. They possess a very large genome for RNA with viruses having the largest identified RNA genome up to 33.5 kilobases (kb) in size with a genome containing a 5′ cap structure along with a 3′ poly (A) tail, which allows for it to act as mRNA for translation of the replicase polyproteins. The gene encoding in the virus is the non-structural proteins (nsps) that occupy two-thirds of the genome, about 20 kb, as opposed to the structural and accessory proteins, which make up only about 10 kb of the viral genomes [1,2,3,4].

The SARS-CoV-2 virus belongs to betacoronaviruses category, such as MERS-CoV and SARS-CoV-1. All three of these viruses originated from bats [5,6]. The genetic sequences found in U.S. patients are similar to the ones that were obtained initially in China, suggesting a likely single, recent emergence of this virus from an animal reservoir [7]. Not often can animal coronaviruses infect people and then spread between people such as with Middle East respiratory syndrome (MERS), CoV, SARS-CoV, and now with this new virus (named SARS-CoV-2). It became evident that several domestic animals had previously tested positive for SARS-CoV-2 in some parts of the world including Hong Kong and Belgium, as well as in the New York City Zoo. However, there is not sufficient evidence that the COVID-19 can be transmitted to humans from these animals [8]. Recently, Pangolins (Manis sp) were reported to have been the prime suspects that could link host for SARS-CoV-2 even though the actual bridge host remains unknown [9].

The first human cases of COVID-19 were identified back in December 2019 in Wuhan City, China. At that time, the mode of transmission between humans was not clearly known. However, most infected people with SARS-CoV-2 reported exposure to a large seafood and wet animal market in Wuhan City, Hubei Province suggesting a potential zoonotic origin. Moreover, SARS-CoV, the virus which caused the SARS outbreak back in 2003, originated from animal reservoir (civet cats, a farmed wild animal) migrated to humans and then spread in the environment. In a similar way, it is thought that SARS-CoV-2 originated from animal species barrier and initially infected humans, but more likely through an intermediate host (that is, another animal species more likely to be handled by humans). This could be wild animal, or a domesticated wild animal and, as of now, has not been identified [10,11]. Older people and people of all ages with medical conditions or immune compromised, seem to be at higher risk of developing serious COVID-19 symptoms [8,9].

The advancement in technologies for the detection of SARS-CoV-2 variants played a critical role in obtaining reliable evidence about whether they are more transmittable, virulent, or more resistant to the available COVID-19 vaccines well before they spread throughout the globe. Genomic surveillance has increased the advantages in the field of next-generation sequencing. Therefore, researching and creating the availability of the whole genome data can aid in advancing the phylogenetic methods [12].

SARS-CoV-2 continuously undergoes mutation due to changes in the genetic code that usually occur during replication of its genome. These mutations have led to the formation of new variants that are genetically closely related with multiple variants being documented in the United States and globally during this pandemic. According to the CDC, there are about 12 lineage groups that inherited common ancestor. The common variants are the alpha (B.1.1.7, first isolated from United Kingdom and then Q lineages) with 50% increase transmission, may increase mortality; beta (B.1.351, first isolated in South Africa followed by descendent lineages, increased immune evasiveness, 50% increased transmission); delta (B.1.617.2) first isolated in India, the variant is almost twice as contagious as earlier variants and might cause more severe illness, may evade fully vaccinated people and increase rate of infection, possibly increases mortality; gamma (P.1, first isolated in Brazil/Japan, likely increased disease transmissibility and severity and then its descendent lineages); epsilon (B.1.427 and B.1.429, first isolated in California, 20% increased risk of transmissibility); eta (B.1.525); and iota (B.1.526, first isolated in New York, reported to likely increase rate of transmission). Other variants being monitored (VBM) are kappa (B.1.617.1), mu (B.1.621, B.1.621.1), and zeta (P.2) and the two most recent variants of concern (VOC) are the delta (B.1.617.2 and AY lineages) and omicron (B.1.1.529 and BA lineages, which are now present in more than 150 countries, it was first isolated in South Africa and presently, the most common strain in both UK and U.S. with over 50 mutations in spike protein). Currently, no SARS-CoV-2 variants were added to the list of variants of high concern (VOHC), as this would necessitate a notification to the World Health Organization (WHO) under the International Health Regulations [13,14,15,16,17].

