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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 5  |  Page : 3-12

Can animals like bats, pangolins, and ticks would be considered as long-term reservoirs of severe acute respiratory syndrome coronavirus 2


1 Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD); Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Date of Submission19-Jun-2020
Date of Acceptance15-Jul-2020
Date of Web Publication13-Aug-2020

Correspondence Address:
Prof. Parissa Farnia
Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Disease (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bbrj.bbrj_120_20

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  Abstract 


In December 2019, there was an outbreak of pneumonia with an unknown cause in Wuhan, Hubei province, China. Within less than 3–4 months, the virus has spread to more than 200 countries. The virus rapidly transmitted from different places of the world with various cultural traditions. Thereby, the question is remained to be resolved about the main intermediate carrier of diseases in different animals. Studied showed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was originated from horseshoe bats, but its intermediate hosts are still largely unknown. Therefore, the possibility of horseshoe bat infection by ticks is high during the flight between plants or when resting in these places. Female ticks can either feed on horseshoe bat blood for 5–7 days before shedding or can form large aggregations by laying several thousand eggs in the right places or on them. Once they feed on horseshoe bat blood containing SARS-CoV-2, they can transfer the infection to the next generations without the need to reuse infections from the reservoir host. With all the potential features that this creature has, it is mandatory to investigate the presence or absences of SARS-CoV-2, especially when we know that ticks co-exist with that horseshoe bats. These factors highlight the importance of studying the viral epidemiology in the tick population. Thereby, based on the wide distribution of ticks and their co-existence with horseshoe bat, we suggest further studies on ticks that might act as one of the main intermediate hosts in different animals.

Keywords: COVID-19, horseshoe bats, intermediate host, severe acute respiratory syndrome coronavirus 2, ticks


How to cite this article:
Aghajani J, Farnia P, Ayoubi S, Farnia P, Ghanavi J, Velayati AA. Can animals like bats, pangolins, and ticks would be considered as long-term reservoirs of severe acute respiratory syndrome coronavirus 2. Biomed Biotechnol Res J 2020;4, Suppl S1:3-12

How to cite this URL:
Aghajani J, Farnia P, Ayoubi S, Farnia P, Ghanavi J, Velayati AA. Can animals like bats, pangolins, and ticks would be considered as long-term reservoirs of severe acute respiratory syndrome coronavirus 2. Biomed Biotechnol Res J [serial online] 2020 [cited 2022 Jan 25];4, Suppl S1:3-12. Available from: https://www.bmbtrj.org/text.asp?2020/4/5/3/292073




  Introduction Top


In December 2019, there was an outbreak of pneumonia with an unknown cause in Wuhan, Hubei province, China. Zhou et al. in 2019 by sequencing of the lower respiratory tract samples of patients named it a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that belongs to coronavirus family.[1] Coronaviruses are a type of RNA virus that is characterized by their ability to recombine and easily jump from one host to another at a specific frequency.[2] This means flexibility to adapt to new conditions and proliferation in new host cells. Within less than 3–4 months, the virus has spread to more than 200 countries. As a result today, more than 11,000,000 individuals got infected by SARS-CoV-2, with 541,000 deaths globally. Besides different clinical symptoms, i.e., acute respiratory syndromes, gastrointestinal problems, and neurological and heart injuries, the virus rapidly transmitted from different places of the world with various cultural traditions. Since the beginning of the pandemic, COVID-19 has been associated with bats. The World Health Organization (WHO) confirms that the natural reservoir of coronavirus is SARS-CoV-2 bats. Today, everyone accepts this as a fixed fact.

The question remains unanswered, but we find more clues that now involve bats. Genetic comparisons show that the coronavirus SARS-CoV-2, which is more similar to the RaTG13 virus, has been isolated from horseshoe bat (Rhinolophus affinis). 96.2% of the SARS-CoV-2 and RaTG13 genes are similar, roughly the same genetic similarity between humans and chimpanzees. However, even if they are very similar, the genomes of the two coronaviruses show more than 1,200 nucleotide differences. SARS-CoV-2 and RaTG13 coronaviruses are thought to have changed about 50–70 years ago![2]

Horseshoe bats are used as biological suppression for pests in various vineyards and farms.[3],[4] This is due to their diet. In fact, insectivorous bats are among the most voracious suppressors of arthropod pests.[3],[4] Bats carry a wide range of viruses.[5],[6],[7] As a result, wherever a person makes a change in the ecology of nature, the likelihood of injury and danger increases and always be risky.

