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Do pets protect their owners in the COVID-19 era?

Original article: Do pets protect their owners in the COVID-19 era?; 12.5.2020

Jan Jurgiel, Krzysztof J. Filipiak, Łukasz Szarpak, Miłosz Jaguszewski, Jacek Smereka, Tomasz Dzieciątkowskig

Table of Content to hide
Introduction
Occurrence of animal coronavirus in domestic animals
Cross-reactivity and mobilization of the immune system
Conclusions
References

Introduction

The outbreak of COVID-19 and the global spread of SARS-CoV-2 occurred in Wuhan, China at the end of 2019. [1]. Following the infection of more than 120,000 people and nearly 5,000 dead, the World Health Organization has declared it a globally controllable pandemic [2]. In April 2020, the number of cases exceeded 2 million and the infection spread to more than 180 countries [3], [4]. Human coronaviruses (HCoV) have caused not only the current pandemic, but also the SARS and MERS epidemics, which have infected and claimed the lives of thousands of people. [5], [6]. Virological and genetic studies have confirmed that bats hosted both viruses, which spread further with civets and dromedaries. [7], [8], [9]. Recent studies suggest that specific animal species may be the source of different coronaviruses: bats for alpha- and beta-coronaviruses, birds for gamma- and delta-coronaviruses, and rodents for line A beta-coronavirus progenitors. [10], [11], [12].

The infection does not only affect wild animals and there are many known strains that affect livestock and domestic animals [13]. Symptoms caused by coronaviruses depend on the type of strain; may include gastrointestinal diseases (diarrhea, vomiting, anorexia), respiratory diseases (dyspnoea, cough, wheezing) and others. The animal origin of the new coronavirus has led to a discussion about the possible transmission of the disease through contact with domestic animals. General fear has increased after confirmation of SARS-CoV-2 in a tiger at a Bronx zoo [14]. In an effort to address these concerns, the World Health Organization has referred to a lack of evidence on the spread of the new coronavirus from pets to humans. [15].

Empirical observations indicate that the presence of domestic animals may have a positive effect on the course of COVID-19. Anecdotal evidence seeks to argue that COVID-19 only rarely affects veterinarians. In an interview, Sabina Olex-Condor, a Spanish doctor in Madrid, indicated that mildness was more common in pet-owned patients (available at: www.vetnolimits.com; www.psy.pl; www.plus.gloswielkopolski.pl) . The correlation between pet ownership and the moderate course of COVID-19 has not yet been confirmed. In our study, we went through a lot of literature and tried to find a possible explanation for this phenomenon. We hypothesize that contact with animal coronaviruses could lead to stimulation of the immune system, creating an effective response to SARS-CoV-2 infection.

Occurrence of animal coronavirus in domestic animals

A possible positive effect of animal ownership may be considered if the presence of animal coronaviruses in the pet population is high. Therefore, we studied works presenting the occurrence of animal coronaviruses. In our analysis, we focus on dogs for two reasons: 1) they are the most common species kept as pets [16], 2) canine coronaviruses can be easily transmitted to humans via drops. Feline coronaviruses are also detected in cats, but their symptoms are mainly related to the gastrointestinal tract or cause an unusual and usually fatal abnormal immune response to a viral infection, but animal-to-human transmission is very limited. [17].

Table 1 shows the detection rate in dogs. According to studies, detection of canine respiratory coronaviruses (CrCoV) is stable from 7.5% to 54.7%. Studies with the most significant sample (Priestnal et al. 2006 and More et al. 2020) showed detection: 54.7% for North America, 36.0% for the United Kingdom and 53.0% for New Zealand.

