Emerging Human Coronaviruses (SARS-CoV-2) in the Environment Associated with Outbreaks Viral Pandemics

*Chourouk Ibrahim, Salah Hammami, Eya Ghanmi and Abdennaceur Hassen*

## **Abstract**

In December 2019, there was a cluster of pneumonia cases in Wuhan, a city of about 11 million people in Hubei Province. The World Health Organization (WHO), qualified CoVid-19 as an emerging infectious disease on March 11, 2020, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which spreads around the world. Coronaviruses are also included in the list of viruses likely to be found in raw sewage, as are other viruses belonging to the Picornaviridae family. SRAS-CoV-2 has been detected in wastewater worldwide such as the USA, France, Netherlands, Australia, and Italy according to the National Research Institute for Public Health and the Environment. In addition, the SARS-CoV-2 could infect many animals since it has been noticed in pigs, domestic and wild birds, bats, rodents, dogs, cats, tigers, cattle. Therefore, the SARS-CoV-2 molecular characterization in the environment, particularly in wastewater and animals, appeared to be a novel approach to monitor the outbreaks of viral pandemics. This review will be focused on the description of some virological characteristics of these emerging viruses, the different human and zoonotic coronaviruses, the sources of contamination of wastewater by coronaviruses and their potential procedures of disinfection from wastewater.

**Keywords:** SARS-CoV-2, human coronaviruses, zoonotic coronaviruses, disinfection procedures, wastewater

## **1. Introduction**

The recent pandemic of the highly contagious coronavirus disease 2019 (COVID-19) caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has developed devastating consequences on human health, economy, and ecosystem services as an important public health concern [1]. Until 13 January 2022, over 307,373,791 cases have been reported, including over 5,492,154 deaths [2]. SARS-CoV-2 is a beta coronavirus that belongs to the family *Coronaviridae* and the order Nidovirales [3]. Coronaviruses (CoVs), and the newly discovered SARS-CoV-2, are spherical or pleomorphic enveloped viruses with a diameter of 100–160 nm [4] characterized by spike proteins projecting to the virion surface [5]. The primary structure comprises four structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N) encoded at the 3′ end of the viral genome [5, 6]. SARS-CoV-2 has a single-stranded genomic RNA (gRNA) positive-sense, approximately 30 kb [7]. This gRNA is among the largest RNA genomes known with a 5′-cap structure and a 3′-poly (A) tail acting like an mRNA for the immediate translation of viral polyproteins [8]. The 5′ and 3′ ends of the gRNA contain highly structured untranslated regions (UTR) that regulate RNA replication and transcription. There is one stem-loop and one pseudo-knot present in the 3′-UTR region mutually exclusive, since their sequences overlap, while seven stem-loop structures are included in the 5′-UTR region. The SARS-CoV-2 genome contains 14 open reading frames (ORFs), preceded by transcriptional regulatory sequences (TRS). The two main transcriptional units, ORF1a and ORF1ab, encode polyprotein replicase 1a (PP1a) and polyprotein 1ab (PP1ab), respectively [9]. These polyproteins are co- and post-translationally processed into 16 nonstructural proteins (NSPS), most of which drive viral genome replication and sub-genomic mRNA (sgmRNA) synthesis [8]. Usually, the transmission of SARS-CoV-2 was accounted occurs through inhalation of respiratory droplets diffused by coughing or sneezing from an infected patient, and through direct contact with contaminated surfaces or objects [10]. This respiratory syndrome leads to developing several chronic or acute disorders in patients such as fever, cough, fatigue, anosmia and ageusia, dyspnea, chest pain, muscle pain, chills, sore throat, rhinitis, headache [11], and gastrointestinal symptoms (nausea, vomiting, diarrhea) [11]. SARS-CoV-2 genomic RNA has been detected in patient stool and urine samples [12], suggesting the possibility that the virus may be transmitted via the fecal-oral route, besides droplet and fomite transmission. Therefore, the mode of transmission of SARS-CoV-2 becomes crucial paramount for human and environmental health. Recently, the world faces a large wave of COVID-19 infections caused by the highly contagious variant of SARS-CoV-2 Omicron can infect people even if they are vaccinated. The record number of people catching the COVID-19 from the beginning of the pandemic has left health systems under severe strain especially in developed countries. However, It has proven the particular importance of WBE (wastewater-based epidemiology) in monitoring the circulation and the transmission of the epidemic in the community, it could provide an early warning sign that reflects possible disease outbreaks in a community [13, 14] and an effective tool for epidemiological surveillance of SARS-CoV-2 viral diversity in samples and to anticipate the detection of certain mutations before they are detected in clinical samples. This communication will provide a basis for understanding SARS-CoV-2 and other viruses from the environmental perspective to design alternative strategies to counteract enteric virus transmission and to reduce the severity of the pandemic [15]. In this review, we present the different human and zoonotic coronaviruses, the sources of contamination of wastewater by coronaviruses, and their potential procedures of disinfection and eradication from wastewater.

