Comparative review of Pestivirus C and Coronavirus: One Health Approach to Tackling Disease Outbreak

Abstract:

Viral diseases have been documented both in animals and humans with related pathogenesis and clinical manifestations. Some of these pathogens are correlated in how they cause disease. Additionally, it’s been noted that disease outbreaks in humans have mostly been caused by viruses of animal origin i.e. zoonotic diseases. To effectively respond to these outbreaks, there is a need to understand disease processes in animals and correlate them with those in humans in a one health model of practice.

With the current COVID-19 outbreak, the causative agent Coronavirus is correlated to Pestivirus C which causes Classical Swine Fever in pigs. We therefore resolved to explore this correlation through desktop review of literature and collation of probable complications which are not being targeted in the current responses.

Pestivirus C causes neurological defects in piglets born of infected pigs. If the same is to be extrapolated to humans, there would be a risk of having children with neurological defects post this pandemic. It’s therefore important to institute extra measures to protect pregnant women from infection.

Key words: Pestivirus, Coronavirus, Zoonosis, One Health and Classical Swine Fever (CSF).

Background:

Viruses have been known to cause disease in animals and humans. In certain cases these diseases can be transmitted from animals to humans and these are termed zoonotic diseases. Disease outbreaks of international concern caused by viruses have to a great extent been attributed to animal sources e.g. Ebola Virus Disease (EVD)[1], Severe Acute Respiratory Syndrome (SARS)[2], Middle East Respiratory Syndrome Coronavirus (MERS-CoV)[3] and the latest Coronavirus disease (COVID-19)[4].

@ Viral zone

Pestiviruses have been known to cause disease in animals especially cattle and pigs with Pestivirus A and B being known to cause Bovine Viral Diarrhoea while Pestivirus C causes Classical Swine Fever in pigs. There are several, at least eight (8), other Pestiviruses[5].

Pestiviruses are enveloped, spherical, positive sense single stranded RNA virus. (+ ssRNA). They are about 50nm in diameter and a mature virion consists of three virus-encoded membrane proteins in addition to the capsid protein i.e. four structural proteins[6]. The genome is about 12kilobase (kb). The virus particle binds to cellular receptors using the E protein (a structural protein on the surface) after which clathrin-mediated endocytosis takes place by fusion with host endosomal membrane[7].

Pestivirus C causes classical swine fever in pigs which has acute and chronic forms. The acute form presents with fever, huddling of sick animals, loss of appetite, dullness, weakness, conjunctivitis, constipation followed with diarrhea, and an unsteady gait. The animals with acute disease die within 1-2 weeks. The low virulence strains may only manifest poor reproductive performance and birth of piglets with neurologic defects such as congenital tremor[8].

Coronaviruses are spherical, enveloped positive-sense RNA (+ ssRNA) viruses with a characteristic club-like spikes on the surface. They have an unusually large RNA genome of up to 33.5kilobases (kb) and a diameter of approximately 125nm. They have helically symmetrical nucleocapsids which is uncommon for +ssRNA viruses. Coronavirus particles contain four main structural proteins all of which are encoded by the 3’ end of the viral genome. The viral particle attaches to the host receptor using Protein S (a structural protein). Many coronaviruses use peptidases such as aminopeptidase N (APN), dipeptidyl-peptidase 4 (DPP4) and angiotensin converting enzyme 2 (ACE2) as their cellular receptor. The entry is then mediated by acid-dependent proteolytic cleavage of S-protein. Fusion generally occurs within acidified endosomes while some use the plasma membrane[9].

@ American Society for Microbiology

Coronavirus disease (COVID-19) which has been declared a global pandemic has manifested with fever, cough, shortness of breath or difficulty breathing, chills, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell. There have also been indications of asymptomatic individuals. The most at risk group have been the elderly and those with comorbidities such as hypertension, diabetes and respiratory ailments[10].

Complications:

Classical swine fever have been reported to manifest with complications on internal organs upon autopsy of the dead. These include hemorrhage of the kidney which look like mottled duck eggs[11], spleen, lungs with characteristic pneumonia signs, tonsillitis and necrotic ulcers in the intestines and heart among other complications 6. Additionally, infection of pregnant pigs was attributed to neurological defects in their piglets manifested as congenital tremors[8].

Coronavirus disease (COVID-19) on the other hand have to a greater extent been associated with pneumonia attributed to destruction of lung tissues. This is the major cause of severe morbidity and mortality associated with COVID-19. Other complications which have been reported include heart damage[12], acute kidney disease[13], formation of blood clots[14] and neurologic complications[15].