Thereby, the question is remained to be resolved about the main intermediate carrier of diseases in different animals. Scientists raise the question about the virus's transmission to animal species.

Liu et al. 2020 reported the identification of the complete genome of a coronavirus in 3 sick Malayan pangolins.[8] The molecular and phylogenetic analyses showed that this pangolin coronavirus is genetically related to the COVID-19 of bat coronaviruses but does not support the emergence of COVID-19 from the pangolin.[8] There are also numerous reports of COVID-19 in cats and dogs, which is debatable.[9],[10],[11],[12],[13],[14],[15],[16] Dogs and cats themselves are suspected of transmitting the coronavirus. They may be able to transmit the virus either by carrying the virus or by licking their owner. Recently, Halfmann et al., 2020, demonstrated that domestic cats inoculated with SAR-CoV-2 showed infection of the virus, although no clinical symptoms were detected in them.[17] Therefore, they propose a cat as a “silent intermediate host of SARS-CoV2.”[17] We also showed that stray cats and dogs in Tehran had a rectal and nasal swab virus positivity (under publication).[18] However, we still need to know how exactly the transmission chains are getting on. In addition to all of the above, there are still questions about the origin of the virus as well as intermediate organisms to transmit the disease. Can it be assumed that a chain of intermediate organisms should be involved in transferring the virus? We were faced with a strange question. Can ticks cause COVID-19? Are they the intermediate host for SARS-CoV2? Is it possible? The ticks had characteristics that raised these questions for us. Today, most infectious diseases, such as West Nile virus and SARS, are caused by zoonotic reservoirs, and many are transmitted by arthropod vectors.[19],[20] Ticks are one of the most common and versatile arthropod carriers of infectious diseases because the ticks of both ages and sexes remain infected for generations without the need to reuse infections from the reservoir host.[19],[20] Given these facts, then why we forgot the ticks? Why hasn't any scientific study been done on the possible role of ticks in coronavirus? When ticks can transfer different viruses, bacteria, and pathogens, then why can't they transfer the coronavirus? Ticks have a high ability to infect different hosts. They can also be easily expanded. They are also capable of transmitting various viral, infectious, and bacterial diseases. The family is distributed around the world and occupies a variety of ecological niches.[21] More than 900 species of tick have been identified globally to date, and most belong to two families, Ixodidae or hard ticks and Argasidae or soft ticks.[21],[22],[23] Furthermore, hard ticks are divided into Prostriata (genus Ixodes) and Metastriata (remaining genera). Ticks become parasites on mammals, birds, reptiles, and even amphibians, infecting them, which are the main hosts of mammals.[21],[24] Many ticks are important carriers of pathogens. In general, most ticks parasitize different hosts; only a few ticks use the host's harsh features, such as ticks that are parasitic, especially in reptiles and bats.[21] More than 16 tick-borne (or tick-caused) diseases have been reported in humans and more than 19 tick-borne diseases have been reported in livestock and companion animals.[25] Many ticks' species can survive for a long time because they can minimize the loss of evaporative water. Due to the details, in laboratory conditions, many of them exhibit physiological flexibility because they can successfully feed using new hosts that are not related to their natural hosts.[26],[27],[28],[29],[30] At the same time, these findings suggest that host diversity is less valuable than ticks, and ticks can use different hosts.

Ticks mostly transmit pathogens – including bacteria, parasites, and viruses – from other vector carriers.[31] The number of diseases caused by ticks and their geographical distribution is increasing, some of which are due to climate change.[32],[33]

China has a relatively high diversity of tick species, and more than 120 species (about 13% of the world's species) have been described throughout its geography and various infected hosts.[34],[35],[36],[37],[38] In China, ticks can infect many vertebrates, including mammals, birds, and reptiles, although their function in these hosts is largely unknown. Most Argasidae ticks and many Prostriata ticks are nidicolous and live in or near nests, burrows, caves, or other shelters used by their hosts.

