Thursday, July 06, 2023

J. Med. Virology: Potential Cross-Species Transmission Risks of Emerging Swine Enteric Coronavirus to Human Beings


Following our unexpected close call with SARS-COV in 2002-2003 (see SARS and Remembrance), influenza viruses were suddenly no longer the only credible pandemic threat facing humanity.  

While a pandemic was averted, in 2012 another coronavirus - MERS-CoV - appeared in the Middle East,  and has been on our watch list for more than a decade (see recent UKHSA Risk Assessment of MERS-CoV).

In 2019, SARS-CoV-2 emerged in China, and exceeded all expectations - killing millions - while  finally cementing coronaviruses as legitimate pandemic threats. 

There are, of course, a lot of other coronaviruses in the wild. Some we know about, and others yet to be discovered.  They can be found in bats, birds, swine, cattle, and other mammals.  Most are thought not to be a threat to humans, but some may be closer to spilling over than we know. 

In 2014, in SECD: Another Emerging Coronavirus Threat - in the wake of several newly discovered coronaviruses detected in North American swine we looked at growing concerns that some porcine-adapted coronaviruses might have zoonotic potential, given the similar physiology between our two species.  

In the summer of 2017 we looked at paper published in the  EID Journal: A New Bat-HKU2–like Coronavirus in Swine, China, 2017, on the recent discovery of a new HKU2-like coronavirus in Chinese pigs showing symptoms of PED (Porcine Epidemic Diarrhea), which they tentatively named porcine enteric alphacoronavirus (PEAV). 

As pigs are physiologically fairly close to humans (if that bothers you, think how the pig feels), we watch porcine adapted viruses with particular interest.

In a follow up in 2020, in PNAS: Swine Coronavirus Replicates In Human Cells, we saw additional evidence to suggest that swine coronaviruses might have the `right stuff' to spill over into humans.  

Specifically, researchers demonstrated that the new HKU2-like virus in the 2017 study above (now dubbed Swine acute diarrhea syndrome coronavirus (SADS-CoV)) virus replicates efficiently in a variety of human cells, making it potentially a zoonotic threat.

All of which brings us to a detailed Letter, published in the Journal of Medical Virology, that uses the above data - and other sources - to make the case for the zoonotic potential of two classes of swine coronaviruses (PDCoV and SADS-CoV).

Due to its length and technical nature, I've only posted some excerpts. Follow the link to read it in its entirety.  I'll have a brief postscript when you return. 

Zhenhua Guo, Qianyue Jin, Peng Li, Guangxu Xing, Qingxia Lu, Gaiping Zhang
First published: 30 June 2023

Dear Editor,

Coronaviruses (CoVs) are a wide group of animal pathogens, which can cause a variety of diseases, and sometimes pose a great challenge on public health.1 CoVs belong to the Nidovirales order, Coronaviridae family, and Coronavirinae subfamily, which contains four genera-Alphacoronavirus (α-CoV), Betacoronavirus (β-CoV), Gammacoronavirus (γ-CoV) and Deltacoronavirus (δ-CoV).2 To date, seven human CoVs (HCoVs) have been identified: HCoV-NL63 and HCoV-229E belong to α-CoV, HCoV-OC43, HKU1, severe acute respiratory syndrome coronavirus (SARS-CoV), MERS-CoV, and the latest SARS-CoV-2 belong to β-CoV.1, 3 Importantly, all of them are descended from animal reservoirs. HCoV-OC43 and HKU1 are considered likely to be originated from rodents, HCoV-NL63 HCoV-229E, SARS-CoV, MERS-CoV, and SARS-CoV-2 are very likely passed from bats to humans in a zoonotic event, although the supposed origins of SARS-CoV and SARS-CoV-2 are still in debate.2, 3 Wild animals (e.g., palm civets for SARS-CoV, camels for MERS-CoV) usually play important roles as intermediate hosts that enable virus spill over from natural hosts to humans.2 Although the exact intermediate host for SARS-CoV-2 spread to humans are controversial, wild animals, including raccoon dogs, bamboo rats, and pangolin, are thought to have the highest likehood.1, 3 The ongoing SARS-CoV-2 pandemic has brought the zoonotic CoVs, especially those with a potential for cross-species transmission, into unprecedented attention worldwide.

Swine CoVs (SCoVs) are the major enteric and respiratory pathogens in pigs. These include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine respiratory coronavirus (PRCV), porcine hemagglutinating encephalomyelitis virus (PHEV), and the latest emerging SCoVs, porcine delta coronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV).3 Among them, TGEV, PEDV, PRCV, SADS-CoV belong to α-CoV, PHEV belongs to β-CoV while PDCoV belongs to δ-CoV.2 All these SCoVs usually infect pigs.
However, the newly emerging PDCoV and SADS-CoV have also shown broad host tropism,4, 5 suggesting a potential challenge to public health. Here, we discussed the recent progress of cross-species transmission and zoonotic potential of PDCoV and SADS-CoV. We also highlight the urgency of implementing preventive interventions.3
In summary, current studies suggest that PDCoV and SADS-CoV represent two possible zoonotic animal viruses for human. It is necessary to take appropriate interventions to reduce the risk of cross species transmission, since poultry and livestock usually become suitable intermediate hosts or mixers for viruses (e.g., influenza viruses) to infect human beings. Considering the wide prevalence of PDCoV in pigs, it is a economically rational strategy to block the potential transmission routes by massive immunization with highly effective vaccine, similar to the successful experience in the H7N9 intervention.20 SADS-CoV is only limited and rarely outbroke in southern China, so it is more reasonable and efficient to adopt the strategy of eradication. Moreover, given that animal CoVs are important viruses seriously endangering human health in the past, present and future, it is also urgent to understand their pathogenic mechanisms and develop broad-spectrum anti-CoV drugs and pan-CoV vaccines.

Like it or not, we live in a pathogen-rich environment. Every few months we learn about some new or expanding disease threat in the wild (see UK HAIRS Timeline below), and there are no signs this trend is slowing down.

When it comes to identifying zoonotic disease threats, we are barely scratching the surface of what is out there.  

Two summers ago, in PNAS Research: Intensity and Frequency of Extreme Novel Epidemics, researchers suggested that the probability of novel disease outbreaks will likely grow three-fold in the next few decades. 

Given the plethora of pathogens in the wild, its hard not to consider that an optimistic assessment.