A new study shows swine α-coronavirus could replicate in human cells: The real-life implications explained.
In the 21st century, we see three novel human beta-coronaviruses: SARS-CoV-1, MERS-CoV, and SARS-CoV-2. We also see three new swine coronaviruses: porcine epidemic diarrhea virus (PEDV), porcine delta-coronavirus (PDCoV), and swine acute diarrhea syndrome-coronavirus (SADS-CoV).
SADS-CoV is an alpha-coronavirus that jumped from bats to pigs in the Guangdong province of China in 2017. It causes lethal diarrhea with a death rate as high as 90% in piglets but only 5% in pigs older than eight days. SADS-CoV has killed 24,693 pigs in four farms — including pigs vaccinated for PEDV — shortly after the jump and before it was contained.
But it re-emerged in 2018 and 2019 in Fujian and Guandong Provinces of China, respectively, on a smaller scale outbreak. The good news is that SADS-CoV has not appeared in any other country besides China.
“While many investigators focus on the emergent potential of the beta-coronaviruses like SARS and MERS, actually the alpha-coronaviruses may prove equally prominent — if not greater — concerns to human health, given their potential to rapidly jump between species.”
What the new study shows
Importantly, SADS-CoV may have the potential to become a zoonotic disease that jumps from pigs to humans, a new study suggests.
The new study, “Swine acute diarrhea syndrome coronavirus replication in primary human cells reveals potential susceptibility to infection,” was published in the Proceedings of the National Academy of Sciences (PNAS) this week. Ralph S. Baric led the study, a distinguished professor of epidemiology, immunology, and microbiology at the University of North Carolina, specializing in coronavirus and emerging zoonosis research.
And the key results are as follows:
- SADS-CoV replicated efficiently in both pig and human cells cultured from the lungs, liver, stomach, and intestines. Specifically, all sorts of human lung cells — including microvascular endothelial cells, fibroblasts, and nasal and airway epithelial cells — were prone to SADS-CoV infection.
- To discern if humans have any existing immunity against SADS-CoV, the study exposed human cells to common cold-causing coronaviruses. And then check if the antibodies generated could cross-neutralize SADS-CoV. It did not, which suggests no existing immunity.
- Remdesivir — an antiviral to treat Covid-19 — stopped the replication of SADS-CoV in human cells. Indeed, remdesivir restrains RNA polymerase — an enzyme RNA viruses (like coronaviruses) use to make their genes.
- SADS-CoV could still infect cells despite blocking the common receptors coronaviruses exploit — i.e., angiotensin-converting enzyme 2 (ACE2; for SARS-CoVs), dipeptidyl peptidase 4 (DDP4; for MERS-CoV), and aminopeptidase N (APN; for other swine coronaviruses). “These data suggest that SADS-CoV does not use any of these known coronavirus receptors for docking and entry into human cells,” stated the authors.
- SADS-CoV could not replicate properly in mice. “We noted little, if any, evidence of reproducible or robust virus replication in the liver, spleen, or various sections of the intestine,” the researchers wrote. This result is expected since mice are poor animal models of coronaviruses.
SADS-CoV follows a fecal-oral transmission route in pigs — a route unlikely to affect human civilizations with proper food and water hygiene and sanitization.
* Source: Yang et al. (2020). Potential routes of interspecies transmission between SADS-CoV and different hosts.
Practical implications of this study
Cell culture studies do not always translate to actual humans. “These assays don’t account for the effect of other viral or host proteins and the parade of biochemical host-pathogen interactions that must occur to support infection and transmission,” explained Nathan D. Grubaugh, an assistant professor of epidemiology at Yale School of Public Health.
That said, SADS-CoV is an alpha-coronavirus. A bioinformatics study in Nature found that “host-switching occurs more frequently and across more distantly related host taxa in alpha- than beta-CoVs.” This means that alpha-coronavirus have a higher potential for interspecies transmission than beta-coronaviruses.
“While many investigators focus on the emergent potential of the beta-coronaviruses like SARS and MERS, actually the alpha-coronaviruses may prove equally prominent — if not greater — concerns to human health, given their potential to rapidly jump between species,” Prof. Baric said.
How likely is it for SADS-CoV to become zoonotic? The odds are low, but not 0%. How big is the outbreak, if it happens, is also a crucial question.
Assuming humans contracted SADS-CoV, it has a slim chance to turn into a large-scale outbreak. SADS-CoV follows a fecal-oral transmission route in pigs — a route unlikely to affect human civilization with proper food and water hygiene and sanitization. However, we also cannot deny that SARS-CoV-2, the current coronavirus that causes COVID-19, can be transmitted via contact with aerosolized feces as well, although it's rare.
* Source: Li et al. (2020). The transmission pathways of the SARS-CoV-2. Although direct droplet transmission is the main route of transmission, fecal excretion, environmental contamination, and fomites might contribute too.
However, the capacity of SADS-CoV to replicate in various types of human lung cells is a concern, as the new study shows, especially when virus particles in feces are aerosolized. Further worries are that humans have no existing immunity against SADS-CoV and its unknown mode of cell infection. But, at least remdesivir is something we can rely on if SADS-CoV becomes a zoonosis.
Notably, no pig-to-human transmission of SADS-CoV has been reported since its first detection in 2017. If zoonosis did not happen after three years, it probably will not. How likely is it for SADS-CoV to become zoonotic? The odds are low, but not 0%. How big is the outbreak, if it happens, is also a crucial question.
Still, it is never a bad idea to take precautions. Research on new vaccines or antivirals against SADS-CoV for pigs should be funded, for example. “Not surprisingly, we are currently looking for partners to investigate the potential of SADS-CoV vaccine candidates to protect swine,” Prof. Baric and the team said. “We recommend that both swine workers and the swine population be continually monitored for indications of SADS-CoV infections to prevent outbreaks and massive economic losses.”
This article was originally published here with modifications.