Tick disease also presents with symptoms similar to coronavirus. Health officials are warning Michiganders to protect against anaplasmosis, a tick-borne disease that mimics COVID-19 symptoms.[39] The symptoms are very similar to those reported with the coronavirus: fever, chills, fatigue, body aches, and headaches. People who experience this range of symptoms are advised to seek medical attention. Government health officials have seen tick bites since early December and January, so they recommend avoiding tick habitats and taking precautions.[39] “It is important to note the differences between COVID-19 and anaplasmosis,” said Dr. Paige Armstrong, director of the U.S. Public Health Service epidemiology team of the Rickettsial Zoonoses Branch.[39] “It is very rare, but anaplasmosis can cause respiratory problems such as shortness of breath and cough,” says Armstrong. See your doctor right away if you have symptoms of fever, headache, muscle aches, or fatigue. It is also important to tell your health-care provider about any bites.[39]

From another perspective, there are reports of ticks in horseshoe bat that can infect them and live with them.[40],[41],[42],[43] For example, Ixodes ricinus is a species of Holarctic parasite that extends its distribution in Europe, Northwest Africa, Central Asia, and North America.[40],[44],[45]

In Europe, three species of hard ticks (Ixodidae: Ixodes ariadnae, Ixodes simplex, and Ixodes vespertilionis) and at least two species of soft ticks (Argasidae: Argas transgariepinus and Argas vespertilionis) are specific to bats.[41] From a medical veterinary perspective, mammals can be considered the most important host group, which may be directly through ticks (for example, due to blood loss or inoculation of biologically active compounds) or indirectly affected by infection with ticks.[41] Molecular evidence suggests that bat ectoparasites (ticks) may have numerous viruses,[46] bacteria,[47],[48] or protozoan parasites[49],[50],[51],[52] of veterinary and medical importance. Their data justify extensive research on bat ecology and host relationships with parasites.[41]I. vespertilionis is a widespread parasite in many bat species the Rhinolophidae and Vespertilionidae families, commonly occurring in Europe, North Africa, and the Middle East.[44]

Despite the wide distribution range of I. ricinus, the first tick's record in horseshoe bat (Rhinolophus euryale) was reported by Siuda et al. in Slovakia.[40] Siouda et al. suggested that transmission of the parasite to the bat host may occur when the bats feed on low vegetation.[40] Tree holes, man-made warehouses, mines, and attics that provide cave-like environments can be good places for male ticks. Transmission of the parasite is likely to occur on grasses or in plants during the flight.[53],[54],[55]

Of course, the hunting strategies of ticks have also changed and evolved. In some species, ticks choose vegetation cover, where they wait for the host to pass (ambush strategy). Others use a hunter-gatherer strategy to search for a host and are attracted to it by CO2, ammonia, and other odors. Hyperparasitism (parasitism of a parasite by another parasite) is another type of food behavior among species of hard and soft ticks. In this way, healthy fed individuals can be surrounded by nonfed ticks that use their hypostomes and chelicerae to imbibe and steal part of the blood meal.[56],[57],[58] Another study by Piksa et al. examined the presence of Ixodes in bats in Portland.[59] A total of 491 I. vespertilionis and 8 I. ricinus were collected from bats and cave walls in southern Poland (hart ticks).[59] Both are important vectors of pathogens in Europe.[60],[61] The presence of these ticks in bats has been mentioned in many articles. These ticks may potentially act as carriers of various pathogens. I. ricinus ticks may have various pathogens with the potential to cause serious human and animal diseases such as borreliosis, babesiosis, and tick-borne encephalitis.

