COVID-19 from veterinary medicine and one health perspectives: What animal coronaviruses have taught us
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1. Introduction
Coronaviruses
(CoVs) are enveloped, single-stranded, positive-sense RNA viruses
displaying an exceptional genetic plasticity driven by accumulation of
point mutations and recombination events. This genetic variation is
responsible for continuous emergence of viral strains with increased
virulence, different tissue tropism and/or expanded host range (Buonavoglia et al., 2006). CoVs are currently classified within four genera, Alphacoronavirus, Betacoronavirus, Gammacoronavirus and Deltacoronavirus, that recognise bats, birds and likely rodents as natural reservoirs.
In
December 2019, cases of undiagnosed pneumonia started being reported in
Wuhan, Hubei, China. On January 9 2020, the Chinese authorities
indicated that a novel CoV was associated with the severe respiratory
disease. The first patient with unexplained pneumonia, identified in
December 8 2019, came from Wuhan South China Seafood Market. Initially,
other patients were linked to the same seafood and live animal market,
suggesting an animal origin for the initial spread to humans. Subsequent
investigations revealed that the crowded seafood market only boosted
circulation of the novel CoV and spread it to the whole city in early
December 2019, whereas based on the genome data the virus likely began
spreading from person to person in early December or even as early as
late November. The first documented human case has been dated back to
November 17 2019.
The novel human CoV (HCoV) is a
betacoronavirus genetically related to Severe acute respiratory syndrome
(SARS) CoV and only distantly related to Middle East respiratory
syndrome CoV (MERS-CoV) and it was designated as SARS type 2 CoV
(SARS-CoV-2). Similar to the other hypervirulent HCoVs, SARS-CoV-2 has a
putative animal origin, likely descended from a related bat CoV that
spilled over to humans either directly or after adaptation in another
animal species, such as the Malayan pangolin (Lam et al., 2020). SARS-CoV-2 is highly related genetically (96% nt) to a SARS-like bat CoV (Zhou et al., 2020)
The
SARS-CoV-2 induced disease, referred to as CoronaVirus Disease 2019
(COVID-19), affects the respiratory tract, with a number of patients
displaying severe pneumonia and requiring hospitalisation and admission
to intermediate or intensive care units. Unlike SARS and MERS, COVID-19
is characterised by low lethality rates and high frequency of
asymptomatic or paucisymptomatic infections that likely favoured the
spread of this new pandemic (Lai et al., 2020).
As SARS-CoV-2 started spreading globally, between February and March
2020, potential spill over exposure (viral RNA) was noted in companion
animals, likely due to their strict social interactions with humans.
SARS-CoV-2 RNA was detected in two dogs and a cat without clinical signs
in Hong Kong and in a cat with gastroenteric and respiratory signs in
Bruxelles, all which lived in close contact with infected COVID-19 human
patients.1
,
2
This noted analogous findings observed during the 2002–2003 spread of SARS-CoV.3
2. Animal coronaviruses: the experience of veterinary medicine
Before
the emergence of SARS-CoV, the first highly pathogenic HCoV,
information was very scarce about HCoVs, whereas there was extensive
knowledge in veterinary medicine about animal CoVs, their evolution and
pathobiology. Infectious bronchitis virus (IBV) of poultry and feline
infectious peritonitis virus (FIPV) have been known since the early
1900, representing animal examples on how CoVs can evolve, changing
their tissue tropism and virulence (Decaro and Lorusso, in press).
In addition, swine CoVs are paradigmatic on how CoVs may cross the
species barriers infecting new hosts. Transmissible gastroenteritis
virus of swine (TGEV, alphacoronavirus), likely originated from the
closely related canine coronavirus (CCoV) (Lorusso et al., 2008)
and in turn TGEV gave rise to the less virulent porcine respiratory CoV
(PRCoV). Also, a TGEV-like CCoV was generated by recombination in the N
terminal end of the S gene (Decaro et al., 2009).
