Insect vectors of human viral diseases: Can they transmit COVID-19?

Insects are carriers of diseases to humans, other animals and plants. Centuries ago, they have been suggested as being possibly entailed in the spread of disease, especially with the outbreak of war (MacGregor, 1918). In 1577 Mercurialis, an Italian physician, suggested that plague, which was then ravaging Europe, was spread by flies feeding upon the diseased and dead, and later depositing fecal matter on food consumed by healthy persons (MacGregor, 1918). The connection between insects and diseases such as Yellow fever, Malaria, Anthrax, Filaria were also established a long time ago (MacGregor, 1918). The Dengue fever, whose global incidence has grown in recent decades was named as breakbone fever at the time and was stated as an insect-borne disease of unknown origin. Sandflies and mosquitoes were named as potential vectors, but the mosquito vectors were identified as Culex fatigans and Stegomyia fasciata (MacGregor, 1918). In 1937, Cook stated of 135 species of insects as vectors of viral diseases in plants. Species of aphids (causing “curl” disease to potatoes, Bermuda Lily disease) and leafhoppers (causing “Dwarf of Rice” disease in Japan, curly top disease of sugar beet in America) were identified as some of the important plant disease vectors (Cook, 1937). Received: 05 Oct 2020


Introduction
Insects are carriers of diseases to humans, other animals and plants. Centuries ago, they have been suggested as being possibly entailed in the spread of disease, especially with the outbreak of war (MacGregor, 1918). In 1577 Mercurialis, an Italian physician, suggested that plague, which was then ravaging Europe, was spread by flies feeding upon the diseased and dead, and later depositing fecal matter on food consumed by healthy persons (MacGregor, 1918). The connection between insects and diseases such as Yellow fever, Malaria, Anthrax, Filaria were also established a long time ago (MacGregor, 1918). The Dengue fever, whose global incidence has grown in recent decades was named as breakbone fever at the time and was stated as an insect-borne disease of unknown origin. Sandflies and mosquitoes were named as potential vectors, but the mosquito vectors were identified as Culex fatigans and Stegomyia fasciata (MacGregor, 1918). In 1937, Cook stated of 135 species of insects as vectors of viral diseases in plants. Species of aphids (causing "curl" disease to potatoes, Bermuda Lily disease) and leafhoppers (causing "Dwarf of Rice" disease in Japan, curly top disease of sugar beet in America) were identified as some of the important plant disease vectors (Cook, 1937).
Today we are aware that insects are very common vectors of disease and transmit viral, bacterial and protozoan pathogens via their bite, or via their feces. The diseases can be asymptomatic to fatal and are commonly grouped as invasive neurological diseases, hemorrhagic fever and systemic febrile illness (Dehghani & Kassiri, 2020). Viruses transmitted by insects cause diseases that are important world-wide, and result significant morbidity and mortality in humans. However, the literature on the subject is scattered and rarely has been assembled into a single source. The present review attempts to address some key points on the subject regarding human viral diseases transmitted by insects, and the global distribution and symptoms of these diseases, virus types responsible for the diseases and species of the insect vectors are considered. Further, the possibility of insects in transmitting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19) is discussed.