It should be noted that the WHO stated in a report that there is no scientific reason to believe that mosquitoes can transmit the coronavirus (SARS-CoV-2).[62] But so far, no scientific study has been done on the possible role of ticks in the coronavirus.[62]

Using published documents, we have compared the geographical distribution of Ixodes ticks with pangolin and horseshoe bat in different parts of the world [Table 1]. Thereby, based on the wide distribution of ticks and their co-existence with horseshoe bat, we suggest further studies on Ixodes ticks that might act as one of the main intermediate hosts in animals.
Table 1: Distribution of three species of Ixodidae ticks, horseshoe bats, and pangolins in different parts of the world (based on available documents)

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  But How Can a Bat Be Infected by Ticks? Top


Previous studies have shown that the diet of horseshoe bats consists mainly of Diptera and Lepidoptera,[3],[88],[89],[90],[91] including species that are considered pests.[88] Numerous studies have reported the presence of some pests harmful to corn, pecan orchards, macadamia orchards, cotton, and rice.[92],[93],[94],[95] Among fruit products, grapes have the highest area under cultivation and the highest global income.[96] It is attacked by several pests and pathogens during spring and summer. The lesser horseshoe bat (Rhinolophus hipposideros), commonly reported in vineyards,[97],[98],[99] exhibits particularly adaptive forage behavior. Bats use vineyards for commuting and foraging.[97],[100],[101] As a result, such bats can be infected by ticks during the flight between plants to provide food or when resting in these places. As mentioned, ticks have a high ability to infect different hosts.

According to [Figure 1], as mentioned earlier, adult ticks (most females), as well as nymphs, can infect and feed on the horseshoe bat. Horseshoe bat can be infected by ticks while flying through the vineyard for feeding or resting in these areas. Ticks find their hosts by detecting animals' breath and body odors or by sensing body heat, moisture, and vibrations. Some species can even recognize a shadow. Besides, ticks pick a place to wait by identifying well-used paths. Then, they wait for a host, resting on the tips of grasses and shrubs. Ticks cannot fly or jump, but many tick species wait in a position known as “questing.”[102]
Figure 1: A schematic view of our theory of ticks functions as an intermediate host in COVID-19

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While questing, ticks hold onto leaves and grass by their third and fourth pairs of legs. They hold the first pair of legs outstretched, waiting to climb on to the host. When a host brushes the spot where a tick is waiting, it quickly climbs aboard. Some ticks will attach quickly and others will wander, looking for places such as the ear or other areas where the skin is thinner.[102] Female ticks can either feed on horseshoe bat blood for 5–7 days before shedding or can form large aggregations by laying several thousand eggs in the right places or on them.[41],[103] Once they feed on horseshoe bat blood containing SARS-CoV-2, they can transfer the infection to the next generations without the need to reuse infections from the reservoir host. The shedding eggs resulted in nymphs that would be in grasses or twigs into their next host before they get dehydrated. These nymphs feed on small-to-medium-sized mammals. With all the potential features that this creature has, it is mandatory to investigate the presence or absences of SARS-CoV-2, especially when we know that ticks co-exist with that horseshoe bats.[41],[42],[104]

As well the adult and eggs a ticks can be shed by the bat on the vineyard, there is possibility of wide range of hosts for ticks. It is important to note that ticks can transmit the various viruses and pathogens they receive from their previous host during feeding and sucking blood. However, we think that with all the potential that ticks have, they are more likely to get the SARS-COV-2 virus from the bat and pass it on to their next host. They may also be a factor for the mutation in the virus. As a result, further studies in this area are essentially needed to refute or confirm this hypothesis.


  Tick Feeding and Pathogen Transmission Top


Vertebrates respond to skin damage caused by stinging by creating a hemostatic plug, vasoconstriction, inflammation, and tissue repair.[105] An important biological substance that weakens the host's defenses and facilitates blood flow (thus providing adequate feeding) is saliva.[105] However, to facilitate blood flow and ensure the feeding, ticks have developed a sophisticated and advanced drug weapon that blocks pain and itching, inhibits homeostasis, innate and adaptive immune responses, and angiogenesis, and regulates wound healing in its host.[106],[107],[108],[109],[110],[111] These molecules have been shown to create a favorable environment for tick-borne pathogen (TBP) transmission, survival, and proliferation in vertebrate hosts.[107]