Correlation:

Pestiviruses and Coronaviruses share a commonality in the nature of their genome i.e. both are spherical enveloped positive-sense single stranded RNA viruses with attachment and fusion of host cells being mediated by endosomes.

Both viruses are known to cause respiratory distress, fever, fatigue and dullness as the main clinical symptoms. Additionally, both pigs and humans have been observed to share clinical complications especially with regard to acute kidney injury (AKI) and cardiac damage.

Both viruses are of animal origin and in this case coronavirus happened to have been transmitted to humans from an animal source. It is therefore imperative to infer that there is a correlation in the pathogenesis of these viruses.

One health concept focuses on establishing an interconnected system for animal, human and environmental health. In this case, it is evident that with advanced understanding of pathological processes in animals we can prevent or better manage them in humans.

Public health communication on COVID-19 have not explicitly stated any heightened risk to pregnant women. This would have a counter-productive outcome in case evidence later emerges to show otherwise. Basing on the evidence of neurological involvement of Pestivirus C in pigs, it’s imperative to take extra caution among the pregnant women to protect them from unforeseen harm caused to their unborn children.

Additionally, from scientific evidence it is reported that Pestivirus was shed in feces of pigs while for Coronavirus particles have been obtained in maternal[16] and neonatal feces[17]. It therefore shows there would be probable transmission through feces which is yet to be confirmed.

Recommendations:

New information about COVID-19 keeps coming up and the best way to respond to this pandemic is to seal all probable loop-holes and to integrate a one health approach model of care. We therefore recommend that the WHO and national public health authorities;

  1. Incorporate probable risk to pregnancy which would ensure pregnant women take extra caution with regard to this disease outbreak.

  2. Champion for research in animal diseases as a means to establish pool of evidence to help mitigate transmission to humans as well as enable better response in case of an outbreak.

Acknowledgement: We acknowledge insight from Simon Njenga that pointed us to further research into Pestivirus C and probable correlation with novel Coronavirus-2019.

Authors: Ms. Kelly Wanyonyi; Fourth Year Pharmacy Student, Kabarak University and Dr. Odhiambo David, Co-founder, Ryculture Health and Social Innovation.

[1]What is Ebola Virus Disease?: https://www.cdc.gov/vhf/ebola/about.html [2] SARS (Severe Acute Respiratory Syndrome): https://www.who.int/ith/diseases/sars/en/ [3] Middle East respiratory syndrome coronavirus (MERS-CoV): https://www.who.int/news-room/fact-sheets/detail/middle-east-respiratory-syndrome-coronavirus-(mers-cov) [4]Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19): https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf [5] Proposed revision to the taxonomy of the genus Pestivirus, family Flaviviridae: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656787/ [6] Classical Swine Fever—An Updated Review: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408692/ [7]Pestivirus: https://viralzone.expasy.org/39?outline=all_by_species [8] Classical Swine Fever (CSF): https://www.oie.int/en/animal-health-in-the-world/animal-diseases/Classical-swine-fever/ [9] Coronaviruses: An Overview of Their Replication and Pathogenesis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369385/ [10] Coronavirus (COVID-19): https://www.cdc.gov/coronavirus/2019-ncov/index.html [11] Classical swine fever (Hog cholera): https://thepigsite.com/disease-guide/classical-swine-fever-csf-hog-cholera-hc [12] Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19): https://jamanetwork.com/journals/jamacardiology/fullarticle/2763843 [13] COVID-19 and Kidney Failure in the Acute Care Setting: Our Experience From Seattle: https://www.ajkd.org/article/S0272-6386(20)30618-1/fulltext [14] Blood Clot Complications in Patients With Coronavirus Disease 2019 (COVID-19): https://www.pulselive.co.ke/bi/tech/blood-clots-are-the-latest-life-threatening-complication-of-the-coronavirus-but/204sd2l [15] Neurologic Complications in Coronavirus Disease 2019 (COVID-19) Patients: https://bestpractice.bmj.com/topics/en-us/3000168/complications#referencePop448 [16] INITIAL GUIDANCE: Management of Infants Born to Mothers with COVID-19: https://downloads.aap.org/AAP/PDF/COVID%2019%20Initial%20Newborn%20Guidance.pdf [17] Information for Pediatric Healthcare Providers: https://www.cdc.gov/coronavirus/2019-ncov/hcp/pediatric-hcp.html