Mosquitoes as vectors of human viral diseases
Amongst insects, mosquitoes are the prominent vectors of viral diseases as 3,500 species are found widely spread worldwide. These species belong to 112 genera of which four genera are repeatedly linked with disease transmission to humans in the tropics and in cooler climates: Aedes, Anopheles, Culex, and Ochlerotatus. The genus Aedes is the most relevant species regarding disease transmission due to their adaptability to urban life and high susceptibility to emerging and reemerging arboviruses (Monteiro et al., 2019).
Although numerous viral diseases are transmitted by mosquitoes, four have caused the most human suffering over the centuries and are continuing today. These are the viral diseases yellow fever, dengue, chikungunya and Zika fever (Powell, 2018). Dengue is associated with human epidemic diseases in urban areas and yellow fever is found in rural areas (Sarwar, 2016). Africa is clearly the ancestral home of yellow fever, chikungunya and Zika viral fever, and likely the dengue viral fever. Several species of mosquitoes, primarily in the genus Aedes, have been transmitting the viruses of these diseases among African primates for millennia allowing for coadaptation among viruses, mosquitoes and primates. One African primate (human) and one African Aedes mosquito (Aedes aegypti) have escaped Africa and spread around the world making it likely that when the next diseasecausing virus comes out of Africa, Aedes aegypti will be the major vector to humans (Powell, 2018).
When considering the viral pathogens of the diseases transmitted by mosquitoes, most viruses are of the families Flaviviridae and Togaviridae (Table 1). The family Flaviviridae consists of at least 68 viruses and is divided into four genera: Flavivirus, Pestivirus, Pegivirus and Hepacivirus (Ludwig & Iacono-Connors, 1993;Salas-Benito & De Nova-Ocampo, 2015). The Flavivirus genus consists of 53 virus species (Huhtamo et al., 2009), and is divided into four categories as mosquitoborne, tick-borne, no known vector and insectspecific viruses (Salas-Benito & De Nova-Ocampo, 2015). The mosquito-borne Flavivirus diseases are emerging as the cause of some of the most serious and widespread arthropod-borne viral diseases in the world and have caused large outbreaks in many countries (  (Das et al., 2018). The Togaviridae viral diseases transmitted by mosquitoes are mostly characterized by rashes and joint pains and are more restricted in distribution. These diseases such as Chikungunya fever, Pogosta disease, Mayaro fever and Barmah Forest Virus disease are transmitted by mosquitoes of the genera Aedes, Culex, Haemogogus, Anopheles, Mansonia, Psorophora and Sabethes and have caused outbreaks to a lesser extent ( Table  1). The family Togaviridae consists of the genus Alphavirus with more than 30 species which are mosquito-borne and transmitted between mosquito vectors and vertebrate hosts (Chen et al., 2018).

Other insect vectors of human viral diseases
Insects other than mosquitoes transmit viral diseases to a lesser extent. In 1965, Greenberg stated that flies harbor over 100 different species of pathogenic organisms and transmits bacterial diseases and infections by parasites. According to Greenberg (1965) flies also transmit viral diseases such as poliomyelitis, coxsackie virus infection and hepatitis, a fact which has also been stated by Lindsay & Scudder (1955). However, reports of the isolation of viruses from flies are rare and their role in disease transmission are mostly circumstantial. Most viruses carried by flies are of veterinary importance such as the Senecavirus A whose natural hosts are pigs and cows, the porcine reproductive and respiratory syndrome virus which causes diseases to pigs, and Avian influenza virus and Newcastle disease virus that affects birds (Khamesipour et al., 2018). Dutto et al. (2016) reports the role of several insects in spreading the Ebolavirus which causes a severe disease in humans. Periplaneta americana (Blattaria, Blattidae), Messor capensis (Hymenoptera, Formicidae), Homoptera and Ephemeroptera have been identified as possible natural Ebolavirus reservoirs and their transmission of the virus from bats to humans needs to be established by further studies. However, it has been demonstrated that there is low potential for the mechanical transmission of Ebolavirus via houseflies (Haddow et al., 2017). Further, houseflies are not considered as a major factor in the dissemination of poliovirus and any role played by them in disease transmission has considered to be incidental (Cirillo, 2016 (Horne & Vanlandingham, 2014).
Cockroaches are considered as efficient vectors of pathogens like bacteria, protozoa, fungi, eggs of pathogenic intestinal worms and viruses such as the Polio virus (Tatang et al., 2017). The poliomyelitis virus has been isolated from domiciliary species of cockroaches and the successful laboratory transmissions of a number of viral infections to cockroaches indicates their capability of acting as a vector to other viral diseases such as hepatitis (Tarshis, 1962).

Insects and Covid-19
The coronavirus is a RNA virus of the family Coronaviridae, genus Coronavirus (Miller, 1999), which was first isolated in 1937 (Dehghani & Kassiri, 2020). As the largest known RNA viruses, coronaviruses are divided into four genera: alphacoronavirus, beta-coronavirus, gamma-coronavirus and delta-coronavirus. To date, there have been six human coronaviruses (HCoVs) identified, including severe acute respiratory syndrome-CoV (SARS-CoV) and Middle East respiratory syndrome-CoV (MERS-CoV) (Wu et al., 2020). New coronaviruses appear to emerge periodically in humans, mainly due to the high prevalence and wide distribution of coronaviruses, the large genetic diversity and frequent recombination of their genomes, and the increase of human-animal interface activities (Wu et al., 2020). The novel coronavirus reported in late December 2019, has now created a public health emergency of international concern and brought the world to a standstill. The novel coronavirus is the seventh member of the family coronaviruses, and is a betacoronavirus with over 70% similarity in genetic sequence to the SARS coronavirus. Bats are the most possible host of this pathogen, and snakes, minks and pangolins are also potential hosts (Wu et al., 2020).
The novel coronavirus is transmitted from person to person via respiratory droplets, close contact, aerosols, and possibly the faecal-oral route (Dehghani & Kassiri, 2020). There have been no reports of COVID-19 transmission by bloodsucking arthropods such as mosquitoes or any other such insects (Dehghani & Kassiri, 2020). However, viruses may be transmitted by arthropods in two ways, either biologically or mechanically. In mechanical transmission insects become contaminated with viruses during normal feeding behavior, and virus persists on their mouthparts or body until the next feed (Carn, 1996).
The disease mostly affects children.