the authorNumber of samples (n)Detection rateMethodRegion
Priestnal et al. (2006) [18]1000
824		54.7%
36.0%		Serological testingNorth America
UK
More et al. (2020) [19]101553.0%Serological testingNew Zealand
Priestnal et al. (2007) [20]49023.3%Serological testingItaly
An et al. (2010) [21]48312.8%Serological testingKorea
Hielb et al. (2019) [22]2647.5%Serological testingAustria
Knesl et al. (2009) [23]25129.0%Serological testingNew Zealand
Mitchell et al. (2017) [24]24747.0%
7.7%		Serological testingEurope
Decarao et al. (2007) [25]21532.0%Serological testingItaly
Schulz et al. (2014) [26]1519.8%Molecular testingGermany
Erles et al. (2003) [27]11937.0%Molecular testingUK
Erles and Brownlie [28](2005)11338.9%Serological testingUK
Sowman et al. (2018) [29]9350.5%Serological testingNew Zealand
Wille et al. (2020) [30]8814.7%Molecular testingSweden
Table 1
Summary of coronavirus studies in dogs.

The data show that the incidence of CrCoV is high in dogs, which may indicate that people who have pets may have more frequent contact with different types of canine coronaviruses. Because infected pets may not have symptoms, owners' contact with pathogens may be asymptomatic.[31].

Cross-reactivity and mobilization of the immune system

The human immune system fights a variety of viral infections in three ways: 1) mediated by interferon, 2) mediated by cytotoxic cells, and 3) mediated by antibodies. [32]. The first is an interferon that provides an effective immune response by activating NK cells and macrophages, suppressing viral protein production, and regulating antigen presentation by T cells. Second, cytotoxic cells can directly kill virus-infected host cells with specific receptors and enzymes, stopping further infection. [33].

Antibody-mediated arrest of infection can be accomplished by various mechanisms: agglutination, phagocytosis, or complement systemic degradation, but all are stimulated by antibody opsonization. [32]. The effectiveness of this process is related to the specificity of the antibody - the ability of the antibody to distinguish between similar and different antigens. However, due to cross-reactivity, antibodies may react to another antigen due to the similarity of its structures [34]. A response to a similar antigen can lead to effective immune protection, as if it were performed against the primary target. Cross-reactivity is related to the degree of similarity of the primary antigen to the second, for example: neutralizing antibodies against the "old" SARS-CoV have a slight binding strength to the new coronavirus SARS-CoV-2.

The coronavirus genome encodes four structural and sixteen nonstructural proteins, approximately [35], [36]. Spike proteins (S-proteins) are structural proteins that recognize and attach to ACE2 located on the cell membrane of the airway epithelium and lung parenchyma. In their study, Tilocca and colleagues sequenced the amino acid sequence of SARS-CoV-2 and compared it with sequences derived from other animal coronaviruses. [37]. The analysis showed that the whole sequence similarity between SARS-CoV-2 and canine respiratory coronavirus (CrCoV) is 36,39% (comparison of GI protein QHR63290 with QAY30030). However, further investigation of the epitope sequence shows high homology: 57,14%, 80,00%, 83,33% and 100,00% in the CrCoV epitopes: 789-799, 754-764, 424-437 and 1139-1152. Based on the data, we hypothesize that repeated contact with animal coronaviruses may lead to immunization. This effect was confirmed by experimental studies. Research by Luo and colleagues showed that a CrCoV-derived nucleocapsid protein expressed in E. coli showed antigenic cross-reactivity with antisera against human coronaviruses [38].

Furthermore, Zhao and colleagues propose another explanation for the protective effect of contact with zoonotic coronaviruses [39]. Cross-reactivity with T-lymphocytes may elicit an immune response. CD4 + memory T cells in the airway epithelium can efficiently produce interferon-gamma, leading to the activation of other cells and an efficient response.

Thus, pet-owned patients may have had a mild course of SARS-CoV-2 infection, as observed in Spain. Repeated contact with pathogens can function as an immune mobilization against SARS-CoV-2 in many different ways.

Conclusions

  1. Canine respiratory coronaviruses are common in dogs.
  2. Ownership of the animal can lead to contact with canine coronaviruses.
  3. Repeated exposure to canine coronaviruses may stimulate the human immune system and provide an effective response to SARS-COV-2.
  4. A further examination of the correlation between pet ownership and the course of COVID-19 is needed. Such data, although recovered, is worth analyzing.

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