## **2. Human coronaviruses**

Coronaviruses (CoV) are enveloped viruses with a single positive-strand RNA genome (∼26–32 kb). They belong to the subfamily *Ortho-Coronaviridae* of the family *Coronaviridae* and are classified into four genera: *Alpha coronavirus (α), Beta coronavirus (β), Gamma-coronavirus (γ)* and *Delta-coronavirus (δ)* [16].

*Emerging Human Coronaviruses (SARS-CoV-2) in the Environment Associated with Outbreaks… DOI: http://dx.doi.org/10.5772/intechopen.103886*

Until the present time, seven human coronaviruses (HCoVs) can be transmitted between humans. Human alpha coronaviruses, 229E and NL63, and beta-coronaviruses, OC43, and HKU1 are common respiratory viruses usually causing mild upper respiratory illness. Unlike these, the three other human beta-coronaviruses, severe acute respiratory syndrome coronavirus (SARS), Middle East respiratory syndrome coronavirus (MERS), and SARS-CoV-2, are highly pathogenic in humans [17]. All seven HCoVs are the product of a Spillover, they have a zoonotic origin from bats, mice, or domestic animals. Multiple justifications support an evolutionary origin of all HCoVs from bats, where viruses are non-pathogenic and well adapted, so they show great genetic diversity. Genome analysis of the virus identified a high sequence similarity with Chinese bat coronaviruses (highest homology to bat coronavirus RaTG13). Beta coronavirus phylogenetic tree showing that SARS-CoV-2 is related to bat coronaviruses ZC45 and ZXC21. SARS-CoV-2 showed 99% sequence homology with pangolin CoV according to the findings of a research team from the South China University of Agriculture [18].

### **2.1 HCoV-229E and HCoV-OC43**

HCoV-229E is the first strain isolated from patients with upper respiratory tract contamination in the year 1966 [19]. Patients infected with HCoV-229E showed cold symptoms, including headache, sneezing, malaise, and sore throat, with fever and cough in 10–20% of cases [20]. Later, in 1967, HCoV-OC43 was disengaged from organ culture, resulting in a sequential entry in the cerebrum of nursing mice. The clinical features of HCoV-OC43 infection give off an impression of resembling those caused by HCoV-229E, which are indistinguishable from diseases with other respiratory tract pathogens such as influenza A viruses and rhinoviruses [21]. Both HCoV-229E and HCoV-OC43 circulate globally, and they are prevalently diffused during the cold period in a moderate climate [22]. Developing these two viruses is less than one week, straggled by around a 2-week disease [21]. According to a human volunteer study, healthy individuals infested with HCoV-229E developed a slight common cold [23].

### **2.2 SARS-CoV**

The first case of SARS-CoV-1 was discovered in late 2002 in Guangdong Province of China. SARS is an infectious disease caused by a virus belonging to the coronavirus family, SARS-CoV-1. The SARS epidemic has expanded across many countries and continents and caused about 8096 reported cases with 774 deaths. The incubation period of SARS-CoV-1 was 4 to 7 days and the peak of viral load was estimated on the 10th day of illness.

Patients infected with SARS-CoV-1 showed initial symptoms of myalgia, headache, fever, malaise, and chills, followed by dyspnea, cough, and respiratory distress as late symptoms of lymphopenia. However, deranged liver function tests and elevated creatine kinase are common laboratory abnormalities of SARS [24, 25]. The insectivorous bat has been identified as an animal reservoir of the SARS coronavirus. The intermediate host that allowed the virus transmission to humans is the masked palm civet, a wild animal sold in markets and eaten in southern China [26].

### **2.3 HCoV-NL63 et HCoV-HKU1**

In late 2004, HCoV-NL63 was isolated from a 7-month-old child in the Netherlands. It was initially prevalent in young children, the elderly, and immunocompromised patients with respiratory illnesses [27]. The common symptoms of the disease caused by HCoV-NL63 are coryza, conjunctivitis, fever, and bronchiolitis [28]. It is distributed globally and it has been estimated that HCoV-NL63 accounts for nearly 4.7% of common respiratory diseases, and its peak incidence occurs during early summer, spring, and winter [22].

In the same year, HCoV-HKU1 was isolated in Hong Kong from a 71-year-old man hospitalized with pneumonia and bronchiolitis [29]. HCoV-HKU1 was reported to be associated with acute asthmatic exacerbation besides community-acquired pneumonia and bronchiolitis [30]. Alike to HCoV-NL63, HCoV-229E, and HCoV-OC43, HCoV-HKU1 was found worldwide, producing mild respiratory diseases [30].