Species of genus Aedes: Aedes aegypti is the primary vector, but
Ae. albopictus and Ae. polynesiensis may also act as vectors (Malavige et al., 2004).
Has caused outbreaks in the countries of the Indian ocean region, Africa and America (Deeba et al., 2016).
Transmitted by mosquitoes of the genus Aedes. Aedes aegypti is the most important vector and has extensive worldwide distribution. Aedes albopictus is reported from Southeast Asia, several European countries and some Asian countries; it is poorly distributed in the African continent (Monteiro et al., 2019).
Arthritis, maculopapular rash, low fever, fatigue, muscle pain (Kurkela et al., 2004). The main clinical symptoms are related to joints, and are swelling and tenderness of the ankle, knee, wrist or fingers, especially the metacarpophalangeal joints (Turunen et al., 1998).
European Mediterranean countries from Spain to Turkey, the North African countries of Tunisia and Morocco (Howell et al., 2015).
. Insects such as cockroaches and houseflies, which are major mechanical vectors of pathogens, can transmit diseases by contact with contaminated surfaces and studies have associated insects such as beetles and domestic insects as mechanical carriers of pathogens (Dehghani & Kassiri, 2020). SARScoronavirus, MERS-coronavirus and influenza virus can survive on surfaces for extended periods, sometimes upto months, depending on the strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity of the environment (Otter et al., 2016). COVID-19 virus mainly occurs in respiratory samples of infected persons but have been reported in feces samples in a limited number of cases (Dehghani & Kassiri, 2020). According to Eslami & Jalili (2020), SARS-CoV-2 excretion by stool has been confirmed in some patients. Nath and Gupta (2020) reveals that the virus can be found in a person's stool and can remain viable for days in favourable atmospheric conditions. Therefore, any organism in contact with or feeding on human feces may play a role in COVID-19 transmission, and thus the role of insects such as houseflies and cockroaches becomes important. These insects are capable of transmitting more than 100 pathogens through their legs, body hair, mouthparts, feces and vomit which may occur on human food waste, sputum, nasal secretions, fresh and dried blood and stool (Dehghani & Kassiri, 2020).
Currently insects are known to transmit viruses of families Flaviviridae, Togaviridae and Bunyaviridae, and insect transmission of viruses of family Coronaviridae has not been documented. Further, when considering the deadly pandemics recorded in history, pandemics caused by viruses are few and when viruses are the pathogens, transmission is usually air-borne. Smallpox that has now been eradicated from the world was caused by the variola virus and transmitted by the air-borne respiratory route (MacIntyre et al., 2020). Therefore, the biological transmission of COVID-19 by insects may not be a possible route for the disease to spread. However, the mechanical transmission of the virus by insects other than mosquitoes cannot be entirely ruled out. The new coronavirus was detected in the feces of confirmed patients in Wuhan, Shenzhen and the United States, indicating that the virus can exist and replicate in the digestive tract. However, it is not certain that eating virus-contaminated food causes infection and transmission (Wu et al., 2020). The mode of infection transmission has profound implications for effective containment of diseases by public health interventions. Therefore, it is important that the methods of COVID-19 transmission be further examined and understood.

Conclusions
Insects are important vectors of human viral diseases. Amongst insects, mosquitoes are the prominent vectors causing biological transmission of diseases, and sandflies, houseflies and cockroaches can cause mechanical transmission. COVID-19 is a deadly infectious disease caused by the most recently discovered coronavirus. It is an ongoing pandemic spread by air when people are physically close. However, it may also be transmitted via contaminated surfaces, although this has not been conclusively demonstrated. Therefore, insects in contact with or feeding on contaminated surfaces may play a role in COVID-19 transmission. At the moment the link is theoretical and under possible investigation. However, in the past insects and pandemics seem to be inextricably linked in a negative manner in the minds of people and thus their role in COVID-19 transmission is compelled for attention.