Two additional swine alphacoronaviruses emerged more recently, the
porcine epidemic diarrhoea virus (PEDV) and the severe acute diarrhoea
syndrome CoV (SADS-CoV), both derived from CoVs circulating in bats. The
betacoronavirus porcine haemagglutinating encephalomyelitis virus
(PHEV) was a derivative of bovine CoV, which in turn is believed to have
descended from a bat virus through adaptation in a rodent species. More
recently, porcine deltacoronavirus (PDCoV), the causative agent of
severe diarrhoea outbreaks in North America and Asia, emerged from avian
deltacoroviruses (Wang et al., 2019).
The observed repeated events of inter-species transmission by animal
CoVs rely on the exceptional ability of CoVs to expand their host range.
This strongly supports the natural origin of SARS-CoV-2, confuting
conspiracy theories of a laboratory origin (Liu et al., 2020).
Animal
CoVs may also represent excellent host models for development of
SARS-CoV-2 vaccines, which could require much more time than initially
anticipated. The majority of vaccines licensed for the veterinary market
have been developed for CoVs causing enteric infections, such as BCoV
and the swine CoVs TGEV and PEDV. These vaccines are intended for
parenteral use in pregnant cows/sows or oral use in sows (TGEV, PEDV) to
transfer maternal immunity to their offspring and protect them in the
first weeks of life, when they are more susceptible to severe of
disease. These vaccines take advantage of different technologies, since
BCoV/TGEV vaccines are inactivated or modified-live virus (MLV)
formulations that are produced according to traditional protocols. For
PEDV prophylaxis, in addition to killed and MLV preparations,
vector-based vaccines expressing the spike protein are commercially
available (Gerdts and Zakhartchouk, 2017; Saif, 2020).
BCoV is also responsible for respiratory disease in 2–3 month-old
calves or older animals, but specific vaccines currently are not
available for prevention of the respiratory disease (Decaro et al., 2008).
Also, some vaccines (i.e., CCoV) have been introduced into the market,
used for years and later abandoned, after cost-effectiveness
evaluations.4
The CCoV vaccines were administered parenterally, induced good systemic
but poor mucosal immunity and did not protect pups against infection
with virulent virus (Pratelli et al., 2003, Pratelli et al., 2004; Decaro et al., 2011).
The
only licensed animal CoV vaccines targeted to prevent respiratory CoV
infections are IBV vaccines for chickens. These vaccines, administered
parenterally, may not protect against the infection but they can reduce
the severity of the respiratory signs and prevent involvement of the
kidney and reproductive tract (Saif, 2020).
One of the main issues of parenteral vaccination against respiratory
CoVs in animals is that it does not trigger strong local immunity,
usually represented by mucosal immunoglobulin A (IgA). Mucosal immunity,
even if not preventing the infection, is able to reduce viral shedding
(in terms of duration and extent) and the severity of the respiratory
disease. Also this may be the case for SARS-CoV-2, which primarily
affects the respiratory tract and, to a lesser extent, the enteric
tract, with limited viremia and/or systemic involvement (Wong et al., 2020).
Also, the duration of immunity elicited by natural infection with
SARS-CoV-2 is not known yet. For animal CoVs, immunity after infection
may be of short duration. For instance, feline enteric coronavirus
(FECV) may induce short-term immunity that does not confer protection
from reinfections. FECV is an avirulent biotype of feline coronavirus
(FCoV) and it is the precursor of the hypervirulent biotype FIPV (Addie et al., 2020b).
Interestingly, FIP vaccines are paradigmatic of how difficult the
development of vaccines against human CoVs may be. FIP is a sporadic but
highly lethal disease of cats that originates as a consequence of the
switch from FECV to FIPV due to specific mutations in the spike protein
gene (Chang et al., 2012).
Despite considerable efforts so far, no effective FIPV vaccine has been
developed. One of the main issues is that most experimental vaccines
triggered an antibody-dependent enhancement (ADE) mechanism, which
causes a more severe disease in immunised animals than in control cats
after virus challenge (German et al., 2004).
ADE is triggered by antibody-mediated virus entry into macrophages via
Ig Fc receptors and might represent an obstacle to the development of
SARS-CoV-2 specific vaccines (Rauch et al., 2018).