3. Symptoms

COVID-19’s symptoms appear to be similar to those of Middle East respiratory syndrome (MERS), starting from 2–14 days of exposure to SARS-CoV-2, the symptoms include but are not limited to fever, tiredness, and dry cough. In some cases, patients may have aches and pains, nasal congestion, runny nose, sore throat or diarrhea, the new loss of taste or smell, repeated shaking with chills. These symptoms are usually mild and begin gradually. Some people (asymptomatic) become infected but do not develop any symptoms and don’t feel unwell [18,19,20,21]. More recently, a study of over 26,000 French adults was conducted wherein persistent physical symptoms were reported [22].

Some of the extreme COVID-19 symptoms were reported to involve tissue damaging by patients’ immune system and the study indicated an increase in the immune system molecule activities and Interleukin (IL-6) was reported to aid in cell regulations [23]. Long-term inflammation of lungs was reported to be one of the severe respiratory symptoms of COVID-19 which has been reported to be from the specific immune cells. A study conducted on 88 subjects with severe pneumonia caused by SARS-CoV-2 infection with most of the individuals having a high number of T-cells found in the lungs indicated that almost 70% of the alveolar macrophages which are typical immune cells situated in the lungs contained SARS-CoV-2 [24].

Almost all of the variants including delta and omicron cause similar COVID-19 symptoms that may stay over time. These symptoms include fatigue, shortness of breath or difficulty breathing, cough, joint pain, chest pain, memory concentration or sleep problems, dizziness, depression, or anxiety, fast or pounding heartbeat, worsened symptoms after physical or mental activities and this may cause muscle or body aches, pale, gray, or blue-colored skin, lips, or nail beds, depending on skin tone, inability to wake or stay awake, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, and in some cases diarrhea and or gastrointestinal (GI) symptoms due to shedding of the virus. On the other hand, omicron is less likely to cause severe disease such as pneumonia that may require hospitalization but has a higher rate of spread with some evidence that fewer people lose their sense of taste and smell [25,26,27,28,29].

4. Biological Nature SARS-CoV-2 and Mechanism of Cell Entry

The SARS-CoV-2 membrane has the transmembrane (M) glycoprotein, the spike (S) glycoprotein, and the envelope (E) protein, and surrounds the flexible helical nucleocapsid. The viral membrane is unusually thick, probably since the carboxy-terminal region of the M protein forms an extra internal layer, as revealed by cryo-electron tomography [24]. Coronavirus enters in human cell through membrane ACE2 exopeptidase receptor, the mechanism of entry SARS-CoV-2 into the host cell is like the other coronaviruses such as SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), and infectious bronchitis virus (IBV). SARS-CoV-2 becomes attached to the plasma membrane or use receptor-mediated endocytosis and fuses with endosomes based on the nature of the cells or tissues. The interaction between the virus-receptor and the cell allows for viral genetic material to be delivered to the host cell cytoplasm for replication, once delivered, the enzyme hemagglutinin-enterase (HE) dimer enhances spike protein (S)-assisted viral entry into the cell by binding to the host angiotensin converting enzyme 2 (ACE2) and the virus spreads throughout the mucosa. The envelope protein (E) facilitates the assembly and release of the virus. The membrane glycoprotein (M) provides structure to the virus and binds to the nucleocapsid protein (N), which binds to RNA helping to link the viral genome to the replicase-transcriptase complex, packaging the encapsulated genome into viral particles [30,31,32,33].

The close look at the isolate of a 2019-nCoV from a patient after performing genome sequencing of the 2019-nCoV in a study conducted by Lu et al and Hui et al in 2020 revealed that 2019-nCoV has 89.1% nucleotide similarity with CoVZC45 virus of bat origin and even exhibits 100% amino acid similarity in the nsp7 and E proteins. In another study involving nine patients, the data from the genome sequencing of the 2019-nCoV that were analyzed exhibited about 100% similarity in their identities [34,35].