These four community-acquired HCoVs have been well accustomed to humans and are less probable to mutate to produce exceptionally pathogenic diseases, however, accidents can occur for unclear details as in the uncommon case of subtype HCoV-NL63, which is more virulent and has recently been reported to cause severe lower respiratory tract infection in China [31].

As it has been shown for HCoV-NL63, HCoV-229E, and HCoV-OC43, HCoV-HKU1 has a worldwide distribution and causes mild respiratory diseases [30]. However, the subtype HCoV-NL63, which was found to be more virulent, caused recently severe respiratory tract infection in China [31].

## **2.4 MERS-CoV**

In 2012, a new respiratory virus called MERS-CoV for Middle East Respiratory Syndrome coronavirus was detected in the lung of a 60-year-old patient who developed acute pneumonia and renal failure in Saudi Arabia [32, 33].

The virus was then reported in several countries in the Middle East. Since then, 1219 cases have been diagnosed, resulting in 449 deaths. Few cases have been detected in Europe, including 2 cases in France and 3 cases in Tunisia in 2013 [34]. Later in 2015, 186 confirmed cases were reported in South Korea. Compared to SARS, MERS is a similar disease with a progressive acute pneumonia. However, unlike SARS, many patients with MERS also developed acute renal failure [32, 33]. Over 30% of patients also showed gastrointestinal symptoms, such as diarrhea and vomiting [32, 33].

As of February 2020, over 2500 confirmed cases were accounted for with an intense case fatality of 34.4%, making MERS-CoV one of the most pathogenic viruses known to humans [35].

### **2.5 SARS-CoV-2**

SARS-CoV-2 was first reported in a group of pneumonia patients of unknown etiology who witnessed their visit to Huanan Seafood Wholesale Market in December 2019 in Wuhan, Hubei Province, China [36, 37]. At the beginning of the 2020s, the 2019 coronavirus disease emerged around the world and become a pandemic, which disrupts human activity through general confinements and strict sanitary measures. The incubation of SARS-CoV-2 lasts from 2 to 14 days [38]. The most frequent signs in patients were fever, cough, fatigue, anosmia, ageusia, muscle pain, chills, sore throat, rhinitis, and headache head [11]. Additionally, gastrointestinal symptoms have been reported, diarrhea, stomach pain, vomiting, nausea, and poor appetite [11]. The nucleotide sequence of SARS-CoV-2 revealed about 51.8 and 79.0% of similarity with MERS-CoV and SARS-CoV-1, respectively, and is closely related to SARS-like coronavirus of bald origin—mouse (bat-SL-CoVZC45) with 87.6–89%

### *Emerging Human Coronaviruses (SARS-CoV-2) in the Environment Associated with Outbreaks… DOI: http://dx.doi.org/10.5772/intechopen.103886*

identity [16–25, 27–33, 35–39]. Recent studies strongly support the hypothesis that SARS-CoV-2 may have originated in bats and may have undergone host jumping to another intermediate mammal, including pangolins (Manis javanica) [10, 40]. Phylogenetic analyzes of the SARS-CoV-2 genome revealed this virus bind with the same human cellular receptor (ACE2: Angiotensin-Converting Enzyme 2) as same as SARS-CoV-1 to get into host cells with 10 times affinity higher than SARS-CoV-1,


### **Table 1.**

*Variants to follow VOI of SARS-CoV-2 [46].*


### **Table 2.**

*Variants under intensive care or VUM of SARS-CoV-2.*

while MERS-CoV uses another (DPP4) [41, 42] … Genetic variability of SARS-CoV-2 can be the consequence of nucleotide incorporation errors by viral RNA polymerase, genomic editing by cellular restriction factors, or even homologous recombination. The expansion of SARS-CoV-2 variants was observed in fall 2020 [43]. The evolutionary mutation rate of SARS-CoV-2 is estimated at 1.103 nucleotide substitutions per site per year [44] equivalent to approximately one substitution every two weeks in the genome [45]. Currently, the WHO considered five variants as "worrying," which were first detected in England, South Africa, and then later in Brazil (two variants were observed there, including P1 classified as worrying). In October 2020, a fourth variant (Delta) appeared in India received particular attention. This country of 1.3 billion people has seen an explosion of cases is resisted by other nations. At the end of November 2021, it was the Omicron variant, detected in South Africa, which caused the recent wave and concern all over the world.

Besides other variants called VOI ("variant under investigation" or "variant of interest" in English) has been detected in multiple countries and identified with mutations that lead to amino acid changes associated with phenotypic changes (confirmed or suspected) responsible for community transmission or multiple confirmed cases or clusters (**Table 1**) [46].

And diverse variants called under evaluation, or VUM ("variant under monitoring") exhibit genetic changes suspected of affecting the characteristics of the virus, indicating that it may pose a future risk without evidence of phenotypic or epidemiological repercussions being clear at this time, and which should be investigated repeated evaluation and enhanced surveillance pending confirmation of new evidence (**Table 2**) [46].