An alternative mechanism for ADE has been described recently for
MERS-CoV, for which neutralizing antibodies bind to the spike protein,
triggering a conformational change of the spike and mediating viral
entry into IgG Fc receptor-expressing cells through canonical
viral-receptor-dependent pathways (Wan et al., 2020).
Analogous to cats affected by FIP, in human patients with severe
COVID-19, a cytokine storm syndrome is frequently observed that requires
treatment of hyperinflammation to reduce fatality rates. This cytokine
storm, which at the same time causes immunosuppression, is characterised
by increased interleukin (IL)-2, IL-6, IL-7, granulocyte-colony
stimulating factor, interferon-γ inducible protein 10, monocyte
chemoattractant protein 1, macrophage inflammatory protein 1-α, and
tumour necrosis factor-α (Mehta et al., 2020). Notably, a similar cytokine pattern is observed in cats with FIP (Paltrinieri, 2008).
Tocilizumab, an IL-6 receptor blocker monoclonal antibody, seems to be
highly effective in reducing the severity of SARS-CoV-2 induced
pneumonia (Favalli et al., 2020).
A
number of antivirals have been tested to control FIP. After several
unsuccessful attempts, research efforts have focused on two promising
antiviral classes, namely protease inhibitors and nucleoside analogues,
which inhibit viral replication either by blocking viral polyprotein
cleavage or terminating viral RNA transcription. Treatment of cats with
naturally occurring FIP with the 3C-like protease inhibitor GC376
induced a significant remission of disease signs and regression of
lesions in 19/20 animals, although only six of these animals remained in
remission for a long period (Pedersen et al., 2018).
In contrast, long-term and repeated treatment with nucleoside analogue
GS-441524 was successful in 25/26 cats with FIP, with only one animal
not responding to retreatment (Pedersen et al., 2019). In addition, the same drug was able to stop faecal shedding of FECV in naturally infected cats (Addie et al., 2020a).
Interestingly, a similar compound, the adenosine nucleoside
monophosphate prodrug GS-5734, is the active molecule of remdesivir,
largely employed as a potential antiviral against COVID-19. This drug
was shown to be more effective than lopinavir, which, similar to GC376,
acts against the viral 3C-like protease (Baden and Rubin, 2020).
3. Conclusions
Considering
the long-term experience gained with animal CoVs, veterinary medicine
could help to forge a better understanding of the origin and spread of
SARS-CoV-2 and drive future research in human medicine towards the
development of immunogenic and safe vaccines and effective antiviral
drugs. The successes and failures encountered with prophylaxis and
treatment of animal CoV diseases, such as FIP, might be useful to
address issues related to COVID-19 in a One Health approach. Likewise
the atypical pneumonia evident in pigs infected with PRCV, despite mild
clinical signs, and the pneumonia in cattle triggered by BCoV in complex
with respiratory bacteria and the stress of transport, may provide
models to understand factors that precipitate severe pneumonia in
COVID-19 patients.
Progressive
deforestation and anthropization of natural environments have largely
compromised some ecological niches where CoVs of wildlife are usually
confined. Also, human consumption of endangered wildlife, even if not
demonstrated to play a role in the onset of SARS-CoV-2, should be
restricted or banned, particularly in the unsanitary conditions
prevalent in live animal markets. Considering that animal CoVs spilled
over into humans in three different occasions in the short time span of
two decades, a more reverent management of the environment will be
fundamental to prevent future emergence of pandemic CoVs. Under these
circumstances, veterinary medicine should support policy makers to adopt
and promote sound and sustainable measures for management of the
environment and of animals and advance the global ‘One Health’ movement.
Footnotes
1SciCoM
- Comite Scientifique de l'Institué auprès de l'Agence Fédérale pour la
Sécurité de la Chaîne Alimentaire, 2020. Risque zoonotique du SARS-CoV2
(Covid-19) associé aux animaux de compagnie: infection de l'animal vers
l'homme et de l'homme vers l'animal (SciCom 2020/07). www.afsca.be.