SARS-CoV-2 continuously undergoes mutation due to changes in the genetic code that usually occur during replication of its genome. These mutations have led to the formation of new variants that are genetically closely related with multiple variants being documented in the United States and globally during this pandemic. According to CDC, there are about 12 lineage groups that inherited common ancestor. The common variants are the alpha (B.1.1.7 and Q lineages), beta (B.1.351 and descendent lineages), gamma (P.1 and descendent lineages), epsilon (B.1.427 and B.1.429), eta (B.1.525), iota (B.1.526), kappa (B.1.617.1), 1.617.3, mu (B.1.621, B.1.621.1), zeta (P.2) and the two most recent variants of concern delta (B.1.617.2 and AY lineages) and omicron (B.1.1.529 and BA lineages) [36].

5. Mode of Spread

The respiratory tract might not be the only route for the SARS-CoV-2 into the human body. SARS-CoV-1 is predominantly transmitted through direct or indirect contact with mucous membranes in the eyes, mouth, or nose [37], and this could be the case too with SARS-CoV-2 in contact with unprotected eyes. This can cause acute respiratory issues [38].

According to the CDC, SARS-CoV-2 (COVID-19) frequently spread from person-to-person who come in close contact (within about 2 m). This type of transmission occurs via respiratory droplets as the infected person coughs or sneezes. However, the virus has also been found in blood and stool, which raises questions about other possible routes of transmission [39,40]. On the other hand, the transmission of novel coronavirus to persons from surfaces contaminated with the virus has not been documented but recent studies indicate that asymptomatic people are likely to play a role in the spread of COVID-19. Recent evidence suggests that SARS-CoV-2 may remain viable from a few hours up to some days on surfaces based on the nature of the surface [41].

The new variant B.1.1.7 was first isolated in the United Kingdom and later was found circulating in Israel. A study conducted by Kustin et al., 2021 in evaluating the vaccinated and unvaccinated to compare the breakthrough infection. The comparison revealed that infections in partially immunized people were slightly more likely to be caused by B.1.1.7 as were those in unvaccinated people [42]. A Costa Rican PANGOLIN lineage B.1.1.389 with a spike (S: T11171) was reported to be the cause mutation T11171 in SARS-CoV-2 genomic sequence which was believed to be responsible for almost 30% of the cases that were reported in Costa Rica back in December of 2020 [43]. In another instance with the Costa Rican lineage, the B.1.1389 lineage happened to be transient as it began to disappear and gave room to more advantageous variants such as alpha and gamma. The mutation in S:T11171 that was found in Costa Rican lineage B.1.1.389 was believed to be a product of natural selection with some effects on the activity of the function and interaction of the spike protein [44].

The concept of co-infection (simultaneous infection of a host by multipleSARS-CoV-2 variants) cannot be overemphasized as there are recent studies that demonstrated genomic evidence of the existence of co-infection or within-host variation [45]. According to a study conducted by Chekuri et al. (2021). Patients with SARS-CoV-2 along with a non-influenza respiratory virus happen to have less severe disease and were more likely to be admitted but did not experience more severe effects than those infected with SARS-CoV-2 alone which could be due to the viral interference. Their study involved 306 SARS-CoV-2-positive patients with respiratory pathogen panel (RPP) and they observed severe COVID-19 effect in 111 (36.3%) patients in the SARS-CoV-2-only group and 3 (21.4%) patients in the co-infected group, even though the result was not significantly different [46]. Molina-Mora et al. (2022) have utilized two different approaches one being the metagenomic pipeline which is based on the inference of multiple fragments such as amplicon sequence variant (ASV-like) from sequencing data and a custom SARS-CoV-2 database to identify the concomitant presence of divergent SARS-CoV-2 genomes which were used to analyze 1021 cases of COVID-19 from Costa Rica to investigate the possible occurrence of co-infections and compared this with another strategy which was based on the whole-genome (metagenome) assembly; the results indicated an accuracy of about 96.2% with for ASV-like and 46.2% for the whole—genome assembly strategy [47].

The emergence of the new variants has led to more research in order to correctly characterize the nature of the mutant virus in terms of changes in transmission, severity of the disease, symptoms, mortality rate, and effectiveness of the available vaccines [48].