Saliva shows cytolytic activity, vasodilator, anticoagulant, anti-inflammatory, and immunosuppressive.[105] During their long evolution with ticks and the host of vertebrates, microorganisms have, in fact, developed various strategies for exploiting mite saliva molecules to ensure through ticks and transmission, local infection, and systemic release in the host of vertebrates.[105]

In addition, tick serine protein inhibitors also regulate the host response of vertebrates during biting, affecting homeostasis, immune responses, or angiogenesis.[112] During this feeding process, all ticks inject saliva and alternately absorb blood.[112] For most TBPs, transmission to a new host occurs through saliva during feeding and emphasizes the importance of both salivary glands (SGs) and saliva in the transmission process.[105],[112]

The unique physiological and morphological activity of this tissue is closely related to the parasitic lifestyle. During feeding, the ticks insert saliva and absorb its meal in an alternating pattern through the same channel.[105]

TBP is eaten while ticks feeding with infected hosts. From the gut, TBP crosses the digestive epithelium and attacks the hemorrhoids, so they can penetrate the SG epithelium to attack the SG.[105] From there, TBP can be transmitted to the new host through saliva injected during a new blood meal [Figure 2].[105],[113]
Figure 2: (a) Schematic representation of the acquisition, development, and transmission of pathogens by ticks.[1] Pathogens are eaten by ticks with a meal when bitten.[2] Pathogens attack the gut and, depending on the type, remain in the middle until the next feeding or immediately pass through the gastrointestinal epithelium[3] to attack the tick's body.[4] Pathogens travel through the epithelium to the salivary gland and attack the acini.[5],[6] Pathogens are injected into a new host during feeding, along with saliva, which counteracts host homeostasis, inflammation, and immune responses, thus facilitating host-pathogen infection.[105] (b) Structural view of the salivary gland and midgut in the Ixodea

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  Ticks on Your Pets Top


Cats and dogs can easily become infected while walking outdoors and in tick-infested environments. As a result, ticks can wait in the open area for a questing position so that cats and dogs can approach and climb them. Then infect them. After infecting them, cats and dogs in the house can be shedding ticks and their eggs into your living environment by scratching, and this can be dangerous for us. On the other hand, it is possible that a tick infected with the coronavirus (previously acquired from a bat or any other host) can transmit it to cats and dogs by fomite and mechanical transmission [Figure 3].
Figure 3: A view of how your pet is infected by ticks

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The transmission of coronavirus through infected surfaces is quite clear. If you touch a surface or objects that have the virus on it, you can also get the virus and then touch it to your mouth, nose, or eyes. Coronavirus can survive for hours to days on surfaces such as desks and narrow tables. How long it lasts depends on the material from which the surface is made. Different types of surfaces from metal, wood, plastic, stainless steel and glass, COVID-19 can stay from 2-5 days.[114],[115]

The question that raised here is that if our tick is infected with the coronavirus, can it infect the environment in which it is present? After shedding from a cat and dog, and disappearing due to not finding the next host, can their residues cause the virus to spread in the form of aerosols? All of these theories need further study to refute or prove.


  Conclusion Top


Doesn't that sound interesting? Ticks with their potential and abundant abilities can play an important role in the disease transmission chain as an intermediate host or even the main source. The virus has required a common carrier between different species to move and transmit in the world, and it could be ticks. Today, the epidemiological status of many bacteria caused by ticks is very clear, although the viruses caused by ticks are not yet relatively well studied. These factors highlight the importance of studying the viral epidemiology in the tick population.

Thereby, based on the wide distribution of ticks and their co-existence with horseshoe bat, we suggest further studies on ticks that might act as one of the main intermediate hosts in animals.

On the other hand, the role of the animal reservoir should not be forgotten here. Even if the vaccine is produced and delivered, it is still possible to transmit the virus between animals. As a result, the reservoir role of animals in this virus should be considered.

In any case, whatever the origin, whether it is a bat or any other creature, none of them play a more important role than the transfer of person to person. Regardless of the source of the epidemic, illegal trade and the sale of wildlife species without health control is one of the most important factors in the transmission of diseases. As a result, to prevent future epidemics, the international community must resolutely fight this problem to maintain health and biodiversity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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