3Consensus document on the epidemiology of severe acute respiratory syndrome (SARS). https://apps.who.int/iris/handle/10665/70863
References
- Addie D.D., Curran S., Bellini F., Crowe B., Sheehan E., Ukrainchuk L., Denaro N. Oral Mutian®X stopped faecal feline coronavirus shedding by naturally infected cats. Res. Vet. Sci. 2020;130:222–229. [PMC free article] [PubMed] [Google Scholar]
- Addie D., Houe L., Maitland K., Passantino G., Decaro N. Effect of cat litters on feline coronavirus infection of cell culture and cats. J. Feline Med. Surg. 2020;22:350–357. [PubMed] [Google Scholar]
- Baden L.R., Rubin E.J. Covid-19 - the search for effective therapy. N. Engl. J. Med. doi. 2020 [PMC free article] [PubMed] [Google Scholar]
- Buonavoglia C., Decaro N., Martella V., Elia G., Campolo M., Desario C., Castagnaro M., Tempesta M. Canine coronavirus highly pathogenic for dogs. Emerg. Infect. Dis. 2006;12:492–494. [PMC free article] [PubMed] [Google Scholar]
- Chang H.W., Egberink H.F., Halpin R., Spiro D.J., Rottier P.J. Spike protein fusion peptide and feline coronavirus virulence. Emerg. Infect. Dis. 2012;18:1089–1095. [PMC free article] [PubMed] [Google Scholar]
- Decaro N., Lorusso A. Novel human coronavirus (SARS-CoV-2): a lesson from animal coronaviruses. Vet. Microbiol. 2020 (in press) [Google Scholar]
- Decaro N., Campolo M., Desario C., Cirone F., D’Abramo M., Lorusso E., Greco G., Mari V., Colaianni M.L., Elia G., Martella V., Buonavoglia C. Respiratory disease associated with bovine coronavirus infection in cattle herds in southern Italy. J. Vet. Diagn. Investig. 2008;20:28–32. [PubMed] [Google Scholar]
- Decaro N., Mari V., Campolo M., Lorusso A., Camero M., Elia G., Martella V., Cordioli P., Enjuanes L., Buonavoglia C. Recombinant canine coronaviruses related to transmissible gastroenteritis virus of swine are circulating in dogs. J. Virol. 2009;83:1532–1537. [PMC free article] [PubMed] [Google Scholar]
- Decaro N., Mari V., Sciarretta R., Colao V., Losurdo M., Catella C., Elia G., Martella V., Del Giudice G., Buonavoglia C. Immunogenicity and protective efficacy in dogs of an MF59™ adjuvanted vaccine against recombinant canine/porcine coronavirus. Vaccine. 2011;29:2018–2023. [PMC free article] [PubMed] [Google Scholar]
- Favalli E.G., Ingegnoli F., De Lucia O., Cincinelli G., Cimaz R., Caporali R. COVID-19 infection and rheumatoid arthritis: faraway, so close! Autoimmun. Rev. 2020;20:102523. [PMC free article] [PubMed] [Google Scholar]
- Gerdts V., Zakhartchouk A. Vaccines for porcine epidemic diarrhea virus and other swine coronaviruses. Vet. Microbiol. 2017;206:45–51. [PMC free article] [PubMed] [Google Scholar]
- German A.C., Helps C.R., Harbour D.A. Proceedings from the 2nd international FCoV/FIP Symposium, Glasgow, 4-7 august 2002. J. Feline Med. Surg. 2004. FIP: a novel approach to vaccination; pp. 119–124. 2004 Apr;6. [PMC free article] [PubMed] [Google Scholar]
- Lai C.C., Liu Y.H., Wang C.Y., Wang Y.H., Hsueh S.C., Yen M.Y., Ko W.C., Hsueh P.R. Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): facts and myths. J. Microbiol. Immunol. Infect. 2020;1182(20):30040–30042. Pii: S1684. [PMC free article] [PubMed] [Google Scholar]
- Lam T.T., Shum M.H., Zhu H.C., Tong Y.G., Ni X.B., Liao Y.S., Wei W., Cheung W.Y., Li W.J., Li L.F., Leung G.M., Holmes E.C., Hu Y.L., Guan Y. Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins. Nature. 2020 2020 Mar 26. [PubMed] [Google Scholar]
- Liu S.L., Saif L.J., Weiss S.R., Su L. No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2. Emerg. Microbes Infect. 2020;9:505–507. [PMC free article] [PubMed] [Google Scholar]
- Lorusso A., Decaro N., Schellen P., Rottier P.J., Buonavoglia C., Haijema B.J., de Groot R.J. Gain, preservation, and loss of a group 1a coronavirus accessory glycoprotein. J. Virol. 2008;82:10312–10317. [PMC free article] [PubMed] [Google Scholar]
- Mehta, P., McAuley, D.F., Brown, M., Sanchez, E., Tattersall, R.S., Manson, J.J.; HLH Across Speciality Collaboration, UK, 2020. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet pii: S0140-6736(20)30628–0. [PubMed]
- Paltrinieri S. The feline acute phase reaction. Vet. J. 2008;177:26–35. [PMC free article] [PubMed] [Google Scholar]
- Pedersen N.C., Kim Y., Liu H., Galasiti Kankanamalage A.C., Eckstrand C., Groutas W.C., Bannasch M., Meadows J.M., Chang K.O. Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. J. Feline Med. Surg. 2018;20:378–392. [PMC free article] [PubMed] [Google Scholar]
- Pedersen N.C., Perron M., Bannasch M., Montgomery E., Murakami E., Liepnieks M., Liu H. Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis. J. Feline Med. Surg. 2019;21:271–281. [PMC free article] [PubMed] [Google Scholar]
- Pratelli A., Tinelli A., Decaro N., Cirone F., Elia G., Roperto S., Tempesta M., Buonavoglia C. Efficacy of an inactivated canine coronavirus vaccine in pups. New Microbiol. 2003;26:151–155. [PubMed] [Google Scholar]
- Pratelli A., Tinelli A., Decaro N., Martella V., Camero M., Tempesta M., Martini M., Carmichael L.E., Buonavoglia C. Safety and efficacy of a modified-live canine coronavirus vaccine in dogs. Vet. Microbiol. 2004;99:43–49. [PMC free article] [PubMed] [Google Scholar]
- Rauch S., Jasny E., Schmidt K.E., Petsch B. New vaccine technologies to combat outbreak situations. Front. Immunol. 2018;9:1963. [PMC free article] [PubMed] [Google Scholar]
- Saif L.J. Vaccines for COVID-19: perspectives, prospects, and challenges based on candidate SARS, MERS, and animal coronavirus vaccines. Euro. Med. J. 2020 [Google Scholar]
- Wan Y., Shang J., Sun S., Tai W., Chen J., Geng Q., He L., Chen Y., Wu J., Shi Z., Zhou Y., Du L., Li F. Molecular mechanism for antibody-dependent enhancement of coronavirus entry. J. Virol. 2020;94(5) Pii: e02015-19. [PMC free article] [PubMed] [Google Scholar]
- Wang Q., Vlasova A.N., Kenney S.P., Saif L.J. Emerging and re-emerging coronaviruses in pigs. Curr. Opin. Virol. 2019;34:39–49. [PMC free article] [PubMed] [Google Scholar]
- Wong S.H., Lui R.N., Sung J.J. Covid-19 and the digestive system. J. Gastroenterol. Hepatol. 2020 [PubMed] [Google Scholar]
- Zhou P., Yang X.L., Wang X.G., Hu B., Zhang L., Zhang W., Si H.R., Zhu Y., Li B., Huang C.L., Chen H.D., Chen J., Luo Y., Guo H., Jiang R.D., Liu M.Q., Chen Y., Shen X.R., Wang X., Zheng X.S., Zhao K., Chen Q.J., Deng F., Liu L.L., Yan B., Zhan F.X., Wang Y.Y., Xiao G.F., Shi Z.L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–273. [PMC free article] [PubMed] [Google Scholar]
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138383/?fbclid=IwAR2ts9maaoEZSDJrJfiRvseJvQOpoQ8JIYSVHyvCCNgIX-vT4req1Wfi4kY#!po=2.27273
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